Table of Contents - American Association of Clinical Endocrinologists

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Table of Contents
2010 ABSTRACT
1
Adrenal
18
Diabetes
67
Hypoglycemia
68
Lipid Disorders
74
Metabolic Bone Disease
96
Obesity
102
Other
123
Pituitary Disorders
137
Reproductive Endocrinology
144
Thyroid Disease
181
Subject & Author Index
209
Author Index
ABSTRACTS
ADRENAL DISORDERS
Therefore, additional noninvasive tests are still required to
be helpful in the differential diagnosis of adrenal masses.
Previous studies reporting increases in MMP-9 levels with
norepinephrine administration support the findings of the
present study. In the present study, similar with PC patients,
we determined high levels of MMP-9 in the patients with CS,
which significantly decreased in the postoperative period.
Conclusion: In this study we demonstrated higher
MMP-9 levels in functional adrenal tumors compared to nonfunctional adrenal tumors for the first time in the literature.
Our data suggest that serum MMP-9 levels may be useful
in the differential diagnosis of benign subclinical functional
adrenal tumors from nonfunctional benign adrenal tumors.
Abstract #100
USING SERUM MATRIX METALLOPROTEINASE-9
LEVELS IN THE DIAGNOSIS OF FUNCTIONAL
ADRENAL TUMORS
Serhat Isik, MD, Dilek Berker, MD, Gonul Erden, MD,
Yasemin Ates Tutuncu, MD, Hatice Nursun Ozcan, MD,
Sedat Caner, MD, Bekir Tekelek, MD, Yusuf Aydin, MD,
Serdar Guler, MD
Objective: The aim of the present study is to demonstrate
the diagnostic value of serum matrix metalloproteinase-9
(MMP-9) levels in functional benign adrenal tumors.
Methods: Among 370 adrenal tumor cases, 52 patients
with adrenal incidentaloma that met the inclusion criteria and
25 healthy individuals were included in the study. Of the 52
patients, 2 patients with adrenocortical carcinoma have been
excluded. Remaining patients were divided into 2 groups.
Group I included 20 patients with functional adrenal tumor
[14 with Cushing syndrome (CS) and 6 with pheochromocytoma (PC)] and group II included 30 patients with nonfunctional adrenal tumor. Patients underwent routine endocrinologic examinations and MMP-9 levels were compared
pre- and post-operatively.
Results: Matrix metalloproteinase-9 levels were higher
in patients with non-functional adrenal tumors and functional
adrenal tumors compared to healthy controls (p<0.001). In
addition, MMP-9 levels of patients with functional adrenal
tumors were significantly higher than those with non-functional adrenal tumors (p=0.002). After the surgical operation
MMP-9 levels decreased significantly both in patients with
CS and in those with PC (p<0.001); however, patients with
CS and with PC had similar MMP-9 levels both pre- and
post-operatively. There was no significant linear correlation
between the tumor volume and MMP-9 levels (r=0,214 and
p=0,136). A significant positive correlation was determined
between preoperative MMP-9 and cortisol levels obtained at
the baseline and also after classic DST (r=0.402, p=0.003;
r=0.357, p=0.006 respectively). A significant positive correlation was determined between MMP-9 levels and 24-hour
fractionated metanephrine and adrenaline levels (r=0.938,
p=0.006 and r=0.965, p=0.002, respectively).
Discussion: Endocrine tests may sometimes be inadequate, especially in subclinical functional adrenal tumors.
Abstract #101
PHEOCHROMOCYTOMA SECRETING LARGE
QUANTITIES OF BOTH EPINEPHRINE AND
NOREPINEPHRINE PRESENTING WITH EPISODES
OF HYPOTENSION AND SEVERE ELECTROLYTE
IMBALANCE
Issac Sachmechi, MD, FACP, FACE, Harigopal Reddy, MD,
Wiroon Sangsiraprapha, MD, Ricardo Lopez, MD, FCCP,
David Reich, MD, FACE, Paul Kim, MD, FACE,
Gurpreet Singh, MD
Objective: To report an unusual case of Pheochromocytoma. Who presented with palpitations, headaches, sweating, anxiety and severe electrolyte imbalances.
Case Presentation: A 51 year old woman with type 2
diabetes mellitus presented with chest pain and vomiting. She
had episodes of palpitations, sweating and weakness for the
last 3-4 years. These episodes were self-resolving and lasted
10-15 minutes. On admission, her blood pressure was 130/80
mmHg, pulse 117/minute, respirations 24/min and spO2 100%
on room air. While in the hospital, she had episodes of orthostatic hypotension, sweating, palpitations and anxiety lasting
for 15-20 minutes. Her pulse remained high, ranging between
110-140/min. Her electrolyte panel revealed persistently
low magnesium, potassium and calcium despite aggressive
replacement. She also had persistent hyperglycemia requiring an insulin drip. Adrenal MRI revealed an 11x11 cm right
suprarenal heterogeneous mass. Further workup revealed 24
hr urine metanephrine 34,400 mcg (90-315mcg/24 hr), serum
potassium 3.1mEq/liter (3.5-5.5 mEq/liter), magnesium
0.62 mg/dL (1.7-2.7 mg/dL), ionized calcium 3.23 mg/dL
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ABSTRACTS – Adrenal Disorders
(4.25-5.25 mg/dL), 24 hr urine and calcium magnesium
1460 mg (100-150 mg/24 hr), 24 hr urine calcium 369mg
(<250 mg/24 hr), vitamin D, 25 OH 12ng/ml (20-100 ng/
ml). A diagnosis of pheochromocytoma was made, after 3
weeks of Preoperative management with doxazosin 1mg
once daily, propanolol and intravenous fluid. A right adrenalectomy was performed. Postoperatively, she remained
hemodynamically stable. Her electrolytes, blood glucose
and 24 hour urine metanephrines, calcium and magnesium
remained normal.
Discussion: Hypotension in our patient can be
explained by down regulation of vascular alpha-1 adrenergic receptors from exposure to large amounts of catecholamines, resulting in decreased peripheral resistance. Decreased intravascular volume also plays a role.
Persistent hypokalemia is explained by epinephrine
stimulating the beta 2 receptors causing an intracellular
shift of potassium. Hypomagnesaemia is explained by
the increased urinary loss of magnesium, due to hypokalemia. Hypocalcaemia in our patient is likely explained
by increased urinary loss of calcium due to hypokalemia,
hypomagnesaemia and low 25(OH) vitamin D, as well as
calcium sequestration in the tumor and within platelets.
Conclusion: Although most pheochromocytomas
present with episodes of hypertension, rarely pheochromocytomas can present mainly with hypotensive episodes. The clinician should be aware of the possibility
that hyperglycemia, hypokalemia, hypomagnesaemia and
hypocalcaemia can be part of the presentation of a pheochromocytoma in the absence of hypertension.
determined each study’s risk of bias. Standard deviation
score (SDS) for final height and corrected height (defined
as final height SDS – mid-parental height SDS) were estimated from each study and pooled using random-effects
meta-analysis. The I2 statistic was used to assess heterogeneity across studies.
Results and Discussion: We found 35 eligible studies most of which were retrospective single-cohort studies. The final height SDS achieved by CAH patients on
treatment was -1.38 (-1.56, -1.20; I2 = 90.2 %). This was
not significantly associated with age at diagnosis, gender, type and dose of steroid and age of onset of puberty.
Mineralocorticoid users had a better height outcome
in comparison to the non-users (p=0.02). The corrected
height SDS was -1.03 (-1.20, -0.86; I2 = 63.1%). Most of
the observed inconsistency across studies remains unexplained. Data on the use and efficacy of growth-enhancing
drugs and on parents’ or patients’ satisfaction with height
achieved were sparse.
Conclusion: Very low quality evidence suggests that
the final height of CAH patients treated with glucocorticoids is lower than the population norm and is lower than
expected given parental height.
Abstract #103
A CURIOUS CASE OF MEN 2 A WITH
SPORADIC NON-SECRETORY PITUITARY
MACROADENOMA
Lubna Mirza, MD, Hal Scofield, MD,
Nelson Agudelo, MD
Abstract #102
HEIGHT IN PATIENTS WITH CONGENITAL
ADRENAL HYPERPLASIA: A SYSTEMATIC
REVIEW AND META-ANALYSIS
Objective: Timely diagnosis and treatment of MEN
2A syndrome is important. Prophylactic thyroidectomy
with autotransplantation of the parathyroids is the primary
preventive measure for individuals with an identified
germline RET mutation and genetic testing recommendation for biological children to prevent significant morbidity and mortality with medullary thyroid cancer.
Case presentation: A 62 year old hypertensive white
man underwent elective unilateral adrenalectomy and
nephrectomy for an incidentally discovered 13 centimeter
pheochromocytoma. This was seen on a magnetic resonance imaging study which was performed due to back
pain. The day after surgery he had headaches and blurred
vision. An MRI brain revealed a 1.8 centimeter pituitary
macroadenoma. The pituitary macroadenoma was nonsecretory. Further work-up revealed an elevated high
parathyroid hormone level with normal calcium; probably
related to a low 25 OH-D3 level. There was a low total
testosterone level, low luteinizing and follicle stimulating
hormone levels. Thyroid function tests were abnormal suggestive of the euthyroid sick syndrome. A non-stimulated
Kalpana Muthusamy, MD, Mohamed B. Elamin, MBBS,
Hassan M. Murad, MD, MPH,
Victor M. Montori, MD, MSc
Objective: To determine the distribution of achieved
height in patients with classic CAH diagnosed at infancy
or early childhood and treated with glucocorticoids. We
also sought to determine patients’ satisfaction with their
achieved height and predictors of final height.
Methods: We searched MEDLINE, EMABSE,
Cochrane library, ISI Web of Science and Scopus through
September 2008 and the reference section of included
studies. Eligible studies included patients diagnosed with
CAH before age 5 and followed to final height. There
were no restrictions in terms of study design or language. Reviewers working in duplicate, independently
extracted data on study characteristics and outcomes, and
–2–
calcitonin level was elevated. Retrospective review of the
surgical pathology suggested an aggressive pheochromocytoma; and a neck ultrasound neck showed thyroid nodules. This patient had mixed features of MEN1 and MEN2
syndrome. Genetic testing for MEN1 returned negative.
A DNA sequence analysis for the mutations in exons 10,
11,13,14,15 and 16 of the RET proto-oncogene demonstrated a known pathogenic mutation Cys618Ser in exon
10. This mutation was consistent with a diagnosis of MEN
2A/ familial medullary thyroid carcinoma. The patient
subsequently underwent total thyroidectomy. Pathology
showed the expected medullary carcinoma of the thyroid.
A daughter, his only biological child was found to not
express this mutation.
Discussion: MEN 2 A syndrome is associated with
development of medullary thyroid cancer (100%), pheochromocytoma (50%) and hyperparathyroidism (30%). It
is an unusual finding to see a pituitary adenoma in MEN
2 which is typically present in MEN 1 syndrome. This
seems to be a sporadic finding in this patient.
Conclusion: Genetic testing can guide treatment
decisions in these types of cases where a clear diagnosis
cannot be made by other clinical and biochemical measurements alone.
Adrenal vein sampling was performed and a greater cortisol secretion from the right than the left adrenal gland was
detected. After right adrenalectomy, all her biochemical
markers improved, including 24 hour urinary free cortisol and midnight salivary cortisol levels. The ACTH level
gradually increased to a maximum of 85 pg/ml (N= 10-60
pg/ml) at 18 months post-surgery and declined to 45 pg/
ml at 27 months. However, dexamethasone suppression
remains abnormal.
Conclusion: We describe a unique case of a woman
with hypercortisolism due to both a pituitary adenoma
and an ACTH dependent adrenal adenoma. The evidence
for the Cushing disease included the biochemical testing,
pituitary pathology and post-operative normalization of
glucocorticoids. The recurrence of hypercortisolism in a
patient with an adrenal nodule raised the important clinical
differential of recurrent Cushing disease vs. primary adrenal pathology. The adrenal adenoma was ACTH dependent since both cortisol levels and tumor size declined
post-hypophysectomy and the cortisol levels declined
more than 50% with dexamethasone suppression. Urinary
free cortisol, ACTH, and cortisol levels are normal and
salivary cortisol levels show a normal circadian rhythm,
but dexamethasone suppression remains abnormal.
Abstract #104
Abstract #105
RECURRENCE OF HYPERCORTISOLISM DUE
TO AN ACTH-DEPENDENT ADRENAL NODULE
AFTER THE RESECTION OF ACTH-PRODUCING
PITUITARY ADENOMA: CASE REPORT
IMPACT OF CONTINUOUS AND PULSATILE
CORTISOL INFUSIONS ON RESTRAINING
ACTH SECRETION
Paul Aoun, DO, PhD, Jean Wigham, Joy Bailey,
Daniel M. Keenan, PhD, John M. Miles, MD,
Johannes D. Veldhuis, MD
Jhosvani Miguel, MD, Alan Burshell, MD,
Amer Kassar, MD, Saba Khayal, MD
Hypothesis: Pharmacologically continuous and physiologically pulsatile cortisol infusions exert unequal negative feedback on ACTH secretion.
Methods: Preliminary aggregate data on 11 (6M/5F)
healthy participants, ages 45-72, pretreated with leuprolide prior to either placebo or sex-steroid addback.
Subjects were assigned randomly to 4 overnight visits
in a within-subject, placebo-controlled crossover design.
Experimental interventions included: 1) oral placebo and
a 14-h saline infusion (22:00-12:00), 2) saline infusion
during reversible inhibition of adrenal cortisol synthesis
with ketoconazole (KTCZ), 3) KTCZ + 14-h continuous
cortisol infusion (7 mg/m2/14h), and 4) KTCZ + 10-min
cortisol pulses every 90 min (total 7 mg/m2/14h). Blood
was sampled every 10 min for a total of 8 h (04:00-12:00)
for measurement of cortisol and ACTH. Oral hydrocortisone was given at the end of each session. The primary
endpoints were mean, peak, and nadir ACTH concentrations and approximate entropy (a sensitive measure of
ensemble feedback control).
Objective: To present the management challenges
associated with hypercortisolism with both an ACTH producing pituitary adenoma and an ACTH-dependent cortisol secreting adrenal adenoma.
Methods: We present the clinical and laboratory findings before and after surgical interventions to the pituitary
gland and the adrenal gland in a patient with Cushing
syndrome.
Results: A 62 year old patient underwent transsphenoidal resection of the pituitary gland for Cushing disease
based on biochemical testing. Brain MRI did not show any
pituitary gland abnormality but a right adrenal adenoma
and a thickening of the left adrenal gland were detected
by CT scan. Surgical pathology revealed the presence of
an ACTH secreting pituitary adenoma. Clinical and biochemical improvement lasted for about one year followed
by return of the hypercortisolism. MRI of the pituitary
showed an empty sella. CT scan of adrenal gland showed
a decreased in the size of the right adrenal adenoma.
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Results: The paradigm achieved statistically comparable mean cortisol concentrations during both continuous
and pulsatile infusions compared with double placebo (11
mcg/dL ± 0.35). Cortisol peaks were lower (p<0.001) in
the continuous (13 mcg/dL ± 0.88) and pulsatile (14 mcg/
dL ± 0.84) groups compared with placebo (19 mcg/dL ±
0.81). Cortisol nadirs were higher in the continuous (8.9
mcg/dL ± 0.63; p<0.01) but not pulsatile group relative
to placebo. Both infusions normalized mean, peak, and
nadir ACTH concentrations relative to the double placebo (21 ± 2.3; 42 ± 4.7; and 11 ± 1.4 ng/L, respectively).
Cross-approximate entropy of cortisol feedback on ACTH
showed greater irregularity during both continuous (1.21
± 0.057) and pulsatile (1.11 ± 0.03) infusions compared
with placebo (0.88 ± 0.059; p<0.01). Cross-approximate
entropy did not differ between the two infusions groups.
Conclusion: Both continuous and pulsatile cortisol
infusions restrain ACTH secretion albeit with incomplete
normalization of irregularity. We postulate that normalized
regularity requires adequate peak cortisol concentrations.
laboratory was 45 pg/mL for plasma MN, 100 pg/mL for
plasma NMN, 350 μg/24h for urinary MN and 600 μg/24h
for urinary NMN. Putative thresholds were calculated by
receiver operating characteristic (ROC) an analysis to balance between sensitivity (Sens) and specificity (Spec).
The Local Ethical committee approved the study.
Results: Plasma MN and NMN were significantly
higher in PHEO than in INCID and HBP groups (136
[20-3365], 16 [10-62] and 14 [10-80] pg/mL respectively,
P<0.05; 1381 [150-6030], 42 [15-150] and 47 [12-167]
pg/mL respectively, P<0.05). Urinary MN and NMN were
also significantly higher in PHEO than in INCID and
HBP groups (404 [112-3000], 94 [49-400] and 77 [14499] μg/24h respectively, P<0.05; 1500 [444-120000],
347 [120-1000] and 316 [100-1422] μg/24h respectively,
P<0.05). ROC analysis indicated plasma-free NMN as
the best single test in the diagnosis of pheochromocytoma
(AUC=0.999 [CI 95%, 0.98-1.0]) followed by urinary
NMN (AUC=0.963 [CI 95%, 0,886-0,993]), plasma-free
MN (AUC=0.945 [CI 95% 0,902-0.972] and urinary MN
(AUC=0.927 [CI 95%, 0,837-0,976]). The best cut-off
value for the diagnosis of pheochromocytoma, as indicated by ROC analysis, is 143 pg/mL for plasma-free
NMN (100% Sens, 98.9% Spec), 440 μg/24-h for urinary
NMN (100% Sens, 85.7% Spec), 27 pg/mL for plasma
MN (88.2% Sens, 88.6% Spec) and 186 μg/24-h for urinary MN (91.7% Sens, 85.7% Spec).
Conclusions: EIA provides a good alternative to
HPLC for measurement of plasma and urinary metanephrines. Plasma-free normetanephrine has the best singletest accuracy in the diagnosis of pheochromocytoma.
Abstract #106
EVALUATION OF AN ENZYME
IMMUNOASSAY FOR PLASMA AND URINARY
METANEPHRINES IN THE DIAGNOSIS OF
PHEOCHROMOCYTOMA
Dan Alexandru Niculescu, MD,
Monica Livia Gheorghiu, MD, Ionela Baciu,
Ana Maria Stefanescu, Corin Badiu, MD,
Catalina Poiana, MD, Serban Radian, MD,
Raluca Trifanescu, MD, Mihail Coculescu, MD
Abstract #107
RETROCAVAL CATECHOLAMINE-SECRETING
PARAGANGLIOMA
Objective: High performance liquid chromatography
(HPLC) is the gold standard method for measurement
of plasma and urinary metanephrines but it is a cumbersome, time-consuming technique with limited availability. Our objective was to assess the diagnostic accuracy of
an enzymatic immunoassay (EIA) for plasma and urinary
metanephrine (MN) and normetanephrine (NMN) in the
diagnosis of pheochromocytoma.
Methods: This retrospective, single-center study
included 227 patients: 26 with histologically proven pheochromocytoma (group PHEO), 103 patients with adrenal
incidentalomas (group INCID) of whom 17 with exclusion
of pheochromocytoma at histological examination and
98 patients tested for high blood pressure and clinically
considered not to harbour adrenal tumors (group HBP) of
whom 29 with negative CT/MRI scans. All patients had
at least one spontaneous plasma sample and/or one 24-h
urine sample. Plasma-free and urinary MN and NMN
were measured by an enzyme immunoassay. Results are
given as median (range). Upper limit of normal of our
Soumia Vijayan, MD, Shwetha Thukuntla, MD,
Pratima Kumar, MD
Objective: To describe a case of paraganglioma (PGL)
presenting as refractory hypertension and retrocaval mass
Case Presentation: A 75 yo female with poorly controlled HTN who was on multiple medications was referred
to our hospital for evaluation of GI bleed. CT Abdomen
revealed a 5.7 cm mass between the inferior vena cava
and the right adrenal gland as well as right 2.9 cm and
left 2.7 cm adrenal masses. Biopsy of the mass done at
another hospital revealed a neuroendocrine tumor. 24 hour
urine metanephrines were 2254 mcg/d (30-350), normetanephrines 3151 mcg/d (50-650); epinephrine 51 mcg/d
(0-25), norepinephrine 146 mcg/d (0-100), dopamine 242
mcg/d (60-440) and creatinine was 806 mg/d (500-1400)
Plasma free metanephrines were 3.82 nmol/L (0-0.49),
–4–
normetanephrines 8.1 nmol/L (0.0-0.89) and chromogranin A was 5115 ng/ml (0-50).There was no evidence of
primary hyperaldosteronism or Cushing syndrome. Serum
calcitonin and calcium levels were normal. I-123MIBG
scintigraphy revealed positive uptake in the retroperitoneal mass, consistent with a PGL with no definite adrenal
activity. MRI abdomen showed a 4.6 x 4.4 cm retrocaval
mass with hyperintensity on T2 images most likely a PGL
and bilateral benign adrenal adenomas. Patient underwent
a successful resection of the PGL along with right adrenalectomy after adequate alpha and beta blockade. Surgical
pathology was consistent with a 5.5 cm PGL and 3 cm
right adrenal adenoma. Chromogranin A was 1292 ng/ml
one week after surgery and her BP was normal at follow
up .Genetic testing for succinate dehydrogenase B, C and
D (SDHB, SDHC and SDHD) mutations were negative.
Discussion: PGL are rare neuroendocrine neoplasms
that arise from extra-adrenal chromaffin cells and can be
familial or sporadic. They may be associated with VHL
disease, MEN 2, neurofibromatosis and succinate dehydrogenase (SDHx) gene mutations. The PGL of sympathetic origin are usually catecholamine secreting, are
intraabdominal and are associated with SDHB mutation
while the PGL of parasympathetic origin are mostly nonfunctioning, are in the head and neck and are SDHC- and
SDHD- related.
Conclusion: Our case emphasizes that paraganglioma
should be considered in the work up of an abdominal mass
and must be evaluated for excess catecholamine secretion so adequate alpha blockade can be achieved prior to
resection. Genetic testing for SDHx mutations should also
be done in all patients with paragangliomas and if positive, genetic testing should be done in their first-degree
relatives because of the high risk of malignancy associated with these mutations particularly in those with SDHB
mutations.
CT. Left Adrenal lesion (LAL) measured 5.7 x 4.7 cm
described radiologically as angiomyolipoma, and Right
Adrenal lesion (RAL) measured 4.6 x 3.5 cm suggestive of
adenoma. Plasma rennin activity 1.2 ng/ml/h, Aldosterone
<2 ng/dl, Aldosterone/rennin of 1.7. Norepinephrine 71
mcg/24hr, Epinephrine 8 mcg/24hr, Dopamine 176mcg/
dl, Normetanephrine 211mcg/24hr, Metanephrine 58
mcg/24hr, Venillymandelic acid 2.2 mg/24hr, all metanephrines and catecholamines were within normal limits.
Fasting cortisol 13.56 ug/dl, dexamethasone suppression
test was positive with cortisol levels @ 8 am of 10.58
ug/dl, ACTH < 5pg/ml, Urine free cortisol was 37.3
mcg/24hr and 17 ketosteroids 7.1 mg/24hr evidencing a
SCS. Patient underwent bilateral adrenalectomy by open
laparotomy due to size of both masses. Pathology reported
LAL was consistent with angiomyolipoma and the RAL
was consistent with non functional adenoma associated
with adrenal cortex hyperplasia.
Discussion: Adrenal incidentaloma is a lesion greater
than 1cm in diameter found by radiologic imaging when
investigating for unrelated symptoms and/or signs of an
adrenal tumor. The prevalence peaks between the 50th
and 60th year and is particularly high in patients with features of the metabolic syndrome. Discovery of an adrenal
mass raises two important questions: Is it malignant? Is
it functioning? Bilateral adrenal masses can be seen with
metastatic disease, congenital adrenal hyperplasia, cortical adenomas, lymphoma, hemorrhage, ACTH-dependent
Cushing syndrome, pheochromocytoma, amyloidosis,
infiltrative disease of the adrenal glands, among others.
After evaluation of our patient a SCS was diagnosed,
which is the most frequent hormonal abnormality detected
in patients with adrenal incidentalomas. The risk of malignancy is low, but it increases with the size of the mass,
for this reason our patient underwent surgery. Nonetheless
after bilateral adrenalectomy was performed, our patient
improved her blood sugar levels and hypertension.
Conclusion: Bilateral adrenal incidentalomas is a
very rare condition and surgical intervention can improve
the metabolic derangement present in SCS.
Abstract #108
BILATERAL ADRENAL INCIDENTALOMAS
AND SUBCLINICAL CUSHING SYNDROME IN A
DIABETIC PUERTO RICAN WOMAN
Abstract #109
Mariela Nieves-Rodriguez, MD,
Myriam Allende, MD, FACP, FACE, MBA,
Margarita Ramirez-Vick, MD, FACP, FACE,
Marielba Agosto, MD, Meliza Martinez, MD
CUSHING SYNDROME AND SECONDARY
ADRENAL INSUFFICIENCY IN ASTHMATIC
PATIENTS ON HAART (HIGHLY ACTIVE
ANTIRETROVIRAL THERAPY)
Objective: To describe a case of bilateral adrenal
masses and subclinical Cushing syndrome (SCS) in a diabetic and hypertensive puerto rican woman.
Case Presentation: A 64 y/o woman with DM-2, HTN,
Dislipidemia and Osteoporosis who came to our clinics
due to bilateral adrenal masses found on abdomino-pelvic
Praveena Gandikota, MD, Kara Rysman Fine, MD
Objective: To increase awareness regarding a potentially life threatening interaction between inhaled steroids
and HAART.
–5–
Abstract #110
Case Presentation: A 57 year old woman was admitted with hyperglycemia for 3 weeks without response to
maximal doses of Glucophage and Diabeta. The patient
had a history of HIV, diabetes mellitus diet controlled
since 2004 and asthma. Her HAART regimen was stable
since 2005 and included Ritonavir, Atazanavir, Abacavir
and Lamuvidine. She was hospitalized for pneumonia 5
weeks prior to admission and was placed on antibiotics,
steroids and Advair 250/50 mcg (Fluticasone/ Salmeterol)
inhaler twice daily. Intravenous steroids were given for
5 days followed by oral taper. Last dose of oral steroids
was 3 weeks before this admission. She reported 15
pound weight gain over 3 weeks, predominantly in face
and abdomen. She required 70 units of insulin daily to
keep blood sugars between 150 and 200 mg/dl. Physical
examination was significant for buffalo hump and moon
facies. Further evaluation showed that with 250mcg
ACTH (Adrenocorticotropic Hormone) stimulation, cortisol at 0min, 30min and 60min were <0, 3 and 4 mcg/dl
respectively.
Discussion: Ritonavir is commonly used as part of
HAART and is a potent inhibitor of cytochrome P450
3A4.Normally, plasma levels of inhaled fluticasone are
low due to extensive first pass metabolism through cytochrome P450 3A4. Administration of both fluticasone
and ritonavir leads to increased plasma levels of fluticasone because of inhibition of its metabolism. This leads
to iatrogenic Cushing syndrome and secondary adrenal
insufficiency as seen in our patient. This phenomenon
has been described with as little as 2 weeks of fluticasone
therapy in patients on ritonavir. Additionally, cases have
been reported with low dose of 500 mcg/day of fluticasone
and the lower boosting dose of ritonavir of 100 mg/day as
well. Patients with HIV can also develop HIV- associated
lipodystrophy which can delay the diagnosis of Cushing
syndrome. During periods of stress, these patients need
additional corticosteroid support. It is also important to
note that on abrupt discontinuation of fluticasone, patients
can develop signs and symptoms of adrenal insufficiency
necessitating slow taper or temporary oral corticosteroid
therapy.
Conclusion: It is imperative that physicians are aware
of interaction between ritonavir and inhaled fluticasone
leading to iatrogenic Cushing syndrome and secondary
adrenal insufficiency. High index of suspicion is needed as
HIV-lipodystrophy can confound recognition of Cushing
syndrome.
BILATERAL ADRENAL HEMORRHAGE
FOLLOWING UNCOMPLICATED CAESAREAN
SECTION: A CASE REPORT AND REVIEW
Brian Ellis Michael, MD, FACE
Objective: To report the occurrence of bilateral adrenal hemorrhage in a healthy young female after uncomplicated Caesarean section.
Case Presentation: A 20 year old gravida 1 para 1
presented to the hospital with abrupt onset progressive left
upper quadrant and left flank pain. She was one week post
partum from an uncomplicated C-section with estimated
600ml blood loss. There was no recent trauma. There was
no GI or urinary symptoms. Past history was negative.
Family history was negative for any known coagulopathy. She took no medications. Physical findings included
mild left upper quadrant and left flank percussion tenderness and were otherwise completely normal. Routine lab
evaluation was within normal limits. CT imaging of the
abdomen revealed stranding of the left adrenal gland consistent with adrenal hemorrhage and no other findings.
Random AM cortisol value was 12ug/dl and stimulated
cortisol after 250ug cosyntropin was 32ug/dl. The patient
was treated conservatively and improved sufficiently for
discharge within 48 hours. One week later she presented
with identical spontaneous symptoms in the right upper
quadrant and right flank. Routine laboratory values were
all normal. CT imaging was repeated and demonstrated
right adrenal hemorrhage with no other findings. Repeat
basal and stimulated cortisol values were similar to the
initial hospitalization. Upright aldosterone values were
normal. Complete hematologic evaluation for coagulation
abnormalities was within normal limits. After conservative treatment with analgesics she again improved sufficiently for discharge. Subsequent course over two years
has been uneventful, including additional uncomplicated
out patient surgeries. Additional cosyntropin stimulation
testing at three months after the second episode of adrenal
hemorrhage was normal.
Discussion: Unilateral or bilateral adrenal hemorrhage has been reported as a complication of sepsis,
hypotension, anticoagulant therapy, trauma, hypotension, bleeding disorders and some surgical procedures.
This patient report appears to be the first reported case of
late onset bilateral adrenal hemorrhage shortly following
uneventful normal Caesarean section with no identifiable
precipitating cause.
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Abstract #111
concurrently. Even when an adrenal adenoma is identified, AVS is an important diagnostic step because a contralateral adrenal adenoma may not be visible on computed
imaging.
COMBINED CONN ADENOMA AND
SUB-CLINICAL CUSHING SYNDROME
Abstract #112
Amitpal Kohli, MD, George Dailey, MD,
William Young, MD
NORMOTENSIVE PHEOCHROMOCYTOMA
Objective: To report a patient with bilateral adrenocortical adenomas - one producing excess aldosterone and
the other producing excess cortisol.
Case Presentation: A 54-year-old man presented
with hypertension and hypokalemia. The plasma aldosterone concentration (PAC) was 12 ng/dL (N<28 ng/dL)
and the plasma renin activity (PRA) was 0.1 ng/mL/hr
(N<0.65 ng/mL/hr). After a 2-h saline infusion, the PAC
increased from 10 to 16 ng/dL (N<5 ng/dL). Abdominal
CT revealed a 1.8 cm right adrenal mass and an apparent normal appearing left adrenal. The 24-h urinary free
cortisol was 222.5 mcg (4-50 mcg), and 24-h urine metanephrine was 109 mcg (N<315 mcg). The serum ACTH
concentration was <5 pg/mL (N 7-50 pg/mL). The serum
cortisol concentrations after 1-mg and 8-mg dexamethasone suppression tests were 16.9 mcg/dL and 17.8 mcg/
dL, respectively. The patient lacked signs or symptoms
of clinical Cushing syndrome. A second opinion was
requested. Adrenal venous sampling (AVS) showed a cortisol step-up on the side of the right visible adenoma, and
an aldosterone step-up on the left. A surgical consultant
declined to operate on the normal appearing left adrenal
gland. After a year of marginally successful medical therapy for hyperaldosteronism, repeat adrenal CT showed an
apparent 9 mm left-sided adenoma. Repeat AVS at Mayo
Clinic Rochester showed aldosterone concentrations of
9700 ng/dL (left AV), 180 ng/dL (right AV), and 40 ng/
dL (IVC). Cortisol concentrations were 94 mcg/dL (left
AV), 1016 mcg/dL (right AV), and 21 mcg/dL (IVC).
Subsequent bilateral adrenalectomy found a 9 mm left
adrenal adenoma and a 2.5 cm right adrenal adenoma.
Glucocorticoid and mineralocorticoid autonomy were
cured.
Discussion: Conn adenoma and adrenal-dependent
Cushing syndrome are uncommon disorders. The occurrence of bilateral simultaneously functioning adrenal
adenomas is extremely rare. Most reported cases have
involved a single adrenal adenoma overproducing aldosterone and cortisol. In most cases, patients lacked typical signs and symptoms of Cushing syndrome - termed
sub-clinical Cushing syndrome. We describe a rare patient
with a right adrenal cortisol-producing adenoma and a left
adrenal aldosterone-producing adenoma. Our patient also
lacked signs and symptoms of Cushing syndrome.
Conclusion: As previously reported, Conn adenoma
and adrenal-dependent Cushing syndrome can exist
Archana Reddy, MD, G. Matthew Hebdon, MD, PhD,
Ved V. Gossain, MD, FACP, FACE
Objective: To present a case of normotensive pheochromocytoma and discuss outpatient preoperative
management.
Case Presentation: A 74 year old woman had a CT
angiogram for evaluation of leg pain when an adrenal
mass was incidentally discovered. She denied history of
hypertension, headaches, sweating, palpitations, weight
loss, abdominal or chest pain. She had a history of rheumatoid arthritis and hypercholesterolemia. Physical exam
revealed blood pressure (BP) 100/60 without orthostatic
hypotension. The remainder of the examination was unremarkable except for choreoathetosis of arms and face.
CT angiogram revealed a 4.5cm left adrenal mass which
was confirmed by MRI. PET-CT with FDG showed 4-5
cm lesion with density of 17-18 Hounsfield units. Plasma
free metanephrines were 18.9 nmol/L (normal <0.5) and
free normetanephrines were 3.49 nmol/L (normal < 0.90).
A diagnosis of normotensive pheochromocytoma was
made and left adrenalectomy was recommended. A baseline low BP precluded the initial use of α blockers. The
patient increased her salt intake, received intravenous normal saline at home and her BP increased to 118/70. After
two days of outpatient hydration Phenoxybenzamine, 10
mg/day was started and gradually increased to 20mg/
day. She was hospitalized two days before surgery and
Phenoxybenzamine was titrated to 30mg/day, at which
point she developed orthostatic hypotension. A laparoscopic adrenalectomy was planned but she required
open abdominal adrenalectomy. Her BP remained stable
intraoperatively but she developed hypotension and atrial
fibrillation post operatively, which reverted to normal
sinus rhythm upon hydration. Plasma fractionated metanephrines normalized postoperatively and choreoathetosis
improved. Histopathology confirmed pheochromocytoma.
Discussion: Pheochromocytoma is a rare neuroendocrine tumor that usually presents with stable or paroxysmal hypertension. Normotensive pheochromocytomas are
extremely rare. Despite elevated catecholamines, as in our
patient, the BP remains normal, the mechanism for which
is not clear. Preoperative preparation with hydration, α
blockers and β blockers (if needed) is required even in
normotensive patients, but this may cause hypotension in
–7–
such patients. Therefore hospitalization for 7 to 10 days is
usually recommended. We have shown that such preparation can be safely done as an outpatient.
Conclusion: Pheochromocytoma with low/normal
BP is an unusual presentation. In normotensive patients,
although preoperative preparation is required, it can be
safely done in the outpatient setting with close monitoring, thus saving a major expense.
successful treatment of an adrenocortical carcinoma is
surgical resection of the adrenal tumor.
Conclusion: Adrenocortical cancer is a rare tumor
which may pose a diagnostic dilemma. Clinicians and
pathologists need to be aware of the diagnostic challenges
and appropriate staining of a presumed renal mass should
be performed as dictated by patient’s presentation.
Abstract #114
Abstract #113
ADRENOCORTICAL CARCINOMA SHOULD
BE CONSIDERED WHEN ADRENAL
NODULE SIZE IS GREATER THAN 3.5
CENTIMETERS IN PATIENTS WITH PRIMARY
HYPERALDOSTERONISM
ADRENOCORTICAL CANCER MISTAKEN
FOR A RENAL MASS
Rabia Cherqaoui, MD, Wolali Odonkor, MD,
Gail Nunlee-Bland, MD
Barbra Sue Miller, MD, Paul G. Gauger, MD,
Gary D. Hammer, MD, Gerard M. Doherty, MD
Objective: To report a case of a functional adrenocortical cancer, initially misdiagnosed radiologically as a
renal cell carcinoma and review the current literature on
this subject.
Case Presentation: 57-year-old postmenopausal
African American female with history of hypertension
and diabetes was admitted for a hip abscess. Physical
findings were notable for a cushingoid appearance with
a buffalo hump, truncal obesity, abdominal striae and
ecchymoses. There were no signs of hirsutism or virilization. Ultrasound and computerized tomography revealed a
large mass appearing to originate from the upper pole of
the right kidney. Cushing syndrome was suspected on the
basis of physical findings. Biochemically, there was evidence of hyperandrogenism and hypercortisolism suggesting an adrenal tumor. Core-biopsy of the presumed renal
mass was performed but cytological examination failed
to demonstrate any renal cells. Given that the patient had
Cushing syndrome, a staining for adrenal cell carcinoma
was done confirming the mass to be an adrenocortical
carcinoma. On immunohistochemical analysis, the tumor
cells were positive for inhibin and vimentin supporting the
diagnosis of an adrenocortical neoplasm.
Discussion: Primary adrenocortical carcinoma is a
rare tumor with an estimated incidence of 1 per 1.7 million. Approximately, half of these carcinomas are hypersecretory tumors associated with increased production of
glucocorticoids, sex steroids or more rarely mineralocorticoids. Most of adrenocortical cancers are large (>6 cm)
at presentation. Radiologically, the diagnosis can be easily
confused with renal lesions. There have been few reported
cases of non functioning adrenocortical carcinoma mimicking renal cell carcinoma based on preoperative imaging and histologically proven postoperatively to actually
originate from the adrenal cortex. In adults, median survival without treatment is 3 months and with treatment
14 months. The single most important procedure for
Objective: In extremely rare cases adrenocortical carcinoma (ACC) can present as primary hyperaldosteronism (PHA). We sought to compare adrenal nodule size
and imaging characteristics to differentiate benign from
malignant aldosterone producing adenomas (APA) and
allow optimal preoperative planning and selection of an
open surgical approach.
Methods: A retrospective review of patients with
PHA undergoing surgery at a tertiary referral institution
from 2004-2009 was performed. Demographics, imaging, laboratory, operative, and pathology results were
reviewed. Results are reported using descriptive methods
and chi square analysis.
Result: Of 91 patients undergoing surgery for ACC, 5
had evidence of excess production of aldosterone (APACC)
without biochemical evidence of other adrenal hormone
excess. 37 patients underwent surgery for PHA secondary to benign disease. Median age for those with APACC
was 48 years (range 39-53) and 54 years (32-72) for those
with APAs (p=0.07). Median nodule size of patients with
APACC was 6.5cm (3.9-18.0). Two of five were suspected
to be APACC preoperatively and appropriately underwent
open adrenalectomy. Three underwent laparoscopic resection at outside institutions. All APACCs had indeterminate
imaging characteristics noted (washout/signal loss criteria, etc.). Median nodule size in those patients with APAs
was 1.5cm (0.4-3.1) (p<0.005). Twenty-three patients
with APAs had comments regarding imaging characteristics other than size. Four (17%) showed heterogeneity,
inadequate washout or loss of signal despite being benign.
Median APACC size appears less than for all ACCs but
didn’t reach significance [10.2cm (3.2-27)] (p=0.24).
Discussion: ACC continues to be a deadly disease.
Awareness of PHA has increased among clinicians.
Because pure APACCs are extremely rare, the diagnosis
–8–
Discussion: CS is a very rare disorder with an incidence of 5 per million. The majority of the cases (80%)
result from pituitary secretion while 10% of the cases
are due to ectopic secretion of ACTH. CS from ectopic
corticotrophin-releasing hormone (CRH) by a pheochromocytoma has been documented. Criteria to prove ectopic secretion of ACTH/CRH include: Hypercortisolism,
elevated hormone level in the venous effluent from the
pheo site, plasmatic normalization after pheo removal and
hormonal activity in the pheo. Our patient fulfills some of
these criteria and the most important one that is the presence of CRH in the tumor tissue is under processing.
Conclusion: Ectopic Cushing syndrome as a consequence of ACTH or CRH production carries a high mortality rate of 57%. It is crucial as Endocrinologists to have
a high index of suspicion and to use a systematic approach
to reliably diagnose pheochromocytoma as a source of
ectopic CS.
may not be entertained in the preoperative setting. Most
APAs are removed laparoscopically. Recently presented
data has shown that laparoscopic resection of ACC is
inappropriate. PHA is usually associated with very small
adrenal nodules averaging 1-2cm.This study shows that
APACCs are significantly larger than APAs. Size may
be a more important assessment tool for differentiating APAs from APACCs than the use of other imaging
characteristics.
Conclusion: APACCs are extremely rare. Clinicians
should carefully examine available imaging when evaluating patients with PHA to identify potential malignancies and allow selection of an open approach for surgical
resection to optimize oncologic outcome.
Abstract #115
ECTOPIC CUSHING SYNDROME IN A PATIENT
PRESENTING WITH PHEOCHROMOCYTOMA
Abstract #116
Andrea Marcela Sosa Melo, MD,
Ana Cecilia Apaza Concha, MD, Maria del Pilar Solano
BILATERAL ADRENAL MASSES PRESENTING
WITH PRIMARY HYPERALDOSTERONISM
AND SUBCLINICAL CUSHING SYNDROME:
DIAGNOSTIC CHALLENGES AND THE ROLE
OF ADRENAL VEIN SAMPLING
Objective: To report a case of Cushing Syndrome
(CS) due to suspected CRH secretion in a patient with
pheochromocytoma producing paroxysmal hypertension
and brittle diabetes.
Case Presentation: 70 yo female with h/o HTN
and diabetes, presented with 3 months of painless jaundice, was transferred to a tertiary care center after ERCP
with CBD stenting for further evaluation of obstructive
cholestasis. A CT scan of the abdomen revealed a 1.7 by
2.4 cm pancreatic head mass as well as a 4.6 x 5.9 cm
incidental complex right adrenal mass. During admission the patient developed brittle diabetes requiring escalating doses of insulin and repeated episodes of severe
hypoglycemia. The patient had biochemical evidence of
hypercortisolism in conjunction with high ACTH levels
(279 pg/mL), non-suppressible on high-dose dexamethasone suppression testing. The patient complained of palpitations and diaphoresis. She had resistant hypertension.
Biochemical testing confirmed elevated 24-hour urinary
cathecolamines and metabolites. The patient was taken to
OR to perform adrenalectomy and Whipple procedure but
after adrenalectomy she developed sudden hypotension
and Whipple procedure was aborted. ACTH level dropped
to 12 pg/mL. Post-op Immunochemical studies revealed
a pheochromocytoma negative for ACTH. CRH immunochemical study is in process. Six days after surgery
her respiratory status deteriorated. CT angiogram did not
confirm PE, however lower extremities Doppler was positive for DVT. She became lethargic, hypoxic. Intubation
was offered but patient declined. Unfortunately after an
overwhelming hospital course, the patient succumbed.
Autopsy was not done honoring family wishes.
Aparna Madhav Ayyagari, MD, Elias S. Siraj MD, FACE
Objective: To report a case of bilateral adrenal masses
presenting with primary hyperaldosteronism and subclinical Cushing syndrome and discuss the challenges in the
workup.
Case Presentation: A 45 year-old female presented
with hypokalemia ranging 3.3-3.5 mmol/L. She has longstanding history of hypertension which has been treated
with various medications. At the time of her initial presentation, she was on atenolol, amlodipine and potassium supplements. On examination, blood pressure was
130/80 and weight was 227 pounds. Laboratory tests over
a period of several months to rule out primary hyperaldosteronism showed plasma aldosterone levels of 36-38 ng/
dL and plasma renin activity of 0.2 ng/mL/hr. Attempts
at performing oral salt load were unsuccessful on two
occasions. CT scan showed bilateral adrenal lesions measuring 1.6 x 1.4 cm on the right and 1.8 x 1.8 cm on the
left. Bilateral adrenal hyperplasia was favored over bilateral adenoma. MRI showed similar finding but bilateral
adenomas were favored. With the clinical impression of
primary hyperaldosteronism secondary to bilateral adrenal masses (hyperplasia versus adenomas), we decided to
start treatment with spironolactone 25 mg which lead to
resolution of her hypokalemia. Her blood pressure was
controlled with spironolactone and amlodipine. On further follow-up, she was noted to have lower extremity
–9–
edema and weight gain of about 60 lbs over two years
Workup for Cushing syndrome showed an AM cortisol of
13 µg/dl following 1 mg overnight dexamethasone suppression test. Twenty four hours urine free cortisol levels
were 67, 88 & 139 µg/day on three occasions (4-50 µg/
dL). Salivary cortisol levels from 11 PM were 0.11 and
0.19 µg/dL on two occasions (<0.09 µg/dL). ACTH levels
were < 5 pg/mL(5-27 pg/mL) on two occasions. Adrenal
vein sampling was performed. Although the results were
inconclusive, they suggested higher aldosterone secretion
from the right adrenal gland. However there was no clear
lateralization in regard to cortisol. Because of the subclinical nature of her symptoms, we decided to stay conservative and observe.
Discussion: Primary hyperaldosteronism and
Cushing syndrome may coexist as a result of bilateral
adrenal masses. While primary hyperaldosteronism can
be controlled with medications, Cushing syndrome may
necessitate surgery and therefore identifying the relative
significance of each lesion is of importance. Even though
at times adrenal vein sampling may be helpful, at other
times results may be inconclusive.
Abstract #117
PHEOCHROMOCYTOMA CAUSING
ARTERIOVENOUS THROMBOEMBOLISM WITH
RESOLUTION AFTER ADRENALECTOMY
Jagdeesh Ullal, MD, M. Elizabeth Mason, MD
Objective: To describe a case of catehcholamine
secreting adrenal mass causing multiple arterial and venous
thrombembolism with resolution after adrenalectomy.
Case Presentation: A 40 yo lady with a history of
mild hypertension, controlled type 2 diabetes, Grave’s
disease and post ablative hypothyroidism had hemoptysis,
and presented with acute, painful, ischemic right lower
extremity, and immediate right femoral thromboembolectomy was performed. She had both acute and chronic
appearing thrombus of femoral bifurcation and extending
into the popliteal and tibial vessels. The procedure restored
circulation to her right lower extremity and she was continued on intravenous anticoagulation. Two weeks into
hospitalization, she had another episode of arterial thromboembolism which was successful treated with embolectomy. During work up for hemoptysis, 3 months prior to
the acute presentation, a CT scan of the chest revealed a
mobile intracardiac mass in the left ventricle of 2 x 2 x 4
cm, which was a thrombus. Further evaluation revealed
large volume pulmonary embolus involving both left and
right lungs, left renal infarct and a left suprarenal mass
is 7.9 x 7.9 x 9.2 cm containing fine calcifications. The
patient’s symptoms leading up to the episodes described
above included back pain and significant weight loss of
60 pounds over 2-1/2 years. Work up of the adrenal mass
showed no excess cortisol production, normal androgens,
normal renin and aldosterone. Plasma metanephrine level
was 191, plasma normetanephrine level was 11,863. An
open left adrenalectomy was performed with pre operative
treatment with phenoxybenzamine. The histopathology
showed adrenal cortex compressed by the pheochromocytoma, a pseudocapsule without invasion, and immunostaining revealed chromogranin, syaptophysin, CD56 and
vimentin, and stained negative for S-100, and Ki-67 was
less than 1%.There were focal areas of increased mitoses.
No local or distant metastases were noted. After surgery,
patient has been doing well with no recurrence of embolic
phenomena. She is still on chronic anticoagulation.
Discussion: Arteriovenous thromboembolism is
not a known complication of pheochromocytomas.
Furthermore, there are few cases described in humans
with this condition. There are case descriptions of very
high levels of catecholamine production causing persistent
arterial vasospasm which led to marked and irreversible
ischemia. There was clear evidence of recurrent embolic
phenomena that persisted despite anticoagulation and this
was hypercoagulable condition was ameliorated by adrenalectomy. In canine models, epinephrine caused more
coronary thromobosis than norepinephrine. Epinephrine
is a stimulatory factor for platelet aggregation in vitro and
a prothrombogenic agent for arterial thrombosis in vivo.
There is however conflicting data with norepinephrine in
coronary artery circulation in that it inhibited thrombosis.
Conclusion: This is a case of a benign pheochromocytoma that had recurrent arterial and venous thromboembolism. Few cases have been reported so far with such a
phenomenon. It is difficult to make a causal relationship
but it has been known that excess catecholamines have
pro-inflammatory and thrombogenic effects. It is uncertain as to why this phenomenon is not seen more often.
We surmise that it is because of the differential effects of
norepinephrine and epinephrine on vascular endothelium.
Abstract #118
A CASE OF SECONDARY HYPERTENSION IN
A PATIENT WITH CONGENITAL ADRENAL
HYPERPLASIA
Alina Khan-ghany, MD, Reyan Ghany, MD,
Denise Armellini, MD
Objective: To describe a rare cause of secondary
hypertension in a patient with a history of congenital adrenal hyperplasia (CAH).
Case Presentation: A 23 year-old Hispanic male with
a past medical history significant for non-salt wasting
– 10 –
CAH secondary to 21-hydroxylase deficiency presented
to the ER with a hypertensive emergency. He reported a
3 week history of severe headaches, nausea and vomiting and was found to have a blood pressure of 230/130
mmHg. On the physical exam, he was phenotypically a
male, although his genotype was XX at birth. He had no
breast development with scant axillary, facial, chest and
abdominal hair. His genitalia were consistent with a small
penile size and testicular implants as he underwent sexual
reconstructive surgery including clitoridectomy, hysterectomy and testicular implants. During his hospital course,
blood work revealed elevations in serum creatinine of
1.6 mg/dl, 11-deoxycortisol levels of 634 ng/dl, 17-OH
progesterone 5238 ng/dl, ACTH 56 pg/ml, testosterone
200 ng/dl and androstenedione 931 ng/dl confirming the
diagnosis of 11-hydroxylase deficiency. Other secondary
causes of hypertension including coarctation of the aorta
and renal artery stenosis were excluded by imaging studies. Plasma renin activity, aldosterone and plasma metanephrine levels were normal. MRI of the abdomen with
contrast revealed macronodular disease of the adrenals
consistent with CAH. The patient was discharged with
normal blood pressure readings after starting a calcium
channel blocker and a beta-blocker.
Discussion: CAH is an autosomal recessive condition
that may result from several enzymatic deficiencies, most
commonly 21-hydroxylase deficiency. 11-hydroxylase
deficiency produces similar androgenic but different mineralocorticoid effects. Hypertension that ensues results
from increased levels of mineralocorticoid precursors and
is often a clue that a patient has 11-hydroxylase rather
than 21-hydroxylase deficiency. Treatment strategies
may include glucocorticoid therapy in sufficient doses to
reduce ACTH secretion and therefore excess androgen as
well as 11-deoxycorticosterone leading to improvement
in blood pressure control. However, patients may require
concurrent standard antihypertensive therapy.
Conclusion: 11-hydroxylase deficiency is a rare
cause of hypertension that should be entertained in a
patient with a history of CAH. It is therefore important
to define the specific enzymatic defect upon diagnosis of
CAH as this will help recognize specific complications
such as hypertension and prevent sequelae such as chronic
kidney disease, left ventricular hypertrophy, retinopathy,
and macrovascular events.
Abstract #119
CUSHING SYNDROME IN PREGNANCY
Miguel E. Pinto, MD, FACE, Miguel Guillan, MD,
Milagros Ortiz, MD, Jaime E. Villena, MD
Objective: To report a case of a pregnant woman who
developed hyperglycemia and preeclampsia secondary to
Cushing’ syndrome.
Case Presentation: A 39-year-old woman with previous history of hypertension and diabetes, both of them
without regular treatment, presented at 24 weeks’ gestation in her fourth pregnancy with severe headache and
uncontrolled blood pressure. She experienced preeclampsia in her previous pregnancy. Physical examination
showed a blood pressure of 180/110 mmHg, heart rate
of 104 beats/min, respiratory rate of 24 breaths/min, and
BMI of 38. Other findings were acne, hirsutism, and striae
in the abdominal wall. A hypertensive crisis diagnosis was
established, and patient was admitted in ICU for management of blood pressure. Further work up showed, hyperglycemia, severe proteinuria, morning hypercortisolemia
and elevated 24-hour urinary free cortisol. Fetal ultrasonography revealed a single viable fetus with normal
morphology and parameters. Patient was discharged from
ICU with oral methyldopa 3000mg/day. Her pregnancy
is going without complications, and she is continuing her
controls in the outpatient setting of our unit.
Conclusion: The occurrence of pregnancy in the face
of untreated Cushing’ syndrome is rare because of the
high incidence of ovulatory disturbances experienced by
patients with this disorder. Fifty percentage of pregnancies
and untreated Cushing’ syndrome are caused by adrenal
adenoma. In contrast, Cushing’ syndrome in nonpregnant
women is related to pituitary disorders. Cushing’ syndrome in pregnancy follows a hazardous course with an
increased rate of abortion, premature labor, hypertension,
gestational diabetes, cardiac failure and even pulmonary
edema. Fetal complications are also severe, with preterm
deliveries, intrauterine growth retardation, and perinatal
deaths.
– 11 –
Abstract #120
CONGENITAL ADRENAL HYPERPLASIA AND
LEYDIG CELL TUMOR OF OVARIES RARE COMBINATION CAUSING
VIRILIZATION SYNDROME
Jose Maireni Cabral, MD, FACE, Rolando Perez, MD,
Vishal Mundra, MD
Introduction: During the work up of virilization, a
combination of adrenal and ovarian causes, although rare,
may be present. Failure of resolution of hormonal abnormalities after adrenal surgery should raise a suspicion for
ovarian tumors.
Case Presentation: Here we describe a 37-year-old
female who presented with chief complaint of hirsutism.
At birth she was diagnosed with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Despite optimal
medical therapy with glucocorticoids and mineralocorticoids, the patient developed progressive virilization
including excessive hair, and infrequent menstrual cycles
On examination, she had increased musculature and hirsutism, no alopecia or acne. Laboratory work up showed
elevated androgens, total testosterone 466 ng/ml (2-45
ng/ml), free testosterone 75.5 pg/ml (0.1-6.4 pg/ml), and
high 17-hydroxyprogesterone (17-OH-P) of 3153 ng/dL.
LH and FSH were suppressed. CT scan of the abdomen
showed significant enlargement of the adrenal glands, 7
x 4 cm on the left, and 4.5 x 2.5 on the right. Because
of the unresponsiveness to supraphysiologic doses of
glucocorticoids, the patient underwent bilateral adrenalectomy. After surgery, her total testosterone was 29 ng/
ml, free testosterone was 2.8 pg/ml, and 17-OH-P (1.7ng/
dL) was almost undetectable. LH and FSH levels became
normal. However, nine months after, hirsutism was still
present. Laboratory studies showed that her testosterone
levels raised again, with total testosterone being 290 ng/
ml, and free testosterone 60.9 pg/ml, with elevation of
17-hydroxyprogesterone (2532 ng/dL) was found. As the
patient had bilateral adrenalectomy, search for an additional source of androgen production was initiated. CT
scan of the pelvis showed a possible 2 cm right ovarian
mass and the patient underwent hysterectomy and bilateral salpingo-oophorectomy. There were bilateral masses
medial to the ovaries of approximately 2 cm in size.
Pathologic examination showed Leydig cell hyperplasia
in both ovaries. After removal of the ovaries, her total testosterone decreased to 51 ng/ml, and the free testosterone
to 2.4 pg/ml.
Discussion: To our knowledge, this is the only case
of congenital adrenal hyperplasia and bilateral Leydig cell
tumor of ovaries in a female patient to be described in the
English literature.
Virilizing ovarian tumors have been described in patients
with congenital adrenal hyperplasia including ACTHdependent ovarian masses, hilus cell tumor, steroid cell
tumor, and stromal luteoma. In our patient the ovarian
tumor became evident some time after removal of the adrenal glands. We suggest that the bilateral adrenalectomy
could have played a causative role in the development of
Leydig cell hyperplasia. ACTH and LH had been previously suppressed by the use of high-dose exogenous glucocorticoids and endogenous overproduction of 17-OH-P
and testosterone. Normalization of its levels after reduction in the dose of glucocorticoids and surgery could have
been a stimulant for the Leydig cells to eventually become
a new androgen-producing tumor.
Abstract #121
HIRSUTISM AND HYPOKALEMIA IN A PATIENT
WITH A NEUROENDOCRINE TUMOR
OF THE BREAST
Kiarash Zarbalian, MD, Richard Horenstein, MD
Objective: To describe a case of documented ectopic ACTH secretion in a patient with a breast mass with
unusual pathologic features.
Case Presentation: A 60-year-old female presented
to her primary care with a 2 month history of worsening hirsutism of the upper lip and chin, weight gain of 15
lbs, and difficulty getting out of a chair. On lab evaluation, the potassium was 1.6 mmol/L with a blood glucose
338 mg/dl. An abdominal CT without contrast was performed in light of the new hypokalemia showing bilateral symmetrical thickening of her adrenal glands and
multiple low density liver lesions. She was admitted. An
AM cortisol of 57.1 mcg/L was found after 1 mg dexamethasone suppression, with an ACTH level of 871 pg/
ml. Following an 8 mg dexamethasone suppression, the
AM cortisol was 47.1 mcg/L. A 24 hour urine free cortisol
was 1126 ug/L. A pituitary MRI was not completed due to
extreme claustrophobia despite sedation, although a head
CT with contrast showed no masses. DHEA-S was 68
ug/dL with a total testosterone of 128 ng/dL. A chromogranin A level was 17 nmol/L. Biopsy of the liver lesions
showed metastatic adenocarcinoma that was ER and PR
negative, although a breast source could not be ruled out.
Chest CT was otherwise negative except for a 6 mm lung
nodule. A closer exam revealed a left sided breast lesion.
A core needle biopsy revealed features consistent with
neuroendocrine tumor and stained positive for synaptophysin but negative for ACTH and chromogranin. PET/
CT images showed bilateral uptake in the adrenal glands
and liver, and no uptake in the lung lesion, the breasts,
or axillae. Ketoconazole and spironolactone were started
– 12 –
for Cushing syndrome. She received one round of chemoembolization of the liver lesions and chemotherapy. The
patient died one month after treatment was initiated and
before an octreotide scan could be performed for definitive localization.
Discussion: Neuroendocrine tumors comprise
12-20% of the tumors that elaborate ACTH and are usually
found in sites other than the breast such as the pancreas
(see Ilias et al, JCEM 2005; 90: 4955-62). A 2005 review
of tissue from 150 cases of primary breast cancer showed
that ACTH peptides were detected in 16.7% of cases, with
the highest expression in postmenopausal cases. Only five
cases of ACTH elaborating breast adenocarcinoma have
been documented in the literature. It is unusual that this
breast neuroendocrine tumor did not stain for ACTH or
chromogranin. A 2006 case series showed that 5 out of
22 documented ACTH producing ectopic neuroendocrine
tumors did not stain for chromogranin A and eight did not
stain for ACTH despite a substantial postoperative drop in
ACTH and cortisol after surgical removal, (Salgado et al,
Eur J of Endocrinol; 155: 725-33).
Conclusion: Diagnosis of ectopic ACTH syndrome
can be problematic and immunohistochemistry negativity
does not rule out a hormone elaborating tumor.
Abstract #122
BILATERAL ADRENAL HYPERPLASIA
PRESENTING WITH HYPERCORTISOLISM
function tests, routine urinalysis, chest X-ray and ECG,
which revealed a concomitant finding of a granuloma over
the right lower lobe, left ventricular hypertrophy with
strain pattern most likely a complication of long-standing
hypertension and incidental finding of subclinical hyperthyroidism (TSH IRMA 0.046 n.v. 0.27-3.75; FT4 RIA
16.584 n.v. 8.8-33.0). Hormonal studies revealed elevated
basal plasma cortisol levels (8am 1808.821 nmol/L, 9am
1736.447 nmol/L) with a loss of diurnal variation. A dexamethasone suppression test was also done which revealed
an elevated plasma cortisol level (1646.407nmol/L). An
abdominal CT scan done revealing both adrenal glands to
be enlarged but remained in proportion with no contour
abnormality which was subsequently signed out as bilateral adrenal hyperplasia.
Discussion: Cushing syndrome is a relatively rare
endocrine disorder resulting from excessive exposure to
the hormone cortisol. This condition is most commonly
cause by taking medications containing this hormone for
long periods of time. A more rare form of the disorder
occurs when the body itself produces an excessive amount
of cortisol. Bilateral adrenal hyperplasia is a distinct but
uncommon cause of Cushing syndrome.
Conclusion: Bilateral adrenal hyperplasia resulting
to increase serum cortisol levels may present in a wide
and varied clinical spectrum making establishing a preoperative diagnosis difficult.
Abstract #123
Jimmy B. Aragon, MD, FACE, Nerissa Sia Ang, MD
Objective: To present a rare case of Cushing syndrome who presented to us with generalized body weakness, hypokalemia, edema, hypertension and metabolic
alkalosis
Case Presentation: An 89-year-old female, single,
menopausal, presented to us with generalized body weakness, especially of the proximal muscles, with decreased
in functional capacity and activities of daily living. Patient
was also noted to have an increase in sleeping time with
significant loss of appetite. She denied any history of
headache, vomiting, visual field cuts, polyuria, polydipsia, polyphagia, back pain nor weight loss. On examination, she was hypertensive, overweight, no note of purple
striations on the skin of the abdomen, thighs and breasts
nor excess body hairs, excessive bruisability nor characteristic moon facie and truncal obesity. There was a
noted hyperpigmentation of the face and grade 2 bipedal
edema for one month prior to consultation. Upon initial
investigation, she was noted to have severe hypokalemia
with a serum potassium level of less than 2.0mmol/L and
metabolic alkalosis. Other tests were carried out; including complete blood count, serum chemistries, thyroid
A RARE CASE OF AUTOIMMUNE PRIMARY
ADRENAL INSUFFICIENCY
Debmalya Sanyal, MBBS
Objective: To report a case of Autoimmune Primary
Adrenal Insufficiency (PAI) in a 44 year-old lady preceding Primary Antiphospholipid Syndrome (PAPS).
Case Presentation: A 44 year-old Indian woman,
P1, presented with haemoptysis, cough and shortness of
breath for 1 day. She had a 4-month history of progressive
darkening of skin along with weakness, anorexia, nausea,
and weight loss of 3 kg. No prior history of DVT, PE,
connective tissue disorder. On examination she had fever,
tachycardia, anemia and skin and mucosal pigmentation.
A CTA of the lungs showed right descending pulmonary
artery embolism. Duplex scan revealed partially recanalised right superficial femoral vein. Platelets were 86,000,
Prothrombin time: 13.8(Normal [N]: 11.2-14.2), APTT:
142secs (N: 31-42), lupus anticoagulant and anticardiolipin antibody were markedly positive. ANA, dsDNA,
ANCA, RA factor were negative. CT of adrenal along
with CTA was normal. A 250mcg ACTH stimulation test
showed a baseline cortisol of 2.3mcg/dL with an ACTH
– 13 –
of 306pg/mL, and one-hour cortisol level after ACTH was
2.5mcg/dL. Ant adrenal Abs titers (21-hydroxylase Abs)
was 315 IU/ml, i.e. markedly positive. She was started
on hydrocortisone 100mg three times daily and heparin.
She was subsequently discharged on replacement dose of
hydrocortisone and warfarin.
Discussion: PAI is a well-recognized, albeit rare,
manifestation of the antiphospholipid syndrome, in 36%
AI was the first clinical feature of APS. The pathogenesis
of PAI in APS involves hemorrhagic adrenal infarction.
CT in PAI with APS will show in over 80% of the cases
an enlargement of the adrenal glands consistent with hemorrhage with H/P showing haemorrhagic infarction &
thrombosis. In this case PAI preceded other clinical evidence of APS by several months. PAI in our case was due
to autoimmune etiology with positive adrenal antibody
without any evidence of adrenal hemorrhage or infarction in CTA. These features are at variance with previous
cases described in the literature. In patients with autoimmune thyroid disease circulating aPL have been detected,
however, no clinical manifestations of APS have been
described.
Conclusion: Endocrinologists need to have a high
clinical suspicion for PAI in APS or APLA positive
patients especially with abdominal pain, nausea, weakness, asthenia given the high mortality rate when this condition goes undiagnosed and untreated. Though adrenal
imaging shows hemorrhage in most cases, it may be rarely
normal as PAI may be of autoimmune origin with positive
adrenal antibody.
Abstract #124
ADRENAL CRISIS SECONDARY TO BILATERAL
ADRENAL HEMORRHAGE IN A PATIENT WITH
HEPARIN INDUCED THROMBOCYTOPENIA
(HIT)
with heterogeneous appearance prompting an endocrinology consult. A previous CT scan done at another facility
four months earlier showed normal adrenals. On exam
the patient looked sick. His blood pressure and heart rate
were ranging between 93/52-125/77 mm Hg and 60-126/
min respectively. His over all clinical situation started to
deteriorate with significant hypotension and lethargy. In
the setting of the newly discovered HIT, bilateral adrenal hemorrhage leading to adrenal insufficiency was suspected. A random cortisol was low at 2 mcg/dL supporting
the clinical impression. He was started on stress doses of
hydrocortisone resulting in prompt improvement in his
clinical condition. A dedicated CT scan of adrenals was
performed later which showed findings consistent with
bilateral adrenal hemorrhage. The steroid regimen was
tapered and patient was discharged home on maintenance
dose of hydrocortisone.
Discussion: HIT is seen in about 1-5% of patients
exposed to heparin. Adrenal vein thrombosis leading to
adrenal hemorrhage may be associated with HIT. If bilateral, it can lead to acute adrenal insufficiency and can be
potentially life threatening. Most patients who survive
the acute situation will have chronic adrenal insufficiency
requiring long-term steroid replacement. The need for
mineralocorticoid replacement is variable. A high index of
suspicion in the right setting is the key, as the manifestation is often nonspecific and can be similar to other more
common problems seen in acutely sick patients. Once suspected, a dedicated CT scan of adrenals is the imaging of
choice.
Conclusion: Physicians must be aware of the possibility of adrenal crisis resulting from bilateral adrenal
hemorrhage in patients with HIT and other coagulopathies. A high index of suspicion is the key to timely diagnosis and prompt treatment.
Abstract #125
Swapnil Khare, MD, Madhavi Yarlagadda, MD,
Elias S. Siraj, MD, FACE
PARAGANGLIOMA OR MALIGNANT
PHEOCHROMOCYTOMA?
Objective: We present a rare case of bilateral adrenal
hemorrhage associated with heparin induced thrombocytopenia (HIT), causing adrenal insufficiency.
Case Presentation: A 43 year-old man was admitted for complications after a recent Nissen’s fundoplication and underwent repeat surgery. Postoperative course
was complicated by hypoxia, recurrent fevers and poor
recovery. He had a CT scan of chest, abdomen and pelvis as part of his postoperative evaluation. This revealed
bilateral pulmonary emboli as well as thrombi in the large
veins of the neck. These findings along with thrombocytopenia after heparin exposure raised the suspicion for HIT.
Incidentally the CT also revealed bilateral adrenal masses
Louis C. Chen, MD, MBA, Karen Barnard, MD
Objective: Discuss the importance of differentiating
paraganglioma (PGL) from pheochromocytoma (Pheo)
Case Presentation: A 62 yo male with HTN was
found to have an incidental retroperitoneal mass on MRI
in 2001 (12.8cm X 6.5cm). CT showed an 8mm lingular nodule, 1.1cm lesion in R kidney (26 HU), and normal adrenal glands. Biopsy was chromogranin and S-100
positive, with indeterminate cytokeratin test. The patient
denied HA, palpitations, or sweats. Family history was
negative for thyroid CA, malignant HTN, adrenal lesions,
renal cell CA, cerebellar disease, or polypoid skin lesions.
– 14 –
Surgery revealed tributaries between the tumor and inferior vena cava, with fibrous attachments to the R renal
vein and vertebral bodies. Pathology of the 271gm mass
showed clean margins, severe nuclear atypia, and adrenal
cortex at the periphery. Because cytokeratin and inhibin
stains confirmed adrenal cortex, a diagnosis of Pheo was
made. In 2009, lytic lesions were found in the left humerus.
CT showed unchanged lingular and renal lesions, normal
adrenal glands, and a large left hydrocele. Biopsy and
resected humerus were chromogranin-positive and cytokeratin-negative, consistent with a diagnosis of PGL. PET
and MIBG scans showed uptake in a lytic lesion at the
T12 vertebral body, and the patient was referred for radiotherapy. Testing for SDHB, SDHD and vHL was negative.
Discussion: An initial diagnosis of Pheo was made
because the retroperitoneal lesion connected to the adrenal
cortex. Our patient’s adrenal glands were noted on multiple scans to be normal. Malignant Pheo occurs in 10% of
cases and arises from intraadrenal lesions, where as 50% of
PGL cases develop metastases. PGL is the correct diagnosis here based on staining characteristics and tumor behavior. PGL requires close attention on follow-up. Familial
PGL is autosomal dominant and is found in the head and
neck but could occur elsewhere. Syndromic PGL is rare,
but syndromic Pheo is noted in 10-20% of patients with
vHL, 50% with MEN2, and 0.1-5.7% with NF-1. Gene
mutations in sporadic catecholamine-secreting tumors are
common: Neumann (NEJM 2002; 346:1459) identified
mutations in 66/271 cases, including 30/271 with vHL,
12/271 with SDHB and 11/271 with SDHD mutations. In
this series, the majority (14/22) of patients with PGL had
genetic mutations.
Conclusions: It is important to distinguish PGL
from Pheo. The two entities have distinct clinical significance. PGL requires attention to genetic testing, just as
syndromic or familial Pheo does. SDHB, SDHD and vHL
gene mutations should be evaluated in the diagnosed PGL.
Abnormal findings have significant impact on kindred.
Abstract #126
HYPOCORTISOLEMIA IN A PATIENT
WITH NEWLY DIAGNOSED GRAVE’S
THYROTOXICOSIS
of 110 beats per minute, blood pressure (BP) of 140/90
(mmHg) sitting and 110/70 (mmHg) standing. She was
also found to be thyrotoxic with thyrotropin (TSH) less
than 0.01 miu/ L (0.35-5.5 miu/ L), free T3 was 631 pg/
dL (228-423 pg/dL) and free T4 was 1.9 ng/dl (0.7-1.8
ng/dl) with a normal serum albumin of 49 g/l (normal
range 34-50 g/l). The diagnosis of Grave’s disease was
confirmed with a positive thyroid uptake scan and thyroid
antibodies. Random cortisol was performed at 12:30 hours
when she was an in-patient in the hospital, because of the
symptoms of postural hypotension and dizziness, to rule
out the possibility of concomitant autoimmune adrenal
insufficiency and was found to be low at 1.9 μg/dl (4.322.2 μg/dl). Short synacthen test (250 mcg cosyntropinstimulation) was performed and showed a baseline cortisol of 2.0 μg/dl, however this had risen at 30 minutes with
serum cortisol of 18.8 μg/dl and a 60 minutes cortisol of
22.5 μg/dl; unfortunately the ACTH sample was haemolysed. She was adequately treated with Carbimazole and
short synacthen test was repeated a few months later when
she was clinically and biochemically euthyroid; baseline
cortisol was 11.4 μg/dl, with a 30 minutes cortisol of 22.5
μg/dl and a 60 minutes cortisol of 24 μg/dl. Full biochemical assessment including LH, FSH, prolactin, renin and
aldosterone, renal and liver function tests were all normal
and her adrenal antibodies were negative.
Discussion: Our case report confirms the emerging
evidence of hypocortisolemia in Graves’ hyperthyroidism
without adrenal insufficiency, recently reported by Karl
et al. However, this was reported in 2 patients with longstanding Graves’ disease. It also illustrates that hyperthyroidism can be associated with low basal serum cortisol
and is not always associated with concomitant adrenal
insufficiency in patients with Graves’ thyrotoxicosis. This
could be explained by the transient increase in cortisol
disposal and transient corticotropin deficiency in early
thyrotoxicosis.
Conclusion: Hypocortisolemia may be present in
patients with new onset hyperthyroidism and can resolve
with adequate treatment of hyperthyroidism.
Abstract #127
Ibrahim Mamoun Ibrahim, MD
Objective: To report a case of hypocortisolemia in
a patient with Graves’ thyrotoxicosis resolved with the
treatment of the underlying hyperthyroidism.
Case Presentation: A previously healthy 26-year-old
lady presented with palpitations, headaches, fatigue and
intermittent dizziness and collapse when standing up. On
examination she was unwell, tachycardic with heart rate
CONGENITAL ADRENAL HYPERPLASIA
PRESENTING AS AN ADRENAL
INCIDENTALOMA.
Afokoghene Rita Isiavwe, MBBS, HC Wainwright, MD,
NS Levitt, MD
Objective: To highlight the fact that Congenital
Adrenal Hyperplasia (CAH) may present as an adrenal
incidentaloma.
– 15 –
Case Presentation: A 43 year old lady presented
with chronic lower backache. MRI showed a large right
suprarenal mass and degenerative changes throughout
the spine, but no significant nerve root compression to
explain the patient’s symptoms. CT abdomen showed a 53
x 50mm mixed density mass arising from the upper pole
of the right kidney. A renal cell carcinoma (RCC) was suspected. During preparation for radical nephrectomy, she
was discovered to be virilized, with ambiguous genitalia.
History revealed primary amenorrhea, and she had never
been sexually active. Examination revealed a BMI of 23
kg/m2. Cardiovascular examination was normal. She had
ambiguous genitalia, with fully developed labia and a 6
cm micro penis. There was no visible introitus, no testes
were palpated. Chromosomal studies demonstrated a 46,
XX karyotype, and human chorionic gonadotrophic hormone stimulation test excluded the presence of testicular
tissue. Pelvic ultrasound scan showed normal internal
female genitalia and a uterus which was small for age.
Serum testosterone concentration as well as oestradiol
were normal but there was a 20 fold elevated 17 OHP
concentration. In view of the large mass she underwent
exploratory surgery, and a 7 x 7cm adrenal mass, with
normal kidneys was found; she subsequently had a right
adrenalectomy. Histology confirmed an adrenocortical
myelolipoadenoma.
Discussion: In South Africa, the most common cause
of ambiguous genitalia in adulthood is true hermaphroditism. CAH may present as an adrenal incidentaloma,
and this is particularly common in the homozygous
form. Although mostly asymptomatic, adrenal myelolipoma can manifest as non-specific abdominal pain due to
mechanic compression of adjacent tissues from the tumor
bulk or due to development of the tumor necrosis. Our
patient’s was discovered during investigation for back
pain. Adrenal myelolipomas are uncommon, benign and
hormonally inactive tumors; most commonly occurring in
patients in their fourth to sixth decades of life. Prevalence
of myelolipomas in adrenal incidentalomas is 7 – 15%,
with an equal sex distribution. Although rarely associated with endocrine disorders, there are isolated reports of
myelolipoma with Cushing syndrome and with CAH. It is
of interest that our patient successfully tolerated surgery,
without the need for glucocorticoid cover, and the question arises if there is need for glucocorticoid replacement
in her. Some authors believe it is more prudent to provide
supplementary hydrocortisone on an intermittent basis
for surgical and medical stress. The issue of her primary
amenorrhea raises the question of the role of hormone
replacement therapy to induce cyclical bleeding. Her risk
for osteoporosis was considered little as her estrogen levels were not low. Adrenal CT is generally thought to be
none specific regarding the histology of adrenal incindentalomas, except for myelolipomas; however it is of
interest that our patient’s adrenal tumor was mistaken for
a RCC. We were unable to relate her degree of virilisation
to her normal testosterone levels. We concluded that we
picked up the tumor in its degenerative state; as there was
histological evidence of both old and new hemorrhage,
areas of extensive necrosis, sclerosis and very scanty
viable tumor remaining. Literature reports confirm hemorrhage is more common in larger lesions – diameter > 10
mm, (our patient’s adrenal gland measured 68 x 53 x 45
mm and weighed 74g). Although the risk for developing
malignancy or hypersecretion is low in adrenal incindentalomas, it is important to exclude them.
Conclusion: There is a need to exclude CAH in
patients with adrenal incindentalomas. The role of hormone replacement therapy and inducing menstrual cycles
in CAH patients with primary amenorrhea needs further
evaluation. There is also a need for psychological support
of these patients.
Abstract #128
CARCINOID AND DEXAMETHASONE
SUPPRESIBLE CUSHING
Timothy Kevin Jackson, MD, Sarah Sofka, MD
Introduction: Cushing Syndrome is a rare endocrine
condition with complex diagnostic pathways. High dose
dexamethasone suppression testing is the main study used
to classify pituitary versus ectopic causes. Imaging is
also the mainstay of localizing ectopic sources. We present the case of a patient with dexamethasone suppressible
Cushing syndrome from an ectopic source, namely bronchopulmonary carcinoid tumor. The tumor was only able
to be localized on bronchoscopy.
Case Presentation: The patient was a 52 year old
female who presented with unilateral adrenal hemorrhage.
She also had the typical signs and symptoms of hypercortisolism. Cortisol levels and ACTH levels were significantly elevated. Cortisol production was suppressed by 8
mg of dexamethasone. However, inferior pertrosal sinus
sampling and MRI failed to show a pituitary source. High
resolution computed tomography and nuclear somatostatin receptor imaging of the chest, abdomen and pelvis did
not localize a source. The patient continued to have high
cortisol levels with resulting hyperglycemia, refractory
hypertension and hypokalemia, and depression. In order
to avoid adrenalectomy, a bronchoscopy was empirically
performed which revealed a small bronchopulmonary carcinoid tumor which was partially resected.
Conclusion: Since bronchopulmonary carcinoid
tumor is in the differential diagnosis of dexamethasone
suppressible Cushing syndrome if a pituitary source is not
localized, we suggest that bronchoscopy be added to the
– 16 –
ABSTRACTS – Diabetes Mellitus
DIABETES MELLITUS
study include: small sample size (not yet FDA approved
for patients receiving insulin), brief period of follow up
and inability to control the effect of diet and exercise on
the study parameters. Future studies should include a
larger sample size and longer follow up.
Abstract #200
EFFECTS OF SITAGLIPTIN ON GLYCEMIC
CONTROL IN PATIENTS RECEIVING INSULIN
Abstract #201
Amitha Padmanabhuni, MD, Daniel Rosenberg, MD,
Margot Boigon, MD
Objective: The purpose of this study was to evaluate the benefits of adding sitagliptin to patients receiving
insulin in terms of glycemic control, lipids, and blood
pressure.
Methods: This was a retrospective chart review
comparing data at baseline and 3 months after starting
sitagliptin. All patients had follow up data for 3 months.
Patients who were receiving insulin and sitagliptin simultaneously with or without oral hypoglycemic agents were
selected from a database at the outpatient endocrine clinic
between December 2006 and March 2009. Total of 25
charts were selected. Fourteen, who met the inclusion
criteria, were included in the study. The only intervention done was sitagliptin added to their regimen. Patients
served as their own controls. All patients in the study
received 100mg of sitagliptin daily.
Results: There was a significant decrease in HBA1c
(1.1% ±1) (p =.002) and weight (9 lbs ±14) (p =.034), and
an increase in HDL (5 mg/dl ± 6) (p = .011) after 3 months
of adding sitagliptin to a patients regimen regardless of
the type of insulin they received. Although not statistically
significant there was a trend toward a decrease in systolic
blood pressure (8.7 mm ± 16) (p = .066), total cholesterol
(13 mg/dl ± 45) (p =.304), LDL cholesterol (10 mg/dl ±
36) (p = .305) and triglycerides (23 mg/dl ± 58) (p =.15).
13 out of 14 patients did not have a change in insulin
requirements. Two patients reported to have an episode
of hypoglycemia. 13 out of 14 patient’s renal status was
unchanged after 3 months on sitagliptin.
Discussion: The incretin effect is decreased in type
2 diabetes. Sitagliptin (Januvia™) is a DPP-4 (Dipeptidyl
Peptidase enzyme) inhibitor that inhibits the breakdown
of incretin hormones. Sitagliptin has multiple effects in
lowering blood glucose; it stimulates glucose–dependent
insulin secretion by pancreatic beta cells, suppresses glucagon secretion, alters insulin resistance and restores first
phase insulin response.
Conclusion: When compared to baseline there was
statistically significant decrease in 3 primary outcomes
decrease in HBA1c, weight, and increase in HDL at the
end of 3 months when sitagliptin is added to insulin. There
was a downtrend in systolic blood pressure and triglycerides but was not statistically significant. The drug was
well tolerated by most of the patients. Limitations of the
CONTINUOUS GLUCOSE MONITORING
IMPROVED DETECTION OF HYPOGLYCEMIA
IN HOSPITALIZED PATIENTS
Margaret Ryan, MD, Vincent Savarese, MD,
Brian Hipszer, PhD, Mary Kate McCullen, MD,
Tessey Jose, MD, Jeffrey Joseph, DO
Objective: To determine whether the use of continuous glucose monitoring (CGM) in hospitalized patients at
high risk for hypoglycemia led to improved detection of
hypoglycemic events.
Methods: In an interim analysis of an ongoing study,
14 patients with a documented hypoglycemic event during their hospitalization were recruited from the general
floors of a tertiary care referral center. A CGMS® iProTM
Continuous Glucose Recorder (Medtronic Diabetes,
Northridge, CA) was inserted on each patient and CGM
data was collected until either the patients anticipated day
of discharge or completion of 144 hours of CGM data
collection. Point-of-care (POC) and laboratory blood glucose levels were monitored as per usual hospital protocol
throughout the study. The investigators, subjects, and hospital staff were blinded to the results of the CGM. A recurrent hypoglycemic event was defined as a CGM-estimated
blood glucose of less than 70 mg/dL. CGM data was analyzed retrospectively.
Result: Study participants included nine patients with
type 2, three with type 1, and two without diabetes. Ages
ranged from 31 to 79 (mean age 56). The average BMI was
32 kg/m2 (SD +/- 9.4) The mean duration of diabetes was
17 (+/-10 ) and 25 (+/- 1.7) years in the groups with type 2
and type 1 diabetes, respectively. The overall mean hemoglobin A1c was 7.6% (+/- 1.7). Nine subjects reported
using insulin prior to admission. The CGM devices were
worn for an average of 47.15 hours and picked up a total of
35 separate episodes of hypoglycemia with a mean duration of 68 minutes occurring in 10 patients. 8 episodes of
recurrent hypoglycemia, the highest number in the study,
were noted in a single patient. POC testing detected only
14 hypoglycemic episodes occurring in 8 patients, with
no more than 3 episodes detected in any one patient. Of
hypoglycemic episodes detected by both CGM and POC
testing, these episodes were detected a mean 102 minutes
earlier with CGM. There were five instances in which
POC testing documented a blood glucose of <70mg/dL,
– 18 –
while CGM reported glucoses in the 70s but not dropping
below 70 and there were 3 episodes in which the CGM
documented a hypoglycemic episode, but coincidental
POC testing documented a blood glucose in the normal
range (85, 93 and 104mg/dL, respectively).
Conclusion: In our study, CGM use in high risk hospitalized patients detected hypoglycemic episodes earlier and more often than POC testing alone. Real-time
CGM use in hospitals could lead to earlier detection of
hypoglycemia and prevention of hypoglycemia related
complications.
Abstract #202
FACTORS INFLUENCING GLYCEMIC
CONTROL STRATEGIES AMONG ADULT
DIABETICS IN SUB-SAHARAN AFRICA:
A CALL TO ACTION
Kelvin M. Leshabari, MD
Objective: To explore factors influencing glycemic
control strategies among adults with diabetes mellitus in a
metropolitan area of sub-Saharan Africa.
Methods: A cross-sectional survey was conducted in
Dar es Salaam, a business capital of Tanzania involving
adult diabetics attending municipal diabetes clinics. Thus
the study considered Dar es Salaam to be representative of
a typical African metropolitan zone primarily based on its
rich African ethnic varieties. A semi-structured questionnaire was the main tool used. Variables also included 10
likert items that were used to assess attitudes on exercise,
lifestyle modifications and oral hypoglycemics. Data were
analyzed using epi-info version 3.3.2 with X2 test used to
check for the association between independent variables
and P-value <0.05 used to rule out chance in findings.
Chronbach’s alpha co-efficient was applied for determining internal consistency reliability test.
Results: A total of 400 diabetes patients were surveyed out of whom 136 (34%) were males. Mean chronbach’s alpha score ( r ) was 0.725. Only 2% of the respondents declared to have glucometers/urine dipstick kits
at home. Almost all (92.5%) respondents declared oral
hypoglycemics to be very expensive (r=0.86). About a
quarter (22%) revealed skipping meals to be an option in
maintaining glucose levels in a euglycemic state (r=0.68).
Significant amount (36.5%) perceived regular exercise
to have limited/no role once a desirable body weight has
been achieved (r=0.71). About a third (33.75%) declared
weight gain to be acceptable once a euglycemic state has
been achieved (r=0.66). The usage of traditional remedies
for glycemic control was inversely related to the level of
education of the respondent (P=0.0001).
Conclusion: Cost of oral hypoglycemics was perceived to be very expensive in this study population. Poor
glycemic control among adult diabetics in this study was
found to be multi-factorial in origin.
Abstract #203
CARDIOMETABOLIC RISK BEHAVIORS
AMONG ADULTS LIVING WITH DIABETES IN
TANZANIA: ROADMAP FOR INTERVENTIONS
Kelvin M. Leshabari, MD, Elizabeth Licoco, RN
Objective: To assess practices on cardio metabolic
risk behaviors among adults with type 2 diabetes attending a tertiary diabetes clinic in Dar es Salaam, Tanzania.
Methods: A cross-sectional survey was done in
July-Sept 2007 involving adult type 2 diabetes patients
attending a tertiary diabetes clinic at Muhimbili National
Hospital. Data were collected using semi-structured questionnaires. Data were analysed using epi-info version
3.3.2. Statistical significance tests included the usage of
X2 test to check for the association between different variables and P-value < 0.05 to account for the role of chance
in findings.
Results: A total of 108 diabetes patients were surveyed. Out of whom, 66(61.1%) were females. Significant
amount (22.4%) of respondents declared to be regular alcohol drinkers with males outweighing females in
frequency (P=0.05) Almost 10% of male respondents
revealed to have had smoked at least once within 24
hours prior to the survey time (P=0.0000). None among
the study respondents revealed to perform blood/urine
sugar on a daily basis. Long duration of diabetes state was
strongly associated with higher frequency of blood/urine
sugar tests (P=0.003). Significant number (87.75%) of
respondents perceived eating practices to affect diabetes
and its outcomes.
Conclusion: Significant amount of respondents were
active smokers and alcohol users.
Abstract #204
PRIORITY SETTING FOR DIABETES MELLITUS
INTERVENTION AND RESEARCH IN NIGERIA
Bridget Akudo Nwagbara, MBBS,
Chioma N. Unachukwu, MBBS, FWACP, FACE,
Emmanuel Effa, MBBS
Objective: To identify priority issues on intervention
and research on Diabetes Mellitus in Nigeria. Diabetes
Mellitus is an emerging public health problem in Nigeria
– 19 –
with substantial morbidity and premature mortality. To
deliver evidence-based interventions in Nigeria, it is
important to ensure that national priority issues on this
disease are identified and addressed.
Methods: Multi-disciplinary team developed and
piloted study methodology and tools. Collection of data
relevant to burden of Diabetes Mellitus in Nigeria from
the National Health Management Information Systems,
information from key informants (health professionals,
researchers, NGOs and patients ) drawn from all six geopolitical zones in Nigeria and literature review. The key
steps included compilation and ranking of a comprehensive list of cross cutting issues on the disease with reference to Nigeria; summary of existing strategies for disease
control in Nigeria; identification of gaps in existing system for disease control; searching PUBMED, Cochrane
Library and other electronic databases for research done
on the identified priority areas using a defined search strategy. Analysis of search outputs to identify gaps in previous research; and listing of new priority issues on intervention and research using predetermined criteria.
Results: Eight broad areas were identified as priority for control and research of diabetes mellitus in Nigeria
addressing issues such as culturally appropriate health
education, integration of Diabetes Mellitus control into
the primary health care system, treatment adherence, the
use of treatment guidelines, follow up of patients, paucity
of epidemiological data, phyto- medications as treatment
adjuncts, management of infectious diseases in synergy
with diabetes mellitus. 3 topics were identified for systematic reviews. Specific intervention strategies and research
topics will be presented and discussed.
Discussion: A consultative approach including
patients provided an equitable and bias free patient centered and public health perspective to this research.
Despite adequate knowledge on pharmacological interventions among healthcare personnel, huge treatment
gaps still persist in diabetes mellitus control in Nigeria.
Findings draw attention on the need for researchers to
shift from basic bio-medical research to other forms of
research to facilitate informed decisions on the control of
diabetes mellitus in Nigeria
Conclusion: Prioritization of issues relevant to
the management and research on diabetes mellitus will
improve the opportunity to scale up interventions and
deliver evidence-based and equitable healthcare to
patients. These issues are likely to be also important for
Diabetes Mellitus control in other resource-poor settings.
Abstract #205
A COMPARATIVE STUDY OF KNOWLEDGE,
ATTITUDES AND PRACTICES OF
COMPLICATIONS OF TYPE 2 DIABETES
AND ASSOCIATED RISK FACTORS AMONG
PATIENTS WITH TYPE 2 DIABETES IN DAR ES
SALAAM, TANZANIA AND NEW HAMPSHIRE,
USA
Goodluck Willey Lyatuu, MD,
Mohammad Bakari, MD, MMed, PhD
Objective: An analytical, cross-sectional study was
done to compare the differences in Knowledge, Attitudes
and Practices of complications of type-2 diabetes and
associated risk factors, among patients with type 2 diabetes in Tanzania and USA.
Methods: Swahili and English structured questionnaires were administered to 86 diabetic patients attending clinics in 3 hospitals in Dar es Salaam, Tanzania and
77 patients attending at Dartmouth Hitchcock Medical
Centre (DHMC) in New Hampshire, USA respectively.
Study participants were selected by simple random sampling over a period of 6 weeks in each country. Data from
both study areas were analyzed using SPSS data analysis
tool.
Results: This study revealed no significant difference
in proportion of patients knowledgeable of complications
of diabetes and associated risk factors in the two communities with both communities 84.9% in Dar es Salaam and
92.2% in New Hampshire scoring high on knowledge, P
= 0.15. There was also no significant difference in attitude
towards diabetes whereby majority had a positive health
promoting attitude towards the disease, i.e. only 9.3% in
Dar es Salaam and 5.2% in New Hampshire considered
regular physical exercise to have little influence on diabetes management, P = 0.29, and 5.8% in Dar es Salaam
and 5.2% in New Hampshire considered weight management to have little influence on the management of their
Diabetes, P = 0.86. There were however significant differences in practice whereby; only 11% of study participants
in Dar es Salaam compared to 93.9% in New Hampshire
reported to be doing blood glucose check-ups at least once
a week, P < 0.001; only 63% of study participants in Dar
es Salaam compared to all in New Hampshire reported
to weigh themselves at least once a month, P < 0.001;
and 48% in Dar es Salaam compared to 69.4% in New
– 20 –
Hampshire reported to be doing physical exercise at least
4 to 6 times a week for at least 15 minutes, P = 0.02.
Conclusion: In conclusion, although knowledge on
Diabetes Mellitus was high in both settings, and attitude
positive, significant differences in practice were noted
with Dar es Salaam scoring poorer compared to New
Hampshire. More elaborate studies assessing multi-factorial of issues that influence positive health attitudes and
behaviors towards Diabetes Mellitus should be conducted,
especially in less developed countries. Furthermore efforts
should be done to further expand the diabetes health education being provided at the health care facilities in Dar
es Salaam so as to reach out to more diabetes patients in
other health facilities in the country.
Abstract #206
PATTERN OF FASTING DYSGLYCEMIA AND
DYSLIPIDEMIA IN HIV POSITIVE PATIENTS ON
HIGHLY ACTIVE ANTIRETROVIRAL THERAPY
Ayoola Olukunmi Oladejo, MBBS,
Jokotade O. Adeleye, MBBS, FWACP,
Yetunde A. Aken’ova, MBBS, FWACP, FMCPath
Discussion and Conclusion: The prevalence of both
HIV and diabetes mellitus has reached a pandemic proportion. Sub-Sahara Africa bears the greatest burden of HIV
infection and non-communicable diseases such as obesity and diabetes mellitus are emerging diseases of public
health importance in this region. The greater risk of occurrence of type2 diabetes and other metabolic disorders such
as atherogenic dyslipidemia, systemic hypertension and
obesity associated with the use of highly active antiretroviral therapy may thus constitute a double tragedy in this
low-resource region of the world. Previous studies have
shown a higher prevalence of impaired fasting glucose,
impaired glucose tolerance and overt diabetes mellitus in
HIV positive patients on prolonged therapy with HAART
which this study has also clearly demonstrated. The management of HIV should therefore be holistic in approach
and metabolic parameters should be routinely assessed
and strategies such as lifestyle modification, early diagnosis and prompt treatment should be employed in order
to improve the overall survival and quality of life of HIV
positive patients.
Abstract #207
Objective: To determine the pattern of fasting plasma
glucose and lipid profile abnormalities in HIV positive
patients on HAART and to compare with the pattern seen
in HAART naïve HIV positive patients.
Methods: One hundred and eighty HIV positive
patients were selected by systematic random sampling.
Ninety-two were on HAART therapy while eighty-eight
were HAART naïve. Blood samples for fasting plasma glucose and fasting lipid profile were obtained after an overnight fasting. Fasting plasma glucose was determined in
the chemical pathology laboratory by the glucose oxidase
method using 4-aminophenazone as the oxygen acceptor
as described by Trinder while the fasting lipid profile was
determined by the enzymatic colorimetric method. Data
obtained were analyzed using the SPSS 16.0 version.
Results: The mean ages of the HAART and the
HAART naïve groups were 40.1± 9.5 and 37.7± 9.3
respectively, p=0.081. The mean fasting plasma glucose
was 125.5± 44.3 in the HAART group versus 88.3± 31.8 in
the HAART naïve group (p< 0.001). The mean serum triglyceride was 66.7± 31.6 and 112.7± 60.0 in the HAART
and HAART naïve group respectively (p< 0.001). The
mean HDL-Cholesterol was lower in the HAART group
than the HAART naïve group but the difference was not
statistically significant( 42.3± 13.1 versus 44.1± 14.5, p=
0.38).The overall prevalence of diabetes mellitus in the
total study population was 25.6% being 45.7% in the
HAART group and 4.5% in the HAART naïve group, p<
0.001.
DIABETES RELATED KNOWLEDGE AMONG
RESIDENTS AND NURSES: A MULTICENTER
STUDY IN KARACHI, PAKISTAN.
Asma Ahmed, MBBS, Lubna Zubairi, Abdul Jabbar,
Muhammad Islam, Khusro Shamim, MBBS
Objective: To evaluate and compare the knowledge
related to the management of diabetes among nurses and
trainee residents of internal medicine, family medicine
and surgery at tertiary care hospitals of Karachi, Pakistan.
Methods: A validated questionnaire consisting of
20 questions related to diabetes awareness was acquired
through a study done at Thomas Jefferson University
Hospital, Philadelphia with the permission of primary
author. The questionnaire was administered at 5 tertiary care academic hospitals including The Aga Khan
University Hospital to residents and nurses.
Results: 169 internal medicine residents (IMR), 27
family medicine residents (FMR), 86 surgery residents
(SR) and 99 nurses (RN) participated. The survey had
a good reliability coefficient (Cronbach α of 0.81).The
overall mean correct percentage was 50% ± 21. There was
no difference in total scores of IM & FPM residents (64%
± 14 vs. 60% ± 16, p= 0.47).The total scores of SR and
RN were quite low (40 % ± 16 & 31% ± 15 respectively).
Although FMR scored higher than IMR on items regarding outpatient management of diabetes but that difference
was not statistically significant (p=0.128).For inpatient
diabetes care the scores of IMR were higher than FMR but
– 21 –
not statistically significant either(p-value 0.175).SR and
RN had profound deficit in both inpatient and outpatient
management. Surprisingly, despite of the fact that RN are
actively involved in in-patient management of diabetes,
they didn’t answer correctly on most of the items regarding in-patient management of diabetes (Mean score 40%).
Conclusion: Since the prevalence of diabetes has
been rapidly rising, it has become one of the major public
health problems. Pakistan is also one of those countries
estimated to have the highest number of people with diabetes. To be able to face this enormous number of diabetes cases, health care providers need to have adequate
knowledge to deliver optimal care to these patients. There
are several studies that have examined the diabetes knowledge of nurses, but the data assessing the knowledge of
diabetes among trainee residents’ especially surgical residents is lacking. As there are no prior studies in our setting
evaluating knowledge related to diabetes management
among residents and nurses, this study is quite significant.
Based on these results, there are significant gaps in diabetes knowledge among residents and nurses. Due to high
burden of disease and considering the fact that our residents and nurses are actively involved in diabetes management this raises important concerns and needs to be
addressed.
Abstract #208
COMPARISON OF PATTERNS OF TYPE 2
DIABETES BETWEEN NATIVE PAKISTANI AND
UK IMMIGRANT SOUTH ASIANS
Asma Ahmed, MBBS, Abdul Jabbar
Objective: This study was designed to assess whether
the pattern of diabetes in native South Asians is different
from immigrant South Asians.
Methods: Data on Pakistan based South Asians
acquired from a sample of 100 type 2 diabetics attending
outpatient clinic of The Aga Khan University Hospital
(AKHU) at Karachi, Pakistan during year 2005 was collected for a cross sectional survey and compared with
the data from UK based South Asians acquired through a
study carried out at Ealing Hospital, London enrolling 889
UK immigrant South Asians. This was done after gaining approval for the inclusion of data from the author Dr.
H.M.Mather.
Results: The age of the native diabetic male patients
was less 58 ± 11.6 as compared to the age of UK based
South Asians53 ± 13.3 (p=0.006) however, the age at
diagnosis; the duration of diabetes as well as the BMI
were similar among the two groups. Smoking was significantly more common among Pakistani male patients compared to the UK counterparts. However, this difference
was not observed among female patients. Moreover, the
prevalence of HTN was found to be more among the
Pakistani female patients. The prevalence of IHD was
similar among both groups. Retinopathy prevalence was
higher with statistical significance only among Pakistani
males (p=0.037). As far as treatment was concerned South
Asians were more likely to be on oral hypoglycemic
agents when compared to Europeans in our quoted UK
based study. However, there was no significant difference
in treatment among Pakistani and UK based South Asians.
Conclusion: In conclusion, it appears that besides
environmental factors, genetic influence appears to be significant influencing the pattern and mode of presentation
of type 2 diabetes among South Asians and it should be a
focus of future research.
Abstract #209
RELATIONSHIP BETWEEN HBA1C AND
2-HOUR PLASMA GLUCOSE
Abdullah Ndaman Adamu, MBBS
Objective: There is paucity of existing studies on use
of HbA1c as a screening tool for type 2 diabetes among
blacks, with high risk factor like systemic hypertension.
To evaluate the performance of HbA1c as a screening tool
for type 2 diabetes among black people with systemic
hypertension.
Methods: Two-hundred and seven subjects attending cardiology and renal out-patient department of Lagos
University Teaching Hospital were recruited, out of which
131 of the subjects had OGTT done, 2hrs post glucose
load plasma glucose assay was used as a gold standard
for the diagnosis . Using random sampling of one out of
every four, thirty three of the subjects had HbA1c assessment using DCA2000® machine produced by Bayer®,
USA. Two of the assay revealed error report and were
thus excluded from the analysis. The data was entered into
Microsoft Excel, and transported to SPSS 11 for analysis.
Glycated hemoglobin of <6.7% was considered to be negative while glycated hemoglobin of ≥6.7 was considered
to be positive for the screening. Two hour plasma glucose
of <11.1mmol/l (200mg/dl) was considered to be negative while ≥11.1mmol/l (200mg/dl) was considered to be
positive for the diagnostic test. A 2x2 table was made to
calculate specificity, sensitivity, positive predictive value,
negative predictive value, efficiency of the test and prevalence of the disease using HbA1c. Pearson correlation,
bivariate and Receiver Operative Characteristic Curve
was also plotted. Results: The mean age of the subjects that had
HbA1c assay was 54.26 ± 6.6 years. The subjects were
made up of 25 (80.6%) females and 6 (18.4%) males.
– 22 –
Mean HbA1Cwas 6.6% and mean 2hour plasma glucose
was 169.47mg/dl. The sensitivity was 57.14%, specificity
of 62.5%, positive predictive value of 30.77%, negative
predictive value of 83.33%, efficiency 61.29, prevalence
of 41.94. The correlation of HbA1c to 2hrs post glucose
load was 0.42, y = -13.18 + 29.54x, P = <0.05.The area
under ROC was 0.682 which was significant.
Conclusion: The performance of this screening test
is low compare to the results of other studies among the
Caucasians.
Abstract #210
IS DIABETES MELLITUS REALLY CURED
BY GASTRIC BYPASS SURGERY?
fasting glucoses and required a GTT to show that diabetes
was not “cured”.
Conclusion: HbA1C and FBG are not sufficient criteria to establish DM2 “cure” after gastric bypass surgery.
Measurement of postprandial blood glucoses, possibly
GTT, or even continuous glucose monitoring should be
considered postoperatively to provide a clear assessment of glycemic status specific to gastric bypass surgery
effects in those with established DM2. Many individuals
may need pharmacologic intervention, such as the presented patient, to optimize glucose control. And certainly,
being told that a “cure” has taken place, when it has not,
has significance for patients’ psychological well-being.
Abstract #211
Anna Leonidovna Marina, MD,
Dace Lilliana Trence, MD, FACE
Objective: Gastric bypass surgery is increasingly
receiving attention as a potential “cure” for type 2 diabetes
mellitus (DM2). Mechanisms of action are not completely
understood, but include improvement in insulin resistance
and insulin secretion, likely mediated by the action of
incretins and other hormonal factors. Surgical outcome
reports rely on fasting blood glucose (FBG) and normal
hemoglobin A1C (HbA1C) as criteria for “cure”. We present a case where these criteria were present, but did not
support remission of diabetes on further evaluation.
Case Presentation: 55-year-old male with BMI of
45.2 kg/m2 and 7-year history of DM2 underwent Rouxen-Y gastric bypass (RYGB). Immediately after surgery,
insulin requirement decreased from 100 to 30 units daily.
In 4 months, with weight loss of over 100 lbs, FBG was
90-150mg/dl, HbA1C decreased from 9 to 6.1%, and insulin was discontinued. At 7 months’ follow-up, HbA1C was
6.2%. Patient reported unremarkable FBGs but sporadic
glucose excursions to 180mg/dl after meals. Subsequent
three-day blinded continuous glucose monitoring (CGMS)
revealed FBG of 65-102 mg/dl, but frequent postprandial
glucoses in the 200s (up to 294 mg/dl), consistent with
persistent diabetes mellitus.
Discussion: Based on published surgical criteria,
the patient’s FBG and HbA1C were indicative of complete remission of DM2. However, diabetes could not be
considered cured. CGMS clearly documented spikes in
blood glucose above 200 mg/dl after meals. Therapy with
repaglinide was required to reduce postprandial hyperglycemia. Our observation is consistent with very recently
presented data by Roslin et al, who performed a glucose
tolerance test (GTT) in 38 subjects after RYGB (more than
6 months post-op). 6 patients had had diagnosed diabetes
before surgery but were not on any prescribed glycemic
modifying medications post-op. 5 out of the 6 had normal
THE MENOPAUSE AND THE METABOLIC
SYNDROME IN TYPE 2 DIABETES MELLITUS
Anthonia Okeoghene Ogbera, MBBS, FMCP, FACE,
Olufemi Fasanmade, MBBS, FWACP, FACE,
Sanjay Kalra
Objective: To determine the frequency and pattern
of the Metabolic syndrome (Mets), the age of onset and
occurrence of menopausal symptomatology in Nigerian
women with type 2 DM.
Methods: This is a cross-sectional study in which
201 menopausal women with type 2 DM aged between
40-85 years were studied. Anthropometric indices, fasting lipid, glucose parameters, uric acid and HbA1c were
documented. The presence of the metabolic syndrome
and menopausal symptoms were determined using the
National cholesterol Panel -ATP definition and MENQOL
questionnaire respectively. The tests statistics used include
t test, chi square and correlation coefficient.
Results: The mean age (SD) of the onset, median age
and age range of menopause was 50.3 (4.8) years, 50 years
and 40-57 years respectively. The frequency of occurrence
of menopausal symptoms studied ranged from 14%-76%.
Musculoskeletal symptoms were prominent with vasomotor symptoms of hot flushes, night sweats and dry skin
occurring in 38%, 31% and 30% respectively of the subjects. The pattern of occurrence of the menopausal symptoms was comparable in subjects with and without the
Mets. The prevalence of the Mets was 69% and increased
with increasing duration of the menopause. There was
no risk factor of the Mets in 4 (7%) of the subjects. The
prevalence of having at least two, three and four MetS
diagnostic criteria were met in 38.6%, 29.3% and 6.7% of
the cases, respectively. The most prevalent risk factor for
the Mets was abdominal obesity, affecting 75% of women.
The frequency of occurrence of hyperuricemia in the
– 23 –
study population was 42% and proportion of subjects with
the Mets who had hyperuricemia was comparable to those
without the Mets (47% vs 32 %, p-0.05). Plasma uric acid
levels did not increase with the number of MetS components present. There was however no significant correlation between the age of onset of menopause and the duration of DM(r=0.06, p=0.3), waist circumference(r=0.05,
p=0.9) and body mass index (r=0.1, p=0.8).
Conclusion: The age of onset of menopause in
Nigerian women with type 2 DM is comparable to what
is commonly reported and the Mets is highly prevalent in
this group of women. The pattern of occurrence of menopausal symptoms is unaffected by the presence of the
Mets. We conclude that the pathophysiological basis for
the symptomatology of the menopausal state is most likely
unrelated to that of the Mets.
Abstract #212
INSULIN PUMP THERAPY USING A SIMPLE
DOSING REGIMEN SAFELY IMPROVED
GLYCEMIC CONTROL AND PATIENT
REPORTED OUTCOMES IN PATIENTS
WITH TYPE 2 DIABETES SUBOPTIMALLY
CONTROLLED WITH MULTIPLE DAILY
INJECTIONS
Juan P. Frias, MD, FACE, Steve V. Edelman, MD,
Bruce W. Bode, MD, Timothy S. Bailey, MD,
Mark S. Kipnes, MD, Xiaojing Chen, MS
of patients at least once during the 16-wk study, with no
episodes of severe hypoglycemia. At Wk 16, the mean
daily basal, bolus, and total insulin doses were 66±36U,
56±40U, and 122±72U (1.2U/kg), respectively. 90% of
patients were treated with 2 basal rates per day (1 basal
rate 80%; 2 basal rates 10%). Body weight increased by
2.7±2.6kg (p<0.001). PRO measures improved significantly from baseline (Treatment satisfaction: 65±15 vs
81±15, p<0.001; Overall treatment preference: 58±14 vs
93±16, p<0.001; Scale of 0-100, Mean±SD).
Discussion: Insulin pump therapy is an important
treatment option for patients with T2DM suboptimally
controlled with MDI. Limited data exist about pump therapy in this patient population. Though having multiple
basal rates and the ability to deliver very precise insulin
increments is important for many patients with T1DM, it
is unlikely necessary for most patients with T2DM. The
improved PROs with pump therapy are important, since
improved patient medication experience may result in better compliance, ultimately improving long-term outcomes.
Conclusion: Insulin pump therapy using a simple
dosing regimen significantly improved glycemic control
in patients with T2DM who were suboptimally controlled
with MDI therapy. Patients experience moderate weight
gain, no severe hypoglycemia and preferred pump therapy
to baseline treatment with insulin injections. Future controlled trials are needed to further assess the benefits of
insulin pump therapy in T2DM.
Abstract #213
Objective: To assess the efficacy, safety and patient
reported outcomes (PRO) of 16 wks of pump therapy in
patients with type 2 diabetes (T2DM) suboptimally controlled with multiple daily injection (MDI) therapy.
Methods: In this sub-analysis of a 16-wk, open-label,
multicenter study, 21 insulin pump naïve patients treated
with MDI±oral agents (9 male/12 female, age 57±13y,
DM duration 15±6y, A1C 8.4±1.0%, FPG 165±58mg/dl,
body weight 98±20kg, BMI 34±5kg/m2, total daily insulin
dose 99±65U [1.0U/kg], mean±SD) discontinued all DM
medications except metformin and initiated pump therapy
(Animas® 2020) with one daily basal rate and bolus doses
at each meal. Insulin doses were titrated to safely achieve
the best possible glycemic control. Outcomes included
insulin dose and dosing patterns, A1C, FPG, weight, PRO
(Insulin Delivery System Rating Questionnaire), and
hypoglycemia.
Results: Glycemic control improved significantly
after 16 wks of pump therapy: A1C 7.3±1.0% (-1.1±1.2%,
p<0.001) and FPG 129±37mg/dl (-36±74mg/dl, p<0.001).
In patients with baseline A1C >8.5% (n=11, mean baseline A1C 9.1±0.5%), A1C was reduced by 1.9±1.3%
(p<0.005). Mild hypoglycemia was experienced by 81%
PENTOXYPHYLLIN IN DIABETIC
NEPHROPATHY
Piyush Harshadrai Desai, MD, Shyamla N.,
Ashwin Aiyangar, Sumedh Hoskote, MD, Bharat Shah,
Vijay Panikar, MD, MBBS,
Shashank Joshi, MD, FACP, FRCP, FACE
Objective: Diabetic nephropathy is the leading cause
of chronic kidney disease in the world. Current therapeutic targets in the management of diabetic nephropathy
are good glycemic control, BP control, lipid control and
reduction in the glomerular hypertension/hyperfiltration.
In addition, there are measures to reduce proteinuria, e.g.
RAAS blockers and novel agents with various mechanisms of reducing proteinuria. Among novel agents is
pentoxiphylline which is a nonselective phosphodiesterase inhibitor. To analyze the effectiveness of Pentoxiphylline in the reduction of proteinuria in patients of diabetic nephropathy.
Methods: 38 subjects were prospectively studied over
6 months. Subjects with DM and a urinary albumin to creatinine ratio (UACR) greater than 0.03 (30mg/gm) were
– 24 –
included. These subjects were started on Pentoxiphylline
1200mg/day in divided doses and followed up at 2 monthly
intervals. BP, blood sugar and proteinuria was monitored
at each visit. Proteinuric response was defined as a 25%
reduction in proteinuria as compared to baseline.
Results: 73.7% of the subjects experienced a response
in UACR. Mean values of UACR obtained were 0.63
at baseline and 0.55, 0.49 and 0.47 at 2, 4 and 6 months
respectively. A reduction in UACR was observed even in
those who were on RAAS blockers, suggesting an additive
effect of PTX. UACR reduction was similar in both hypertensive and non-hypertensive subjects. Higher reduction
was seen with a higher baseline UACR and in those with
a longer duration of DM.
Conclusion: Pentoxiphylline reduces proteinuria in
patients with diabetic nephropathy. It works well even in
those in whom the RAAS is blocked, and hence a useful
agent in diabetic nephropathy.
Abstract #214
STRESS HYPERGLYCEMIA AS PROGNOSTIC
MARKER IN SEPSIS
Mukhyaprana M. Prabhu, MD, Hanumath Rao Madala,
Balasubramanian R., MD, Madhusudhan Sangar, MD,
Vishwanathan S., MD, Abdul Razak MD
Objective: To study the clinical and laboratory characteristics of patients with sepsis and baseline hyperglycemia and investigate the impact of hyperglycemia on the
final outcome. Hyperglycemia has been noted in acute
medical emergencies and stress hyperglycemia is associated with increased mortality in myocardial infarction,
stroke and poisonings. There are no major studies regarding stress hyperglycemia in sepsis patients.
Methods: Prospective study done in Kasthurba
medical college hospital attached to Medical College in
south India.150 patients admitted with severe sepsis during a 2-years period were included in the study. Patients
were divided in 4 groups according to their glycemic
profile at admission: patients with stress hyperglycemia
(number 23) defined as random blood sugar at admission
> 200mg/dl and normal glycosylated hemoglobin (Hb
A1C), with diabetes mellitus (number 24), (patients with
history of diabetes / on treatment) with newly detected
diabetes (defined as no history of diabetes but HbA1c
>6.5 Gm%(number 8) and with normal glucose level and
no diabetes (number 95). All patients were studied with
respect to final outcome, duration of intensive care stay,
total duration of hospital stay and APACHE 2 score.
Results: A total of 36.6% of patients with severe
sepsis had baseline hyperglycemia with 15.3% having
sepsis-induced stress hyperglycemia. A higher percentage
of septic patients with stress hyperglycemia died compared
with patients with normal glucose levels (43.4% versus
24.2%) and diabetics who had hyperglycemia at admission had higher mortality compared to patients with normoglycemia(37.5% versus 24.2%). All patients required
insulin for control of hyperglycemia. Majority of diabetics were changed to diet and insulin (60%) at the time of
discharge. A positive correlation was detected between
the fasting blood glucose levels of Stress hyperglycemia
group and the severity of sepsis indicated by sepsis-related
organ failure assessment score.
Discussion: Sepsis is the systemic inflammatory
response to severe infections with high morbidity and
mortality rates, according to the disease state, by several
clinical and laboratory markers, like age, severity scores
(simplified acute physiology score, SOFA, acute physiology and chronic health evaluation, etc.), organ dysfunction, C-reactive protein, or procalcitonin levels. All
patients undergoing critical illness, including sepsis, are
at risk for stress induced hyperglycemia. Mortality rate in
patients with stress hyperglycemia in our study was 43.5%
(24.2% in controls). A higher percentage of patients with
stress-induced hyperglycemia died compared with controls with severe sepsis.
Conclusion: Baseline/ admission hyperglycemia,
including stress-induced hyperglycemia, is common in
patients with severe sepsis. Stress-induced hyperglycemia
is related to a more severe disease and poorer prognosis.
– 25 –
Abstract #215
SUCCESSFUL REMISSION OF TYPE –B
INSULIN RESISTANCE WITH
IMMUNOSUPPRESSIVE THERAPY
Bhanu Iyer, MD, Mariana Garcia Touza, MD,
Christos Paras, DO, Kyaw K. Soe, MD,
Agnieszka Gliwa, MD
Objective: To describe a case of type B insulin resistance (IRS-B) in a woman in whom normoglycemia was
restored with immunosuppressive therapy.
Case Presentation: A 21 year old black female presented in December 2008 with progressive weight loss,
polyuria, polydypsia, darkening of the skin, severe acne,
amenorrhea, and was noted to have hyperglycemia.
She was placed on bolus-basal insulin 50 units a day,
but eventually required escalation of her insulin dosage
without gaining control over her blood glucose. Physical
exam was significant for acanthosis nigricans, acne and
hirsutism. Work-up revealed extremely high serum insulin levels 238 uU/ml (nl. <2.60), elevated c-peptide 4.5
ng/ml (nl.0.8-3.1), negative islet cell antibodies, low
triglycerides 33 mg/dl (nl. <150), elevated testosterone
level at 916 ng/dl (nl.20-81), elevated hemoglobin A1C
(HgBA1C) 13.7% (nl. <6), and polycystic ovaries. ANA
and all other autoimmune markers were negative. IRS-B
was suspected and confirmed with positive insulin receptor auto antibodies (IR-Abs). Patient was placed on insulin
U-500 with maximum daily dose of 600U. She received
2 cycles of rituximab along with dexamethasone in July/
August 2009 and cyclophosphamide 100 mg/day was continued. There was a gradual resolution of her hyperglycemia and insulin was discontinued in October 2009. Her
HBA1C improved to 6.5 and testosterone normalized to
37.5 ng/dl by November 2009. Patient remains euglycemic and continues to be on cyclophosphamide.
Discussion: Type B insulin resistance is rare and is
characterized by the presence of auto antibodies to the
insulin receptor. The majority of patients are women of
African American descent; with the mean age of onset
at 40 yrs. Nonspecific autoimmune features are common in these patients with the most consistent underlying
syndrome complex being systemic lupus erythematosus
(SLE). Signs of hyperandrogenism and insulin resistance
are the prominent presenting features that disappear with
the clearance of IR-Abs. Different immunosuppressive
therapies like glucocorticoids, azathioprine, cyclophosphamide, rituximab and plasmapheresis have been used in
the past with variable results. Our patient presented with
classical features of IRS-B in the absence of any systemic
autoimmune condition, which to our knowledge is quite
rare. Immunosuppressive therapy with rituximab and
cyclophosphamide was successful in achieving remission
in our patient.
Conclusion: In our patient treatment with cyclophosphamide, rituximab and glucocorticoids helped achieve
remission of type B insulin resistance.
Abstract #216
DIABETIC KETOACIDOSIS IN OBESE
ADOLESCENT, A CASE REPORT
Helard Andres Manrique, MD, Pedro Aro, MD,
Edith Hernandez, MD, Carlos Calle, MD,
Miguel E. Pinto, MD, Rubelio E. Cornejo, MD,
Jose Solis, MD
hyperglycemia. The diagnosis of severe diabetic ketoacidosis was established and treatment was started with
intensive hydration, correction of electrolyte abnormalities and insulin therapy. Further work up showed elevated
hemoglobin A1c and the glutamic acid decarboxylase
antibodies were negative. Glucose management in the
non-ICU setting included NPH and pre-meal regular insulin. He was discharged from hospital with NPH insulin
and metformin 850mg twice a day. After one month of the
episode, he discontinued insulin, and after three months
he was treated only with metformin 850mg once a day.
His last fasting blood glucose and hemoglobin A1c were
normal.
Discussion: The prevalence of type 2 diabetes in
children and teenagers has increased the last decade. The
clinical characteristics of our patient are typical of a type
2 diabetes adult patient, with obesity, cervical acantosis
nigricans and familiar diabetes antecedent. Severe diabetic
ketoacidosis typical picture of a debut of a type 1 diabetes,
there are some publications that in certain afroamerican
ethnias the diabetic ketoacidosis(DKA) is presented in the
way of debut in young men , in our population the way of
presentation of DKA in adult type 2 diabetes is frequent
and the presented the clinic characteristic that a 50% were
a way of diabetes debut. At the beginning of the discussion we named the clinic characteristics associated to type
2 diabetes and the antibodies anti GAD were negative , it
is true that a 15% type 1 diabetes patients have negative
antibodies but the phenotype of our patient is type 2 DM.
Conclusion: Type 2 diabetes has traditionally been
viewed as a disorder of adults. However, as the prevalence
of obesity in youth is increasing, type 2 diabetes is now
occurring in children and adolescents. Sustained hyperglycemia can impair the secretion of insulin by the betacells of the pancreas. Glucose toxicity explains why some
patients newly diagnosed with type 2 diabetes have weight
loss, diabetic ketoacidosis, and low measured insulin and
C-peptide. Diabetic ketoacidosis in obese adolescents
with new-onset diabetes does not imply the diagnosis of
type 1 diabetes.
Abstract #217
Objective: To report a case of an obese adolescent
presenting with diabetes and severe ketoacidosis.
Case Presentation: A 14 year-old obese male presented with a four weeks history of polyuria, polydipsia
and weight loss. Physical examination at presentation
showed Kussmaul breathing, severe acanthosis nigricans,
and his left knee was swollen and tender. Laboratory
tests showed severe metabolic acidosis, ketonuria, and
NOT ALL SULFONYLUREAS ARE THE SAME.
TO REDUCE CARDIOVASCULAR MORBIDITY
AND MORTALITY LETS SAY GOODBYE TO
GLYBURIDE.
Gauranga Chandra Dhar, MD
Objective: To present 2 cases of T2DM patients under
increased risk of cardiovascular (CV) events due to use of
glyburide.
– 26 –
CasePresentation: A 42-yo man presented with frequent episodes of hypoglycemia and left sided chest pain.
He is diabetic for 2 years, had no complaints when he was
under metformin and statin except A1C >8.5% for which
glyburide was added 6 months back after which his A1C
came down to 7% and lipids in normal limit. Ischemic
changes in ECG & ETT. CIMT & CT angiogram were non
specific. Glyburide was changed to glimepiride. After 3
months, patient was free from chest pain and relieved from
hypoglycemic episodes and ECG found normal. A 63-yo
woman with T2DM presented with MI, died after 8 hours
of hospital admission. Retrospective analysis shows that
after diagnosis of T2DM >20 years back she was noncompliant, used to have A1C >9.5% and dyslipidemia which
continued for approximately 5 years. Although she had no
complaints, decided to go for proper control, started with
insulin, metformin and statin. A1C came down to 7% and
lipids to normal in 2 years. Six months before her death, as
per her request glyburide was prescribed instead of insulin. Blood glucose and lipid were normal 2 months before
her death but felt symptoms of hypoglycemia.
Discussion: Increased CV morbidity and mortality
due to use of glyburide can be explained by two different
mechanisms: First, Sulfonylureas (SUs) work by inhibiting KATP channels in beta cells causing cell membrane
to depolarize leading to voltage-dependent Ca2+ channel
to open, causing increase in Ca2+ in beta cells leading to
insulin secretion. Glyburide exerts non specific affinity
to SU receptors (SUR) e.g. acts on SUR-1 in beta cells,
SUR-2A and SUR-2B in cardiac myocytes and cells on
vascular bed respectively. Chronic inhibition of the KATP
channel with glyburide abolishes ischemic preconditioning of explanted myocardium might be the reason of
increased CV mortality. Such inhibition of the cardiac
KATP channel with glyburide has been shown to increase
ischemia-reperfusion damage. Second, Glyburide continues to stimulate insulin secretion to a greater extent than
other SUs in the setting of profound hypoglycemia. In
addition, glyburide is known to accumulate in the beta
cells where it can prolong insulin secretion, whereas other
SUs do not. Sympatho-adrenal activation and counterregulatory hormone secretion due to hypoglycemia lead
myocardial ischemia and infarction. Additionally counterregulatory mechanisms may lead to prolonged cardiac
repolarization causing “Torsade de pointes” and death.
Conclusion: During selecting sulfonylurea for the
treatment of T2DM, better to go for selective SU having
affinity only to SUR-1 and avoid glyburide, a non-selective SU.
Abstract #218
HYPOGONADISM: A HIDDEN DANGER IN MEN
WITH DIABETES MELLITUS
Sonny Chinenye
Objective: The relationship between hypogonadism
(H) and the risk of development of cardiovascular diseases
in men with diabetes mellitus (DM) has not been widely
studied in sub-Saharan Africa. We set out to determine the
frequency of occurrence of H, the prevalence and correlates of the metabolic syndrome (Mets) in Nigerian men
with type 2 DM who have H.
Methods: This was a cross sectional study of 200 men
with type 2 DM aged 30-86 years receiving care at the DM
Centre of the Lagos State University Teaching Hospital
(LASUTH), Ikeja. The clinical parameters that were
determined included history pertaining to DM and hypertension. The laboratory parameters that were assessed
included blood glucose, total testosterone (TT), uric acid,
lipid parameters and highly sensitive CRP. Hypogonadism
(H) was determined by the combination of positive ADAM
score (clinical features of hypogonadism were determined
by usage of the ADAM questionnaire) and TT less than
300ng/dl. The presence of the Mets was determined using
the ATP III criteria. Test statistics used included logistic
regression, correlation coefficient analysis, and t test. P
values of <0.05 were considered statistically significant.
Results and Discussion: The overall prevalence of H
was 70% and the mean (SD) age of the subjects with H
was comparable to that of those without H (60.3± 11.8
vs 57.7± 12, p- 0.1). The proportion of H subjects with
the Mets was higher than that of the non H group with
the Mets (81% vs19%, p- 0.006). The mean TT level in
subjects with the Mets was lower than in those without
the Mets (200± 220ng/dl vs 290±300ng/dl, p-0.02). The
prevalence of high hs.CRP was 68% in subjects with, and
32% in those without the Mets (p- 0.03). The occurrence
of the Mets was associated with low testosterone levels
(OR: 0.3,95%CI: 0.148-0.647,p-0.004) which in turn
was significantly correlated with elevated hs CRP levels
(r=+0.3, p-0.001). The clustering of the components of
the Mets were in the following proportions: elevated TG
(13%), reduced HDL- (84%) central obesity 41 (49%),
and hypertension 58 (70%)). The overall prevalence of
hyperuricaemia was 11% and this was noted in only 8% of
the subjects with the Mets. The frequency of occurrence of
hyperuricaemia in H and non H patients with the Mets was
comparable. LDL-C was the only lipid parameter that had
possible relationship with H. The mean level of LDL-C
was significantly higher in H than non H men (144mg%
– 27 –
± 51 vs 108 mg % ± 48 , p-0.03) and LDL-C had a significant correlation with testosterone levels (r = + 0.2,
p-0.002).
Conclusion: Given the more frequent occurrence
of the Mets, prominence of elevated hs CRP levels and
higher LDL levels in hypogonadal than non hypogonadal
men, we conclude that testosterone deficiency in men with
DM places them at greater cardiovascular risk compared
with those without hypogonadism. Elevated hs-CRP but
not hyperuricaemia is a dominant feature of the Mets in
hypogonadal men with type 2 DM. The underlying association between testosterone deficiency and the Mets
remains unclear and needs to be studied.
Abstract #219
TACROLIMUS INDUCED DKA IN A PATIENT
WITH RENAL TRANSPLANTATION AND
LAURENCE-MOON-BIEDL SYNDROME
Muhammad Qamar Masood, MD,
Madiha Rabbani, MBBS
Objective: To describe a case of new onset diabetes
mellitus with diabetic ketoacidosis (DKA) as initial presentation in a patient with Lawrence moon Biedl syndrome receiving tacrolimus for renal transplantation.
Case Presentation: A 17-year-old Sudanese male
patient was brought to the Emergency Room (ER) with
polyuria, nocturia, dry mouth, and poor appetite of three
days duration and intractable vomiting, altered mentality
and irritability for one day. Although impaired fasting glucose (IFG) had been documented on a few prior occasions,
overt diabetes had never been present. The patient was a
known case of Laurence-Moon-Biedl syndrome (LMBS).
Deterioration in kidney function was noted at the age of
12 years gradually progressed to end stage renal disease
(ESRD) leading to pre-emptive renal transplantation one
year prior to this presentation. He had been receiving
immunosuppressive treatment in the form of tacrolimus
(6 mg bid), mycophenolate mofetil (1gram bid) and prednisolone(5 mg qd) in the post-transplant setting. Physical
examination showed moderate dehydration and without
any overt focus of infection. He was afebrile, had a heart
rate of 140 beats per min, blood pressure of 126/70 mm
Hg, respiratory rate of 30 per minute. His physical exam
otherwise is significant for marked obesity, acanthosis
nigricans, vision was limited to light perception only,
polydactyly and absence of secondary sexual characteristics. His blood glucose was 702 mg/dl with large ketonuria and high anion gap metabolic acidosis (pH-7.1, anion
gap 25 mEq/l, serum bicarbonate 06 mEq/l). The patient
was managed with intravenous fluids, insulin infusion and
potassium replacement as per standard protocols. Insulin
infusion was discontinued within 24 hours with the normalization of arterial pH, serum anion gap and disappearance
of urine ketones. However, large doses of subcutaneous
insulin (up to 130 units per day) were still needed to keep
serum glucose within normal range. In view of extremely
high daily insulin requirements, tacrolimus was substituted with cyclosporine A. Following this regime modification, his insulin requirements significantly reduced
(40 units per day). Complete insulin independence was
achieved within 2 weeks and he has not required any insulin or oral hypoglycemic agents hitherto (approximately
1.5 years after his presentation with DKA). Serum fasting
plasma glucose levels have remained within normal range.
Anti-GAD and islet cell antibodies were both negative in
this patient. Serum insulin levels and C-peptide levels
were, however, not checked.
Discussion: The diagnosis of drug induced DM in our
patient presented a diagnostic dilemma because of consideration for competing etiologies including DM secondary to LMBS and ketosis-prone type 2 DM. LMBS is an
autosomal recessive condition characterized by rod-cone
dystrophy, postaxial polydactyly, central obesity, mental
retardation, hypogonadism, and renal dysfunction. In a
large series of 109 patients, non-insulin dependent DM
(NIDDM) was described in 6% of the patients. In recent
years, an increasing number of DKA cases have also been
reported in children, adolescents and adults without any
precipitating cause; these have been referred to as atypical
diabetes or ketosis-prone type 2 DM. Increasing evidence
indicates that this subtype of diabetes accounts for more
than half of newly diagnosed black and Hispanic patients
with DKA. These patients are usually obese, have a strong
family history of diabetes, have a low prevalence of autoimmune markers, and lack a genetic association with
HLA. While our patient was obese and had negative autoimmune markers, he also didn’t have a family history of
DM. A diagnosis of drug induced DM leading to DKA is
the most likely etiology in our patient because of the rapid
decline in insulin requirement and insulin independence
after withdrawal of tacrolimus. Tacrolimus inhibits the
transcription of the insulin gene by inhibition of calcineurin after binding to FK506-binding protein 12. Tacrolimus
as compared to is more commonly associated with post
transplantation diabetes mellitus, in an open label, randomized trial the six month incidence of new onset diabetes after transplantation or impaired fasting glucose was
33.6% with tacrolimus and 26.0% with cyclosporine. In
another study using the used data from the United States
Renal Data System, the three-year incidence of de novo
diabetic ketoacidosis was 1.56% in patients using tacrolimus vs. 0.35% in patients using cyclosporine. DKA is
usually sudden in onset in these individual and total insulin independence was described in one case report after
withdrawn from tacrolimus.
– 28 –
Conclusion: Clinicians should be cognizant of the
possibility of hyperglycemic crisis presenting as sudden
onset of diabetic ketocidosis in patients receiving tacrolimus. Substituting these patients to alternative calcineurin
inhibitor may provide a safer solution to minimize future
morbidity.
Abstract #220
DIABETES CONTROL AMONG HAITIANS
VERSUS AFRICAN-AMERICANS IN AN URBAN
SAFETY-NET HOSPITAL
Varsha Vimalananda, MD, Karen E. Lasser, MD, MPH,
Howard Cabral, PhD, MPH, James Rosenzweig, MD
0.19-0.59), PVD (OR 0.17 95%CI 0.06-0.47), and ulcers
(OR 0.20, 95%CI 0.06-0.63).
Discussion: Despite a lower BMI and similar rates
of lab testing, Haitians have poorer glycemic and BP
control than do African-Americans. Studies of Haitians’
health care utilization and behavioral factors are indicated.
A strikingly lower rate of several diabetic complications
among Haitians may be due to under-diagnosis and underdocumentation or other factors.
Conclusion: Haitians have poorer glycemic and
BP control, but equivalent rates of lab testing and
lower rates of many documented complications than do
African-Americans.
Abstract #221
Objective: Haitians comprise 19% of the black population in Boston. We describe the burden of diabetes in this
ethnic subgroup.
Methods: We conducted a retrospective, crosssectional study of diabetes control, quality of care, and
complication rates among Haitian and African-American
patients at an urban safety-net hospital. Patients were
>20 yo with two primary care visits over the past two
years. Self-identified Haitians (n=715) who spoke
English or Haitian Creole were compared to AfricanAmericans (n=1472). We defined poor glycemic control
as A1C≥9%. Quality of care indicators were yearly testing of A1C, LDL, and urine microalbumin(UMA), as well
as LDL<100mg/dl and BP <130/80mmHg. Diagnoses of
retinopathy, neuropathy, CAD, ischemic stroke, peripheral
vascular disease (PVD), and lower extremity ulcers were
on problem lists or billing codes. We defined nephropathy
as GFR<60ml/min or renal transplant. We used chi-square
analyses and Student’s t-test. We used multiple logistic
regressions to control for age, sex, BMI, BP, language,
and payor group (insurance of poverty, Medicare, private,
and other). For regression analysis of complication rates,
we also controlled for A1C.
Results: Thirty-two percent of Haitians spoke
English. Haitians had a lower mean BMI than AfricanAmericans (30.8±6.0 vs. 33.8±6.0, p<0.0001), but rates of
hypertension were similar (80% vs. 83%). Haitians had a
higher mean A1C (8.2±1.9 vs. 7.8±2.0, p<0.0001), and a
higher proportion of A1C ≥ 9% (24% vs. 18%, p=0.003).
BP was more often >130/80 in Haitians (64% vs. 58%,
p=0.009). In the adjusted model to identify predictors
of A1C≥9%, only age (OR 0.97, 95%CI 0.96-0.98) and
Haitian ethnicity (OR 1.41, 95%CI 1.006-1.98) were significant. Rates of yearly testing for A1C, LDL or UMA
were similar. Haitians had similar retinopathy and stroke
rates, but lower rates of diagnosed and documented
nephropathy (OR 0.52, 95%CI 0.35-0.76), neuropathy
(OR 0.40, 95%CI 0.28-0.58), CAD (OR 0.34, 95%CI
IMPACT OF DIABETES EDUCATION ON
HBA1C AND WEIGHT REDUCTION
Issac Sachmechi, MD, FACP, FACE, Saman Ahmed, MD,
Vincent Rizzo, MD, David Reich, MD, FACE,
Hildegarde Payne, RN, CDE,
Betty Meenattoor, RN, CDE, Paul Kim, MD, FACE
Introduction: Diabetes education and dietitian counseling are one of the most important components of diabetes management to improve the outcome of patients.
In spite of many clinical challenges by serving a largely
uninsured population with generally poor health literacy
at Queens Hospital Center (QHC), the outcome of referred
patients to Diabetes Center of Excellence in term of weight
loss and Hemoglobin A1c (A1c) reduction has been above
the national average.
Objective: This study was designed to measure the
sole effect of diabetes education and dietitian counseling
without the intervention of an endocrinologist on glycemic control and weight on patients who were referred by
primary care physicians.
Methods: This was a retrospective case control study.
The study group (n=150) was selected from those patients
with type 2 diabetes (type 2 DM) who were referred by
their primary care physician to two diabetes educators and
a dietitian for counseling from the period of January 2007
to June 2008.The control group (n=150) was selected
from those patients with type 2 diabetes in the primary
care clinic who were not seen by a diabetes educator and
a dietitian during the same period of time. A1c and weight
were compared before and six months after diabetes education and dietitian counseling in the study group as well
as in the control group.
Results: In the study group, the mean A1c was
reduced by 1.02% (from 8.47% to 7.46%) with p< 0.01.
In the control group the mean A1c was reduced by 0.59%
(from 7.8% to 7.24%) with p< 0.01. In the study group,
– 29 –
the mean weight was reduced by 2 lb (from 175 lb to 173
lb) with p < 0.05. In the control group, the mean weight
was reduced by 0.71 lb (from 190.48 lb to 189.77 lb),
which was not statistically significant (p=0.365).
Discussion: This study demonstrates that diabetes
education and dietitian counseling alone by three personnel were effective and resulted in an improvement in glycemic control and weight loss in the study group patients
compared to the control group patients although both
groups received similar diabetes treatment from the physicians in the primary care clinic.
Conclusion: This study demonstrates that diabetes
education and dietitian counseling by two diabetes educators and a dietitian without an endocrinologist’s intervention can improve glycemic control and promote weight
loss in patients with type 2 DM and poor health literacy.
This is one of few study demonstrating a measurable
improvement in diabetes control and weight loss which
are solely due to diabetes education and diet counseling in
a municipal hospital with limited resource.
Abstract #222
Cglu <10 mmol>L) as assessed by CGM over standard 24
hour periods. Additional endpoints will include analysis
of fructosamine, Glycomark, pharmacodynamics following a meal challenge, insulin antibody data, hypoglycemia
and other adverse events.
Discussion: Nasulin is an ultra-rapid acting intranasal insulin formulation with a PK profile that more closely
mimics the onset of normal pancreatic secretion with a
faster onset time at 5-10 min and a faster Tmax of ~15-20
min than current rapid acting mealtime insulins. This profile allows for more optimal pharmacodynamic activity at
the time of caloric ingestion. In addition, this profile could
potentially result in less hypoglycemia, less weight gain
and could replace the missing early phase insulin release
in Type 2 diabetic patients. CGM methodology was chosen as it will determine both the reduction of hyperglycemia as well as the reduction of hypoglycemia.
Conclusion: This is an ongoing study. A total of 94
subjects have been randomized and enrollment is complete. The final efficacy and safety results will be presented for the 1st time at the meeting.
Abstract #223
COMPARISON OF NASULIN VS. PLACEBO
THERAPY ON GLYCEMIC CONTROL IN
TYPE 2 DIABETIC PATIENTS UTILIZING
CGM TECHNOLOGY
SERTRALINE INDUCED HYPOGLYCEMIA
Sol Virginia Guerrero, MD, Jennifer Pedersen-White, MD
Poul Strange, MD, Janet McGill, MD,
Randall Severance, MD, Lance Berman, MD,
Robert Stote, MD
Objective: To compare the effect of Nasulin™ (intranasal insulin) vs. Placebo on plasma glucose control in
subjects with Type 2 diabetes utilizing CGM technology.
Methods: This is a randomized, parallel design, double-blind, placebo-controlled, two arm, multi-center trial.
Type 2 subjects with diabetes (≥18 years of age, HbA1c
between 6.5-10.0%, BMI ≤40.4 kg/m²) on OADs and
basal insulin were eligible for the study. After a singleblind, placebo run-in phase of 4 weeks during which diet
and lifestyle counseling were given and glargine doses
were optimized (target morning fasting plasma glucose
between 90 and 120 mg/dl), patients entered a 6-week double-blind period and were randomized to placebo or 50 IU
Nasulin to be administered at the start of each of 3 meals.
Using a simple titration guideline based on postprandial
glucose measurements, the blinded study medication dose
could be increased to 100 IU per meal. Doses of the background long-acting insulin were to be kept constant during
the double-blind period. The primary analysis will assess
whether Nasulin™ achieves a larger increase from baseline compared with placebo in the percent of time spent in
euglycemia (70 mg/dL<Cglu<180 mg/dL or 3.9 mmol/L<
Objective: To report the association between sertraline use and hypoglycemia
Case presentation: A 46 year old female with a 10
year history of type 2 diabetes (controlled with diet and
glipizide) was admitted on 09/10/09 for evaluation of
recurrent, symptomatic hypoglycemia. During hospitalization, adrenal, hepatic and renal etiologies of hypoglycemia were excluded. Additionally, screening for MEN,
exogenous insulin and sulfonylurea was negative. A
symptomatic hypoglycemic episode occurred shortly after
admission (blood glucose of 40mg/dl). Hypoglycemia
with associated Whipple’s triad first occurred in May of
2009. At that time, glipizide was decreased from 5 mg to
2.5 mg daily. Despite this, hypoglycemic episodes persisted. Three weeks later, glipizide therapy was discontinued after random blood work reported blood glucose of
36 mg/dL. Despite discontinuation of glipizide, hypoglycemic episodes continued for several months. Review of
medication history revealed that Sertraline 100mg daily
was prescribed on 05/04/09 with the first episode of hypoglycemia occurring 05/09/09. Sertraline was then discontinued and patient was discharged home in stable condition with no further episodes of hypoglycemia.
Discussion: The prevalence of depression in diabetic
patients is estimated to be between 8-27%. Depression
can affect treatment and dietary compliance which can
– 30 –
impact the development of long term complications. Little
is known about the effect of selective reuptake inhibitors
on glycemic control. Here we report a case of sertraline
induced hypoglycemia (SIH) which persisted despite discontinuation of sulfonylurea therapy. To our knowledge,
there have been only 2 reported cases of SIH, one occurring in a non diabetic and the other in diabetic on sulfonylurea therapy. Diabetic and non diabetic rat models have
suggested several mechanisms for SIH including increased
insulin secretion, increased insulin uptake in muscle and
stimulation of insulin-like growth factor release. Others
however, have reported a significant reduction in blood
glucose with no concomitant increased in insulin levels.
Furthermore, others suggest that the addition of sertraline
to sulfonylurea therapy may predispose to hypoglycemia
due to enzymatic competition of P 450.
Conclusion: There are currently no established treatment guidelines to assist practitioners in the medical management of depression in diabetic patients. We report an
association between sertraline use and persistent hypoglycemia. The potential impact of antidepressant medications
on glycemic control should be considered prior to initiation of therapy in diabetic patients.
Abstract #224
MICROALBUMINURIA AMONG DIABETIC
PATIENTS IN ZARIA, NIGERIA.
Adamu Girei Bakari, MBBS, FWACP,
Ahmad Bello Muhammed, BSc,
Fatima Bello-Sani, MBBS, FWACP,
Anaja P.O, BSc, MSc, PhD
Background: Microalbuminuria reflects an abnormal glomerular capillary permeability to protein and is an
early marker of diabetic nephropathy. It is also thought
that microalbuminuria reflects generalized endothelial
dysfunction and is also considered a risk factor for cardiovascular morbidity and mortality among diabetic patients.
Objective: to determine the prevalence of microalbuminuria among diabetic patients attending the diabetic
clinic of Ahmadu Bello University Teaching Hospital,
Zaria, Nigeria.
Methods: A cross sectional study involving 170 diabetic patients who did not have overt Proteinuria or urinary
tract infection and 100 control subjects. Urinary albumin
was measured using immunoturbidimetric method on
spot urine samples. Serum and urinary creatinine, blood
glucose and glycosylated hemoglobin (HBA1c), were
measured using standard methods. Microalbuminuria was
defined as ACR of 3-30mg/mmol
Results: The prevalence of microalbuminuria is 20%
among diabetic patients. Microalbuminuria correlated
significantly with HBA1c suggesting that poor glycemic control was a risk factor for the development of
microalbuminuria.
Conclusion: Microalbuminuria is related to poor glycemic control in this study. Concerted efforts are therefore
required to improve on glycemic control in our patients
to prevent microalbuminuria and possibly diabetic
nephropathy.
Abstract #225
LIPID ABNORMALITIES IN ADULTS WITH
NEW-ONSET TYPE 1 DIABETES: ANALYSIS OF
BASELINE DATA FROM DEFEND
Aoife M. Brennan, DR, Mark Christiansen, MD,
Richard Weinstein, MD, Bruce Belanger, PhD,
Charlotte McKee, MD, Louis Vaickus, MD
Objective: Examine relationships between fasting
lipid levels, endogenous insulin secretion (C-peptide), and
glycemic control in new-onset type 1 diabetes mellitus
(NOT1DM). Autoimmune T1DM is a risk factor for development of cardiovascular disease and is associated with an
atherogenic lipid profile. Glycemia mediates some of these
abnormalities, but whether fasting lipid levels are abnormal
at first diagnosis of T1DM and whether they are related to
insulin secretion is unknown. DEFEND is a multinational
placebo-controlled Phase 3 study of the safety and efficacy
of an investigational targeted T cell immunomodulator, an
anti-CD3 monoclonal antibody (otelixizumab), in subjects
with NOT1DM. Otelixizumab has been shown to preserve
insulin secretion in a Phase 2 trial.
Methods: Subjects were enrolled within 90 days of
diagnosis; had BMI < 32; screening stimulated C-peptide
> 0.20 and ≤ 3.50 nmol/l; at least one T1DM‑associated
autoantibody; and were otherwise healthy. Baseline data
were examined for the percentage of subjects outside of
AACE targets for total cholesterol, LDL, HDL, and triglycerides. Stepwise regression was used to identify factors associated with lipid levels. Gender, age, and BMI
were base explanatory variables; stimulated C‑peptide
time-normalized area under the curve (AUC; in response
to a mixed meal), unstimulated C‑peptide, time from diagnosis, and HbA1c were candidate variables for inclusion
in the model.
Results: Data were available from 124 adult subjects
(mean age 26 years, 34% female, mean BMI 24 kg/m2).
Excluding the 5% on lipid lowering therapy, analyses
included 118 subjects. Total cholesterol was > 200 mg/
dl in 18%, LDL was > 130 mg/dl in 14%, HDL was < 35
mg/dl in 6%, and triglycerides were > 150 mg/dl in 6%.
In multiple regression analysis, age (p < 0.001), C-peptide
– 31 –
AUC (p < 0.001), and HbA1c (p = 0.002) were independently and positively associated with LDL. Adjusting for
age and C-peptide AUC, mean LDL increased 5.6 mg/dl
(SE = 1.8) for every 1% increase in HbA1c. Adjusting for
age and HbA1c, mean LDL increased 15.1 mg/dl (SE =
4.3) for every 1 nmol/l increase in C-peptide AUC.
Conclusion: In NOT1DM, lower insulin secretion
was associated with lower LDL levels. Possible explanations include a) reduced LDL in subjects with severe insulin deficiency prior to diagnosis and b) elevated LDL in
subjects with higher insulin secretion due to insulin resistance prior to diagnosis. Mechanistic studies are needed to
explore these observations. The effect of otelixizumab on
serum lipid levels is being evaluated in DEFEND.
Abstract #226
respectively, to 65 for the scorecard group and 62 for the
control group.
Conclusion: The use of diabetes scorecards to
improve risk factor control in adults with uncontrolled
Type II diabetes did not appear to be beneficial in addition
to the standard care as measured by a scoring system at a
subsequent visit. Further research is needed to study the
use of scorecards over multiple visits over a longer period
of time and to see whether certain subgroups of patients
could benefit from the use of diabetes scorecards.
Abstract #227
FAMILIAL PARTIAL LIPODYSTROPHY
COMPLICATED BY UNUSUAL LIVER LESIONS
Anders Carlson, MD, Muriel Nathan, MD, PhD
USE OF A SCORECARD TO IMPROVE RISK
FACTOR CONTROL IN PATIENTS WITH
UNCONTROLLED TYPE II DIABETES
Poonam Sood, MD, Tim Amass, Sheena Khurana, MD,
Vimala Jayanthi, MD, Suzanne Adler, MD,
Alexander Rilling, MD, Michael Irwig, MD
Objective: Type II diabetes mellitus (DM) has
become a worldwide epidemic. Since education is essential for patients to self manage their diabetes, our study
tested the use of diabetes scorecards during clinic visits to
see whether they improved glycemic control, BP control,
LDL-cholesterol, aspirin usage, and amount of exercise.
Methods: 85 patients with type II DM from a university practice were recruited in clinic by endocrinologists
and internists. Inclusion criteria were men and non-pregnant women ≥ 40 years old with HbA1c levels ≥ 8%. In this
single-blinded controlled trial, patients were randomized
to receive a scorecard (n=42) or not (control group; n=43).
At each clinic visit, providers reviewed with the patients
whether their HbA1c, BP, LDL-cholesterol, aspirin usage,
and exercise were at target. Points were assigned to each
of the five previous variables, an overall total score (maximum of 100) was calculated for each visit, and scores
were provided to the patients in the scorecard group only.
The primary endpoint was the change in total overall score
between the scorecard and control groups at a subsequent
visit 2-4 months after the initial visit.
Results: The patients in the scorecard and control
groups were similar demographically. The average age
was 56 years, 57% were women, and 69% were AfricanAmerican. The average education level was some college, 17% had CAD and the average duration of DM was
9.9 years. At baseline, the average total score was 59 for
the scorecard group and 55 for the control group. At the
subsequent visits, the scores increased by 6 and 7 points,
Objective: To describe a case of familial partial lipodystrophy with telangiectatic hepatocellular adenomas, a
rare type of liver lesion.
Case Presentation: A 35 year old female with a history of familial partial lipodystrophy, Dunnigan variety,
presented with abdominal pain and vomiting. Her diabetes is well controlled by insulin pump. She does not take
oral contraceptives. She has a history of pancreatitis due
to hypertriglyceridemia, and incidental liver lesions (up to
2 cm) were seen on MRI 2 years ago. Her physical exam
shows marked fat atrophy of the limbs and chest, with significant fat deposits around the face, neck and abdomen.
Hirsutism is present. The largest liver lesion has grown to
over 5 cm. Lipase is normal. Biopsy of the largest liver
lesion shows necrotic tissue and fatty liver, worrisome for
malignancy. Pathology from resection of the largest liver
lesion reveals a telangiectatic hepatocellular adenoma
with peliosis, along with marked fatty liver changes in the
surrounding tissue.
Discussion: Familial partial lipodystrophy type 2,
Dunnigan variety (FLP2), is an autosomal dominant
mutation in the lamin A/C gene, encoding a nuclear
envelope protein. The exact mechanism is unknown,
but genes involved in adipogenesis are altered. FPL2
patients have normal fat distribution until puberty, when
there is a spontaneous loss of subcutaneous fat from the
upper and lower extremities, gluteal region and trunk.
Accumulation of fat the face, neck and intraabdominal
regions then occurs, resulting in a Cushingoid appearance.
Hypertriglyceridemia is common; hirsutism and PCOS
are infrequent. While other forms of lipodystrophy are
well known to have fatty liver, previous reports of FPL2
have not described a high prevalence of liver abnormalities. Treatment involves lifestyle modification and management of lipids and hyperglycemia. Leptin therapy in
small trials has been effective. The type of liver lesion in
– 32 –
this case is unusual. Formerly called telangiectatic focal
nodular hyperplasia, telangiectatic hepatocellular adenomas are lesions with marked sinusoidal dilatation and
peliosis, without fibrosis. They also show a monoclonal
pattern, raising concern for malignancy and distinguishing them from focal nodular hyperplasia. While most
commonly seen in young women on birth control pills,
their presence in lipodystrophic patients is not previously
reported.
Conclusion: Familial partial lipodystrophy, Dunnigan
variety, is a rare disorder of fat metabolism, with fatty
liver as a known complication. In these cases, telangiectatic hepatocellular adenomas are a possible type of liver
lesion.
Abstract #228
FREQUENCY OF OCCURRENCE AND
CORRELATES OF ASYMPTOMATIC
BACTERIURIA IN DIABETES MELLITUS
Adeleye Olufunmilayo Olubusola, MD,
Anthonia O. Ogbera, FMCP, FACE, FACP,
Ayotunde Oladunni Ale, MD, Ekere F., MD,
Orolu MO, MD, Iyayi F., MD
Objective: The diabetic state is associated with
immunosuppression hence the predisposition of persons
with diabetes to infections. Asymptomatic bacteriuria
(AB) is a risk factor for pyelonephritis and renal dysfunction. This study sets out to determine the frequency of
asymptomatic bacteriuria in diabetic subjects attending
the diabetes centre, associated risk factors and the prevalent microorganisms.
Methods: 280 consecutive patients with type 2 DM
were recruited. The demographic and anthropometric
indices were obtained. Early morning urine samples were
collected into sterile universal bottles for microscopy, culture and sensitivity. Fasting blood samples were analyzed
for glucose and glycosylated hemoglobin. Subjects with
symptoms of urinary tract infection (UTI) and benign
prostatic hypertrophy were excluded.
Results: The mean (SD) age of the subjects’
59.8yrs±10.8 .Mean (SD) BMI 28.3±5.6. 69.3% were
females, 30.4% were males. 31.4% of the study subjects
had positive urine culture (>105cfu). A higher proportion
of females (33%) had positive cultures compared with
males (24%).This was however not statistically significant
p-value 0.51. There was positive correlation between level
of hyperglycemia and presence of infection and negative
correlation between duration of diabetes and presence of
infection. Isolated organisms include, atypical coliforms,
Escherichia coli, Klebsiella species, proteus mirabilis,
staphylococcus, and streptococcus spp. E coli were the
most prevalent pathogen isolated both with males and
females.
Conclusion: A significant percentage of subjects with
DM had asymptomatic bacteriuria and this was associated
with levels of hyperglycemia. We propose that patients
with DM be routinely screened for AB in order to offer
appropriate and timely management.
Abstract #229
A CASE OF MATURITY ONSET DIABETES OF
THE YOUNG PRESENTING WITH BLINDNESS
Marian Gaber Saad, MD,
Faramarz Ismail-Beigi, MD, PhD
Objective: Understanding the different mutations
associated with maturity onset diabetes of the young
(MODY) and the resulting phenotypes can aid the clinician in predicting the course of the disease, in counseling the patient and other family members, deciding on
the treatment regimen and frequency of follow-ups. We
believe that better understanding of the pathophysiology
of MODY at the molecular and genetic level through basic
science research will further our understanding of the optimal diagnostic and therapeutic approaches, and aid clinicians in recognizing this disease entity.
Case Presentation: We present a case of a 21 year
old Caucasian male who presents to the outpatient
clinic with a chief complaint of progressive worsening
of vision over months. He denies any other complaints.
Ophthalmological testing confirmed diabetic proliferative
retinopathy resulting in legal blindness. Laboratory data
confirmed diabetes mellitus of non-autoimmune origin.
The patient responded to long acting secretagogue and
metformin and once HbA1c improved patient was managed solely with metformin with good control.
Discussion: Maturity onset diabetes of the young
(MODY) accounts for 1-5% of all cases of diabetes in the
Western world. Several clinical characteristics distinguish
MODY from type 2 diabetes mellitus. A presentation of
non-ketotic diabetes mellitus, autosomal dominant mode
of inheritance noted over several generations, absence of
obesity and onset of diabetes before age 25, are all characteristics of MODY. Mutations in at least 6 different genes
account for the different types, presentations and ultimately management modalities used for MODY patients.
Conclusion: Since genetic testing for MODY mutations is expensive and only available in select research laboratories throughout the country, we emphasize through
this report the importance of recognition, early diagnosis
and appropriate management that may prevent inevitable
complications with wrong or suboptimal management,
especially in primary care setting.
– 33 –
Abstract #230
Conclusion: These data demonstrate that salsalate, as
an anti-inflammatory agent, reduces insulin resistance and
glycemia in prediabetic patients. The optimal duration of
treatment and ability to prevent overt diabetes must further be studied.
SALSALATE IMPROVES GLYCEMIA AND
INSULIN RESISTANCE IN PREDIABETIC
PATIENTS
Abstract #231
Elham Faghihimani, MD, Peyman Adibi, MD,
Hasan Resvanian, MD, Ashraf Aminorroaya, MD,
Masoud Amini, MD
Objective: Insulin resistance plays a primary role
in the development of type 2 diabetes mellitus and is a
characteristic feature of obesity, metabolic syndrome, prediabetes and diabetes mellitus. The mechanism by which
insulin resistance occurs is unknown but may be related
to a cascade of inflammatory process involving IKK-β.
The aim of the present study is to evaluate the efficacy of
salsalate as an inhibitor of IKK-β to decrease hyperglycemia and insulin resistance in prediabetic patients, before
proceeding to overt diabetes mellitus.
Methods: In a double-blind, placebo controlled
trial, we enrolled 120 prediabetic adults (40 to 70 years)
according to ADA criteria (fasting glucose level 100
mg/dl to 126 mg/dl or glucose level two hours after 75
gram oral glucose 140 mg/dl to 200 mg/dl). Participants
were first degree relatives of diabetic patients attending in Endocrine and Metabolism Research Center. The
intervention was salsalate 3 g/day or identical placebo for
three month. Participants (20% men) were enrolled in the
project after a brief informational meeting and giving a
signed written consent. We measured fasting plasma glucose, HOMA-IR (fasting glucose× fasting insulin/22.5),
lipid profile, HbA1C and serum insulin level before and
after intervention.
Results: Salsalate reduced fasting plasma glucose by
11% (from 129.8±28 mg/dl to 108.6±18 mg/dl) (p<0.03).
There was no significant decrease in plasma glucose after
an oral glucose tolerance test. HOMA-IR as an insulin
resistance index changed from 5.1±3.0 to 3.0±1.5 in salsalate group and from5.3±4 to 4.8±3 in placebo group
(p<0.02). HbA1C, insulin level, triglycerides did not
change after treatment with salsalate in the participants.
These were not age- or gender- dependent. There was no
serious complication, although some participants complained of tinnitus which was not persistent after reducing
the dose of salsalate.
Discussion: Insulin resistance is at least in part a
chronic inflammatory process. The direct role of the
IKKβ/NF-κB pathway in development of insulin resistance has been validated. Salsalate as an inhibitor of this
pathway reduces insulin resistance and improves glycemia, though, can be used as a preventative intervention in
diabetes mellitus.
SALSALATE IMPROVES GLYCEMIA IN
DIABETIC PATIENTS
Elham Faghihimani, MD, Peyman Adibi, MD,
Hasan Resvanian, MD, Ashraf Aminorroaya, MD,
Masoud Amini, MD
– 34 –
Objective: chronic inflammation may contribute to
insulin resistance and type 2 diabetes mellitus through
activation of the IKKβ/NF-κB pathway. The present study
investigated whether treatment with salsalate, an anti –
inflammatory medication, would improve glycemia and
insulin resistance in a group of diabetic naïve patients.
Methods: The study was a randomized, double – blind,
placebo controlled clinical trial conducted at the Isfahan
Endocrine and Metabolism Research Center. Diagnosis of
diabetes was based on ADA criteria if their diagnosis had
been established during the last 2 months before the study
and they had not received any anti- glycemic agent. The
participants were 60 adults (21% men) 40 to 70 years old,
all were enrolled in the project after a briefing session and
signing written consent. They were randomized in two
intervention and placebo groups. The intervention was
salsalate 3 g/day or placebo for 3 months. We measured
fasting plasma glucose, glucose response two hours after
75 gram oral glucose, HbA1C, serum insulin, HOMA-IR
(fasting glucose× fasting insulin/22.5), lipid profile before
and after treatment.
Results: Comparing with controls, salsalate reduced
fasting glucose 14.5% (from 129.8±28 to 108.6±18)
(P<0.01), glycemic response after an oral glucose tolerance test 7% (from 198.4±45 to 156.9±66) (P<0.03), TG
12.5% (from 200.4±123 to 158.3±89) (P<0.04). HbA1c in
the placebo group increased during the study from 5.9±0.6
to 6.4±1.8 but decreased in the intervention group from
5.8±1.2 to 5.6±0.8 (P<0.04), Total cholesterol, HDL and
LDL cholesterol did not change after treatment with salsalate. HOMA-IR as an insulin resistance index did not
reduce in the intervention group but insulin level increased
25% (from 17.5±1.6 to 21.6±3.9) (P<0.02). Our patients
did not have any serious complications.
Discussion: Salsalate affects the IKKβ/NF-κB pathway which supposed to be one of the causes of developing diabetes mellitus and the study demonstrates that it
reduces fasting glucose level in diabetic patients and
increases insulin possibly due to reduced clearance.
Conclusion: These data show that an anti- inflammatory drug can decrease glucose level in diabetic patients.
The optimal duration of treatment and sustainability of the
effect should further be studied.
Abstract #232
COMPARISON OF MORTALITY AND
READMISSION RATES OF HEART FAILURE
PATIENTS WITH AND WITHOUT
DIABETES MELLITUS
Vijay Gopal Eranki, MD, Marian Manankil, MD,
Sorin C. Danciu, MD, German Rossell, MD,
Michael Niaki, MD, Mercy Chandrasekaran, MD,
Efren Jason Jorge, MD, Claudius Mahr, DO
16 had A1C ≥ 6.5. 4 of the 15 patients who survived (and
had an A1C checked) had an A1C <6.5 while 11 had an
A1C ≥ 6.5. By Fisher’s Exact test this was not statistically
significant with a p value of 0.7. The OR was 0.75 (95%
CI 0.223 – 2.524) for the cohort of patients with A1C <6.5
while the OR was 1.091 (95% CI 0.749-1.588) for the
cohort with A1C ≥ 6.5.
Conclusion: Patients with HF and a history of DM
did not show any difference from those without DM in
mortality or readmission rates including a sub analysis of
HbA1C. Our study is limited by the small sample size but
still has interesting results.
Abstract #233
Objective: Patients with diabetes mellitus (DM) are
more likely to develop heart failure (HF) compared with
those without DM. Earlier studies showed increased risk
of HF with DM. We focused on mortality and readmission
rates in HF patients with DM.
Methods: Data from 100 patients admitted with HF
at our facility from 01/2005 to 01/2006 was obtained retrospectively from electronic records. Patients with limited
information were excluded. HbA1C values ≥ 6.5 were
considered diabetic. The endpoints were readmission due
to HF 6 months after the index hospitalization and 3-year
mortality data based on the Social Security Death Index.
Statistical analysis was done and significant 2-tailed
p-value was set at <0.05.
Results and Discussion: 91 of 100 patients had data
on history of DM. 45 patients had DM while 46 did not. A
total of 47 patients expired since discharge. Of these, 25
had DM and 22 did not. 44 patients survived of which 20
had DM and 24 did not. This was not statistically significant with a p value of 0.461 with Pearson Chi – Square
analysis. The Odds ratio (OR) was 1.17 (95% CI 0.7691.782) for the cohort of patients with DM who expired
while the OR was 0.858 (95% CI 0.571-1.289) for the
cohort without DM. In patients with a past history of DM
and readmission rates, we had information on 92 patients.
51 patients were readmitted, of these 28 had DM and 23
did not. 41 patients were not readmitted and 18 patients
among them had DM while 23 did not. This was not statistically significant with a p value of 0.294 with Pearson
Chi – Square analysis. The OR was 1.251 (95% CI 0.8171.915) for the cohort of patients with DM who were readmitted while the OR was 0.804 (95% CI 0.536-1.207) for
the cohort without DM. A further analysis on patients who
expired based on HbA1c data was performed. A1C was
checked on 35 patients, of these 8 patients had an A1C
< 6.5 and 27 had an A1C ≥ 6.5. 4 of the 20 patients who
expired (and had an A1C checked) had an A1C <6.5 while
PREVALENCE OF METABOLIC SYNDROME
AND INSULIN RESISTANCE IN WESTERN INDIA
Piyush Harshadrai Desai, MD, K. N. Bhatt,
Syamala Nadiminty, MD, Ashwin A., Lovleen Bhatia,
Niti Shah, Vijay Panikar, MD, MBBS,
Background: Based on recent Adult Treatment Panel
(ATP III) diagnostic guidelines, it has been estimated that
upwards of 50 million individuals in the United Stages
older than 20 have the metabolic syndrome and this is
likely to be a gross underestimate Not surprisingly, in
the recent years there has been a tremendous increase in
interest in understanding the cause, consequences and
treatment of insulin resistance. Hence early detection of
insulin resistance and its treatment can revolutionize the
approach to primary prevention of the epidemic of coronary artery disease and Type 2 Diabetes.
Objective: To measure prevalence of metabolic syndrome and to calculate Insulin Resistance in apparently
normal population.
Methods: The patients were above 18 yrs. of age. The
total number of patients studied was 100 and all of them
were not previously known to have diabetes or hypertension or any significant disease or disorder. Known cases of
Ischemic Heart disease, renal disease, liver disease, pregnancy, and women on contraceptives, were excluded from
this study Detailed clinical and laboratory evaluation of all
the patients was carried out and their Insulin Resistance
was calculated with the help of 4 methods, followed by
a comparative assessment of results obtained with each
method. Prevalence of metabolic syndrome measured with
clinical criteria according to ATP III guidelines revised in
2005. The four different insulin resistance scores used
were: Insulin Sensitivity Index (ISI), American Diabetes
Association Score (ADA), Finnish Diabetes Risk Score
and Indian Diabetes Risk Score (IDRS)
– 35 –
Results: According to that criteria 26% patients were
having metabolic syndrome and 74% patients were not fit
into the criteria for metabolic syndrome. Insulin resistance
was calculated by 4 methods. Most important one is by
measuring Insulin sensitivity index through Normogram
developed by comparing gold standard hyperinsulinemic
euglycemic clamp method. According to ISI 40% of the
patients had high Insulin resistance, While High insulin
resistance was defined as ISI <6.3. According to ADA,
Finnish , Indian diabetic risk score insulin resistance were
found in 41%,24% and 33 % respectively.
Conclusion: High insulin resistance is the predecessor and precursor of the metabolic syndrome and can be
and should be detected in normal individuals for implementing effective preventive measures. Finnish score is
more nearer to prevalence of metabolic syndrome, while
ADA score and Indian Diabetic Score results are comparable to ISI results.
Abstract #234
BLOODPRESSURE AND INSULIN RESISTANCE
IN WESTERN INDIA
Piyush Harshadrai Desai, MD,
Syamala Nadiminty, MD, Ashwin A.
a mercury sphygmomanometer in a standardized fashion.
All patients were divided into 3 sub-groups depending
upon their blood pressure status according to the JNC
VII guidelines. The 3 sub groups were - hypertensives,
Prehypertensives and Non hypertensives with blood pressure level > 140 or > 90, 120-139 or 80-89, < 120 and
< 80 mmHg respectively. Prevalence of metabolic syndrome measured with clinical criteria according to ATP
III guidelines revised in 2005, while prevalence of insulin resistance was calculated by Insulin Sensitivity Index,
with high resistance defined by ISI<6.3
Results: According to JNC VII, 30% of our study
group were hypertensive, 47% were pre hypertensive and
23% were normotensive. Prevalence of metabolic syndrome was high (73.33%) in hypertensive group while
very low in pre hypertensive (9.09%) and normal 0%.
Same way insulin resistance is also very high in hypertensive patients (73.33%) while only 15.3% in normotensive
group. In prehypertensive group insulin resistance was
found slightly higher 31.8%.
Conclusion: The presence of insulin resistance and
metabolic syndrome found higher in the hypertensive
group as compare to pre hypertensive and non hypertensive group.
Abstract #235
Background: With the receding threats of communicable diseases, and looming over threats of Coronary
Artery Disease, Hypertension and Diabetes Mellitus, the
research in the later has been focused on detection of their
preclinical stages i.e. detection of genetic, cellular, metabolic and biochemical mechanisms and processes so as to
arrive at the ability to forestall their progress to clinical
illness. The changes associated with insulin resistance
that contribute to the increased risks are: dyslipidaemia,
hypertension and inflammation, vascular endothelial dysfunction; a prothrombotic state due to disturbance of the
clotting and fibrinolytic system, and platelet dysfunction.
Insulin Resistance is now considered as one of the causative factor for development of essential hypertension and
hypetension is one of the important criteria for presence of
metabolic syndrome.
Objective: To measure prevalence of metabolic syndrome and to calculate Insulin Resistance in hypertensive
prehypertensive and normotensive study group.
Methods: The patients were above 18 yrs. of age.
The total number of patients studied was 100 and all of
them were not previously known to have diabetes or any
significant disease or disorder. Known cases of Ischemic
Heart disease, renal disease, liver disease, pregnancy,
and women on contraceptives, were excluded from this
study. A complete physical and cardiovascular examination was performed. Blood pressure was measured with
MICROALBUMINURIA AND CORRELATES
IN NEWLY DIAGNOSED DIABETICS-A
PRELIMINARY REPORT
Anthonia O. Ogbera, FMCP, FACE, FACP,
Ayotunde Oladunni Ale, MD, DADA O, FMCP
Objective: Microalbuminuria (MA) is associated with
increased cardiovascular risk in diabetic subjects and it
is found to correlate with a cluster of other risk factors
such as dyslipidemia, retinopathy, left ventricular hypertrophy and hyperuricaemia. This study seeks to document
the prevalence of MA and its associated factors in newly
diagnosed diabetic subjects as there is insufficient data in
this subset of diabetics in our environment.
Methods: This is a prospective ongoing study involving people with newly diagnosed DM (of less than 4
months duration). The demographic and anthropometric
indices and information pertaining to DM complications
and hypertension were documented. Early morning urine
samples were collected and tested for MA. Subjects whose
urine samples tested positive (+vet) for MA had a repeat
of same test after 2 weeks (wks) period. (MA was said to
be present if a positive result was obtained after the repeat
test). Fasting blood samples were obtained for glucose,
uric acid, lipid profiles and glycosylated hemoglobin. 12
– 36 –
lead electrocardiography was done. Subjects with urinary
tract infection, proteinuria, heart failure, renal failure and
sepsis were excluded. The test statistics used included t
test and correlation coefficient. A p value of ≤ 0.05 indicated statistical significance.
Results: 27 subjects so far have been recruited within
a 4 month period. The Mean (SD) age was 51.8(12.2)
years. MA was present in 13 subjects (48%). Mean (SD)
age of MA +ve individuals is 56.2(12.5), mean (SD) age
of MA negative 47.8(10.96) p value 0.075. Mean duration of DM in MA +ve is 8.4 wks, MA negative 6.7wks.pvalue 0.46. Mean (SD) BMI of MA +ve 30.6(5.9),
MA –ve 27.03(3.6) p 0.06. Mean uric acid for MA +ve
4.9(1.3)mg/dl, those without MA 5.3(1.7). Mean total
cholesterol, HDL, LDL, TGs for MA +ve are 201.9(50),
33.5(11.7), 144.5(44.0), 108(47) respectively. For MA –ve
184.8(50.8), 37.4(10.6), 128(45), 99(46)respectively with
p-values of 0.40,0.40,0.37 and0.67 respectively. Mean
systolic and diastolic blood pressure of MA +ve individuals 143(16) and 86.15(11.3), for MA negative 124.7(17)
and 78.9(8.0) with pvalues of 0.009 and 0.066 respectively. Only one individual had marginally elevated uric
acid level. All other subjects had normal uric acid values.
Discussion/Conclusion: Subjects with MA were
older, with higher BMI, higher total cholesterol, LDL and
triglyceride levels, lowerHDL, and higher systolic and
diastolic blood pressure than those without MA. A significant proportion of the study subjects showed evidence of
constellation of cardiovascular risk. It is therefore important to screen all diabetic subjects adequately at diagnosis
to enable prompt intervention.
Abstract #236
DIABETES AND DYSGLYCEMIA IN
HOSPITALIZED SURGICAL PATIENTS:
DOES ENDOCRINE INTERVENTION PAY?
insulin order sets, and 2 endocrine consultations at the discretion of the surgical team. Intervention Period. Results
of blood glucose (Glu), whether tested in the laboratory or
by point of care, were obtained from the central lab computer and analyzed within 24 hours for all patients admitted from 7/1/2008 through 6/30/2009 (FY09). Patients
were selected for endocrine intervention when glucose
<50 or >199. Comparisons were made between FY08
versus FY09, the presence (DM+) or absence (DM–) of
diabetes. Outcomes: length of stay (LOS), LOS in the ICU
(LOS-ICU) and hospital expenses (EXP). These data were
obtained on a per case basis from the hospital accounting
system. Subgroup analyses and Contemporaneous Control
Groups. The subgroup of patients with Glu always >49 &
<200 served as a contemporaneous control (NORM) in
both FY08 and FY09. Other factors considered were age,
sex and race. Statistics: Statistical analysis was performed
using SPSS 8.0 for Windows.
Results: DM+ are older than DM– 60.7 v 49.7 (FY08)
and 59.4 v 48.7 (FY09). Race and sex did not differ among
groups. DM+ stay longer and cost more than DM –. ICU
days are similar. In FY08 (average values) for these were
5.77, $9301, 0.90 for DM+ and 4.37, $7548, 0.87, for
DM–. In FY09 these results were 5.04, $8009, 0.69 for
DM+ and 4.05, $7440, 0.88, for DM– . While NORM
showed improvement (FY09 v FY08) in both DM+ and
DM– it was greater in DM+. For all patients the total savings (FY09 v FY08) in LOS & EXP was 1342 days and
$1.15M, of which 656 days and $1.06M occurred through
improvements in DM+ patients.
Conclusion: Endocrine intervention in surgical
patients with diabetes and dysglycemia pays. Nearly 50%
of the savings year to year in days and over 90% of the
savings in EXP was seen in DM+.
Abstract #237
Arthur Chernoff, MD, FACE
Objective: The management of diabetes and dysglycemia in hospitalized patients remains controversial and
problematic. It is unclear whether intervention pays outside the ICU. This study seeks to determine whether endocrine intervention in surgical inpatients with blood sugars
< 50mg/dl or > 199 mg/dl affected economic outcomes.
Methods: Subjects: Adult patients over 18 years old
on the surgical service of an urban tertiary care hospital.
Historic Control Period: Patients from 7/1/2007 through
6/30/2008 (FY08) served as the control group. Endocrine
intervention in these patients was limited to 1. The use
of previously deployed protocols for the management of
hyperglycemia in the ICU, hypoglycemia in all units and
PHYSICIAN COMPLIANCE WITH TRIPRONGED ADA RECOMMENDATIONS IN AN
ACADEMIC SETTING: BLOOD PRESSURE
CONTROL LAGS BEHIND
Akshay Bhanwarlal Jain, MD, Leela Mary Mathew, MD
Objective: To examine the success rate of academic
physicians practicing in a resident-teaching clinic, in
achieving the American Diabetes Association (ADA)
goals for reducing vascular disease risk in patients with
diabetes mellitus type 2 (DM-2).
Methods: As part of a quality improvement project, a retrospective chart review was performed on all
patients coded for diagnosed DM-2 in a seven-member
faculty group practice of internists. Only adult patients
– 37 –
with DM-2 who were in the practice for at least one year
were included. Levels of glycohemoglobin (HbA1c), lowdensity lipoprotein (LDL) and blood pressure (BP) for 6
months preceding data collection were used for analysis.
Results: Of the 244 patients in the inclusion group
(ages 25-96, mean age 64), 30 adults (12.3%) met ADA
recommendations on all three parameters, as compared
to the national estimate of 7.3%. Overall, 131(53.7%)
had HbA1c<7%, 145(59.4%) had LDL<100mg/dl and
83(34.0%) had BP<130/80. Comparatively, the national
average values were 37.0%, 49.2% and 35.8% respectively. In our study, 84.8% of the hypertensive patients
with DM-2 were either on an angiotensin converting
enzyme inhibitor (ACEI) or angiotensin II receptor
blocker (ARB).
Discussion: The National Health and Nutritional
Examination Survey(NHANES) 1999-2000 data showed
that only 7.3% of adults in the United States with diabetes mellitus met ADA goals of: HbA1c <7%, LDL<100
mg/dL and BP<130/80 mmHg. Subsequent studies have
emphasized the importance of controlling these parameters for the prevention of microvascular and macrovascular complications of diabetes.
Conclusion: Being an academic clinic, we expected
greater adherence to the ADA recommendations than
the national average, six years after the data being first
published. Although HbA1c and LDL levels were better
controlled in this practice, BP was not. This led to a low
proportion of patients with DM-2 meeting the tri-pronged
ADA goals. With the nation veering towards a pay-forperformance model for healthcare, further efforts are
needed to effectively control blood pressure in the study
population, to reduce vascular complications. We speculate that although physicians did prescribe the correct antihypertensive medication, they were less vigilant in followup monitoring and conclude that they need to adequately
titrate blood pressure medication dosages. Faculty physicians and residents were informed of individual results as
part of quality intervention, with a subsequent follow-up
study proposed after one year.
Abstract #238
THE PREVALENCE OF HYPERTENSION AND
ITS CORRELATES AMONG TYPE 2 DIABETES
IN NIGERIA.
presentation and severity of cardiovascular disease. This
study is therefore set to determine the prevalence of
hypertension (HT) and its correlates among type 2 DM in
Nigeria.
Methods: In this cross-sectional study 205 DM
patients were randomly selected in LASUTH. Their
clinical characteristics and occurrence of cardiovascular
events(cv) were documented through interviewer-administered questionnaires. Fasting blood samples were collected for biochemical analysis and urine samples for persistent albuminuria. Test Statistics used were t-test, χ2 and
correlation coefficient to test for associations. A p value of
<0.05 denoted statistical significance.
Results/Discussion: The prevalence of hypertension
(HT) was 66%, the proportion of females (F) with HT
was higher than males (M) (71.7% vs 28.3%, p=0.001).
The mean age of hypertensives & DM was 60.4 yrs ± 9.3.
The mean age of F and M were comparable (60.2 ± 8.8 vs
61.2± 10.8, p=0.68). The mean age of the HT and duration
of DM were significantly higher than without HT (60.4 ±
9.3 vs 56.6 ± 11.6, p = 0.04 and 8.2 yrs ± 5.8 vs 4.9 yrs ±
3.8, p = 0.005.) Their mean BMI was 27.5 ± 5.0.BMI were
comparable in both sexes (F = 28 ± 5.2 vs M = 26.1 ± 4.3,
p = 0.21). The mean BMI, Lipid parameters, blood glucose and clinically evident non-fatal cv events were comparable in both groups. Proteinuria and microalbuminuria
were significantly higher in the HT than without HT only
( 68.85% vs 31.2% p=0.005 & 74.4% vs 25.6%, p=0.01).
The overall prevalence of metabolic syndrome Mets using
NCEP ATPIII criteria was higher(74%) in the HT group
than without 52% p=0.04
Conclusion: The prevalence of hypertension in
Nigerian DM is high and is associated with increasing
age, female sex, longer duration of DM and albuminuria.
The documented high prevalence of Mets lends credence
to the great CVS risk posed by the presence of HTN in our
patients with DM.
Abstract #239
ADMISSIONS TO A SAFETY-NET HOSPITAL
IN PATIENTS WITH DIABETES DURING
ECONOMIC DOWNTURN ARE LARGELY
PREVENTABLE
Elizabeth Batcher, MD, Ana Uribe, MD, Eli Ipp, MD
Ayotunde Oladunni Ale, MD,
Adeleye Olufunmilayo Olubusola, MD, A.O. Dada
Background/Objective: Hypertension is more
prevalent among blacks than Caucasians. The summation of hypertension and diabetic mellitus augment the
Objective: To test the hypothesis that largely preventable acute illnesses account for many hospital admissions
in people with type 2 diabetes and are therefore an important target for cost reduction in health care delivery.
Methods: Cross sectional data on 100 patients
admitted to Harbor UCLA Medical Center in 2009 with
uncontrolled type 2 diabetes (A1C>8%) was obtained by
– 38 –
questionnaire and electronic medical record. Potentially
preventable admissions were defined as glycemic crises
and those associated with infection.
Results: Participants had a mean (+SD) age of 48+
9.1years, 62% were male, 85% minority (59% Latino,
26% African American). Mean A1C was 11.2+2.04%;
diabetes duration was 6.4+6.5 years with 29% newly
diagnosed. Potentially preventable illnesses accounted for
68% of admissions (infection 41%, glycemic crisis 27%)
and 19% cardiovascular events (13% other). Mean length
of stay (LOS) was 6.6+6.2 days for all; LOS for glycemic
crises 4.3±2.5days, infections 7.8±7.3days and amputations 11.7±10.7days. Patients without a primary care provider (PCP) accounted for 68% of admissions for glycemic crisis or infection. Most (58%) did not have a PCP
before admission, and on discharge 22% of patients had
neither appointment nor referral to a PCP or endocrinologist for diabetes care. Finally, 75% were uninsured, 42%
unemployed, 41% new to the public hospital system and
15% recently lost insurance.
Discussion: Hospitalizations make up 50% of the
direct costs of care for diabetes in the US. Glycemic crises and infections are potentially preventable with regular
ambulatory care, yet comprised 68% of admissions and
65% of hospital days in this study. Considering the high
percentage of preventable admissions in patients without a
PCP (68%) in this study, we suggest that prevention of illness may be enhanced and hospital usage mitigated in this
population by access to primary care. This is supported by
our finding that among those with a PCP 93% had seen
that provider in the last 6 months, suggesting that this
population will utilize primary care when made available.
Conclusion: Public hospitals are assuming care for
diabetic patients with high burden of disease and potentially preventable illnesses. We found that these admissions are associated with poor access to ambulatory care
both before and after hospitalization. Interventions to
make affordable outpatient care available to uninsured
and ethnic minority patients with diabetes may diminish
preventable admissions and thus have a major impact in
reducing costs of care in this population.
DM from sub-Saharan Africa, hence this report sets out
to bridge the gap. In an earlier preliminary analysis, we
reported the prevalence of hyperuriceamia to be 90% and
this was found to have significant associations with hypertension, high total cholesterol, high triglyceride and poor
glycemic control. This study is to further evaluate other
clinical and biochemical correlates of hyperuricemia.
Methods: This is a prospective study involving 100
patients with DM attending the Diabetes center of Lagos
State University Teaching Hospital. A symptom –analyzed
and macrovascular complications documented through
interviewer administered questionnaire was carried out.
Glycosylated hemoglobin (HbA1c), urinary proteinuria and ECG were carried out. 50-age and sex matched
healthy controls were recruited into the research.
Results/Discussion: The mean duration of DM and
Hypertension (HT) was significantly higher in the hyperuricemia (p=0.03 and p=0.04 respectively). An appreciable proportion of hyperuricemia group was on antihypertensive and oral hypoglycemic agents only 88.2% .The
mean HbAic was 7.2±3.6. The prevalence of albuminuria
was 79.8% of which Macroalbuminuria was 18.3% and
microalbuminuria was 61.5% in the hyperuricemia group
compared with normal uric acid level of 14%,10% and 4%
respectively (p=0.03,0.014 and 0.04). Non-fatal cardiovascular events were significantly higher in the hyperuricemia subjects compared with normal uric acid level: 80%
vs20% of total stroke p=0.04 ,90.9%vs9.1% chest pains
with significant ECG changes p=0.03 and 96.4% vs4 .6%
had intermittent claudication compared with normal uric
acid level. The mean age, uric acid, BMI and FBS of the
healthy controls (44.4yrs ±11.7,5.1mg/dl ±0.7, 25.74kg/
m2 ±4.9 and 83.64mg/dl ±10.35) were significantly lower
than hyperuricemia group, p<0.05. None of the controls
had hyperuricemia.
Conclusion: Hyperuricemia was significantly associated with longer duration of DM and HT, albuminuria,
hypertension ,high total cholesterol ,high triglyceride
levels as well as clinically evident cardiovascular events.
Uric acid level was significantly high in DM compared
with the healthy controls.
Abstract #240
Abstract #241
URIC ACID LEVEL IN TYPE 2 DIABETES IN AN
URBAN HOSPITAL IN NIGERIA
DISEASE CONTROL AMONG ADULTS WITH
TYPE 2 DIABETES MELLITUS, HYPERTENSION
AND OBESITY
Anthonia Okeoghene Ogbera, MBBS, FMCP, FACE
Objective: Hyperuriceamia is a known cardiovascular risk factor and it is a key feature of the metabolic
syndrome which has cardiovascular implications. There
is a dearth of reports on uric acid levels in people with
Helena Wachslicht Rodbard, MD, FACP, MACE,
Kathleen M. Fox, PhD, Elise Hardy, MD,
Susan Grandy, PhD
Objective: To evaluate self-reported glycemic and
blood pressure control among adults with type 2 diabetes
– 39 –
mellitus (T2DM) alone and those with T2DM plus hypertension and obesity.
Methods: Respondents to the Study to Help Improve
Early evaluation and management of risk factors Leading
to Diabetes (SHIELD), a large US survey, provided their
most recent (past 12 months) HbA1c and blood pressure
readings, height, weight, comorbid conditions and medication list. Respondents reporting a diagnosis of T2DM
and hypertension with a body mass index (BMI) >30 kg/
m2 were identified and compared with respondents reporting a diagnosis of T2DM and no self-reported diagnosis of
hypertension and BMI <30 kg/m2.
Results: For respondents with the triad comorbid conditions of T2DM, hypertension, and obesity who reported
an HbA1c (n = 593), 59.7% (354/593) reported having achieved the American Diabetes Association (ADA)
HbA1c goal of <7%, whereas 36.3% (215/593) reported
achieving the AACE HbA1c goal of <6.5%; of the respondents with T2DM only (n = 117), 68.9% reported HbA1c
<7% and 45.3% reported <6.5% (p = 0.10). A similar
proportion of respondents in each group reported HbA1c
<7% across different diabetes treatment regimens: oral
antidiabetic therapy (70% of triad group vs. 73% of T2DM
alone, p = 0.61), insulin only (30% vs. 33%, p = 0.88), and
insulin and oral therapy (39% vs. 56%, p = 0.34). Fewer
respondents with T2DM, hypertension, and obesity had
systolic blood pressure <130 mm Hg (56.0%) or diastolic
blood pressure <80 mm Hg (65.6%), despite the fact that
92% of them were on anti-hypertensive medication, compared with respondents with T2DM only (72.7% <130
mm Hg and 78.8% <80 mm Hg; 48% on anti-hypertensive
medication; p <0.001). Fewer respondents with the triad
comorbid conditions were in control for both HbA1c and
blood pressure (11.5%) compared with respondents with
T2DM only (21.1%, p = 0.004). More respondents with
the triad conditions were on lipid-lowering medications
(62.5%) compared with respondents with T2DM only
(53.5%, p =0.001).
Conclusion: Respondents with the triad comorbid
conditions of T2DM, hypertension, and obesity did not
differ in their glycemic control but were more likely to
have uncontrolled blood pressure despite anti-hypertensive therapy than respondents with T2DM only. There is
an unmet need for effective therapeutic strategies among
adults with this triad of comorbid conditions despite
the availability of anti-hypertensive and anti-diabetic
treatments.
Abstract #242
THE IMPACT OF LY2189265 (GLP-1 ANALOG)
ON GLYCEMIC CONTROL IN HISPANIC
AND NON-HISPANIC CAUCASIANS WITH
UNCONTROLLED TYPE 2 DIABETES:
AN EGO STUDY ANALYSIS
Edward James Bastyr, III, MD, Julio Noriega,
Fady T. Botros, PhD, Rebecca Threlkeld, RD,
Jianfen Shu, MS, James H. Anderson, MD,
Leonard C. Glass, MD
Objective: The US Hispanic population has a disproportionately increased incidence and severity of type 2
diabetes mellitus. Little research has been conducted to
compare drug effectiveness between ethnicities. In this
retrospective analysis of data from the EGO study we
examine differences in metabolic outcomes comparing
Hispanic (H) versus non-Hispanic (NH) Caucasian populations following treatment with the long-acting glucagonlike peptide-1(GLP-1) analog (LY2189265).
Methods: 262 patients were randomized to onceweekly subcutaneous injections of either placebo or 1 of
3 LY dose regimens: 1) 1.0 mg for 16 weeks; 2) 0.5 mg
for 4 weeks then titrated to 1.0 mg for 12 weeks; or 3)
1.0 mg for 4 weeks then titrated to 2.0 mg for 12 weeks.
The 177 patients randomized to LY treatment (62 H and
115 NH) had similar baseline characteristics compared to
the entire randomized population. The primary metabolic
measure for comparison between the 2 ethnic groups was
glycemic control, as measured by HbA1c change from
baseline at 16 weeks. Secondary measures were change
in 1) fasting serum glucose (FSG), 2) glucose excursion (AUC) response to a solid mixed meal test, and 3)
the homeostasis model assessment examining indices of
beta cell function (HOMA2-%B), insulin resistance and
sensitivity (HOMA2-%IR and HOMA2-%S). Differences
between groups were tested using two-sample T-test using
a nominal significance level of 0.05 for comparisons.
Results: In all randomized patients, the H group had a
statistically significantly higher baseline HbA1c compared
to the NH group (8.44±0.97%, n=88 vs. 8.09±0.88%,
n=150, p=.006). In response to LY treatment, the H population experienced a larger reduction in HbA1c as compared
to NH at endpoint (-1.47±0.99%, n=61 vs. -1.14±0.80%,
n=111, p=.020). There was also a 6-fold larger decrease
in postprandial AUC glucose excursion in the H group
compared to the NH group (-2.82 ± 3.78, n=56 vs. -0.46
± 5.69, n=89, [mmol/L] hr, p=.003). Controlling for baseline HbA1c (H 8.45±1.00%, n=62 vs. NH 8.55±0.84%,
n=82), the larger decrease in postprandial AUC glucose
excursion in the H group compared to the NH group
– 40 –
was maintained (-2.82±3.78, n=56 vs. -0.05±6.17, n=66,
p=.003). Changes in FSG, HOMA2-%B, HOMA2-%IR,
or HOMA2-%S in response to LY treatment were not significantly different between groups.
Conclusion: Treatment with LY is associated with
significantly greater reductions in HbA1c and postprandial
glucose excursion in H compared to NH. Further studies
are warranted to prospectively evaluate differential effects
of LY treatment in the Hispanic population with type 2
diabetes mellitus.
Abstract #243
FACTORS ASSOCIATED WITH INPATIENT
SEVERE HYPOGLYCEMIA
Sunil Asnani, MD, FACE, Adrian Scaunasu, MD,
Taral Jobanputra, MD, Bhavikaben Babaria, MD
42% had alteration in ability to self report symptoms of
hypoglycemia.
Discussion: Elderly patients with renal insufficiency
admitted to ICU are at high risk of developing severe
hypoglycemia. Steroids, prolonged admission, sepsis &
shock, altered mental status, altered route of nutrition,
imaging and other inpatients procedures including surgery, and insulin use, especially sliding scale increased the
risk of hypoglycemia. Lastly, patients with prior history of
hypoglycemia were at risk of another episode during the
hospitalization.
Conclusion: Developing strategies to prevent or
reduce hypoglycemic events should include identifying
high risk patients, recognizing precipitating factors, use of
appropriate scheduled insulin, and appropriate nutritional
support in hospitalized patients.
Abstract #244
Objective: To identify factors associated with and
likely causative of inpatient severe hypoglycemia.
Methods: Severe hypoglycemia was defined as hypoglycemia necessitating a rescue with intravenous dextrose.
Pharmacy generated report on 50% dextrose (D50) utilization from July-Dec 2007 was used to identify patients
with hypoglycemia. All code-blue and hyperkalemia
associated use were excluded. Charts were reviewed for
labs, admitting service, medications, co-morbid illnesses,
scheduled procedure or surgery and other variables affecting glycemia.
Results: A total of 579 D50 orders were reviewed;
105 orders were excluded (hyperkalemia, code-blue or
D50 not administered). 474 severe hypoglycemia were
confirmed. 268 patients had single episode while 72 had
multiple episodes during their admission; 12 had more
than 3 episodes. The mean glucose level (serum or capillary) was 41 mg/dl. The average age was 73.7 years; 54%
were females. The average incidence rate was 4.5% in
medical admits and 4.2% in surgical admits. 258 episodes
(54%) occurred in ICUs. 20% episodes occurred in Type 1
DM patients & 52.5% in Type 2 DM; 27.5% patients had
no diagnosis of diabetes. 31% episodes occurred between
12AM and 6AM. The median hypoglycemia day of 8th
day of admission; the median A1C was 6.9%; the median
Sr. Creatinine, AST and ALT were 1.4 mg/dl, 30 U/L and
24 U/L respectively. Oral hypoglycemic agents (except
SFU 4%) had minimal representation in this cohort.
Sliding scale insulin was ordered for 71% patients; 34%
had bolus and 32% had basal insulin ordered as well. 21%
were on steroid taper; 38% were NPO, 21% on tube feeds
and 4% on TPN. 9% had a procedure/imaging scheduled the day of hypoglycemia and had been transported
off their floor; 11% had surgery on the day of or the day
before the episode. 21% had sepsis; 17% were in shock;
CLINICAL PRACTICE IMPROVED
GLYCEMIC CONTROL IN TYPE 2 DIABETES
PATIENTS USING THE V-GO™
AS INSULIN DELIVERY DEVICE
Cheryl R. Rosenfeld, DO, FACE, Bruce Bode, MD,
Nancy Bohannon, MD, Adam Kelman, MD,
Shari Mintz, MD, Sridhar Nambi, MD, Alan Schorr, DO,
Mark Sandberg, MD, Poul Strange, MD, Leon Shi, PhD
Objective: To retrospectively describe glycemic
control before, during and after insulin delivery with the
V-Go.
Background: The V-Go is a disposable, continuous
subcutaneous insulin delivery device that delivers a preset basal infusion rate as well as on-demand insulin in 2U
increments. 10 physicians treated 31 patients with diabetes mellitus using the V-Go. The anecdotal information
regarding glucose control was positive.
Methods: After IRB approval, 8 physicians participated. Data were collected from before V-Go initiation,
after 12 weeks of use, at the end of V-Go treatment, and 12
weeks after the patients discontinued the V-Go. Analyses
employed non-parametric statistical tests.
Results: 23 patients (15 white and 6 black) gave
informed consent. Patients were 61 (31-83) years old
(average range), with BMI of 30 (25-35) kg/m2, diabetes
for 16 (4-39) years and treated with insulin for 7 (0.5-23)
years. Baseline insulin use included 17 patients on insulin glargine, 2 on NPH, and 4 on premix. 10 patients also
used rapid acting insulin. Concomitant diabetes medications (baseline/V-Go/12 weeks after) included metformin
(10/7/8), pioglitazone (4/5/5), sulfonylureas/meglitinides
(7/4/4), sitagliptin (3/3/3), exenatide (2/1/1), and pramlintide (1/1/1). Patients’ insulin was delivered using the
– 41 –
V-Go for 194 (43-289) days. Total daily insulin dose was
50±14U (Mean±SD) at baseline, 46±13U while on V-Go,
and 51±16U 12 weeks after stopping V-Go treatment.
A1C decreased from 8.8±2.8% at baseline, to 7.6±1.1 on
V-Go (p=0.005), increasing to 8.2±1.8 12 weeks after end
of treatment (p=0.021). Morning fasting glucose trended
similarly from 205±117 mg/dl, down to 135±43 (p=0.055)
while on V-Go, with increase to 164±77 mg/dl (NS) after
V-Go was stopped. Despite improvement in glycemic
control, weight was essentially unchanged from baseline
201±35 pounds, to 202±37 (NS) on V-Go, and tended to
increase to 210±34 (NS) after V-Go was discontinued.
No differences in hypoglycemic events were found. 12
weeks after V-Go discontinuation, 0/19 (incomplete data)
patients were treated with premixed insulin and at least
15/19 were treated with rapid acting insulin analogue.
Discussion: Glycemic control improved while
patients were treated using the V-Go and deteriorated
when the V-Go was discontinued. The cause of this temporary improvement may be better matching of insulin delivery with demand and possibly, as suggested by
individual patient data (not shown), that the simplicity of
using the V-Go device enabled patients to achieve better
compliance with therapy.
Abstract #245
HYPOGLYCEMIC EFFECT OF LEPECHINIA
CAULESCENS (LABIATAE) IN SUBJECTS WITH
TYPE 2 DIABETES MELLITUS
administration, we observed a significant diminution in
the levels of insulin at 30 minutes of the test in patients
with diabetes type 2.
Discussion: With the presented results, it is evident
that although the plant has hypoglycemic properties, the
unique dose with the used concentration did not get to
have statistically significant effect. On the other hand, still
does not know the time of impregnating of the components
of this plant, as well as the possible routes of their metabolism; reason why it is required to evaluate the answer to
the administration of this type of infusions per prolonged
periods of time, and also greater doses and different concentration and furthermore in different stages from the
disease. The significant diminution in the levels of insulin
at 30 minutes of the test in subjects with diabetes mellitus in the presence of the Labiatae, could explain by the
effect of the components of the Lepechinia caulescens on
the modification of sensitivity to the insulin of peripheral
tissues.
Conclusion: In this work we found that the unique
dose of watery extracts of Lepechinia caulescens preparations by means of infusion of 5 g of dry leaves in 200 ml
of water, in agreement with the popular practice, does not
induce hypoglycemia in subjects with diabetes mellitus
type 2 of recent diagnosis. Although this plant has been
reported as having hypoglycemic properties, according
to this study design there was not a significant difference
either with or without the infusion of Lepechinia caulescens leaves using described doses.
Abstract #246
Estanislao Ramirez Vargas, MD, PhD,
Maria del Rosario Arnaud Vinas
Objective: To investigate the effect hypoglycemic of
the Labiatae (Lepechinia caulescens) - is a “purple flower
Bretonica”- in type 2 diabetic subjects with recently diagnosed pathology, according to the popular practice.
Methods: 20 subjects were divided in two groups,
whom were engaged in same clinical and laboratory tests.
One, control group included healthy subjects and the other
group, patients with type 2 diabetes mellitus. Both groups
were overloaded with 75 g of glucose for the tolerance
test. Glucose and insulin were assayed for a period of four
hours. Both groups had another glucose tolerance test (75
g) plus 200 mL of a 5 g infusion of Lepechinia caulescens
dry leaves. Glucose and insulin were assayed again for a
period of four hours.
Results: The significant differences found when
comparing both groups: the levels of glycemia, glycated
hemoglobin A1c, urea and systolic arterial pressure. The
lowest levels were found in the group control (p < 0.05).
In the test of tolerance with 75 grams of glucose, when
we compared the effects of the Lepechinia caulescens
A CASE OF NEW ONSET DIABETES AND DKA
PRESENTING WITH DISSEMINATED MRSA
Daniel S. Hsia, MD
Objective: To describe a presentation of diabetic ketoacidosis complicated by disseminated MRSA infection in
an otherwise healthy adolescent.
Case Presentation: A 14-year-old female with no
significant medical history presented with complaints
of multiple joint pain for 3 weeks (especially worsening right shoulder/arm pain not relieved with NSAIDS),
weight loss (50 lbs over the past 6 months), and fever for
2-3 days. She was taken to an outside ER due to bilateral
leg pain and a new facial rash. She also reported a 3-4
day history of polyuria (10-12 times per day) and polydipsia. Her labs showed: pH 7.27; bicarb 9; glucose 475.
She was diagnosed with new onset diabetes with DKA
and transferred to our hospital’s PICU. On exam her Temp
was 103°F; HR 130; RR 30; BP 120/60; wt 96.6 kg; BMI
34. She was obese, tired appearing, and had dry mucous
membranes. She did not have acanthosis nigricans, but
– 42 –
she did have multiple pustular lesions on her face. She
had diffuse muscle tenderness with profound pain in her
right shoulder and decreased range of motion. Her labs
showed: pH 7.21; Na 132; K 3.6; Cl 107; bicarb 9; BUN
9; Cr 0.6; glucose 400; serum beta-hydroxybutyrate 4.1
mmol/L (<0.3); HbA1c 11.5%. Her U/A showed: 4+ glucose and ketones. She was started on a regular insulin drip
at 0.1 units/kg/hour and a 2 bag IV fluid system (LR/D10
LR + KPhos 2mmol/100mL and KCl 1.5mEq/100mL) at
2500 mL/m2/day. Her acidosis corrected overnight, and
she was switched to SC insulin glargine/aspart BID. Her
peripheral blood culture as well as her right shoulder and
left ankle joint aspirates were positive for MRSA. MRI
showed: diffuse myositis throughout the body; osteomyelitis in the proximal right humerus; cellulitis around the
left ankle, right wrist, and left forearm; and septic emboli
in the lungs. She is being treated with a prolonged course
of IV vancomycin for disseminated MRSA.
Discussion: This patient presented with DKA, an
entity most commonly associated with Type 1 diabetes.
However, she is more typical of a Type 2 diabetes patient
given her obese body habitus, negative islet cell antibodies, and family history of Type 2 diabetes. Impaired host
defense has been shown in diabetes patients with poor glucose control, especially with ketoacidosis. Muller et al.,
Clinical Infectious Diseases 2005 41:281–8 showed that
patients with Type 1 and Type 2 diabetes are at increased
risk for lower respiratory tract infection, urinary tract
infection, and skin and mucous membrane infection.
However, it is unclear if the disseminated MRSA infection unmasked her diabetes diagnosis; if diabetes put her
at increased risk for severe infection; or both.
Conclusion: Disseminated MRSA is a serious condition associated with a high complication rate and mortality. This case highlights the increased infection risk in
diabetes patients and presents a pediatric patient with disseminated MRSA and DKA.
Abstract #247
CLINICO-EPIDEMIOLOGICAL
CHARACTERISTICS & GLYCEMIC CONTROL
IN ARAB /NONARAB DIABETIC
POPULATION IN UAE
Satendra Kumar Multani, MD, Meenakshi Jain, MD
Objective: United Arab Emirates is having the 2nd
highest prevalence of Type 2 Diabetes Mellitus (T2DM)
in the World. This retrospective observational study was
carried out in Ras Al Khaimah emirate of UAE to assess
& compare the clinico-epidemiological profile & glycemic control in Arab / Nonarab T2DM population. The predominant Nonarab population in UAE is the South Asian
population contributing to up to 70% of total country
population.
Methods: 392 subjects with T2DM were randomly
selected and divided in Arab / Nonarab group. Their phenotypic features and relevant biochemical parameters
were recorded.
Results: Out of 392 subjects, 328 subjects were of
South-Asian & 64 subjects were of Arab origin. The
mean age of the Nonarab & Arab group was 46.8+8.01
& 47.50+9.18 yrs respectively. The mean duration of
T2DM in Nonarab & Arab group was 5.35 + 5.13 yrs and
4.55+4.96 yrs respectively. The mean BMI and WC in
Nonarab were 27+3.86kg/m2 & 96.05+9.20 cms whereas
in Arab they were 31.2+5.47 kg/m2 &102.55+11.91 cms
respectively. Central obesity was seen in 87.6% of Nonarab
subjects and 66.7% of Arab subjects.66.2% of Nonarab
& 87.5% of Arab subjects were overweight. The baseline
HbA1c was 8.64+1.89% in Nonarab & 8.44+1.75% in
Arab group. 62.1% & 16.5% of Nonarab had post treatment HbA1c of ≤ 6.5% & 6.5-7% respectively while
56.3% & 25% of Arab subjects had achieved the same
target HbA1c. 186/328 (56.70%) of Nonarab and 25/64
(39.1%) of Arab subjects had hypertension and more than
2/3 of them required two or more drugs to control their BP.
294/328 (91.9%) of Nonarab and 56/64 (87.5%) of Arab
subjects had dyslipidemia with high LDL (≥100mg%)
being the commonest lipid abnormality in both the groups.
167/328 (50.9%) of Nonarab & 34/64 (53.1%) of Arab
subjects had both HTN and dyslipidemia. 22% & 24.3%
subjects had microalbuminuria in Nonarab & Arab group
respectively. 31% subjects in Nonarab & 17.8% subjects
in Arab group had abnormal ALT levels suggestive of Non
Alcoholic Fatty Liver Disease (NAFLD).
Discussion & Conclusion: An important observation was significantly higher prevalence of central obesity
in Nonarab & generalized obesity in Arab population.
75-80% subjects in both groups had achieved satisfactory
glycemic control (HbA1c ≤7%). Prevalence of cardiovascular risk factors was similar in both the groups suggestive
of higher risk of cardiovascular complications thus warranting aggressive treatment of each risk factor. Though
most of the clinico-epidemiological characteristics were
comparable in both populations, additional data on Arab
population (as group was small) will be helpful in understanding significant differences if there are any.
– 43 –
especially in cases with a new onset of a severe headache.
Delay in the diagnosis of this condition could be associated with permanent neurologic deficits which may be
mitigated with neuroimaging and anticoagulation in confirmed cases.
Abstract #248
SUPERIOR SAGITTAL SINUS THROMBOSIS
SECONDARY TO DIABETIC KETOACIDOSIS
(DKA)
Abstract #249
Raaid Hassan Mannaa Mannah, MD,
John W. Kennedy, MD
Objective: To present a case of a patient with Type 1
Diabetes Mellitus (DM) who developed superior sagittal
sinus thrombosis as a complication of DKA.
Case presentation: An 18 year old female patient
with a history of uncontrolled type 1 DM, due to non compliance with prescribed insulin, presented to an outside
hospital with lethargy, tachypnea and hypoxia. She was
found to have severe DKA: Glucose 863 mg/dL, CO2 5
mmol/L, Potassium 5.5 mmol/L, Sodium 135 mmol/L,
Chloride 100 mmol/L, anion gap 40, arterial pH 6.9, positive ketones in blood and urine. The patient was treated
for DKA with intravenous fluids and insulin. The DKA
resolved and her mental status improved, but she developed a severe headache. She was discharged home in a
stable condition. Over the next few days, her headache
became intractable. She returned to the outside hospital
and had a CT angiogram that showed possible sagittal
sinus thrombosis. She was transferred to our Neurology
service for evaluation. Further investigation with MRI –
MRV showed findings of superior sagittal sinus thrombosis with extension into the transverse sinuses bilaterally.
She was started on heparin infusion and Coumadin. She
was discharged with no permanent neurologic deficits.
Discussion: Cerebral sinus thrombosis is an uncommon condition. The risk factors include genetic prothrombotic conditions, pregnancy and puerperium, oral
contraceptives, infections, dehydration, hematologic
conditions, malignancies, and systemic diseases. There is
evidence suggesting that DKA promotes a pro-thrombotic
state. Many hypotheses have been formulated for this
mechanism but dehydration is probably the most important factor. In our patient, her severe dehydration due to
diabetic ketoacidosis was most likely the cause of the
cerebral sinus thrombosis. She underwent extensive work
up looking for inherited and acquired pro-thrombotic conditions but results were negative. Only a few cases have
been reported of a cerebral sinus thrombosis in association
with diabetic ketoacidosis in an adult.
Conclusion: DKA is associated with dehydration
and promotes a pro-thrombotic state. During an episode
of DKA, deterioration of the mental status due to cerebral edema or metabolic encephalopathy has been commonly described, however, other less common conditions
such as cerebral sinus thrombosis should be considered,
CLINICAL EXPERIENCE WITH EXENATIDE IN
OBESE NORTH INDIAN PATIENTS WITH TYPE
II DIABETES
Ambrish Mithal, MD, DM, Tarunika Bawa, MBBS,
Vibha Dhingra, Niti Agarwal, MD, Nidhi Malhotra, MD
Objective: To share our clinical experience with the
use of exenatide in Indian patients.
Methods: We share our experience with use of exenatide in 74 patients treated at a tertiary care centre in New
Delhi, India. Subjects included obese / overweight subjects
(mean weight 97.67 kg) with known history of type 2 DM
(median duration 9 yrs) and maintaining suboptimal glycemic control (HbA1c >7.0)) on oral antidiabetic agents
with or without basal insulin. TZDs and DPP4 inhibitors
were discontinued in view of weight gain and mechanism
of action respectively. At initiation, 69.77% of patients
were on metformin, 67.44% on secretagogues, 13.95% on
TZDs and 17.76% on basal insulin either in combination
or alone. 4 Patients discontinued exenatide before completion of one month due to intolerance (severe nausea and
vomiting). The dose of exenatide was increased to 10 mcg
twice a day after 4 -12 weeks. Exenatide was discontinued
in 3 patients due to lack of response (glycemic or weight
loss) and 6 patients discontinued due to cost factor. 56
patients completed a minimum of 3 months on therapy.
42, 32 and 25 patients completed 6 months,9 months completed 12 months respectively. We have analysed data
for patients who were able to complete at least 3 months
therapy.
Results & Discussion: The decline in fasting and PP
blood sugars were significant from baseline at 3, 6, 9 and
12 months with p-value <0.05. The mean weight loss (kg)
at one month, 3, 6, 9, 12 months was 1.75 ± 1.3, 3.86 ±
2.5, 6.26 ± 3.4, 7.75 ± 3.9 and 8.68 ± 4.1 respectively.
The mean HbA1c (%) at baseline was 8.63± 1.26, at 3
months 7.81 ± 0.92, at 6 month 7.69 ± 0.86, at 9 months
was 7.53 ± 0.97 and at one year was 7.26 ± 0.81. The
changes in HbA1c and weight loss from baseline were statistically significant with P value < 0.05. Nausea was the
major side effect which declined with the passage of time
(95% patients in first month, 73.8% at 6 months and 8%
at one year). Incidence of minor hypoglycemia was low
in the first month (1.5%) which increased with improvement in glycemic control (5.35%, 11.9%, 25% and 20%
– 44 –
at 3, 6, 9, 12 months respectively), necessitating sulphonylurea dose reduction. There was no incidence of major
hypoglycemia.
Conclusion: There was a significant improvement in
glycemic control and major weight loss (mean 7.75 kg at
9 months) with the use of exenatide in obese North Indian
patients with Type 2 Diabetes. Nausea was the most common side effect. Exenatide is a useful option for treatment
of diabetes for obese Indian diabetics.
Abstract #250
ABNORMAL URINARY PROTEIN IN TYPE 2
DIABETES IN NIGERIA.
and 0.03). Mean LDL-C significantly correlated with
abnormal proteinuria ( r-0.2,p=0.05). Non fatal clinically
evident cardiovascular events were comparable in both
groups (stroke 63.3% vs 36.4% p=0.8, chest pains 62.5%
vs 37.5% p=0.4).
Conclusion: The prevalence of abnormal protein is
high in Nigerian DM and significantly associated with
high total cholesterol, high LDL-C and ECG abnormalities. Early elucidation would go a long way to reduce
cardiovascular complications. Limitation: Doppler,
Echocardiography, Brain CT Scan and CRP Studies.
Abstract #251
COST OF TREATING DIABETES IN A
DEVELOPING ECONOMY
Adeleye Olufunmilayo Olubusola , MD, Dada, A.O.
Babatope Kolawole, MD, Tomi Olugbodi
Objective: Albuminuria is a strong independent predictor of all-cause of CVD mortality in American Indians
with diabetes. Early assessment and targeted interventions
are necessary to treat and prevent all risk factors associated with diabetic complications. This study sets out to
determine the prevalence of abnormal urinary protein and
its correlates among DM patients in Nigeria.
Methods: This is cross-sectional study in which 200
DM patients were randomly selected in LASUTH. Their
clinical characteristics documented through interviewer
administered questionnaires. The laboratory parameters
assessed included serum lipid profile, uric acid, blood
glucose (FBS) and urine analysis for macro and microalbuminuria. All the study subjects had ECG done to
assess their cardiovascular status. Test Statistics used
were Student’s T-test, χ test and correlation coefficient to
test for association. P value of <0.05 indicated statistical
significance.
Results: The prevalence of proteinuria was 54%.
23% had macroalbuminuria and 31% microalbuminuria
. Females and males made up 62% and 38 %,p=0.01.
More F were affected than M. The mean (SD) age of
the subjects with proteinuria was 58.3±11.4 years. The
ages of the females (F) and male s(M) were comparable
(56.5±11.5 vs. 61.2±10.8 years, p=0.16). The mean BMI
of the study subjects was 27.4±5.13. The mean BMI of
F were higher than M (28.5 ± 5.1 vs 25.4 ±4.8, p=0.02).
Their mean duration of DM was 8.0yrs ± 6.03. A high proportion of subjects (69%) were hypertensives. Their mean
FBS was 183.76 ± 101.56 and mean HbA1c 7.9 ±3.7.
The mean BMI, duration of DM, uric acid levels, HbAic,
hypertension and FBS were comparable in both groups.
However ECG abnormalities were significantly higher in
the proteinuria group. The TOTAL-C and LDL-C were
significantly higher in subjects with proteinuria (p=0.01
Objective: The study set out to determine the out-ofpocket and indirect costs of treating diabetes mellitus in
Nigeria with a developing economy and little or no health
insurance.
Methods: The study was conducted at two tertiary
health facilities that are 25 kilometers apart and operate
under the same management, the Wesley Guild Hospital
(WGH) and the Ife Hospital Unit (IHU) both in southwestern Nigeria. An interview-structured questionnaire and
case note records were used to determine demographic
variables, how much patients had expended on diabetes
care, sources of funds for care, ability to cope with paying,
number of clinic attendance and number of days spent on
admission all in the preceding 12 months.
Results: There were 94 patients in all (M: F= 1:1), the
average age was 62 years, 29 were retirees and 83 % of the
patients were in the low socioeconomic class. The average
clinic attendance was 8/12 months while the average duration of hospital stay was 38 days. The total cost of insulin,
oral hypoglycemics, other drugs and laboratory test was
$51,986.00. Only six patients had their own glucometer.
With respect to the ability to cope with paying for care,
56% of the patients reported that they cope with difficulty
or great difficulty while a third had to depend on relations
for diabetes care payment.
Discussion: The prevalence of diabetes mellitus is
projected to continue to increase world wide and developing countries may bear the greater brunt of this increase.
Diabetes mellitus without doubt places a considerable economic burden on individuals, families and even national
health systems. In some countries, including Nigeria, most
or at least a substantial proportion of healthcare costs are
borne by individuals and their families and indirect costs
e.g. lost production may even be higher. Our study just
as in previous studies recorded a higher prevalence of
– 45 –
diabetes in the elderly population. This group of individuals is particularly vulnerable to cost effects being mostly
retired and having no regular earnings. Majority of our
patients are from the lower socio economic strata with
poor education further compromising their ability to make
wealth and fund their own care. This results inevitably to
poor outcomes hence creating a vicious circle for perpetuating poverty.
Conclusion: The out-of-pocket and indirect cost of
diabetes care appeared intolerably high to these mostly
indigent patients. An effective health insurance scheme
might ameliorate this presently unacceptable situation.
Abstract #252
whose insulin requirements exceed 200 units insulin/day.
The high concentration of U-500 regular insulin makes
its pharmacokinetic profile more closely simulating NPH,
and that helps in delivering high insulin doses in small
volumes. Significant improvement in Hgb A1C level as
well as cost benefit was reported with using U 500.
Conclusion: There is lack of experience in utilizing U
500 in hospital setting. Through our two cases we propose
that U 500 regular insulin as an alternative option in treating
hospitalized patients with high insulin resistance in appropriate clinical settings providing that education and safety
measures are well undertaken. Ordering in mL/units and
using TB syringes can eliminate confusion with dosing.
Abstract #253
UTILIZING U 500 INSULIN IN
HOSPITAL SETTING
Abdul-Razzak Alamir, MD, Joe Chehade, MD
Objective: Review the use of U 500 regular insulin
for highly insulin resistant patients in hospital setting.
Case Presentation: 52 year old male with HIV admitted with fever and confusion. Admission Blood glucose
(BG) 399 mg/dL, normal value a year ago. Patient was
on HAART until a month earlier. Triglyceride 75 mg/dL,
Hgb A1C 16.1%. ID evaluation & work up was negative,
fever and confusion resolved in 24 hours. Despite very
high doses of insulin > 3000 units/day insulin IV (BG)
remained > 200 mg/dL . U 500 (800 U/daily) was effective in tapering off insulin infusion and lowering (BG) to
100 mg/dL range. Insulin requirement declined significantly after 3 weeks and was discharged off insulin on
Pioglitazone 45 mg/d. 48 year old white female with history of chronic pancreatitis and DM type 2 admitted with
abdominal pain and vomiting. Normal lipase, triglyceride
928 mg/dL, Hgb A1C 7.8%. Her home regimen included
Glargine 24 units at bedtime and metformin 2000 mg/d.
TPN 71 mL/hr (contained 156 gm/L dextrose; 40 units/L
regular insulin) was started for severe GI symptoms, her
BG remained >400 despite insulin dose > 400 U/d IV
which persisted even after stopping TPN. U 500 (up to 0.4
ml = 200 U TID) was effective in lowering BG within 48
hours. Triglyceride improved 212 mg/dL. The patient was
discharged on U 500 0.2 mL (100 units qac). Her insulin
requirement continued to decrease post discharge and she
was switched back to her old low dose insulin regimen. In
both cases work up for secondary causes for acute severe
insulin resistance was negative.
Discussion: Despite the fact that U 500 insulin has
been successful in treating patients with severe insulin
resistance, its clinical utilization is still limited. U 500 insulin which is 5 times more concentrated than U-100 insulin, is an alternative option for treating diabetic patients
A MULTIDISCIPLINARY PROTOCOL
SPECIFYING A BASAL/BOLUS REGIMEN OF
SUBCUTANEOUS INSULIN IN TRANSITION
FROM CONTINUOUS INSULIN INFUSION IS
EFFECTIVE FOR GLYCEMIC CONTROL IN
CARDIAC SURGERY PATIENTS.
Agnieszka Gliwa, MD, Peter Terry, MD, Sarah Siu,
Kathleen Salak, NP, Daniel Lee, MD, Vinay Tak, MD,
Haroon Kamran, Wilson Ko, MD
Objective: We investigated whether a protocol for
subcutaneous (SQ) insulin could maintain glycemic control without prolonged continuous insulin infusion (CII) in
patients after cardiac surgery.
Methods: We retrospectively analyzed consecutive
cardiac surgery patients enrolled for up to 5 days in the
Protocol between October 2008 and April 2009. Patients
were treated as usual with CII with target glucose 120 mg/
dL until transition to SQ insulin at first oral feeding after
surgery, no earlier than the morning after surgery. Our
Protocol includes an algorithm calculating the initial dose
of basal insulin to be given on transition from CII, which
occurs at the first post surgery oral feeding; as well as for
ongoing prandial and supplemental dose insulin. Blood
glucose (BG) is obtained at mealtimes, 10pm and 3am. An
algorithm is used daily to titrate insulin doses according to
BG results from the preceding 24 hours. The goal of the
protocol was to achieve a mean daily BG of ≤ 150 mg/dL.
Results: We analyzed 31 diabetics and 59 nondiabetics. Mean duration of CII was 25.7±16 h (median and
mode, 22 h). Of patients extubated after midnight on the
day of surgery, 53% received SQ insulin within 6 hours of
extubation. The dose of basal insulin was higher in diabetics than nondiabetics at protocol initiation (0.56 vs 0.29
U/kg) (p<.000005). Over protocol days 1-5 the absolute
doses as well as the difference in doses of diabetics and
– 46 –
nondiabetics decreased; on protocol day 5 doses were
similar in diabetics and nondiabetics (0.24 vs. 0.16 U/kg)
(p=ns). Mean BG in nondiabetics and diabetics was 129
vs 145 mg/dL for Protocol Day 1 (p-ns), 127 mg/dL vs
138 for Protocol Day 2 (p=ns); and 122 vs 137 mg/dL for
Protocol Days 1 – 5 (p=0.01). Efficacy rate in nondiabetics vs diabetics was 83% vs 58% for protocol Day 1; 89%
vs 81% on day 2 (p=ns for both); and (95% vs 74%) for
Days 1-5 (p = .01). Of 1868 BG results, 6.8% were below
70 mg/dL, 0.7% were below 50 mg/dL, of which one episode was symptomatic.
Discussion: Glycemic control after cardiac surgery
reduces morbidity and mortality, but may require prolonged CII. A practicable SQ insulin protocol would be
a tool to study the benefit of defined glycemic control in
cardiac surgery patients who are not critically ill.
Conclusion: Our SQ insulin protocol is effective
for glycemic control in cardiac surgery patients, without
excessive hypoglycemia. It can be initiated soon after
extubation and reduces the need for prolonged CII.
decarboxylase antibodies (GADA). Subjects with
CT2DM who were GADA positive had a lower mean
BMI (25.64 kg/m2 vs. 26.59 kg/m2) and waist circumference (89.80 kg/m2 vs. 92.47 kg/m2) than GADA negative
subjects; however these differences did not attain statistical significance. Subjects who were GADA positive had
higher mean fasting blood glucose (144mg/dl vs. 125mg/
dl, t=2.20, p=0.14), higher mean HbA1c levels (7% vs.
6.1%, t=3.19 p=0.077) and a higher proportion on insulin
therapy (31.6% vs. 22%, χ 2 = 0.07, p= 0.25) when compared with GADA negative patients.
Conclusion: The prevalence of LADA amongst
Nigerian patients clinically diagnosed as type 2 DM was
11.9%. This high prevalence emphasizes the importance
of GAD antibody testing in our practice settings, so as to
appropriately classify adult patients with diabetes mellitus. This would also help direct appropriate therapy so as
to improve glycemic control and reduce the risk of long
term complications of diabetes mellitus.
Abstract #254
Abstract #255
PREVALENCE OF LATENT AUTOIMMUNE
DIABETES AMONGST ADULTS WITH
TYPE 2 DIABETES
THE EFFICACY OF LIRAGLUTIDE IS NOT
IMPACTED IN SUBJECTS POSITIVE FOR
ANTI-LIRAGLUTIDE ANTIBODIES:
A POOLED ANALYSIS
Arinola Ipadeola, MBBS,
Jokotade Adeleye, MBBS, FWACP,
Kehinde Akinlade, FMCP
Objective: The aim of this study was to investigate the frequency and characteristic features of Latent
Autoimmune Diabetes in Adults (LADA) based on the
presence of Glutamic acid decarboxylase (GAD) antibodies in patients who had been clinically diagnosed as type 2
diabetes mellitus.
Methods: One hundred and sixty patients who had
been diagnosed clinically to have type 2 diabetes mellitus
(CT2DM) participated in the study following selection by
systematic random sampling. Anthropometric measurements (weight, height, waist circumference and hip circumference) were taken and blood samples were obtained
for analysis of fasting blood glucose, glycated hemoglobin (HbA1c) and GAD antibodies from the patients with
CT2DM. The results obtained were analyzed using SPSS
package version 16.
Results: Out of the 160 patients with CT2DM, 65
(40.6%) were males while 95(59.4%) were females. The
mean age (SD) of the patients with CT2DM was 60.49
(10.37) years, the mean BMI (SD) was 26.47 (4.80)
kg/m2 while the mean waist circumference (SD) was
92.16 (11.50) cm. Nineteen persons (11.9%) amongst
patients with CT2DM were positive for Glutamic acid
Alan J. Garber, MD, PhD, FACE,
Michel Marre, MD, PhD, Michael Nauck, MD, PhD,
David Russell-Jones, MD, PhD, Jason Brett, MD, PhD,
Maria During, PhD, Lawrence Blonde, MD
Objective: Peptide drugs have the potential to induce
antibodies, based on homology to the native peptide or
protein. Antibodies can bind to the effective peptide and
alter the pharmacokinetics and thereby decrease efficacy.
GLP-1 receptor agonists vary in their homology to human
GLP-1. Exenatide has 53% homology to human GLP-1;
about 50% of subjects taking exenatide developed antibodies to it during phase 3 trials, with 3-6% having high
antibody titers that were associated with decreased efficacy. Therefore, we evaluated if use of liraglutide, a oncedaily human GLP-1 analog with 97% homology to native
GLP-1 would generate antibodies and, if so, whether this
would affect glycemic control.
Methods: A pooled analysis from four phase 3 studies was done to assess the prevalence of anti-liraglutide
antibodies by radioimmunoassay. All samples positive
for anti-liraglutide antibodies were also tested for crossreactivity to native GLP-1 and in vitro neutralizing effect
on liraglutide. An analysis was also done to determine
whether antibody generation affected efficacy based
on hemoglobin A1c [HbA1c]. Subjects included in the
– 47 –
analysis had end-of-treatment samples taken off drug
(liraglutide 0.6mg, 1.2mg and 1.8mg) for at least 5 days,
ensuring that serum liraglutide levels did not interfere
with the antibody assay.
Result: Anti-liraglutide antibodies were detected in
8.3% of subjects treated with 1.8mg, 8.7% for 1.2 mg,
and 9.2% for 0.6 mg of liraglutide. Overall, 102 (8.6%)
subjects out of 1185 generated antibodies to liraglutide:
and of those testing positive for liraglutide antibodies,
12 (11.8%) subjects had neutralizing antibodies, and 56
(55%) subjects had antibodies that cross-reacted with
native GLP-1. Antibody titers were in the range of 1.610.7%B/T (% Bound/Total) and for subjects on liraglutide, the mean was 3.28%B/T. In the liraglutide 1.8mg arm
subjects positive for anti-liraglutide antibodies had a mean
HbA1c reduction of -1.1%, while those negative for antiliraglutide antibodies had -1.2%, while in the 1.2mg arm,
positive subjects had a mean HbA1c reduction of -1.3%
and those negative for liraglutide antibodies had -1.2%.
There was also no difference in HbA1c reduction in the
liraglutide 0.6mg arm in subjects positive or negative for
liraglutide antibodies. Nine subjects testing positive for
liraglutide antibodies reported injection site reactions, and
none were withdrawn from the trials due to these adverse
events.
Conclusion: Consistent with its high homology to
native GLP-1, the immunogenic potential of liraglutide
is low. The prevalence of anti-liraglutide antibodies was
<10%, with low titers that did not affect efficacy.
Abstract #256
ENDOCRINOLOGIST-SUPPORTED DIABETES
QUALITY IMPROVEMENT INITIATIVE IN
AN INTERNAL MEDICINE RESIDENCY
CONTINUITY CLINIC
James K. Salem, MD, FACE, Ronald Jones, MD, FACP,
Sana Hasan, DO, David Sweet, MD, FACP,
Lynn Clough, PhD
Objective: To assess interdisciplinary team skills in
learners and improvements in diabetes outcomes following implementation of an endocrinologist-supported quality improvement initiative in an internal medicine residency continuity clinic.
Methods: With the support and leadership of an endocrinologist, service delivery in the clinic was incrementally redesigned for patients with diabetes to incorporate
monthly endocrinologist-facilitated team meetings, teambased care visits (2008) and enhanced decision support
with point-of-care (POC) A1c testing (2009). The residency curriculum was also redesigned to include reviews
of practice patterns and optimal use of an interdisciplinary
team. Changes in diabetes outcomes were tracked through
a two year longitudinal study of all diabetic patients in the
clinic who had at least 2 visits each year following implementation (n=560). Educational outcomes were assessed
for all 48 residents in the program through multi-source
evaluations based on direct observations. Descriptive statistics were used to report change in process of care and
achievement of resident competencies. Paired t-tests were
used to measure change in A1c levels. Since the method
of A1c measurement changed in 2009 with the addition of
POC testing, change in A1c levels was only assessed for
2008.
Results: The percent of visits with current A1c results
increased from 62% in 2008 to 77% in 2009 after the
introduction of POC testing. Treatment intensification for
appropriate patients occurred at a higher rate (65%) during visits with a completed POC test than during those
without a completed POC test (49%). Mean A1c levels
for patients not at goal at baseline significantly improved
during 2008 (9.6-9.0%; difference-0.6, 95% CI .29 to .81,
p<.001). Currently, 39% percent of the patients have A1c
levels <7.0 at their most recent visit. During 2008-2009,
the percentage of residents achieving “Competent” or
“Superior” ratings in interdisciplinary team related competencies of Professionalism, Systems-Based Practice,
and Interpersonal and Communication Skills was 81%,
77% and 77% respectively.
Discussion: Use of team-based services and
enhanced decision support at visits significantly improves
the quality of care provided by residents during training
and also improves clinical outcomes for their patients with
diabetes.
Conclusion: This model for collaboration between
endocrinologists and primary care physicians was shown
to be an effective quality improvement strategy in a residency continuity clinic. The elements of the redesign are
not specific to one institution and could be transferred
to others to improve patient care as well as resident
education.
Abstract #257
ASSESSING GLYCEMIC CONTROL WITH
INSULIN PUMP THERAPY IN PATIENTS WITH
Banshi Damodarlal Saboo, MD, Phatak Sanjiv R.,
Brahmkshatriya Priyanka P., Vyas C.,
Sanjiv J. Shah, MD, MBBS,
Objective: Glycemic control is very critical in
patients with Type 1 diabetes mellitus. Recent therapeutic interventions with regards to type 1 diabetes include
– 48 –
Insulin pump therapy. Insulin pumps are used by diabetics
to help manage their diabetes. An insulin pump mimics
the pancreas by giving out a basal rate of insulin, which
is a constant infusion of a small amount of insulin. Before
each meal, a bolus dose (a burst of insulin) is taken based
on the amount of carbohydrate to be eaten.
Methods: The present study was aimed at assessing
the glycemic control in patients who are on insulin pump
therapy. Patients with type 1 diabetes who were on insulin pump therapy since last six months were included in
the study. The blood sugar levels were monitored for 3
months to evaluate glycemic control. The parameter used
for evaluation was glycosylated hemoglobin (HbA1c levels). Glycemic control was compared among pump users
and non users.
Results: The study revealed that those on insulin pump
therapy were having better glycemic control (HbA1c levels not more than 8.5) as compared to non users.
Conclusion: A significant proportion of pump users
had better optimum glycemic control than non users.
Thus insulin pumps help in maintaining glycemic controls
appreciably specially in patients with type 1 diabetes and
are strongly recommended for achieving and maintaining
optimum BSL and preventing diabetic complications.
Abstract #258
EMERGING TRENDS FOR TREATMENT OF
DYSLIPIDEMIA AND HYPERTENSION IN
PATIENTS WITH TYPE 2 DIABETES
Banshi Damodarlal Saboo, MD,
Sanjiv Jayantilal Shah, MD, MBBS,
Brahmkshatriya Priyanka P., Chandarana H,
Sisodiya N, Vyas C., Vyas B.,
Objective: Diabetes is emerging as an epidemic in the
developing as well as developed countries and is affecting
a large section of the health care sector. Along with the
cardinal macrovascular and microvascular complications
observed in diabetes, a commonly observed manifestation
is the concomitant occurrence of hypertension and dyslipidemia. Abnormal lipid levels and hypertension are the
indicators of cardiovascular diseases.
Methods: The present study was aimed at prevention
of cardiovascular disease in diabetic patients by introducing newer drugs. The study was also aimed at establishing
the optimum time to start the drug therapy. Patients with
diabetes were screened for hypertension and dyslipidemia
by observing their blood pressure and fasting total cholesterol, HDL, LDL and triglycerides. The parameters studied were total prevalence of hypertension and dyslipidemia, gender ratio, current treatment and lifestyles. Newer
therapies were introduced to check the efficacy on these
complications as well as patient compliance.
Conclusion: Prevention of hypertension and dyslipidemia would not only help in delaying the long term
complications of diabetes but also improve the lifestyle of
diabetic patients.
Abstract #259
INCIDENCE OF FATTY LIVER IN A
DIABETIC POPULATION
Shashank Joshi, MD, FACP, FRCP, FACE,
Ladha M., Agrawal M.
Objective: Nonalcoholic fatty liver disease (NAFLD)
is the most common cause of abnormal liver function
tests among adults in Western countries. The spectrum
of NAFLD ranges from simple steatosis to nonalcoholic
steatohepatitis (NASH), which can progress to end stage
liver disease. NAFLD is commonly associated with obesity, type 2 diabetes, dyslipidemia and insulin resistance,
all of which are components of the metabolic syndrome,
strongly supporting the notion the NAFLD is the hepatic
manifestation of the syndrome. The prevalence of NAFLD
has been reported to be in the 15-30% range in the general
population in various countries and is almost certainly
increasing. Compared with non diabetic subjects, people
with type 2 diabetes appear to have an increased risk of
developing fibrosis and cirrhosis. It has been estimated
that about 70-75% of type 2 diabetic patients may have
some form of NAFLD. However, the “precise” prevalence of NAFLD in type 2 diabetes is unknown. The few
available studies have been small and performed in highly
selected populations or have estimated only the prevalence of abnormal aminotransferase levels, which are a
poor proxy measure of NAFLD.
Methods: Hence the main purpose of this study was
to determine the prevalence of NAFLD as diagnosed by
patient history, and liver ultrasound, which is the most
widely used imaging test for detecting hepatic steatosis,
and to establish whether there is an association between
NAFLD and CVD in a large cohort of type 2 diabetic
adults. Patients with type 2 diabetes specially associated with obesity and insulin resistance were included
in the study and the fatty liver analyzed by sonographic
techniques.
Results: Studies revealed a significant proportion of
patients with NFALD.
Conclusion: Correct identification of NAFLD in
type 2 diabetes may help in CVD risk prediction with
– 49 –
important management implications. Identifying people
with NAFLD would also highlight a subgroup of diabetic
patients who should be targeted with more intensive therapy to decrease their risk of future CVD events.
Abstract #260
INSULIN PUMP THERAPY AND CONTINUOUS
GLUCOSE MONITORING SYSTEM (CGMS) IN
PATIENTS WITH TYPE 1 DIABETES MELLITUS
Banshi Damodarlal Saboo, MD, Phatak S.R.,
Sanjiv Jayantilal Shah, MD, MBBS
is advantageous over SMBG as SMBG only gives blood
sugars at the different points of time when the patient
chooses to test the blood sugar. Insulin Pump therapy and
CGMS has made the dream of the diabetologist to measure glucose levels continuously a reality. As it is a new
technology, the health care professionals using CGMS
have to become familiar with it and feel comfortable to
use it on patients.
Conclusion: Reduction in the costs and further
improvements in technology would ensure more widespread use of this potential method of continuously monitoring glucose levels.
Abstract #261
Objective: An Insulin Pump is indicated for the continuous delivery of insulin at set and variable rates for the
management of insulin dependant diabetes mellitus. They
have become increasingly popular over the past several
years because of their convenience, flexibility, and ease
of use. The benefit of these pumps includes avoidance
of following regimented meal plan that diabetics in the
past have had to follow. Additionally, insulin pumps are
better than basal insulin injections because they deliver
insulin at a very steady rate opposed to the basal injections that deliver sporadic insulin dosages and allow users
to eliminate invasive injections. Hemoglobin A1c levels
are easier to monitor with a pump and the cost of diabetes
management is reduced. Insulin pump therapy can achieve
near normal glycemia, minimize the risks of severe hypoglycemia and excessive weight gain, and prevent or delay
microvascular complications in brittle type 1 diabetics.
However, insulin pumps also have some unavoidable limitations including high costs, round the clock use and an
increased need of monitoring to avoid hypoglycemia and
ketoacidosis.
Methods: Along with Insulin pumps, patients with
IDDM should be recommended for CGMS to record
interstitial glucose. CGMS refers to the continuous, automatic monitoring of glucose in the subcutaneous tissue.
Continuous Glucose Monitoring Systems (CGMS) act
as “glycemic holters” to help the diabetologist and additionally have the ability to provide Real-time continuous
glucose monitoring. Some available devices approved or
under review include Paradigm® 722 System, Guardian®
RT, MiniLink®, Dexcom® STS (3-day approved and
7-day under review), Navigator® (Under FDA Review),
(CGMS, Medtronic MiniMed, Northridge, California)
and GlucoWatch (Cygnus, Inc, Redwood City, California.
The Continuous Glucose Monitoring System (CGMS) can
help to achieve and improve metabolic control as a result
of a balanced diet, physical activity and correct insulin. It
INVESTIGATION OF PREVALENCE AND
CHARACTERISTICS OF LATENT AUTOIMMUNE
DIABETES IN ADULTS (LADA) IN
A DIABETIC POPULATION
Banshi Damodarlal Saboo, MD, Goyal R.K.,
Brahmkshatriya Priyanka P.
Objective: Diabetes mellitus is one of the most
commonly occurring metabolic disorders. One new
form of diabetes that appears to have characteristics of
both Type 1 and Type 2 diabetes is known as LATENT
AUTOIMMUNE DIABETES IN ADULTS (LADA).
Methods: The present study was aimed at determining the phenotypic characteristics of LADA patients and
establishing critical parameters like C-peptide levels and
glutamic acid decarboxylase (GAD) autoantibodies as
diagnostic markers for LADA. The present study was
carried out to assess phenotypic characteristics of LADA
patients.
Results: Results showed that the prevalence of LADA
patients was nearly equal to that of Type 1 diabetes.
LADA was observed to affect males more as compared to
females. Additionally, LADA patients showed lower basal
metabolic index (BMI) values; age of onset between type
1 and Type 2 patients; higher glycosylated haemoglobin
(HbA1c) and cholesterol levels; and optimum blood sugar
levels by a combined therapy of insulin and oral hypoglycemic agents. The most interesting observations in these
patients were a significant presence of family history,
characteristically low C-peptide levels and a marked presence of glutamate decarboxylase (GAD) auto antibodies.
Since LADA patients constitute a noticeable proportion of
a diabetic population, it is very essential to identify such
cases accurately.
Conclusion: The above characteristics can be utilized to correctly identify LADA patients and prevent their
misdiagnosis as Type 2 diabetic patients. Determination
– 50 –
of C-peptide and GAD autoantibodies is strongly recommended for differential diagnosis of LADA. Accurate
diagnosis can in turn lead to a better understanding of the
underlying mechanisms which lead to development of
LADA and design of rational drug therapy for LADA.
Abstract #262
Abstract #263
HUMAN MACRO AND MICRO-VASCULAR
ENDOTHELIAL CELLS DIFFER IN GENE
EXPRESSION WHEN EXPOSED TO HIGH
GLUCOSE IN-VITRO
Sabyasachi Sen, MD, MRCP,
Abdulrahaman Alkabbani, MD, Saqib Inayatullah, MD
PRESCRIPTION PATTERN OF INSULIN
THERAPY IN A DIABETES CLINIC
Chandarana H, Sisodiya N,
Brahmkshatriya Priyanka P, Vyas C, Vyas B
Objective: Diabetes is one the most commonly occurring metabolic disorders characterized by dysfunction in
insulin secretion or insulin action or both. While certain
forms of diabetes are characterized by destruction of pancreatic beta cells, leading to failure of insulin secretion
and insulin dependency, some forms like type 2 diabetes
are associated with insulin resistance and down regulation
of insulin receptors thus leading to dysfunctional insulin action. Thus optimal insulin therapy according to the
onset of diabetes is very essential to maintain optimum
glycemic control.
Methods: The present study was aimed at establishing
a prescription pattern of insulin therapy according to the
duration of diabetes. Early initialization of insulin therapy
can help in preventing or delaying the diabetic complications. Patients were screened according to their duration
of diabetes, following which optimum insulin therapy was
prescribed as per the requirement. The parameters used
to monitor glycemic control as well as efficacy of the
treatment were Fasting Blood Sugar (FBS), Post Prandial
Blood Glucose (PPBS), HbA1c levels and C-peptide levels in some of the patients. Conclusion: Appropriate initialization of insulin
therapy with respect to the type of insulin prescribed, dose
of insulin and most importantly the duration or stage of
diabetes at which the therapy is prescribed can help in
maintaining optimum glycemic control and delay the diabetic complications thus improving the quality of life of
patients with diabetes.
– 51 –
Objective: Literature on complications of diabetes
suggests that micro and macrovascular outcomes secondary to intensive control of diabetes favor microvasculature. We decided to note if the effect of glycemia on
human micro and macrovascular endothelial cells (EC),
differ as regards to their gene expression.
Methods: We cultured commercially available
human cell lines such human umbilical vein endothelial
cells (HUVEC) as representative of macrovascular cells,
human retinal microvascular endothelial cells (HMEC), as
representative of microvascular cells and a non vascular
human cell line such as human embryonic kidney cells
(HEK) in monolayer. We exposed HUVEC and HMEC
to 5.5 mM (equivalent to 99mg% of glucose) and 25mM
(equivalent to 450mg% of glucose) and noted various
genes expression levels by real time PCR (RT-PCR).
Results: On culturing HEK and HUVEC in 5.5mM
glucose media we identified genes that are clearly overexpressed, in HUVEC rather than HEK, after 7 days of
culture in-vitro. These were CD-31 or PECAM (200fold), VEGFR2 or KDR ( 20-fold), vonWillebrand’s factor or VWR (205-fold), endothelial nitric oxide synthase
or eNOS ( 134- fold). These genes were therefore most
discriminatory between human endothelial and non-endothelial cells and may provide information of vasodilatory
(eNOS) and coagulative (vWR) functions of endothelium.
When we looked at expression of these identified genes in
HMEC and HUVEC after exposure to normal (NG) and
high glucose (HG) for 7 days, we noted that that there was
almost no change in gene expressions in HMEC in HG
however both VWR (4-fold) and eNOS (2.5 fold) gene
expression were reduced in HUVEC in HG compared to
NG. There was no cell death noted in either of the human
endothelial cell lines in HG by PI-dye staining using
FACS analysis. FACS analysis using HUVEC cultured in
HG and reactive oxygen species (ROS) responsive dye,
such as DCFDA indicated ROS accumulation inside the
cells.
Discussion: These findings illustrate that macrovascular cells may be more susceptible to gene expression
deterioration than microvascular EC on short-term exposure to HG. Exposure to HG leads ROS accumulation
intracellularly, which may be the pathogenesis of gene
expression reduction. No obvious EC death was noted,
when exposed to HG up to 7 days. This observation of
gene expression suppression after a short exposure to HG
may indicate why reversal to normal function of EC may
prove to be difficult, even when hyperglycemic state is
resolved, corroborating the data from the clinical trials.
Conclusion: Exposure to HG reduces synthetic gene
expression, of macrovascular EC, more, compared to
microvascular EC, even after a relatively short period of
exposure for 7 days.
Abstract #264
PREVENTION OF DIABETES IN OBESE
PATIENTS WITH PHARMACOLOGICAL AND
NON-PHARMACOLOGICAL TREATMENT
Brahmkshatriya Priyanka P, Chandarana H,
Sisodiya N, Vyas C, Vyas B
Objective: Obesity has assumed a great public health
and clinical significance in our country. Obesity affects
more than 22 million Indians and central obesity leads to
the classic epidemic of diabetes, hypertension, dyslipidemia and CHD. Sedentary lifestyles, increased consumption of junk foods and cola culture are one of the few factors contributing to the increased prevalence of obesity.
Obesity is one of the key factors which play a substantial
role in the development of insulin resistance and diabetes.
Methods: The present study was aimed at screening
of obese patients for presence of IGT (Impaired Glucose
Tolerance) or IFG (Impaired Fasting Glucose). Patients
were characterized as obese based on their BMI values.
The parameters observed in the study were gender ratio,
prevalence in different age groups, family history of obesity and diabetes, current pharmacological treatment and
lifestyle (diet, exercise, tobacco, smoking, alcohol).
Conclusion: Based on results appropriate lifestyle
modifications were recommended. Since obesity plays a
pivotal role in the development of diabetes, prevention
of obesity will not only help prevent diabetes but also
decrease the incidence of cardiovascular complications
resulting from diabetes as well as obesity itself.
Abstract #265
CASE SERIES OF FOUR YOUNG ADULTS
WITH TYPE 1 DIABETES DIAGNOSED WITH
MOYAMOYA DISEASE
Galina Smushkin, DR, Kalpana Muthusamy, MD,
John M. Miles, MD
Background: Moyamoya disease is a rare cerebrovascular condition where progressive stenosis of intracranial internal carotid arteries and the resultant collateral
vasculature predispose patients to ischemic stroke or hemorrhage. Associations with other conditions like sickle
cell disease or Down’s syndrome have been reported. We
report 4 cases of moyamoya disease in Caucasian young
adults with type 1 diabetes managed with insulin pump.
All four underwent STA-MCA bypasses in 2006-2009 at
our institution.
Case presentation: 24 y.o. female w/ type 1 diabetes and migraines, presented with transient visual loss
and headache. Cerebral angiogram demonstrated a neartotal occlusion of the supraclinoid internal carotid artery
branches. There were many bihemispheric small ischemic
infarcts. HgbA1C was 6.0; no microvascular complications. 20 y.o. male w/ type 1 diabetes and poor glycemic
control (HgbA1C 9.0) developed aphasia, left hemiplegia
and DKA. MRI showed a right hemispheric infarct and
cerebral angiogram revealed segmental narrowing of
multiple intracranial arteries. He had microalbuminuria
but no retinopathy or neuropathy. 19 y.o. male w/ type 1
diabetes and migraines, developed aphasia, disorientation
and headache. MRI demonstrated infarcts in caudate and
basal ganglia. Cerebral angiogram showed severe bilateral MCA stenoses. HgbA1C was 9.6; no microvascular
complications or DKAs. 22 y.o. male w/ type 1 diabetes
and migraines, developed spells of morning confusion
and headache. MRI showed a right frontal lobe infarct.
Cerebral angiogram showed bilateral high-grade stenoses
of the supraclinoid internal carotids. HgbA1C was 9.0; no
microvascular complications.
Discussion: The remarkable aspect of these cases is
the concurrence of type 1 diabetes and moyamoya disease. This may be coincidental, but it is possible that type
1 diabetes can precipitate the emergence of moyamoya in
susceptible persons. Dysregulated extra-cellular-matrix
remodeling and angiogenesis is thought to underlie the
arteriopathy. In-vitro studies of smooth muscle cells from
patients with moyamoya show altered responsiveness to
serum mitogens. Glycemic instability may contribute to
this altered responsiveness and to the dysregulation of the
involved enzymes.
– 52 –
Conclusion: This case series suggests that there may
be an association between type 1 diabetes and moyamoya
disease, but formal studies are needed. In the meantime,
clinical endocrinologist should have a low threshold for
obtaining MRI/MRA in a young patient with type 1 diabetes and migraines, since early diagnosis of moyamoya is
of paramount importance.
Abstract #267
Abstract #266
Campbell P. Howard, MD, FACE, Richard Petrucci, MD,
Nikhil Amin, MD, FCCP, Wen Yu, MD,
Paul Lovertin, BS, Anders H. Boss, MD, Peter C.
Richardson, BMedSci, BM, BS
DIABETIC KETOACIDOSIS IN GESTATIONAL
DIABETES. A CASE REPORT
Miguel E. Pinto, MD, FACE, Milagros Ortiz, MD,
Jaime E. Villena, MD
Objective: To report a case of a previously healthy
woman who developed gestational diabetes and presented
with severe ketoacidosis.
Case presentation: A 21-year-old Hispanic woman
with no previous history of diabetes, presented at 29
weeks’ gestation in her first pregnancy with a 6 weeks history of polidypsia, polyuria, and lower abdominal pain.
In the previous week, she was diagnosed and treated for a
urinary tract infection. Two days before she presented at
the Emergency Room, she developed dyspnea, nausea, and
vomiting. At presentation, physical examination showed
Kussmaul breathing and acanthosis nigricans. Laboratory
test showed glucose of 371 mg/dl, arterial pH of 7.16,
bicarbonate of 2.7 mmol/l, and hemoglobin HbA1c of
15%. Urine ketones and leukocyturia were positive. In
the ICU, treatment was started with IV insulin infusion,
intensive hydration, correction of electrolyte abnormalities, and IV antibiotics. She developed some degree of
transient diabetes insipidus associated with pregnancy
and mild hyperchloremic metabolic acidosis because of
renal tubular acidosis. Evolution was favorable, and she
was discharged with NPH insulin and pre-meal regular
insulin. Her pregnancy is normal and she is continuing her
controls in the outpatient setting.
Conclusion: Gestational diabetes mellitus presenting with diabetic ketoacidosis is unusual. Case reports
of diabetic ketoacidosis during pregnancy are related to
undiagnosed type 1 diabetes, complication of previously
diagnosed gestational diabetes by stress (prolonged labor
or infection), use of glucocorticoids, or O’ Sullivan test.
Strict surveillance of glucose homeostasis and aggressive diabetes management during pregnancy might reduce
perinatal morbidity associated with diabetic ketoacidosis
during pregnancy.
PULMONARY FUNCTION TESTS REMAIN
SIMILAR IN PATIENTS WHO RECEIVED
TECHNOSPHERE® INSULIN AND IN PATIENTS
CURRENTLY RECEIVING STANDARD
ANTIDIABETIC THERAPY
Objective: Previous controlled clinical studies
have demonstrated that regimens of basal insulin plus
Technosphere® Insulin (TI) were as effective as basal
insulin plus rapid-acting sc insulin in patients with diabetes. In previously reported studies, we have been unable
to detect a consistent change in pulmonary function tests
(PFTs). Small but clinically non-significant differences
have been observed. This clinical trial was designed to
assess the changes in pulmonary function after cessation
of TI therapy and resumption of standard antidiabetic
treatment in patients with type 1 or type 2 diabetes.
Methods: Adults with diabetes who participated in
any of 4 controlled clinical trials of TI were invited to participate in this follow-up trial to evaluate changes in PFTs
after completing the study and being switched to usual
antidiabetic therapy without TI. Patients were followed
for a total of 3 months after cessation of study therapy.
PFTs were assessed at the end of the parent trial and 1 and
3 months after subjects completed the parent trial.
Results: Of 649 patients in this study, 315 subjects
(121 with type 1 diabetes, 194 with type 2 diabetes)
received TI and 334 subjects (129 with type 1 diabetes,
205 with type 2 diabetes) received the antidiabetic regimen without prandial TI during the parent trials. Small,
non-progressive treatment group differences in mean
changes from baseline in forced expiratory volume in 1
second (FEV1) and carbon monoxide diffusing capacity
(DLCO) observed during the comparative phase of the controlled trials disappeared when comparing the 2 groups at
3 months after cessation of TI therapy and resumption of
standard antidiabetic therapy (FEV1: -0.08 L in the ex-TI
group, -0.11 L in the non ex-TI group [p=0.1388]; DLCO:
-1.29 mL/min/mm Hg in the ex-TI group, -1.37 mL/min/
mm Hg in the non ex-TI group [p=0.9360]), irrespective
of the duration of previous TI exposure. In addition, there
was no statistical difference in FEV1 between the 2 groups
when examining subjects with type 1 and type 2 diabetes
(p=0.6158 and p=0.1795, respectively).
– 53 –
Conclusion: These data suggest that the pattern and
magnitude of PFT changes associated with the use of TI in
subjects with type 1 and type 2 diabetes are not likely due
to any structural alterations in the lungs and are not clinically meaningful.
Abstract #268
DETERMINANTS AND CORRELATES OF DRUG
ADHERENCE AMONG TYPE 2 DIABETES
PATIENTS IN NORTHERN NIGERIA
Andrew Enemako Uloko, MD,
Aishatu A. Abubakar, FPC, Pharm,
Ayekame Tini Uloko, B. Pharm,
Fabian H. Puepet, MD, FMCP
found to be non-adherent in this study. The rather high
proportion of poor adherence observed in this study is in
keeping with findings from other similar studies despite
wide variation in methods. The predominant factors that
strongly correlate to adherence to therapy as in most
studies were quality of glycemic control, blood pressure
control, lifestyle measures and occurrence of drug side
effects.
Conclusion: The population of our type 2 diabetics
who are non-adherent to therapy is unacceptably high and
requires urgent intervention to prevent the growing consequences of uncontrolled diabetes mellitus. A large multicentre study in Nigeria to truly determine the extent of
adherence and its correlates is suggested.
Abstract #269
Objective: Data on adherence to therapy among
Nigerian type 2 diabetics is lacking hence the need for this
study. We aimed to determine the proportion of type 2 diabetic patients that adhere to drug therapy and associated
factors.
Methods: In a descriptive cross sectional study of
type 2 diabetics spanning twelve weeks at the diabetes
clinic of Aminu Kano Teaching Hospital, Kano, Nigeria,
patient adherence to drug therapy was evaluated. A pretested interviewer-administered questionnaire was utilized. A patient self-reporting model was applied to obtain
information on adherence. Data obtained include biodata,
relevant information on adherence, blood pressure, fasting plasma glucose and glycated haemoglobin (HbA1c).
Spearman’s correlation coefficient was used to determine
the correlates of adherence to therapy
Results: A total of 41 type 2 diabetics were recruited
14 (34.1%) males and 27 (65.9%) females. The mean age
of the patients was 52.20±11.93 years; males 49.00±10.08
years; females 53.85±12.64 years. A total of 11 patients
adhered to therapy with adherence rate of 26.8%. The
proportion of males and females adhering to therapy was
28.6% and 25.9% respectively with a male:female adherence ratio of 1.1:1. The mean HbA1c of the study population was 8.72±2.14% respectively. The mean HbA1c of
the adherent compared to the non-adherent patients was
6.42±0.69% and 9.56±1.85% respectively. The main
determinants of drug adherence included presence of drug
side effects, pill burden, drug counseling at the pharmacy,
and duration of consultation with the physician and the
presence of co-morbidities. Correlates of adherence to
therapy included quality of glycemic control (r = 0.91),
blood pressure control (r = 0.76), life style measures (r =
0.51) and drug side effects (r = 0.83).
Discussion: A significant proportion of type 2 diabetics in our setting are non-adherent to therapy. This is
reflected in the poor mean glycemic control of the patients
REDUCED INCIDENCE AND FREQUENCY
OF HYPOGLYCEMIA IN AN INTEGRATED
ANALYSIS OF POOLED DATA FROM CLINICAL
TRIALS OF SUBJECTS WITH TYPE 1 DIABETES
USING PRANDIAL INHALED
TECHNOSPHERE® INSULIN
Campbell P. Howard, MD, FACE, Hao Ren,
Alicia Rossiter, MD, FCP, Anders H. Boss, MD
Objective: Technosphere® Insulin (TI) is an ultra
rapid-acting insulin with a pharmacokinetic profile well
suited for earlier control of postprandial plasma glucose
(PPG). This integrated analysis includes the pooled data
from 3 phase 2/3 clinical trials in subjects with type 1 diabetes mellitus inadequately controlled (HbA1c >7.0% and
11.0%) with standard insulin regimens.
Methods: Subjects were randomized to 1 of 3 treatment regimens to achieve predefined glycemic goals: TI
(n=614) plus a basal insulin; sc insulin (n=599), which
included insulin glargine plus aspart; or “usual care,” with
insulin adjustments according to investigator discretion.
A structured titration regimen was not enforced. When
experiencing hypoglycemic-like symptoms, subjects were
instructed to confirm the event with a blood glucose reading. Subjects experiencing a severe hypoglycemic episode
were required to report the details of third-party assistance
(if needed), the presence of neurologic symptoms, and the
specifics of treatment.
Results: Mean baseline characteristics were similar
for TI and sc insulin (age 38.4, 38.5 years; disease time
since diagnosis 16.5, 16.6 years; baseline HbA1c 8.59%,
8.56%; BMI 26.12, 26.03 kg/m2). Subjects treated with
TI experienced fewer hypoglycemic events with regard
to both incidence and frequency, compared with subjects
treated with other sc insulins. For incidence, fewer subjects reported hypoglycemia with TI: 75.9% vs 81.0%
– 54 –
for total hypoglycemia (OR 0.749; p=0.0413), 75.6%
vs 80.8% for mild/moderate hypoglycemia (OR 0.743;
p=0.0354), and 24.3% vs 27.5% for severe hypoglycemia (OR 0.826; p=0.1576), with the comparison p values substantially in favor of TI for total hypoglycemia
and mild/moderate hypoglycemia. For frequency, TI had a
comparable (not statistically different) number of events,
evaluated by event rate (number of events per 100 subject-months): 138.60 vs 124.06 for total hypoglycemia
(p=0.9242), 133.16 vs 117.74 for mild/moderate hypoglycemia (p=0.9097), and 5.16 vs 6.03 for severe hypoglycemia (p=0.5901). When evaluated for those subjects with
blood glucose values ≤2 mmol/L, TI also was comparable
(not statistically different) to sc insulin treatment with a
lower event rate.
Conclusion: TI, in combination with a basal insulin,
consistently reduced the incidence of total and mild/moderate hypoglycemic events and had a lower frequency of
severe hypoglycemic events under conditions of comparable glycemic control.
Abstract #270
REDUCED INCIDENCE AND FREQUENCY
OF HYPOGLYCEMIA IN AN INTEGRATED
ANALYSIS OF POOLED DATA FROM CLINICAL
TRIALS OF SUBJECTS WITH TYPE 2 DIABETES
USING PRANDIAL INHALED
TECHNOSPHERE® INSULIN
presence of neurologic symptoms, and the specifics of
treatment.
for TI and sc insulin (age 56.2, 55.6 years; disease time
since diagnosis 10.8, 12.4 years; baseline HbA1c 8.82%,
8.84%; BMI 31.07, 31.07 kg/m2). Subjects treated with TI
experienced statistically significantly fewer hypoglycemic
episodes in regard to both incidence and frequency compared with subjects treated with sc insulins. For incidence,
significantly fewer subjects reported hypoglycemia with
TI: 31.8% vs 49.6% for total hypoglycemia (OR 0.466;
p<0.0001), 31.6% vs 49.4% for mild/moderate hypoglycemia (OR 0.466; p<0.0001), and 2.8% vs 7.5% for severe
hypoglycemia (OR 0.359; p<0.0001). For frequency, TI
also had significantly fewer events, evaluated by event
rate (number of events per 100 subject-months): 23.87 vs
38.78 for total hypoglycemia (p<0.0001); 23.16 vs 37.32
for mild/moderate hypoglycemia (p<0.0001); and 0.66 vs
1.37 for severe hypoglycemia (p<0.0184).
Conclusion: TI, often in combination with a basal
insulin, consistently reduced the incidence and frequency
of both mild/moderate and severe hypoglycemic events
under conditions of comparable glycemic control.
Abstract #271
AN UNUSUAL CASE OF EUGLYCEMIA
REQUIRING INSULIN
Nagashree Gundu Rao, MD, Shuchita Gupta, MD
Daniel Louis Lorber, MD, FACP,
Campbell Howard, MD, FACE, Hao Ren,
Anders H. Boss, MD
rapid-acting insulin with a pharmacokinetic profile that
may result in a lower rate of post-prandial hypoglycemia
when used as a prandial insulin. We explored this hypothesis by carrying out an integrated analysis of the pooled
data from 6 phase 2/3 clinical trials in subjects with type
2 diabetes mellitus inadequately controlled (HbA1c ≥6.6%
and £12.0%) despite insulin with or without oral antihyperglycemic therapy.
Methods: Subjects were randomized to treatment regimens to achieve predefined glycemic goals:
TI (n=1795) or sc insulin (n=942), which included BPA
70/30, or insulin aspart and “usual care,” with insulin
adjustments according to investigator discretion in 5 trials
and forced titration in 1 trial. A structured titration regimen was not enforced. When experiencing hypoglycemic-like symptoms, subjects were instructed to confirm
the event with a blood glucose reading. Subjects experiencing a severe hypoglycemic episode were required to
report the details of third-party assistance (if needed), the
Objective: To recognize and differentiate diabetic
ketoacidosis (DKA) in euglycemia from starvation
ketoacidosis.
Case Presentation: A 70 year old Korean woman
with a history of diabetes mellitus was admitted for an
elective intervertebral fusion for scoliosis. She was noted
to have anion gap metabolic acidosis in the post-operative
period with normal lactate levels. Her blood glucose levels remained below 150 mg/dl. She had altered consciousness from excessive opioid administration, which necessitated intubation and mechanical ventilation. Her anion
gap continued to rise, while her lactate and blood glucose
levels remained normal. She had moderate ketonuria and
was started on dextrose infusion for starvation ketosis.
However, her ketonuria and serum acetone levels continued to worsen, while her blood glucose levels never went
beyond 200 mg/dl. Her serum bicarbonate level dropped
from 15 to 10 mg/dl. The patient was then diagnosed with
euglycemic DKA and was started on insulin infusion
along with dextrose. Her anion gap of 25 closed completely and she was subsequently transitioned to subcutaneous insulin. Later, her previous course was reviewed
and she was found to have markedly reduced oral intake
after her surgery.
– 55 –
Discussion: Normoglycemia can occur in DKA due to
fasting. Euglycemic DKA is uncommon, reported in association with diabetes type 1 and starvation, or pregnant
women on insulin. This patient in contrast, is an elderly
type 2 diabetic with poor oral intake. In normal fasting
state, glycogenolysis, gluconeogenesis and fat metabolism, help maintain glucose homeostasis. Accumulation
of ketone bodies results in mild anion gap ketoacidosis.
The fasting state in diabetics leads to rapid depletion of
glycogen stores and the observed lower glucose values.
Also, the inhibitory effect of insulin on lipolysis and ketogenesis is lost. Accelerated ketogenesis and higher anion
gap metabolic acidosis is thus seen in DKA with fasting.
Euglycemic DKA can be differentiated from starvation
ketosis, by the presence of a precipitating cause, leading
to starvation and markedly lowered bicarbonate (less than
18 mg/dl), as in this patient. High anion gap metabolic
acidosis is not seen in isolated starvation ketoacidosis.
The failure of resolution of ketoacidosis till insulin and
glucose are given, confirms the diagnosis of euglycemic
DKA. Management includes correction of fluid and electrolyte abnormalities. Intravenous insulin with dextrose
need to be administered till the acidosis resolves.
Conclusion: It is important to recognize the occurrence of DKA without overt hyperglycemia, due to its
lethal complications.
Abstract #272
MAJOR DISCREPANCY IN FINGERSTICK
CAPILLARY GLUCOSE READINGS IN A
PATIENT WITH FINGER EDEMA
the patient but the patient remained unresponsive. A
venous blood glucose drawn at that time was found to be
19 mg/dl. The patient was given 3 ampules of 50% dextrose and her mental status returned to her baseline. Her
subsequent FS readings were 586 and 460 mg/dl with
serum glucose 392 mg/dl tested at same time. The AccuCheck glucometer used for FS testing was checked and
there was no malfunction noted. We reviewed patient’s
FS glucose readings with the laboratory supervisor and
attributed the discrepancy to patient’s edema in her fingers. We recommended the use of “alternate site” testing
i.e. obtaining capillary blood from sites other than the fingertips concomitantly with venous blood glucose testing.
Alternate site testing was done at the palm where there
was no edema. Alternate site testing at the palm correlated
well with venous blood glucose testing.
Discussion: In our case, we attributed finger edema
to be the primary reason for falsely elevated FS glucose
values. The likely explanation is that due to edema, the
capillary blood was diluted with tissue fluid which lowered the hematocrit resulting in falsely elevated FS glucose readings. In our case, point-of-care glucose testing by
alternate site method at palm correlated well with venous
blood glucose readings.
Conclusion: We conclude that in a patient with finger edema, glucose readings obtained from the fingertip
are not reliable and alternate site testing method should
be considered to assess the magnitude of hyperglycemia
before making important clinical decisions.
Abstract #273
Ankur Gupta, MD, Marina M. Charitou
Objective: Monitoring of blood glucose by fingerstick
method is a key element in the management of diabetes.
We describe an interesting case of finger edema leading to
markedly inaccurate fingerstick glucose readings.
Case Presentation: An 80 year old woman with diabetes mellitus type 2 for 39 years with neuropathy and
coronary artery disease was admitted for management of
atrial fibrillation. During her hospital stay, her fingerstick
(FS) glucose readings varied from 24 to 586 mg/dl. On
physical exam, she had mild edema on her finger tips but
no edema in her lower extremities. On the day of evaluation, the patient’s FS glucose reading before dinner was
245 mg/dl. At 10:17 pm, initial FS glucose reading was
46 and repeat was 231 mg/dl. At 1:45 am, the patient was
found to be unresponsive. The initial FS glucose reading
at that time was 426 mg/dl. The patient’s repeat FS glucose readings within several minutes of each other were
24, 204, and 272 mg/dl. The patient was not assumed to be
hypoglycemic and all measures were taken to resuscitate
KETOSIS-RESISTANT DIABETES MELLITUS
TYPE I: CHRONIC ALCOHOLIC
PANCREATITIS AS PROTECTION
AGAINST DIABETIC KETOACIDOSIS
Brittany Bohinc, MD, John Parker, MD, FACE, ECNU
Objective: To describe a case of a malnourished,
alcoholic presenting with features consistent with hyperosmolar hyperglycemic state (HHS), but shown to have
undetectable serum c-peptide and diagnosed with ketosisresistant diabetes mellitus (DM) type I.
Case Presentation: This is a 50-year-old white
female with history of uncontrolled DM type 2 diagnosed
11 years prior (treated with oral hypoglycemics, initial
c-peptide 3.0 ng/ml), chronic alcoholism, and anorexia
nervosa (BMI 13), who presented with generalized weakness, fatigue, polyuria, polydipsia, nausea and vomiting.
She had no abdominal pain. Lipase was normal at 164 U/L.
Her blood glucose measured 1965 mg/dL. Initial anion
gap was normal at 13. Osmolar gap was 21. Serum and
urine ketones were negative. Arterial blood gas revealed a
– 56 –
pH of 7.309 secondary to respiratory acidosis with normal
serum bicarbonate at 23 mmol/L. Hemoglobin A1c was
14.3%. She was initially diagnosed with HHS and was
placed on an insulin drip and aggressive IV hydration. She
had a history of ongoing alcohol use and elevated lipase,
so consideration was given to pancreatic DM and chronic
alcoholic pancreatitis. Because she was so malnourished
with BMI of 13, a contributing diagnosis of malnutritionmodulated DM (MMDM) was entertained. C-peptide was
<0.1 ng/ml. Anti-glutamic acid decarboxylase (anti-GAD)
and anti-islet cell antibodies were undetectable. Imaging
of the pancreas by computed tomography showed no dilation of pancreatic ducts or pancreatic mass but did show
severe pancreatic atrophy and calcification consistent
with chronic pancreatitis. A 2-hour glucose tolerance test
showed low c-peptide levels that were unable to be stimulated by glucose load and growth hormone levels that were
suppressed from baseline after 2 hours. Glucagon levels
after glucose load were low. The patient was diagnosed
with ketosis-resistant DM type I with hormonal features
consistent with chronic alcoholic pancreatitis.
Discussion: Ketosis-resistant DM type I is an underrecognized diagnosis in the developed world. There are
two clinical considerations including pancreatic DM (both
alcoholic and nonalcoholic/fibrocalculous pancreatic DM)
and malnutrition-modulated DM (MMDM). Our patient
had clinical features consistent with both chronic alcoholic pancreatitis and MMDM. Clinical features and hormonal workup as means of distinction will be described.
In this case, chronic alcoholic pancreatitis led to ketosisresistance because of destruction of both insulin and glucagon-producing cells of the islets of Langerhans.
Abstract #274
were recommended. Subsequent HgbA1c readings were
3.5%, 3.4% and 3.7% (at 4, 10, and 16 months after diagnosis, respectively). At time of consultation, blood glucose
readings demonstrated fasting hyperglycemia (glucose
105-120 mg/dL) and 2-hour post prandial measurements of
120-200 mg/dL. Our laboratory evaluation demonstrated
a total glycosylated hemoglobin of 5.7% (healthy adult
range of 3.9-7.3%), fructosamine of 255 µmol/L (normal
up to 285) and 1-5 anhydroglucitol of 7.1 µg/mL (normal
adult reference range 10.7-32.0). Hemoglobin electrophoresis revealed 50.9% hemoglobin variant pattern consistent
with hemoglobin Raleigh (substitution of acetylated alanine for valine as the N-terminal amino acid on the ß-chain
of hemoglobin), with only 46.6% of the total hemoglobin
comprised of hemoglobin A.
Conclusion: HgbA1c has been validated as an excellent indicator of long-term glycemic control in diabetes
mellitus, but there are several causes of misleading results,
including hemolytic anemia, medication effects, and hemoglobinopathies. A specific etiology should be sought under
these circumstances. In our case, erroneously low readings for HgbA1c can be encountered because the ß-chain
of hemoglobin Raleigh cannot be glycated. Alternative
methods of assessing glycemic control, such as measuring
1-5 anhydroglucitol, fructosamine, with ongoing reliance
on accurate capillary blood glucose measurements, were
recommended.
Abstract #275
ANTIOXIDANT EFFECT OF VITAMIN D ON
THE BETA CELL MAY CONTRIBUTE TO ITS
BENEFIT IN DIABETES THERAPY
Vasile Mihai Bota, MD, Zhengke Wang,
Fang Xiong, Hussain Naseri, MD,
Janet Cevallos-Brennan, MD, Kenneth A. Greer,
Luo Luguang, MD, PhD
HEMOGLOBIN RALEIGH: AN UNUSUAL CAUSE
OF LOW HEMOGLOBIN A1C MEASUREMENTS
IN TYPE 2 DIABETES MELLITUS
Objective: To describe a case of a patient with type
2 diabetes mellitus who, despite high capillary blood glucose readings, was found to have persistently low hemoglobin A1c (HgbA1c) measurements secondary to a rare
hemoglobin ß-chain variant, hemoglobin Raleigh.
Method: Case report and literature review.
Case Presentation: A 62-year-old white male was
diagnosed with diabetes mellitus approximately 16 months
prior to endocrinology consultation. Evaluation at diagnosis included 2-hour oral glucose tolerance test (fasting
glucose of 137 mg/dL, 1-hour glucose of 269 mg/dL, and
2-hour glucose of 263 mg/dL) and HgbA1c of 4.2% (reference range 4.1-5.7%). Dietary and exercise interventions
Objective: To evaluate the role of Vitamin D in
preventing beta cell oxidative stress and in promoting cell
survival and function.
Methods: INS-1 cell line, rat pancreatic beta cells
obtained from an Xray induced insulinoma were cultured
using RPMI 1640 medium, enriched with glucose,
pyruvate, mercaptoethanol, HEPES, penicillin and
streptomycin. Streptozotocin (STZ) was administered to
induce beta cell oxidative stress . We then explored whether
1,25-dihydroxyvitamin D at a physiologic concentration
can reverse beta cell oxidation in this model. Insulin levels
were checked with Rat/Mouse ELISA kit (Millipore,
EZRMI-13K), and the oxidative stress level was checked
by measuring the oxidation reduction potential (ORP)
with a 6230N JENCO meter.
– 57 –
Results: The supernatant was collected and analyzed
after 48 hours STZ and 1,25-dihydroxyvitamin D
treatment. STZ at 45uM decreased insulin levels by 74%
compared with control. Concomitant treatment with
1,25-dihydroxyvitamin D improved insulin secretion
by 13.9% (n=3, p<0.05). 1,25-dihydroxyvitamin D was
able to partially improve cell function after STZ induced
oxidative stress. We found that STZ alone increased
the oxidative stress measured through ORP by 22%
compared to control. After concomitant treatment with
1,25-dihydroxyvitamin D at a physiological concentration,
the level of oxidative stress induced by STZ was reduced
by half (n=4, p<0.05).
Discussion: Our previous study shows that 1,25dihydroxyvitamin D benefits pancreatic beta cell insulin
release and might improve diabetes outcome. We now
demonstrated that 1,25-dihydroxyvitamin D prevents the
oxidative stress induced by STZ in pancreatic beta cell
culture and improves pancreatic beta cell function after
STZ induced oxidative stress. More investigations are
needed in order to clarify the involved mechanisms.
Conclusion: Correcting Vitamin D deficiency in
diabetic patients is definitely beneficial for their clinical
outcome. The antioxidant effect of Vitamin D on the beta
cell may contribute to its benefit in diabetes therapy.
Abstract #276
ABRUPT ONSET TYPE 1 DIABETES MELLITUS
IN A HISPANIC WOMAN
acid decarboxylase antibodies 8.72 U/mL, IA-2 antibodies <0.8, TSH 1.88 mIU/L, amylase 54 U/L, and lipase 26
U/L. The patient was discharged on insulin glargine and
insulin lispro.
Discussion: Fulminant T1DM is a recently described
presentation of T1DM with rapid beta cell destruction and
subsequent development of hyperglycemia and ketoacidosis that has been predominately reported in Japan and
other Asian countries. The classical presentation includes
rapid onset of ketoacidosis within one week of symptoms
of hyperglycemia, with a near normal HbA1c and very
low level of c-peptide (fasting <0.3 ng/mL or non-fasting
<0.5 ng/mL). With the majority of cases being reported
from Asia, it has been hypothesized that there is a genetic
determinant that predisposes Asian individuals to develop
fulminant T1DM. In our patient, the rapid onset of ketoacidosis within one week, a near normal hemoglobin A1c,
and low level C- peptide were consistent with fulminant
T1DM. However, in our patient, the beta-cell destruction
was not complete at time of diagnosis, which thus failed
to meet the published criteria used in the Asian literature
to diagnosis fulminant T1DM. The slightly higher level
of c-peptide, though still insufficient, may reflect genetic
differences between Hispanic and Asian population.
Conclusion: Even though our patient did not fit the
strict laboratory criteria set in the Asian literature, she
did have the clinical presentation mimicking fulminant
T1DM. The addition of this case to the medical literature
supports the need for expanding research in the field of
fulminant T1DM.
Abstract #277
Robert Andrew McCauley, MD, Sundeep Dhillon, MD,
Xaingbing Wang, MD, PhD
Objective: To present a case of abrupt onset type 1
diabetes mellitus (T1DM) mimicking fulminant T1DM in
a young healthy Hispanic female.
Case Presentation: A previously healthy 18 year old
Hispanic female with no recent history of infections presented with one week of fatigue, polydipsia, polyuria and
weight loss. Routine blood work in the outpatient setting
showed elevated blood glucose of 934 mg/dL. Evaluation
in emergency department revealed the following laboratory values: sodium 133 mEq/L, potassium 3.9 mEq/L,
chloride 98 mEq/L, bicarbonate 10.5 mEq/L, blood urea
nitrogen 9 mg/dL, creatinine 1.1 mg/dL, with a calculated
anion gap of 24.5 mEq/L and arterial pH 7.24. Urinalysis
showed 3+ ketones and 3+ glucose. The patient was diagnosed with diabetic ketoacidosis and started on IV hydration and an insulin infusion at 0.1units/kg/hr. Within 12
hours her anion gap had closed and she was transitioned to
a basal/bolus insulin regimen. Additional laboratory evaluation showed: HbA1C 6%, C peptide 0.6 ng/mL, insulin
antibodies <0.4 U/mL, islet cell antibodies <1:4, Glutamic
SQUAMOUS CELLCARCINOMACOMPLICATING
CHRONIC DIABETIC FOOT ULCER
Innocent Onoja Okpe, MBBS, Muazu I. M. MBBS, FMCP,
Felicia Anumah, MBBS, FMCP
Objective: Malignant degeneration of ulcers and scars
has been recognized since the 19th century. Jean Nicholas
Marjolin first described an indolent ulcer arising in burns
scar in 1828. Malignant transformation of diabetic foot
ulcer though rare has been documented in literature as
well. This is a case report showing occurrence of this
malignant ulcer presenting as an ulceration of the foot.
Case Presentation: A 62 year old diabetic who was
diagnosed 2 years earlier was referred to our center with
an 11 month old non-healing right planter ulcer, following
a minor penetrating injury he sustained while walking bare
footed. On presentation he was chronically ill-looking
and cachectic, had mild pallor and there was evidence of
peripheral vascular disease. Glycemic control was fair. He
had a Wagners grade iv ulcer. Concerned at the patient’s
– 58 –
lack of response to conventional therapy, surgical evaluation was requested. X-ray of the foot showed osteopenia
but no periosteal reaction to suggest osteomyelitis. The
surgeons suggested wound debridement with incisional
biopsies and culture. He developed regional lymphadenopathy Biopsy results returned as a well differentiated
squamous cell carcinom.
Discussion: The exact cause of marjolins ulcer is
not known, but chronic irritation has been suggested as
a major factor leading to the initiation of carcinomatous
process . The exact duration of exposure to such irritation
required to cause a malignant transformation of a benign
ulcer is not clear, although most cases of malignant transformation reported in literature occur in long standing
ulcers of over 10 to 15 years. The patient reported here
had his ulcer for only 14 months before the diagnosis of
squamous cell carcinoma was made. The treatment option
for this patient was surgery and radiotherapy but there was
a delay in commencing either because of lack affordability
of the cost of treatment. He however finally had a BKA,
although he died a week after surgery from aneamia attributable to the malignant condition.
Conclusion: Malignancy should be considered in the
diagnosis of foot ulcers in patients with diabetes especially when they are chronic and refractory to conventional treatment.
Abstract #278
THE PREVALENCE OF VITAMIN B12 AND FOLIC
ACID DEFICIENCY IN DIABETIC PATIENTS IN A
GENERAL HOSPITAL
Helard Andres Manrique, MD, Pedro Alberto Aro, MD,
Rubelio Enrique Cornejo, MD, Miguel Pinto, MD,
Jose Solis, MD, Angel Escalante, MD
Objective: To determine the prevalence of vitamin
B12 and folic acid in diabetic patients.
Methods: A cross sectional study of 115 type 2 diabetes outpatients was performed at Arzobispo Loayza
Hospital during 2007. Deficiency of serum vitamin B12
and folic acid were defined as <211 pg/ml and <5.38 ng/
ml, respectively. Were excluded patients with kidney dysfunction, ongoing antifolate drugs, and pregnancy.
Results: The average age was 57.85 ± 8.51 years,
80% were female and the mean time of type 2 diabetes
was 7.52 ± 5.58 years; 64% were taken oral antidiabetic
medication (sulfonylurea, biguanide or both), 73% had
serum glucose >110 mg/dl and 66% hemoglobin A1c
>7%; 72% had vitamin B12 and 23% folic acid deficiency.
Discussion: Vitamin B12 deficiency in type 2 diabetes is very frequent in our population, the reason remains
unclear and further research needs in order to determine
the clinical implications of our findings.
Conclusion: Consequently Vitamin B12 measure
should be considered as a screening test and the differential diagnosis when managing diabetes comorbidities.
Abstract #279
FLATBUSH DIABETES:
NOT ALL DKA IS TYPE 1 DM
Naga M. Yalla, MD, Nicole Dombrowski, DO,
L. Raymond Reynolds, MD, FACP, FACE
Objective: To describe a case of ketosis-prone diabetes mellitus (KPD) in a South Asian male who presented
with diabetic ketoacidosis but was able to discontinue
insulin therapy five months later.
Case Presentation: A healthy 31 y/o male South
Asian graduate student presented to the student health
clinic with an unexplained 50 lb. weight loss over 6
months, polyuria and polydipsia for 2 months, and fatigue
with minimal oral intake for 5 days. His father had type
2 diabetes. Physical exam revealed a BMI of 20 kg/m2
and mild tachycardia. Blood glucose was 363 mg/dl, anion
gap was elevated at 20, bicarbonate was 10 (23-31), and
urinalysis revealed 4+ ketones. HbA1c was 15.4%. The
patient was diagnosed with DKA and starvation ketosis.
Given his hemodynamic stability, the patient was treated
as an outpatient with NovoLog 70/30®. Islet cell and glutamic acid decarboxylase antibodies were negative, and
C-peptide level was 7.1 ng/ml (1.0-4.4). Two months later,
the patient had markedly improved glycemic control and
occasional hypoglycemia requiring insulin dose reduction. At his five-month visit, insulin was discontinued
due to ongoing hypoglycemia and HbA1c of 6.1%. Three
months later, the patient remained euglycemic off insulin
therapy.
Discussion: In 1994, Banerji et al. described a subset of African-Americans who presented with DKA
without autoimmune markers and were eventually able
to discontinue insulin. This presentation of KPD was
termed Flatbush diabetes after the area in New York City
where the patients resided. KPD was thought to be prevalent only in African-Americans and Afro-Caribbeans.
However, case series reveal that KPD can affect multiple
ethnic groups, including South Asians. A widely utilized
classification scheme for KPD is the auto-immunity and
b cell function system proposed by Maldanado et al in
2006. Our patient was A-b+, indicating the absence of
b cell autoimmunity and the preservation of b cell functional reserve. Approximately 50% of these patients have
new-onset diabetes and develop DKA without a clinically
– 59 –
evident precipitating factor. Severe glucotoxic blunting of
an intracellular pathway leading to insulin secretion may
contribute to the reversible b cell dysfunction characteristic of A-b+ patients.
Conclusion: It is important to remember that not all
patients presenting with DKA have type 1 DM. KPD,
although previously rarely described in South Asians, is
increasingly being recognized in multi-ethnic populations.
Often, these patients are able to discontinue insulin therapy over time making appropriate recognition and close
follow-up extremely important.
Abstract #280
THE EFFECT OF METFORMIN THERAPY ON
VITAMIN D AND B12 LEVELS IN PATIENTS
WITH DIABETES MELLITUS TYPE 2.
mechanism of malabsorption, raising the question of
whether there is a similar relationship between metformin
and vitamin D levels in these patients. In addition, older
and elderly patients also suffer from diabetes mellitus type
2, and many are simultaneously afflicted with osteoporosis. If vitamin D was affected similarly to vitamin B12
by metformin, this population could be directly impacted.
Based on the results of this study, the relationship between
metformin use and vitamin B12 deficiency does not appear
to extend to vitamin D.
Conclusion: This study confirms vitamin B12 deficiency in metformin treated type 2 diabetic patients. This
study also suggests that vitamin D deficiency is not a clinical concern among metformin treated type 2 diabetics. In
addition, metformin does not negatively impact treatment
of vitamin D deficiency in these patients.
Abstract #281
Elizabeth Kos, MS, Mary Jo Liszek, MD,
Mary Ann Emanuele, MD, Ramon Durazo, PhD,
Pauline Camacho, MD
Objective: To determine the effect of metformin on
vitamin D and B12 levels in patients with diabetes mellitus type 2.
Methods: We conducted a retrospective chart review
of 706 consecutive patients with diabetes mellitus type 2
treated at the Loyola University Medical Center between
2003-2009. Statistical methods were used to show any
associations between various demographic, anthropomorphic, and biochemical measures.
Results: A total of 706 patients ranging in age from
20-93 with diabetes mellitus type 2 were identified for this
study. The mean age was 63 +/- 13 and the mean BMI
was 33.1. 34% of these patients were on metformin with
a mean dose of 1.5 g per day. 35% of these patients had
been diagnosed with osteoporosis or osteopenia. The
results of previous studies regarding metformin use and
vitamin B12 deficiency were confirmed with statistically
significant lower baseline vitamin B12 levels in those
on metformin therapy. This relationship was not shown
with vitamin D levels, as we found no difference in vitamin D levels regardless of metformin use and dose when
adjusted for age, sex, and BMI. Use of metformin also did
not adversely affect treatment of vitamin D deficiency in
this patient subset. As a secondary endpoint, we found that
those with osteoporosis had statistically significant lower
baseline vitamin D levels compared to those without when
adjusted for all variables, and metformin use did not affect
the treatment of vitamin D deficiency in these patients.
Discussion: Metformin is a widely used therapy for
the treatment of diabetes mellitus type 2. Various studies
have demonstrated a causal relationship between metformin use and vitamin B12 deficiency with a proposed
THE ASSOCIATION OF ENDOTHELIAL
DYSFUNCTION AND LEFT VENTRICULAR
DIASTOLIC DYSFUNCTION AND THE
PRESENCE OF COMPLICATIONS IN PATIENTS
WITH DIABETES MELLITUS TYPE 2
Zarina Guevarra Lorenzo, MD,
Maureen V. Valentin, MD,
Maria Honolina S. Gomez, MD
Background/Objective: Endothelial and diastolic
dysfunctions are common in patients with diabetes mellitus (DM) type 2 making them at higher risk for cardiovascular events. However, these 2 conditions may be clinically silent thus early detection is important. Hence, the
determination of the association of these two conditions in
DM type 2 patients is relevant.The main objective of this
study was to determine the relationship between endothelial dysfunction and left ventricular diastolic function in
patients with DM Type 2.
Methods: A total of 56 Filipino patients with DM
type 2 were included in the study who followed up at
the Department of Medicine, University of Santo Tomas
Hospital, Espana, Manila from June-October 2008.
Endothelial function, measured by flow-mediated dilatation of the brachial artery using ultrasound, was calculated in the two groups. Left ventricular diastolic function was assessed by classical methods of pulse and tissue
doppler imaging. Peak early (E) and late (A) transmitral
filling velocities, their ratio (E/A) and deceleration time
of the mitral E wave (DT), LV isovolumetric relaxation
time (IVRT) and pulmonary vein atrial flow reversal (Pa)
were all calculated by Doppler echocardiography. The
early diastolic mitral annular velocity (E’) and late diastolic mitral annular velocity (A’) were also measured
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Abstract #282
level below 7%. There was no significant decline in body
weight (P 0.07; Fig. 2). The basal insulin dosage showed
a nonstatistical decrease (P 0.08; Fig. 3). Glycemic excursions also declined significantly after patients were started
on CSII (Fig. 4). Hypoglycemic episodes were noted in
only two patients <60mg/dL. However, no episodes were
reported to required assistance or hospitalization.
Discussion and Conclusion: In our study, eight out
of ten patients had an improvement in plasma glucose
concentrations with a fall in A1c levels and three patients
achieved A1c goal of <7%. CSII resulted in improvement
of A1c and potential reduction in diabetes-related complications. CSII is an alternative option for patients with
T2DM who have not met glycemic control goals with use
of standard insulin regimen.
USE OF INSULIN PUMP IN TYPE 2 DIABETES
Abstract #283
Nitin Trivedi, MD, Pearl Dy, MD,
Patachaya Boonchaya-anant, MD
HYPOGLYCEMIA IN PATIENTS WITH TYPE
1 DIABETES MELLITUS INCORPORATING
PRANDIAL INHALED TECHNOSPHERE-INSULIN
INTO THEIR USUAL ANTIHYPERGLYCEMIC
REGIMEN VS CONTINUING THEIR USUAL
ANTIHYPERGLYCEMIC CARE
using tissue Doppler imaging (TDI). The E’/A’ ratio was
calculated.
Results: A total of 17 (30%) had endothelial dysfunction. E’/A’ and Pa were positively correlated with
FMD with (r= 0.325, p =0.015) and (r= 0.248, p= 0.036),
respectively. FMD negatively correlated with HbA1c (r =
-0.374, p = 0.005) regardless of the presence or absence of
microvascular complications.
Conclusion: Flow-mediated dilatation is negatively
associated with HbA1c regardless of the presence or
absence of microvascular complications. It is likewise
correlated with several parameters of diastolic dysfunction such as E’/A’, Pa and IVRT.
Objective: Despite availability of large numbers of
antidiabetic agents in the United States, about 67% of
patients with type 2 diabetes mellitus (T2DM) are unable
to achieve glycosylated hemoglobin A1c (A1c) below the
American Diabetes Association target of less than 7%.
Ideally the multiple dose insulin regimen should mimic
the physiologic insulin secretory pattern. Even after using
basal bolus regimen with analogue insulin mimicking
endogenous insulin secretion may not be possible. Insulin
delivery using continuous subcutaneous insulin infusion
(CSII) using insulin pumps is perhaps the closest to the
physiological insulin secretion. CSII is well accepted way
for insulin treatment in patients with type 1 diabetes mellitus (T1DM). In this retrospective analysis we studied the
efficacy of insulin pumps in patients with T2DM in an outpatient setting who are unable to achieve optimal glucose
control despite multiple subcutaneous doses of insulin.
Methods: In this study we preformed analysis of data
by reviewing patient charts. From the database of our
patients we found that 10 patients T2DM (6 men and 4
women) were started on an insulin pump. All oral antidiabetic medications were discontinued with the exception of
metformin when the patients were started on CSII. During
the first 4-8 weeks, the pump settings were adjusted every
1-2 weeks. Thereafter the patients were encouraged to
follow every 2-3 months with their endocrinologist. The
pump adjustment was performed only by one endocrinologist for all the patients. Efficacy was assessed using
HbA1c values and blood glucose profiles. Glycemic
excursions and hypoglycemic episodes before and up to 6
months of starting on an insulin pump were analyzed.
Results: A1c showed significant decline from baseline (P 0.03; Fig. 1). Three patients achieved HbA1c
Philip Raskin, MD, FACE, Martin Phillips, MD,
Ping-Chung Chang, MS, Alicia Rossiter, MD,
Peter C. Richardson, MD
rapid-acting inhaled insulin with a pharmacokinetic profile well suited for control of postprandial plasma glucose.
This is to report the results of prespecified secondary
safety endpoints from MKC-TI 030, a prospective, multisite parallel-group study comparing the efficacy and safety
of prandial TI vs usual diabetes care (UC) in patients with
type 1 diabetes mellitus and inadequate glycemic control
(HbA1c 6.6% and £12.0%) despite subcutaneous insulin
therapy.
Methods: Subjects with type 1 diabetes were randomly assigned to a 2-year diabetes treatment regimen
consisting of prandial TI plus subcutaneous basal insulin
(TI group, n=267) or usual diabetes treatment regimens
of any insulin (subcutaneous basal and/or prandial), the
UC group (n=271). Insulin doses were adjusted according to investigator discretion to achieve glycemic goals
established by the American Diabetes Association and the
American Association of Clinical Endocrinologists; they
were not instructed to follow a protocol-specified insulin
dose titration regimen. Prespecified endpoints included
change in HbA1c, change in body weight, and frequency
of defined mild, moderate, and severe hypoglycemia.
between the TI and UC groups: mean age 40.0, 39.4 years;
– 61 –
diabetes duration 15.7, 15.1 years; baseline HbA1c 8.7%,
8.5%; and BMI 26.3, 26.3 kg/m2, respectively. The average daily dose in the TI group was 138.3±61.6 U (roughly
20% bioavailability relative to rapid-acting analog). Basal
insulin therapies were similar in both groups. At the 2-year
time point, there was comparable reduction in HbA1c (by
0.29% and 0.31% in the TI and UC groups, respectively).
TI resulted in weight loss, while UC resulted in weight
gain (-0.59 vs +1.38 kg, respectively; p=0.0007). Overall
event rates were 0.86/subject-month for the TI group (2.36
severe events/100 subject-months) vs. 0.70 for the UC
group (3.76 severe).
Conclusion: Diabetes treatment regimens containing
prandial TI resulted in HbA1c reductions that were comparable, weight loss, and less hypoglycemia in patients with
type 1 diabetes mellitus and inadequate glycemic control
compared with conventional diabetic regimens utilizing
subcutaneous prandial insulin.
Abstract #284
ASSOCIATION OF GENETIC POLYMORPHISMS
OF THE PLATELET GLYCOPROTEINS AND
PLATELET RECEPTORS WITH ASPIRIN
RESPONSIVENESS IN THAI TYPE 2 DIABETES
Wallaya Jongjaroenprasert, MD,
Aruchalean Taweewongsoontorn, Napatorn Artchararit,
Katcharin Ar-urachai,
Boonsong Ongphiphadhanakul, MD
SNP with aspirin non-responder was assessed by comparing the allele frequencies of each SNP using chi-square
analysis. Then the associated SNPs from test cohort were
confirmed in the validation cohort. All subjects received at
least 60 mg of ASA.
Results: Six subjects in the test cohort were aspirin
responders (6.2%), and 66 subjects were non-responders
(68%). Most of the subjects with aspirin non-responders were male (83.3%vs48.8%, p=0.04), and had higher
hemoglobin levels (14.2+0.5vs12.9+0.1 g/dl, p=0.03), and
greater waist to hip ratio (0.96+0.02vs0.90+0.01, p=0.02).
Higher frequency of T allele of c.1138T>C of TBXA2R
was found in subjects with ASA non-responder defined by
AA criteria (0.97vs0.80, p=0.03) in test cohort. This finding was subsequently confirmed in the validation cohort
(0.86vs0.74, p=0.02). Subjects with TT genotype had
significantly greater platelet aggregation induced by AA
than those with CT and CC genotype. TBXA2R encodes
thromboxane receptor, therefore our finding was biological plausible.
Conclusion: We demonstrate the association of
higher hemoglobin levels, male gender, central obesity
and T allele of c.1138T>C of TBXA2R gene with aspirin
resistant state in Thais. This finding may be useful for the
pharmacogenetic test before prescribing aspirin to the
high risk patients.
Abstract #285
Objective: Underlying genetic background has been
proposed for aspirin responsiveness. This study was to
examine the genetic susceptibility to aspirin response in
Thai type 2 diabetes patients.
Methods: Two cohorts of subjects from Ramathibodi
Hospital were recruited; the test and the validation group.
Ninety seven of diabetic patients were recruited as the test
cohort and 204 subjects with coronary disease were the
validation cohort. All received aspirin for at least 2 weeks
prior entering our study. Response to aspirin was assessed
using the optical platelet aggregation test induced by 10
µM adenosine diphosphate (ADP) and 0.5 mg/ml arachidonic acid (AA). From the aggregation results, responder,
semi-responder and non-responder to aspirin were defined
according to Gum’s cut-off criteria (% aggregation by
ADP >70%, % aggregation by AA >20%). Four single
nucleotide polymorphisms (SNPs) of platelet glycoproteins and platelet receptors (c.893C>T of P2Y1 gene, the
Kozak T>C polymorphism at -5 position, and variable
number of tandem repeats of GP1BA, and c.1138T>C of
TBXA2R) were genotyped individually in test cohort. The
correlation of clinical parameters and aspirin responsiveness was analyzed by unpaired t-test. The association of
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PROFILE OF NIGERIANS WITH
DIABETES MELLITUS
Andrew Enemako Uloko, MD, Esther Ofoegbu, FWACP,
Anthonia O. Ogbera, FMCP, FACE,
Sunday Chinenye, MBBS, FWACP,
Adesoji Fasanmade, FWACP,
Ogugua Osi-Ogbu, FWACP
Objective: Diabetes mellitus (DM) is the commonest
metabolic condition and one of the most prevalent noncommunicable diseases in Nigeria. There is paucity of
data on the actual prevalence of DM, its complications,
and quality of care. We aimed to assess the clinical and
laboratory profile, and evaluate the quality of care of
Nigerian diabetics.
Methods: In a multicentre study spanning 6 months
across seven tertiary health centers (diabetes clinics) in
Nigeria, the clinical and laboratory parameters of diabetics were evaluated. Some clinical parameters studied
include type of diabetes, anthropometry, history of hypertension, dyslipidaemia, blood pressure (BP), chronic complications of DM and treatment types. Laboratory data
assessed included fasting plasma glucose (FPG), 2-hour
post-prandial (2-hr pp) glucose, glycated hemoglobin
(HbA1c), urinalysis, serum lipid profile, electrolytes, urea
and creatinine.
Results: A total of 531 patients; 39.5% males and
60.5% females enrolled. The mean age of the patients
was 57.1±12.3 years with mean duration of DM 8.8±6.6
years. Majority had type 2 DM (95.4%) compared to type
1 DM (4.6%), p < 0.001. The mean FPG, 2-hr pp glucose and HbA1c were 8.1±3.9 mmol/L, 10.6±4.6 mmol/L
and 8.3±2.2 % respectively. Only 170 (32.4%) and 100
(20.4%) patients achieved the ADA and IDF targets
respectively. Most of the patients do not have glucometers (72.8%) and never practice self monitoring of blood
glucose (73.2%). Concomitant hypertension was found in
322 (60.9%), mean systolic BP 142.0±23.7 mmHg, diastolic BP 80.7±12.7 mmHg. Chronic complications of
DM found were peripheral neuropathy 59.2%, retinopathy
35.5%, cataract 25.2%, stroke 4.7%, diabetes foot ulcers
16.0%, and nephropathy 3.2%.
Discussion: Diabetes mellitus in Nigeria is now an
epidemic with numerous clinical and social consequences.
The poor quality of glycemic control observed in this study
is not different from other parts of the world where similar
studies were carried out recently. As in most resource-constrained third world countries, availability and ownership of
personal glucose meters by our ever-increasing number of
diabetic patients for their self monitoring of blood glucose
remains a practical challenge. More advocacies by professional bodies and non-governmental organizations as well
as funding for diabetes care and education will improve the
quality of life of Nigerian diabetics substantially.
Conclusion: Most Nigerian diabetics have suboptimal glycemic control, concomitant hypertension
and chronic complications of DM. Improved quality of
care and treatment to target is recommended to prevent
DM-related morbidity and mortality.
Abstract #286
KNOWLEDGE, ATTITUDE AND PRACTICE
AMONG NEWLY DIAGNOSED BANGLADESHI
T2D SUBJECTS ATTENDING VARIOUS
DIABETES CARE CENTERS
Methods: A total of 289 newly diagnosed T2D subjects (male 46%, female 54%, age 45+9 years, mean +SD)
were selected from different health care centers of Capital.
Data were collected by a pre-designed, pre-tested, interviewer-administered questionnaire. The responses regarding all knowledge and practice were coded as 1 (correct
ans) and 0 (wrong ans). Five point Likert scale was used
to assess attitude.
Results: The score of kAP among the study subjects
were 23±5, 126±9 and 11±3 (mean ±SD) respectively.
KAP scores did not differ in various age, sex and habitat groups. Compared to the illiterate group (19.02±4.3)
the knowledge score was higher in primary (21.7±4.3,
p<0.0001), secondary (24.3±4.5, P<0.0001) and graduate (25.7±3.7, p<0.0001) groups. Practice score of illiterate group (9.5±3.3) was lower than the graduate group
(11.4±3.1, p<0.01). Attitude did not differ between any
two of the four educational groups. The score of knowledge regarding diabetes were significantly positively
correlated with attitude (r= 0.18, p=0.002) and practice
(r=0.42, p=0.0001) score. Age, sex, education, occupation, monthly income, location and family history of
diabetes and acquisition of information were tested in
a multiple regression model with the KAP score values
as dependent variables entered separately. None of the
independent variables, except education and acquisition
of information, showed any significant association with
KAP scores. Education (ß= 0.39, p=0.0001 and ß= 0.17,
p=0.007 respectively) showed a significant positive association with knowledge and practice score. Acquisition of
information had also significant association with knowledge (ß= 0.18, p=0.001) and attitude score (ß= 0.14,
p=0.01). A significant association was found between total
practice and knowledge score (β= 0.42, p= 0.0001) in this
model.
Conclusion: Education and acquisition of information seem to be the most important determinants of
knowledge which, in turn, is the main factor behind good
attitude and practice. A coordinated development policy
is required to promote knowledge and attitude on healthy
lifestyle and to translate those into practice.
Abstract #287
Fazlarabbi Khan, MBBS, Prof, MD,
Faruque Pathan, MBBS, MD, FACE,
Anisur Rahman, MD
Objective: Evidence based design of diabetes education programs need an understanding of the knowledge,
attitude and practice (KAP) of the respective community.
The aim of the present study was to study the levels of
KAP of the newly diagnosed type 2 diabetic subjects in
the context of demographic and socioeconomic factors
associated with the subjects.
PREVALENCE OF DIABETIC NEUROPATHY IN A
HOSPITAL POPULATION OF 2,031 PATIENT FOR
A PERIOD OF 18 YEARS
Zdravko Asenov Kamenov, MD, PhD,
Rumyana Parapunova, MD, Rumyana Georgieva
Objective: To evaluate the prevalence of diabetic neuropathy DN in a hospital population with diabetes (DM) in
a time course of 18 years.
– 63 –
Methods: This retrospective study was carried out
in a University clinic of endocrinology in the Medical
University in Sofia. Analysis of the patient hospital records
was applied. The time interval covered 1990-2007 years
divided in four periods, starting every 5 years and lasting
for 3 years. The patients were included in the electronic
database only during their first admission to the hospital. Presence of DN was accepted if one of the following
was present: final diagnosis “DN” and/or symptoms of
DN and/or positive instrumental investigation including
EMG.
Results: 2,031 records were analyzed - DM2/DM1 =
83.9/16.1%; female/male = 1130/901; mean age (mean ±
SD) = 55,6 ± 15,7 (DM2 = 60,0 ± 11,9; DM1 = 32,9 ± 13,4)
years; mean diabetes duration of 9,9 ± 8,8 (9,9 ± 8,4 and
10,2 ± 10,9 respectively) years. There was no difference in
HbA1c by gender and type of diabetes. The prevalence of
DN was 75.7% (DM2 = 78.8; DM1 = 59.2; p<0.001), differing in the course of the periods, and correlating significantly with the rate of application of EMG and semi-quantitative instrumental somatic neuropathy diagnostic tests
(modified Neuropathy Disability Score) and/or the test
for sudomotor autonomic dysfunction - Neuropad. When
analyzing the abnormal results of EMG we found out that
the sensory disturbances were most common (91,2%), followed by the motor ones (77,0%) and the combination of
sensory and motor disturbances (76,3%). Least common
was the mononeuropathy (8%). Patients with DM2 and
DN were about 4 years older (60.8 ± 11.5), compared to
those without DN (56.8 ± 13.2; p<0.001). This age difference was 8.8 years in patients with DM1 (36.5 ± 14 vs.
27.7 ± 10.6; p<0.001). Groups with and without DN did
not differ in HbA1c (9.0 ± 2.1 vs. 9.2 ± 2.4%).
Discussion: Data about prevalence of DN worldwide
differ from 10 to 90% depending on the population and
diagnostic criteria. The prevalence of DN in our study was
in the higher range because of the broad diagnostic criteria
including EMG, hospital population, poor diabetes control. In the community DN is largely neglected by both the
physician and the patient, complaining usually on positive symptoms like pain, but not on the loss of sensation,
which represents the actual risk for amputation. Careful
neurological examination is essential for early recognition
and more effective treatment of DN.
Conclusion: DN has a high prevalence, but for its
identification a complex diagnostic approach including
instrumental methods, is necessary.
Abstract #288
EFFICACY OF SALSALATE IN BRACHIAL
FLOW-MEDIATED DILATION IN DIABETES
Noushin Khalili Boroujeni, MD,
Elham Faghih Imani, MD, Masoud Amini, MD,
Shaghayegh Haghjoo, MD, Mohamad Saadatnia, MD
Objective: Obesity and fat deposition in tissues along
with inflammatory response may induce insulin resistance
and finally type 2 diabetes mellitus Salsalate, a prodrug
form of salicylate can inhibit IKKβ and NF-kappaB
inflammatory pathway as a potential pharmacologic target in diabetes. The aim of this study was to determine
the efficacy of salsalate as an anti-inflammatory drug to
resolve endothelial dysfunction in diabetic patients.
Methods: This was a double blind controlled trial
study. Forty newly diagnosed type 2 diabetic patients (30
to 45 years of age) were randomized in the drug and placebo groups. The drug group received 3g Salsalate per day
(two 750 mg tablets every 12 hours orally) for one month.
The placebo group received identical placebo. Fasting
plasma glucose level was assessed in two groups before
and after treatment period. Endothelial function was
assessed via flow mediated dilation (FMD) of the brachial
artery following reactive hyperemia before and after treatment period in two groups.
Results: Thirteen patients in the drug group and 15
ones in the placebo group finished the study. At baseline,
there was no significant difference in mean fasting plasma
glucose level (120 vs. 122 mg/dl, P = 0.621) and FMD
(10.5 ± 5.2 vs. 10.2 ± 5.4%, P= 0.19) between drug and
placebo groups, respectively. Salsalate reduced the fasting
glucose level in the drug group (18mg/dl) significantly, in
comparison with the placebo group (P < 0.05). At the end
of the trial, FMD in the salsalate and placebo group was
11.5 ± 5.6 vs. 10.1 ± 5.3%, respectively (P = 0.09).
Discussion: This study showed that daily use of 3
grams salsalate for one month reduced 15.5% of baseline
blood glucose level in diabetic cases. However, endothelial dysfunction did not change significantly. It might be
because of the short duration of the study. We suggest further studies with longer treatment duration and controlling other factors of insulin resistance, should be done to
investigate the role of salsalate in resolving the endothelial
dysfunction in diabetic patients.
Conclusion: These data demonstrate that salsalate
improves glucose homeostasis, but endothelial dysfunction did not change.
– 64 –
Abstract #289
cell function. We conclude that A1c overestimates glycemic burden in black subjects, and may be inappropriate for
diagnosis of diabetes in that population.
HBA1C AS A PREDICTOR OF GLYCEMIC
BURDEN IN AFRICAN AMERICANS AND
CAUCASIANS
Abstract #290
Samuel Dagogo-Jack, MD, FACE,
Chimaroke Edeoga, MD, MPH,
Nonso Egbuonu, MD, Emmanuel Chapp-Jumbo, MD
IMPACT OF A NIGERIAN TERTIARY DIABETES
CENTER ON PSYCHOSOCIAL DISTRESS IN
TYPE 2 DIABETES MELLITUS PATIENTS
Objective: There is emerging data on ethnic disparities in the relationship between A1c and glycemic burden
among subjects with diabetes or pre-diabetes. However,
it is not known whether such disparities extend to healthy
nondiabetic subjects or whether genetic risk for diabetes
plays a role. We therefore analyzed A1c levels in relation
to glycemia and glycemic predictors in our unique cohort
of nondiabetic African Americans (AA) and Caucasians
(C) who are offspring of diabetic parents.
Methods: We studied 234 subjects (104 C, 130 AA),
all of whom have a parental history of type 2 diabetes.
None of the subjects had a history of diabetes or prediabetes, or use of medications that alter glucose metabolism. Each subject underwent standard anthropometric
measurements (weight, height, waist circumference) and
completed a 75g Oral Glucose Tolerance Test (OGTT)
after an overnight fast and had a second measurement of
fasting plasma glucose (FPG) ~45 days from the date of
OGTT. Blood glucose and insulin levels were assessed at
fasting, 30min and 120min, and HbA1c levels were also
measured. The area-under-the-curve (AUC) for glucose
during OGTT was determined by the trapezoidal rule, and
insulin resistance and b-cell function were assessed using
the homeostasis model (HOMA) method.
Results: The mean (+ SD) HbA1c level was 5.63
+ 0.48% in African Americans and 5.45 + 0.33% in
Caucasians (P <0.0001). The African American and
Caucasian subjects had similar FPG values (mean + SD:
91.9 + 6.20 mg/dl vs. 93.6 + 6.00 mg/dl, P = 0.12), BMI
(BMI AA 31.2 + 7.30 vs. C 28.2 + 6.50 kg/m2, P = 0.10)
and waist circumference (94.6 + 14.4 vs. 91.3 + 15.3 cm,
P = 0.081). Both groups also were similar in age (AA 42.8
+ 9.5 y, C 47.3 + 10y, P=0.06) and had identical values
for HOMAR-IR (AA 2.03 + 1.78, C 2.04 + 1.66] and
HOMA-B (AA 1.87 + 1.35, C 1.86 + 1.54), Notably, the
Glucose AUC was significantly lower in black than white
subjects (14,882 + 1847 mg/dl/T vs. 15,651 + 1908mg/
dl/T, p = 0.016). In a multivariate model, the racial difference in A1c remained significant (P = 0.0006) after adjusting for BMI, age, FPG, HOMA-IR, and HOMA-B.
Conclusion: Among healthy subjects at similar
genetic risk for diabetes, we found that African Americans
had significantly higher A1c levels than Caucasians,
despite similar FPG, 2hPG, insulin sensitivity and beta
Itunuoluwa Yewande Oshungbohun, MBCHB,
Adekunle Adeyemi-Doro, MBBS,
Olufemi Fasanmade, MBBS, FWACP, FACE
– 65 –
Objective: To assess the level of impact of a tertiary
diabetes centre on the psychosocial distress of patients
with type 2DM
Methods: A Cross sectional study was carried out in
the DM clinic of the Lagos University Teaching Hospital
Nigeria, a tertiary health care centre with two sample
groups of 25 patients each (T2DM patients). The first
group comprised of newly referred patients (NRP) and
the second of patients with regular clinic attendance for
> 1year (RCA). Baseline demographic data: age, gender,
and duration of DM were obtained. The Diabetes Distress
Scale questionnaire assessing DM specific psychosocial
burden with four subscales “emotional burden, physicianrelated distress, regimen-related distress and interpersonal
distress” was administered to both groups. The data was
analyzed using SPSS version 16. Statistical significance
was set at p < 0.05.
Results: Demographic properties between the two
groups were similar. The NRP group had a mean age of
55.3 (+\- 8.25) while the RCA group had mean age of 57.1
(+\- 7.4) p=0.42. The mean duration of diabetes in years
in both groups was 8 (+\-6.9) and 7 (+\-6) respectively
(p=0.6). The Diabetes distress score (polonsky et al 2005)
was assessed, the overall mean score for the NRP group
was 2.0 (+\- 1.03) the RCA group had a distress score of
1.8 (+\-1.2) (p=0.5). In the sub-analysis of the four subscales the RCA group had higher mean “emotional burden” (RCA 2.7 (+/-1.1) vs. NRP 2.3 (+/- 1.5), P=0.29) and
“regimen-related distress” (RCA 2.3 (+/-1.5) vs. NRP 2.1
(+/- 1.4), P=0.6), mean “physician-related distress” was
higher in the NRP population (NRP 2.0(+/-1.4) vs. RCA
1.8(+/-1.2),P=0.6), while “interpersonal distress” was
equal in both sample groups (NRP 2.0 (+/-1.3), RCA 2.0
(+/-1.2) P =1), with no statistical difference between the
two groups in any of the subscales.
Discussion: Tertiary centers are expected to have
more effective diabetes care in comparison to primary and
secondary centers. However in this study overall distress
in the NRP and RCA had no statistical significant difference. Overall it may be possible that different factors
cancel out against each other resulting in the non-significant differences in distress.
Conclusion: This study shows no significant difference in diabetes related distress between new and older
patients of a tertiary DM clinic in Nigeria. Evaluating the
effect of different care system components on diabetes
distress between primary and secondary clinics against
tertiary clinics may shed further light on the causes of psychological distress in diabetes patients.
Abstract #291
ALLERGIC REACTION TO INSULIN IN A
TYPE 2 DIABETIC WITH NEWLY DIAGNOSED
PANCREATIC CARCINOMA TREATED WITH
ANTI-MUC1 HUMANIZED ANTIBODY AND
GEMCITABINE.
Conclusion: This case illustrates a very important
point. The first line management of insulin allergy is to
switch insulin to a different preparation. In this case, most
allergic reactions were most likely IgE mediated. Whether
this new onset reaction was triggered by pancreatic cancer
or chemotherapy is unknown. However, the timeframe of
the events may suggest some association. To our knowledge, this is the first case of a new onset insulin allergy in
the setting of a newly diagnosed pancreatic adenocarcinoma treated with anti-MUC1 Humanized Antibody and
Gemcitabine.
Abstract #292
THE PHENOTYPE OF NEWLY-DIAGNOSED TYPE
2 DIABETES MELLITUS AMONG FILIPINOS
Gerry H. Tan, MD, FACP, FACE,
Evangeline P. Costelo, MD, Roselyn E. Sialongo, MD
Juan Pablo Brito, MD, Anup Sabharwal MD, CCD
Objective: Insulin is the mainstay of therapy in Type
1 diabetics and more resistant Type 2 diabetics. Insulin
allergy is one of the most serious reactions associated
with insulin therapy. After the introduction of recombinant
human insulin preparations, insulin allergy became very
uncommon, particularly in patients with Type 2 diabetes.
Multiple endogenous and exogenous risk factors have
been associated with insulin allergy; however, there is no
medical literature about the possible association between
solid tumors, chemotherapy and insulin allergy. We report
a case of a Type 2 diabetic that developed an allergic reaction to insulin after being diagnosed with pancreatic cancer and treated with anti-MUC1 Humanized Antibody and
Gemcitabine.
Case Presentation: This is a case of a 64-year-old
woman with a past medical history of asthma, and Type
2 diabetes since 1997. She was initially treated with
Metformin and Glipizide, as well as Pioglitazone, and
then had to be transitioned to subcutaneous insulin therapy in 2007. In June 2008, she was found to have a nonresectable pancreatic carcinoma and since then, received
anti-MUC1 humanized antibody and Gemcitabine.. After
week number one post completion of cycle#1, she started
to develop subcutaneous nodules, urticaria, and pharyngitis to insulin Glargine injections. She was also challenged
with Novolin R, Novolog, Novolin N, Insulin 70/30, and
found to have similar reactions. Finally, she was placed on
regular insulin before meals and at bed time, and had an
excellent response. During this time, she has maintained
an acceptable glycemic control with an A1c of 7, and
without microvascular or macrovascular complications.
Objective: The study aimed to know the phenotype of
newly-diagnosed type 2 diabetes mellitus among Filipinos
using HOMA-IR index to determine insulin resistance and
using C peptide to determine beta cell function or insulin
secretion.
Methods: A cross sectional study conducted at a diabetes center in a tertiary hospital from January 2006 to
March 2009.
Results: There were 209 newly-diagnosed type 2 diabetes patients in this study (145 female and 64 male; mean
age 56 years; 107(51%) with normal BMI and 103(49%)
were overweight to obese). All patients were drug-naïve.
The mean HbA1c was 8.7% at the time of diagnosis.
Fasting insulin and glucose were used to compute for
HOMA index of insulin resistance. The C peptide level
determination was also used to assess the insulin secretion
of pancreatic beta cell. Four (2%) subjects had a C peptide
< 1 ng/ml, 12 (6%) subjects had a C peptide > 5 ng/ml
and 193(92%) of the subjects with newly-diagnosed diabetes have normal C peptide level (1 to 5 ng/ml) suggesting adequate normal insulin secretion. Among the subjects
with normal C peptide, 141 of the subjects (67%) were
insulin resistant based on HOMA index on diagnosis and
52 subjects (25%) remained insulin sensitive.
Conclusion: This study shows that most Filipinos
with newly diagnosed type 2 diabetes are insulin resistant
but has adequate insulin reserve. The study has major clinical implication in the way we approach and select medications for our newly diagnosed patients.
– 66 –
diagnostic algorithm when conventional imaging studies
fail to reveal the ectopic source. This may result in cure
of the Cushing syndrome and avert the need for bilateral
adrenalectomy or the use of poorly tolerated medical therapy, such as keotconazole.
Abstract #129
PROTRACTED RECOVERY DURING THE
POST-OPERATIVE COURSE IN A PATIENT
WITH ATYPICAL PRESENTATION OF
PHEOCHROMOCYTOMA
Wei-An Lee, DO
Objective: To demonstrate a complicated followup course in a patient with an atypical presentation of
Pheochromcytoma.
Case Presentation: 24 year old male referred for
consultation regarding fatigue with associated dizziness
and weakness. He has had previous episodes of irregular
heart beat in the lasting 5 years. Workup by cardiologist
had been unremarkable. He was placed on beta blocks
empirically. He stated that he has never “felt right.”
Patient reported a presyncopal episode at Disneyland 1
month prior to consultation. During that episode, he had
palpitations, hypotension, and dizziness. Since that episode, he had been feeling extremely fatigued with nausea. He had a cardiology workup again which was unremarkable. Family history remarkable with mother with a
prolactinoma. Weight: 151, Ht: 64 inches, BP: 125/68, P:
75. Physical exam unremarkable. 24 hour urine studies:
epinephrine, urine: 5 mcg/24 hours (2-24) Norepinephrine,
urine: 807 mcg/24 hour (12-86) Dopamine, urine: 319
mcg/24 hours (88-420) Catecholamine, total: 813 mcg/24
hours (14-110) Metanephrines: 0.135 mg/24 hours (0.0520.341) Normetanephrine: 6.021 mg/24 hours (0.88-.444)
Metanephrine, total: 6.156/24 hours (0.140-0.785) CT
Scan: left adrenal mass: 5.2X3X4.4cm with heterogeneous enhancement. Patient had laproscopic removal of
the pheochromocytoma. Post-operatively, patient had
severe orthostatic hypotension which lasted for 3 months.
This gradually improved within 6 months.
Discussion: It is commonly understood that pheochromocytoma is associated with either sustained or episodic hypertension in 80% of patients. Episodic spells is
also described as a common presentation. In our case, we
have a patient with two hypotensive presyncopal hypotensive episodes without any history of hypertension. With a
significantly large adrenal of 5 cm and virtually asymptomatic, the patient most likely developed catecholamine
resistance over time. Due to this, the patient developed
severe hypotension after surgery and had persistent orthostatic hypotension for over 3 months.
Conclusions: Pheochromocytoma should be suspected in patients with unexplained cardiovascular hypotensive episodes. Significant pheochromocytomas can
present without hypertension and severe palpitations. In
this case, this patient had developed desensitization to the
catecholamines over time. In patients with mild symptoms
with pheochromocytomas, the post operative course can
be very protracted.
– 17 –
ABSTRACTS – Hypoglycemia
None submitted.
– 67 –
ABSTRACTS – Lipid Disorders
LIPID DISORDERS
Abstract #401
Abstract #400
THE IMPACT OF STATIN THERAPY ON
CANDIDA COLONIZATION OR INFECTION
AMONG PATIENTS WITH DIABETES TYPE 2
LDL-C GOAL ACHIEVEMENT IN DIABETIC
PATIENTS WITH AND WITHOUT ESTABLISHED
CARDIOVASCULAR DISEASE
Ilias Spanakis, MD, T. Kourkoumpetis, MD,
A. Peleg, MD, G. Livanis, PhD, E. Mylonakis, MD
Pendar N. Farahani, MD, Gray Ellrodt, MD
Objective: Diabetic patients are at high risk for cardiovascular (CV) events and are two to four times more
likely to develop CV disease due to CV risk factors. This
purpose of this study is to compare LDL-C goal achievement with pharmacotherapy in clinical practice in groups
of patients with/without diabetes and previous CV events.
Methods: Demographic, CV risk factors, drug profiles, clinical and laboratory variables from a cross-sectional study on patients filling a prescription for a lipidlowering drug in selected pharmacies across Canada were
obtained. LDL-C goal attainments according to Canadian
guidelines were compared between groups. [Group (A)
primary prevention in patients without diabetes, group (B)
diabetic patients with no previous cardiovascular events,
group (C) secondary prevention in patients without diabetes and group (D) diabetic patients with no previous cardiovascular events]
Results: The number of patients [N (% in the cohort)]
in each group (A, B, C and D) were 585 (53%), 162
(14%), 241 (22%) and 115 (11%), respectively. The average age in each group (A, B, C and D) was 62.3 (10.8)
[mean (SD)], 62.5 (10.6), 68.4 (10.9) and 67.2 (10.3)
years-old, respectively. The proportions of male patients
were 50%, 43%, 68% and 66% in each group (A, B, C and
D). Patients on average had 2.1 (0.8), 3.5 (0.8), 3.4 (0.8)
and 4.7 (0.8) CV risk factors in each group, respectively
(p<0.0001). LDL-C values were 4.6 (1.1), 4.0 (1.0), 4.0
(1.0) and 3.8 (1.1) mmol/L at the baseline (p<0.0001) and
LDL-C was reduced by 1.8 (1.0), 1.7 (0.9), 1.6 (1.0) and
1.8 (1.1) mmol/L in each group, respectively (p=0.05).
LDL-C goals were attained in 81%, 61%, 58% and 71%
of patients in each group (A, B, C and D), respectively
(p<0.0001).
Conclusion: This study demonstrated that patients
using statins as primary prevention attained the LDL-C
goal more often than patients with diabetes or previous
CV events (p<0.001). However, goal attainment was equal
between diabetic patients and patients on treatment as secondary prevention (p>0.05). LDL-C goal achievement
was significantly higher in diabetic patients who received
treatment as secondary prevention compared to those diabetic patients who received the treatment as primary prevention (p<0.01).
Objective: Experimental studies have proposed that
statins can inhibit the growth of fungi by interfering with
the ergosterol synthesis pathway. We evaluated the impact
of statin therapy against Candida colonization or infection
in high-risk hospitalized diabetic type-2 (DM2) patients.
Methods: A retrospective cohort study was performed analyzing the records of all DM2 patients who
were admitted at the Massachusetts General Hospital for
lower gastrointestinal tract surgery between 01/01/2001
and 05/01/2008. We defined statin exposure as the filling
of at least 1 prescription of statins during the last 6-months
prior to and/or during hospitalization. The primary outcome was the presence of any positive culture for Candida
spp. during the hospitalization. Clinical information on a
wide range of covariates was collected which included
comorbidities, as measured by the Charlson comorbidity
index (CCI), length of stay, use of antibiotics, intravascular catheter use, total parenteral nutrition and immunosuppressant use. Logistic regression analysis was used to
adjust for appropriate confounders.
Results: From the total of 1019 patients that were
included, 493 of them (48%) received statin therapy and
526 (52%) did not. Those exposed to statins were older
(67.83 ± 10.98 vs. 64.91 ± 13.67, p<0.001) and had a
higher modified CCI. After adjusting for important confounders the use of statins was associated with a statistically significant 40% reduction in the development of
Candida colonization (p= 0.031, Odds Ratio (OR) 0.60;
95% Confidence Interval (CI) 0.38-0.96). Other covariates
that were independently associated with Candida colonization or infection included length of stay (p<0.001, OR
1.05; CI 95% 1.03-1.07), intensive care unit stay (p=0.002,
OR 2.37; CI 1.39-4.05) colonization of central venous
catheters (p<0.001, OR 3.15; CI 95% 1.78-5.58) and prior
antibiotic use (p=0.005, OR 2.98, CI 95% 1.39-6.42). The
benefit of statins against Candida colonization or infection was more prominent in DM2 patients with greater
co-morbidities (CCI ≥ 2) (53% reduction, p=0.008, OR
0.47; CI 95% 0.27-0.79). The effect of statins did not differ among the different types or dose of statins. However,
these subgroup analyses were limited by small patient
numbers.
Discussion: Candida colonization represents one
of the most important factors for invasive candidiasis.
Our results underline that exposure to statin therapy may
– 68 –
decrease the incidence of Candida colonization or infection among high-risk hospitalized patients. Being the first
clinical study in this field, future studies are inevitably
needed in order to deepen knowledge in this issue.
Conclusion: Statin therapy significantly reduced the
risk for Candida colonization or infection among high-risk
DM2 patients undergoing gastrointestinal tract surgery.
Abstract #402
A PATIENT WITH ARTIFACTUALLY LOW HDL
CHOLESTEROL DUE TO WALDENSTROM
MACROGLOBULINEMIA
practice in the absence of genetic or more obvious secondary causes, a paraproteinemia should be suspected.
Conclusion: Circulating monoclonal proteins may
interfere with one of more laboratory tests performed on
liquid-based automated analyzers. Inaccurate measurement of HDL can lead to misclassification and unnecessary treatment. Clinicians should be aware of interferences
in the clinical laboratory and techniques such as dilution,
using a solid-based assay or semiquantitative electrophoreseis, if available, should be employed to distinguish
between purely in vitro artifacts and real alterations.
Abstract #403
David M. Reich, MD, FACE, Hammad Bhatti, MD,
Paul Kim, MD, FACE, Issac Sachmechi, MD, FACE, FACP
Objective: To report a case of an artifactually low
measured HDL cholesterol (HDL) leading to a diagnosis
of Waldenstrom macroglobulinemia.
Case Presentation: A 68-year-old man presented for
well health maintenance. He had a past medical history of
vitamin B12 deficiency. He had no complaints, appeared
well, and physical exam was unremarkable. Lipid panel
showed total cholesterol (TC) 144 mg/dl, triglyceride
(TG) 79mg/dl, HDL 5 mg/dl and LDL 123 mg/dl. HDL
done three years prior to his presentation was 41 mg/dl.
The patient was prescribed extended release nicotinic
acid (niaspan®) 500 mg at bedtime. Three months later,
his HDL rose to 20 mg/dl, but 1 year later his lipid panel
revealed TC 225 mg/dl, TG 69 mg/dl, HDL 6 mg/dl and
calculated LDL 205 mg/dl. At this point, the patient’s
niaspan dose was raised to 1000 mg at night and pravastatin 40 mg at bedtime was added on. The patient was
also referred to the Endocrinology Clinic. Further work
up revealed serum apolipoprotein A1 97 mg/dl( 94-176),
apolipoprotein B 35 mg/dl (52-109), ratio of apo B/apo
A1 0.36, and direct LDL 28 mg/dl. Serum protein electrophoresis showed normal IgG and IgA and an abnormally
high IgM at 3510 mg/dl (57-266). A bone marrow biopsy
revealed Waldenstrom macroglobulinemia.
Discussion: The artifactually low HDL in this patient
was caused by paraprotein interference in vitro with the
liquid homogenous HDL assay, but a diagnostic work
up for an isolated low HDL unmasking the diagnosis
of Waldenstrom macroglobulinemia has been rarely
reported. Since the values of Apo A1 and Apo B did not
correlate with the high total and LDL cholesterols or the
low HDL, suspicion of an interfering substance became
obvious. Prior observations suggest that some paraproteins may associate with and alter the physicochemical
characteristics of HDL particles, affecting their behavior
in assays designed to measure HDL. When a very low or
undetectable HDL cholesterol is encountered in clinical
COLESEVELAM HCL IMPROVES BOTH
HYPERCHOLESTEROLEMIA AND
HYPERGLYCEMIA IN PREDIABETES:
A RANDOMIZED, PROSPECTIVE STUDY
Yehuda Handelsman, MD, FACP, FACE,
Ronald B. Goldberg, MD, W. Timothy Garvey, MD,
Vivian A. Fonseca, MD, Julio Rosenstock, MD,
Michael R. Jones, PhD, Yu-Ling Lai, RNC, MSN,
Xiaoping Jin, PhD, Soamnauth Misir, PharmD,
Sukumar Nagendran, MD, Stacey L. Abby, PharmD
Objective: Prediabetes (impaired glucose tolerance and/or impaired fasting glucose) increases the risk
of developing microvascular/macrovascular disease and
progression to type 2 diabetes. This study assessed the
lipid- and glucose-lowering effects of colesevelam HCl in
patients with hypercholesterolemia and prediabetes.
Methods: This 16-week randomized, double-blind,
placebo-controlled study included patients aged 18-79
years with untreated prediabetes (2‑hr post‑OGTT ≥140
mg/dL to <200 mg/dL and/or fasting plasma glucose
[FPG] ≥110 mg/dL to ≤125 mg/dL), LDL-cholesterol
(LDL-C) ≥100 mg/dL and triglyceride levels <500 mg/
dL. Patients were randomized 1:1 to unmarked, active
colesevelam HCl (3.75 g/day) or matching placebo. The
primary efficacy endpoint was percent change in LDL-C
from baseline to Week 16 with last observation carried
forward (LOCF). Secondary efficacy endpoints included
changes in FPG, HbA1c, 2-hr post-OGTT glucose, lipid
parameters from baseline to study end/Week 16 LOCF,
and attainment of LDL-C target level. Patients participating in a weight loss program with ongoing weight loss, or
starting an intensive exercise program were excluded.
Results: In total, 216 patients were randomized (colesevelam HCl [n=108] and placebo [n=108]). Treatment
with colesevelam HCl vs placebo resulted in significant
changes in both lipid and glycemic variables: LDL-C
(-13.9% vs +1.7%; mean treatment difference: -15.6%;
P<0.001), non-HDL-C (-8.4% vs +0.7%; mean treatment
– 69 –
difference: -9.1%; P<0.001), apoB (-7.5% vs +0.6%; mean
treatment difference: -8.1%; P<0.001), HbA1c (-0.12%
vs -0.03%; mean treatment difference: -0.10%; P=0.02),
and FPG (-4.0 mg/dL vs -2.0 mg/dL; median treatment
difference: -2.0 mg/dL; P=0.02), from baseline to end of
study. Treatment with colesevelam HCl compared with
placebo did not significantly change 2-hr post-OGTT glucose (mean treatment difference: -1.9 mg/dL; P=0.75).
Significantly more patients receiving colesevelam HCl
vs placebo attained LDL-C <100 mg/dL (29% vs 11%;
P<0.001) at Week 16. More patients receiving colesevelam HCl vs placebo had HbA1c <6.0% (37% vs 25%;
P=0.05) and normalization of glucose with an FPG <100
mg/dL (40% vs 23%; P=0.06) at Week 16. Colesevelam
HCl was weight neutral and well-tolerated. One case of
hypoglycemia was reported in each treatment group.
Conclusion: The use of colesevelam HCl is an option
for managing hypercholesterolemia and may help with the
normalization of glucose in patients at high cardiometabolic risk such as those with hypercholesterolemia with or
without statins and prediabetes. Further study is warranted
to determine whether colesevelam HCl slows or prevents
the progression to type 2 diabetes.
activity by anandamide requires a previously identified nuclear receptor binding site designated as site A.
Furthermore, anandamide-treatment inhibited proteinDNA complex formation with the site A probe. Exogenous
over expression of cannabinoid receptor one (CBR1) in
HepG2 cells suppressed apo A-I promoter activity, while
in Caco-2 cells, exogenous expression of both CBR1 and
cannabinoid receptor two (CBR2) could repress apo A-I
promoter activity. Treatment of HepG2 or Caco-2 cells
over-expressing CBR1 or CBR2 with anandamide had no
additional suppressive effect on promoter activity.
Conclusion: These results indicate that endocannabinoids directly suppress apo A-I gene expression in both
hepatocytes and intestinal cells. This effect may contribute to the decrease in serum HDLc in obese individuals.
Abstract #404
Waqas Ahmed, MD, Naseer A. Khan, Ping Whang, PhD,
Naila Goldenberg MD, Charles J. Glueck MD
INHIBITION OF APOLIPOPROTEIN A-I GENE
EXPRESSION BY OBESITY-ASSOCIATED
ENDOCANNABINOIDS
Senan Sultan, MD, Arshag D. Mooradian, MD,
Michael J. Haas
Objective: Diabetes and obesity are frequently associated with increased serum endocannabinoid (EC) levels and decreases in high-density lipoprotein cholesterol
(HDLc). Apolipoprotein A-I (apo A-I), the primary protein component of HDL is expressed primarily in the liver
and to a lesser amount in the small intestine.
Methods: In order to determine if ECs have a direct
effect on expression of the apo A-I gene, the effect of the
obesity-associated ECs anandamide and 2-arachidonylglycerol on apo A-I gene expression was examined in the
hepatocyte cell line HepG2 and the intestinal cell line
Caco-2.
Results: Apo A-I protein secretion was suppressed
nearly 50% by anandamide and 2-arachidonoylglycerol in
a dose-dependent manner in both cell lines. Anandamide
treatment suppressed both apo A-I mRNA and apo A-I
gene promoter activity in both cell lines suggesting that
anandamide inhibits apo A-I gene expression at the transcriptional level.
Discussion: Studies using apo A-I promoter deletion
constructs indicated that repression of apo A-I promoter
Abstract #405
LOW SERUM 25(OH) VITAMIN D LEVELS
(<32NG/ML) ARE ASSOCIATED WITH
REVERSIBLE MYOSITIS-MYALGIA
IN STATIN-TREATED PATIENTS
Objective: Our specific aims were to determine
whether low serum 25(OH) vitamin D (D2+D3) (<32ng/
ml) was associated with myalgia in statin-treated patients
and whether the myalgia could be reversed by vitamin D
supplementation while continuing statins.
Methods: In the temporal order of their referral to our
outpatient cholesterol center and after excluding subjects
taking corticosteroids or supplemental vitamin D, serum
25 (OH) D was measured in 942 statin-treated patients,
221 with myalgia at entry, and 721 asymptomatic. Vitamin
D therapy was then given to those patients who had myalgia and low vitamin D.
Results: The 221 myalgic patients had lower mean ±
SD serum vitamin D than the 721 asymptomatic patients
(26.4±12.2 vs. 30.4±13.3 ng/ml, p ≤0.0001), were more
likely to be black (11% vs. 6%, p=0.013) and female (63%
vs. 42%, p<0.0001). By analysis of variance, adjusted for
race, gender and age, least square mean (±SE) serum vitamin D was lower in the 221 patients with myalgia than in
the 721 asymptomatic patients, 23.5±1.1 vs. 27.5±0.9 ng/
ml, p<.0001. Serum 25 (OH) D was low (<32 ng/ml) in
165/221 (75%) patients with myalgia vs. 439/721 (61%)
asymptomatic patients (χ2=13.9, p=0.0002). Of the 155
vitamin D deficient, myalgic patients, while continuing
statins, 88 were given vitamin D (50,000 units/week for
4.3±2.5 months), with a resultant increase in serum vitamin D from 20.4±7.0 to 43.7±17.1 ng/ml (p<0.0001). In
– 70 –
these 88 patients, 84 (95%) had no myalgia at their last
visit, and 67 (76%) had normalized vitamin D.
Discussion: We speculate that symptomatic myalgia
in statin-treated patients with concurrent vitamin D deficiency may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle.
Conclusion: We suggest that patients with statin
induced myalgias should be screened and treated for vitamin D deficiency.
Abstract #406
RURAL-URBAN DIFFERENCE IN LIPID
LEVELS AND PREVALENCE OF
DYSLIPIDEMIA: A COMMUNITY-BASED
STUDY IN SOKOTO, NIGERIA
concentration was 36% in urban subjects and 18% in rural
subjects. The most frequent dyslipidaemia was abnormally low HDL-C (17%) which was more common in the
urban subjects (22%) than in rural subjects (12%). There
was no significant difference in the frequency of dyslipidaemia between the males and the females (p=0.178).
Conclusion: This study demonstrated a significant
difference in urban versus rural lipid levels and the prevalence of dyslipidaemia. Dietary changes and less physical
activity resulting from urbanization may be the causes for
the urban-rural difference. The results underline the need
to increase public screening and to emphasize the value of
preventive measures.
Abstract #407
PROFILE OF LIPID ABNORMALITIES IN
OLDER NIGERIANS WITH TYPE 2
DIABETES MELLITUS (T2DM)
Anas Ahmad Sabir, MBBS, Efedaye Ohwovoriole, FMCP,
Olufemi Fasanmade, MBBS, FWACP
Objective: To determine the serum lipids levels and
compare the serum lipids levels and the prevalence of
dyslipidemia of rural versus urban dwellers in Sokoto,
Nigeria.
Methods: A cross-sectional study was conducted
in both rural and urban areas of Sokoto, Nigeria. One
hundred subjects (50 urban; 50 rural) were recruited for
the study using a multi-stage sampling method. Using a
modification of the WHO STEPS, information on sociodemographic data and anthropometric measurements
were obtained. After a 12-hour fast, blood was drawn for
assessment of total cholesterol (TC), triglyceride (TG),
high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. The classification of dyslipidaemia was based on the NCEP ATP III guidelines. Data
was analysed using Epi Info version 3.3.2.
Results: The mean (SD) age of the sample population was 39.9 (13.9) years. The mean (SD) age of the
rural subjects was 38.7(14.3) years and that of the urban
was 40.6(13.6) years (p> 0.05). The urban subjects were
significantly heavier [64.9 vs. 59.4 kg (p=0.038)] and
had higher BMI [23.5 vs. 22.2 kg/m2 (p=0.08)] than the
rural subjects. The mean waist circumference of the urban
subjects [83.8 (9.5) cm] was significantly higher than the
mean waist circumference of the rural subjects [79.2 (11.2)
cm] (p=0.030). The mean TC was significantly higher in
urban [175.9(49.6) mg/dl] than rural subjects [148.3(24.3)
mg/dl] p < 0.001. Mean serum LDL-C, and TG concentrations were increased in urban than in rural subjects but
not statistically significant. The mean serum HDL-C was
higher in the rural [51.1(7.9) mg/dl] than in urban subjects [50.2(11.7) mg/dl] but not statistically significant
(p=0.64). The prevalence of at least one abnormal lipid
Akinyele Taofiq Akinlade, MBBS,
Anthonia Okeoghene Ogbera, MBBS, FMCP, FACE
Objective: To describe the lipid abnormality patterns
in older Nigerians with type 2 DM
Methods: The anthropometric indices, the serum
lipid profile and other characteristics of 203 consecutive
patients, aged ≥60 years, attending our out-patient clinic
were studied.
Results: The mean age of the study was 66 years, with
a male-female ratio of 1:1. The men were older, but this
is not statistically significant (p=0.237). Mean duration of
DM was 8 years, ranging between 1 month and 40 years.
Co-morbidities include systemic hypertension in 68% and
lipid abnormalities in 12% of the subjects. Central obesity was present in 74% of the women but only in 23% of
the men (using waist circumference of 88cm and 102cm
respectively). The mean BMI of this study was 27.7kg/
m2. More women (39%) were obese than men (16%). The
difference in BMI was statistically significant (p=0.000).
Most of the study subjects do not smoke cigarette (84%)
or take alcohol (71%). Mean T-cholesterol of this study
was 196mg/dl, with 48% having values ≥200mg/dl. Most
subjects (74%) had an LDL-C ≥100mg/dl with a mean
of 131mg/dl. HDL-C values ≥40mg/dl was seen in 63%
of the men, with mean value of 46mg/dl. However, the
women had a lower mean HDL-C value of 47mg/dl, with
most (64%) having values ≤50mg/dl. Only 9% had triglyceride values ≥159mg/dl and the mean value was
89mg/dl.
Conclusion: Raised LDL-C is a common finding in
older Nigerians with type 2 DM. In addition, low HDL-C
is more prevalent in the female older T2DM Nigerians.
– 71 –
Abstract #408
to ARVs and HIV status is no longer necessarily a death
sentence in our environment.
FAMILIAL COMBINED HYPERLIPIDEMIA (FCH)
IN AN HIV-POSITIVE PATIENT-COULD THIS
BE DUE TO A PROTEASE INHIBITOR? CASE
REPORT AND REVIEW OF LITERATURE
Abstract #409
INHIBITION OF HEPATIC APOLIPOPROTEIN
A-I SECRETION BY ENDOPLASMIC
RETICULUM STRESS
Anthonia Okeoghene Ogbera, MBBS, FMCP, FACE, FACP,
Abioye I.A., MBBS
Objective: To describe the presentation of an HIVpositive patient with FCH after commencing antiretroviral
therapy.
Case Presentation: A 47-year-old man HIVpositive presenting with polyuria, polydipsia ,extreme
weakness and dysuria about 3 years after commencing
antiretroviral(ARVs),including a protease inhibitor(PI).
No history suggestive of angina He had no family history
of sudden death or heart attack and no significant alcohol
ingestion. Clinical examination revealed an acutely ill man
dehydrated with bilateral arcus corneas. No xanthomas,
no remarkable findings on cardiovascular and abdominal
examination. Lab results revealed a Random Blood Glucose
of 685 mg/dl, urinalysis –glycosuria++,ketones++, fasting
lipid profile- Total Cholesterol 404mg/dl, HDL-c 39mg/dl,
LDL-c 191mg/dl, triglycerides 872mg/dl, VLDL 174mg/
dl.CD4 count 174cells/µl. Liver function tests were normal. Electrocardiography was essentially normal. He was
treated with insulin, as well as combination of fibrates and
a statin, and was discharged home on same with instruction on dietary modification.
Discussion: Familial combined hyperlipidemia is
a common disorder of unknown genetic cause which is
associated with glucose intolerance, obesity, and hyperuricemia. Hyperlipidemia is also recognized sequelae
of antiretroviral treatment, leading to increased cardiovascular risk in HIV infected individuals. HIV infection
has been found to induce proatherogenic lipid changes.
Combination of PIs and nucleoside reverse transcriptase
inhibitors increase the levels of cholesterol and triglycerides in patients treated with these agents. The increase in
risk of cardiovascular disease was found in patients who
have been on these agents (PIs and NRTIs) for over 3
years. Negative association has also been found between
the time on PI therapy and HDL-c levels and a trend to
positive correlation between viral load and cholesterol
levels.
Conclusion: The features of FCH in this patient
underscores the need to properly assess HIV positive individuals on antiretroviral(ARVs) therapy for the presence
of cardiovascular risk factors to reduce the mortality and
morbidity associated now that more patients have assess
Emad Naem, MD, Abdul-Razzak Alamir, MD,
Rosalyn R. Alcade, Senan Sultan, MD,
Norman C.W. Wong, Arshag D. Mooradian,
Michael J. Haas
Objective: Apolipoprotein A-I (apo A-I), the primary
protein component of high-density lipoprotein cholesterol
(HDLc), is reduced in diabetes, obesity, and metabolic
syndrome and is an important risk factor for coronary
artery disease. Endoplasmic reticulum stress (ER stress)
has been shown to be an important mechanism involved
in regulating glycemia and lipidemia in experimental animals and humans. Therefore, we determined whether or
not ER stress regulates apo A-I gene expression and highdensity lipoprotein cholesterol synthesis in hepatocytes.
Methods: HepG2 cells were treated with 0, 0.1, 1.0,
and 10-mM tunicamycin (TM) and 0.1, 1.0, and 10-mg/ml
thapsigargin (TG), two potent inducers of ER stress, and
apo A-I and albumin secretion and apo A-I promoter activity were measured. ER stress was measured using the ER
stress-responsive alkaline phosphatase (ES-TRAP) assay
and a plasmid containing the secreted human placental
alkaline phosphatase gene. TM and TG induced ER stress
in HepG2 cells, as measured by ES-TRAP, in a dosedependent manner. Apo A-I and albumin protein secretion also decreased in a dose-dependent manner, similar to
total protein measured in the conditioned medium.
Results: Unexpectedly, apo A-I gene promoter activity increased with TM- and TG-treatment. Intracellular
albumin levels increased in cells treated with TM and TG
(similar to total intracellular protein content), while intracellular apo A-I levels decreased in TM and TG-treated
cells. At low TM and TG concentrations, the ER stress
inhibitors dimethylsulfoxide (DMSO) and 4-phenylbutyrate (4-PB) suppressed ER stress in HepG2 cells, as measured by ES-TRAP. Also at low TM and TG concentrations, DMSO and 4-PB reversed the effects of TM and TG
on apo A-I and albumin secretion.
Discussion: ER stress was a potent inhibitor of apo
A-I secretion, but not gene promoter activity, in hepatocytes. Therefore, induction of ER stress by exposure to
free-fatty acids and hyperglycemia, both of which have
been shown to induce ER stress, may lead to significant
declines in plasma HDLc.
– 72 –
Conclusion: These results suggest that apo A-I secretion is inhibited by ER stress and that therapeutic strategies targeting the ER stress response may represent a new
approach to treating hypoalphalipoproteinemia.
Abstract #410
IS EXENATIDE THE ANSWER FOR NON
ALCOHOLIC FATTY LIVER DISEASE?
Deepti Bulchandani, MD, Jagdish S. Nachnani, MD,
Betty Herndon, PhD, Agostino Molteni, MD, PhD,
Laura M. Alba, MD
Objective: Non-alcoholic fatty liver disease
(NAFLD), the most common chronic liver disease in the
Western world, associated with obesity and metabolic syndrome. NAFLD can further develop into non alcoholic
steatohepatitis which in turn can lead to liver cirrhosis and
liver failure. At present, there is no definitive treatment
for reversing NASH, however evidence does suggest that
controlling the risk factors including, obesity, diabetes as
well as insulin resistance can delay progression of NAFLD
to NASH and cirrhosis. There is no approved treatment
for fatty liver disease and NASH. Exenatide (exendin-4),
a GLP1 agonist is approved for treatment of diabetes.
Another beneficial effect of exenatide is weight loss. We
originally presented results of beneficial effects of exenatide on the liver enzymes in diabetic patients treated the
medication. This could imply a role of exenatide in treatment of fatty liver disease and possibly NASH .To extend
our findings and delineate the effect of exenatide on liver
we tried to study the effect of exenatide on the liver in a rat
model of fatty liver disease. The aim of the current study
was to evaluate at the effects of exenatide on rat model of
NASH.
Methods: Twenty 8-week-old outbred SpragueDawley male rats were used for this study. Rodents fed
a methionine and choline deficient (MCD) diet have been
extensively studied as a model of fatty liver disease. All
the 20 animals were fed a MCD diet for a period of 75
days. During that time period, ten animals served as baseline and ten were treated with exendin-4. At day 75, the
animals were euthanized, tissues and serum were harvested, and livers were formalin fixed for histology.
Results: The diet was exceptionally efficient at producing fatty livers in MCD control animals, which had a
liver steatosis score of 38 ± 6.7 (of 50 possible). Treatment
with exendin-4 was not associated with a significant
reduction of steatosis (44 ± 5.16, p=0.07). Treatment with
exendin-4 was also associated with significantly lower
adiponectin levels in MCD animals. Exendin-4 had no
effect on the liver enzymes.
Conclusion: In an animal model of NAFLD, exendin-4 therapy was not associated with significant improvement in hepatic steatosis; though it has shown improvement of liver enzymes in human studies.
– 73 –
ABSTRACTS – Metabolic Bone Disease
METABOLIC BONE DISEASE
Abstract #501
Abstract #500
THE PREVENTION AND TREATMENT OF
GLUCOCORTICOID-INDUCED OSTEOPOROSIS
IN PULMONARY CLINIC PATIENTS
VITAMIN D DEFICIENCY INDUCED
HYPOCALCEMIA IN INTENSIVE CARE UNIT
PATIENTS: A CASE SERIES
Melissa Roether Piech, MD, Marc J. Laufgraben, MD
Vanessa Escobar Barboza, MD,
Myriam Lagunas-Fitta, MD, Cristina Gutierrez, MD,
Jean-Paul Menoscal, MD, Tazneem Zahra, MD
Objective: To report 5 cases of hypovitaminosis D
induced hypocalcemia in critically ill patients.
Case Presentation: We report a case series of five
patients with hypocalcemia who were admitted to the
Medical Intensive Care Unit from September 2008 to
March 2009. The group consisted of three women (62.5%)
and two (37.5%) men. We selected all patients with calcium
levels < 8 mg/dl. In hypocalcemic patients, we measured
PTH, phosphate, mg, and 1, 25 vitamin D. In addition,
comorbidities such as diabetes, CHF, HTN, osteoporosis
were evaluated. Finally, length of hospital stay, days of
intubation, and mortality rate were also reviewed. Our
first patient is a 47 years old female with no past medical
history was admitted with acute pancreatitis. Her ionized
calcium level was 3.2 mg/dl, 25 hydroxyvitamin D level
17 ng/ml, and PTH <3.0 pg/ml. Our second patient was a
39 years old female with no past medical history admitted
with sepsis. Her ionized calcium level was 4.64 mg/dl, 25
hydroxyvitamin D levels was 34 ng/ml, and PTH 197 pg/
ml. Our third patient was a 55 years old diabetic female
admitted with DKA. Her ionized calcium was 4.6 mg/dl,
25 hydroxyvitamin D level 19 ng/ml, and PTH 93.7 pg/
ml . Our fourth patient is a 53 years old female admitted
with symptomatic bradycardia. Her ionized calcium level
was 4.88 mg/dl, 25 hydroxyvitamin D level 19 ng/ml, and
PTH 200 pg/ml. Our fifth patient was a 38 years old diabetic male admitted with DKA. His ionized calcium level
was 3.92 mg/dl, 25 hydroxyvitamin D level 12 ng/ml, and
PTH level was 300 pg/ml. The Majority of these patients
were Hispanic females with no previous medical histories.
The length of hospital stay was longer in patients with vit
D levels below 20 ng/ml. Three out of the five vitamin D
deficient patients died
Conclusion: Hypovitaminosis D can be an important
cause of hypocalcemia. Greater awareness of this complication could reduce the incidence of poor outcomes
related to hypocalcemia and hypovitaminosis D.
Objective: Patients treated with glucocorticoids are
at high risk of fracture due to rapid bone loss that occurs
within six months of steroid treatment. The American
College of Rheumatology guidelines address the management of glucocorticoid-induced osteoporosis (GIOP) with
lifestyle risk factor modification, vitamin supplementation, and bone mineral density testing. The guidelines also
recommend bisphosphonates for any patient beginning
therapy with a glucocorticoid equivalent to prednisone
5mg per day or greater for ≥ 3 months. The goal of this
study was to evaluate guideline adherence for the prevention and treatment of GIOP in pulmonary clinic patients at
an academic teaching hospital.
Methods: A retrospective chart review was performed
of all patients seen at the Rhode Island Hospital Pulmonary
Clinic between January 1, 2007 and December 31, 2007.
Eligible patients included men and women ≥ 18 years old
who received glucocorticoids at a dose equivalent to prednisone 5mg or higher for ≥ 3 months. The charts of study
subjects were reviewed for evidence of lifestyle risk factor modification, vitamin supplementation, bone mineral
density testing, and bone-specific pharmacologic therapy
within two years prior to the index visit.
Results: Of the 30 eligible patients, 15 (50%)
received calcium and vitamin D supplementation and 12
(40%) received a bisphosphonate. Bone mineral density
measurements were ordered or assessed in only 3.3%
of study participants. Younger patients (men or women
< 50 yrs. old) were more likely to receive treatment with
calcium and vitamin D (91%) than older patients (26%)
(P value 0.001). In addition, younger patients had higher
rates of bisphosphonate treatment (64% vs. 26%, P value
0.04). When analyzed by age/sex cohorts, the highest rate
of bisphosphonate treatment was found in premenopausal
women (80%), followed by men < 50 (50%), postmenopausal women (30.8%), and men ≥ 50 (16.7%). There was
no significant difference in the prevention or treatment of
GIOP when analyzed by race or gender.
Discussion: The overall rate of guideline adherence
for the prevention and treatment of GIOP in pulmonary
clinic patients was low, most strikingly for the performance
of bone densitometry. Subjects younger than age 50 were
significantly more likely to receive calcium/vitamin D
supplementation and/or treatment with a bisphosphonate.
– 74 –
Conclusion: GIOP guideline adherence was low in
the pulmonary clinic at an academic hospital, particularly
for patients older than 50 years old.
Abstract #502
TRANSIENT REGIONAL OSTEOPOROSIS OF
THE HIP SUPERIMPOSED ON METABOLIC
BONE DISEASE
Prasanna Santhanam, MBBS, Padma Venkatraman,
Tipu F. Saleem, MD, FACE
Objective: To underscore the need to look for other
uncommon conditions when there is sudden worsening of
the bone mineral density. To present a case where a female
with osteopenia and increased fracture risk secondary
to metabolic bone disease developed transient regional
osteoporosis of the hip.
Case Presentation: A 56-year-old female with a
history of menopause since age 36 (induced after total
abdominal hysterectomy and bilateral oophorectomy)
and surgical hypoparathyroidism that occurred after total
thyroidectomy for enlarging non-toxic multinodular goiter (performed few years ago) presented with left leg
and hip pain of 4 months duration. She had been initially
treated with bisphosphonate therapy for a year before she
developed hypoparathyroidism after the surgery. She was
found unsuitable for hormone replacement therapy due
to active smoking. Her lab values were; 25, OH, Vitamin
D 35.5(32-100 ng / ml), 24 hr urine calcium 87 mg/24
hr (<250), calcium 8.2 (8.6-10.2 mg /dl),and PTH was 9
(10-69 pg/ml). The Dual X-Ray Absorptiometry (DXA)
had shown worsening T scores in both the lumbar vertebra ( a decrease from -1.8 to -2.0 within 1 year) and the
left femoral neck (a fall from -1.8 to -2.3 during the same
time frame). The 25-Hydroxy Vitamin D level was within
normal limits of the reference range. The patient underwent an MRI of the hip for evaluation of the pain and it
showed an abnormal edema pattern within the left femoral
neck and the left intertrochanteric area along with a small
amount of joint fluid. The right hip was unremarkable. The
DXA scan was repeated and it showed a further reduction
in T score of the left femoral neck from -2.3 to -2.8 while
the T scores in the right hip were unchanged. It was a case
of transient osteoporosis of the hip superimposed on preexisting osteopenia.
Discussion: Transient regional osteoporosis is a rare
condition that affects the hip, knee, and ankle in middleaged men and women and is usually self limiting in nature.
The etiology is unknown and it is postulated that it may
be a vasomotor response or an early precursor to osteonecrosis. It is also called algodystrophy or Bone marrow
edema syndrome and is characterized by focal osteopenia
and increased signal on T2 images. The biopsy of the bone
usually shows marrow edema, thin seams of woven bone
and active osteoblasts. Early differentiation from other
chronic conditions with increased fracture risk is essential
to avoid unnecessary treatment.
Conclusion: Transient regional osteoporosis is a
self limiting condition and should be differentiated from
osteonecrosis, infection and true osteoporosis.
Abstract #503
AN UNUSUAL RECURRANCE OF
HYPERCALCEMIA DUE TO CONCURRENCE
OF PARATHYROID ADENOMA AND
PARATHYROID SARCOIDOSIS
Leila Chaychi, MD, Sushela Chaidarun,
Allan Golding, Alan Siegel, Vincent Memoli
Objective: To describe a patient presenting with the
rare constellation of synchronous parathyroid adenoma
and parathyroid sarcoidosis.
Methods: We describe the clinical history, physical
examination, laboratory values, imaging findings and
pathologic data of a man who developed recurrent severe
hypercalcemia after a successful parathyroidectomy.
Results: Initial biochemical findings were: calcium
11.1 mg/dl (reference range 8.5-10.6), albumin 4.0 mg/
dl (reference range 3.2-5.2), intact parathyroid hormone
(iPTH) 166 pg/ml (reference range10-69), creatinine 1.9
mg/dl, 25(OH)D 15 pg/ml (reference range 30-80) and 1,
25(OH)2 D 44 pg/dl (reference range 16-72). The chest
x-ray was normal and delayed images from a Tc-99m sestamibi scan showed increased activity in the right lower
pole of the thyroid. Two months after successful parathyroidectomy the patient was admitted to the hospital with
serum calcium of 17 mg/dl. Pathology of the resected
gland confirmed the diagnosis of parathyroid adenoma
and subsequent review disclosed the presence of noncaseating granulomas within the adenoma.
Conclusion: Sarcoidosis with parathyroid involvement causing severe hypercalcemia is unique to this case.
Recurrent after successful resection of a parathyroid adenoma may require consideration of potential causes other
than the initial diagnosis.
– 75 –
Abstract #504
may prevent development of calcifications however care
must be maintained to avoid overzealous correction of
hypocalcemia. Attention to mental status exam and close
monitoring of calcium levels, are essential in the long term
follow up of post-surgical hypoparathyroidism patients.
POST SURGICAL HYPOPARATHYROIDISM
WITH EXTENSIVE INTRACRANIAL
CALCIFICATION PRESENTING WITH
DEMENTIA SYNDROME
Abstract #505
Gina Gerardine Santos Fernandez, MD,
Alexander Sy, MD, Maria Paliou, MD,
Shobhana Chaudhari, MD
PARATHYROID CARCINOMA PRESENTING
AS HIP FRACTURE IN A 27 YEAR OLD WOMAN
Objective: To describe a case of post surgical hypoparathyroidism with extensive intracranial calcification
who presented with symptoms of dementia.
Case Presentation: A 66 yo lady, with post-surgical
hypoparathyroidism since 1959, presented with progressive decline in mental status. On examination, she was
noted to be alert but oriented only to person with mild
slurred speech and hand tremors. Attention span was
noted to be short with decreased concentration and short/
long term memory. Brain CT showed multiple calcifications in the basal ganglia, thalamus, and subcortical white
matter. Later, laboratory data showed elevated levels of
Serum Calcium (17.5mg/dl). Parathyroid hormone (<3.00
pg/ml) and PTHrP (12 pg/ml) were low. On review of
medications, she was on long standing replacement therapy for post-surgical hypoparathyroidism with Calcitriol
0.75 mcg/day and Ca Carbonate 2500 mg/day however it
was unclear if she could have overmedicated herself. She
was treated initially with hydration and diuretics. Initial
symptoms and mental status improved as the calcium
levels trended down. Calcium and Vit D were eventually
restarted.
Discussion: Chronic hypoparathyroidism has been
associated with the development of intracranial calcifications. Although the mechanism for development of brain
calcifications remains unclear, prior studies have suggested that its presence is associated with neuronal loss,
cognitive decline and plausibly reversible dementia in
affected patients. Microscopic analysis of the brain calcifications of postsurgical hypoparathyroidism patients has
shown that these were mainly located in the vascular and
perivascular regions of the brain. If such is the case, then
these calcifications can lead to abnormalities in neuropsychological function akin to a vascular type of dementia. In
this patient, her brain calcifications were noted 50 years
post surgery. It is unclear if her mental status changes
resulted from pre-existing extensive intracerebral calcifications from long standing hypoparathyroidism versus an
overshoot in treatment of her Ca replacements leading to
hypercalcemic dementia or both.
Conclusion: Brain calcifications can be seen in postsurgical hypoparathyroidsim and can lead to cognitive
decline. Prompt treatment with calcium and vitamin D
Pallavi Guddeti, MD, Socorro Vargas, MD,
Andrew Arnold, MD
Objective: To describe unusual presentation of parathyroid carcinoma (PC) associated with HRPT2 mutation
in a young woman.
Case Presentation: A 27-year-old woman presented
with 2 week history of bilateral hip pain triggered by minimal trauma. Radiographs showed bilateral hip fractures
and subperiosteal bone resorption. Labs showed elevated
iCal at 2.52 mmol/l (1.19–1.35); PTH 1407 pg/ml(24-91);
alkaline phosphatase 1084 U/L (38-126); Phosphorus 2.8
mg/dL (2.5- 4.5); 25OH D 6.1 ng/mL(25-80); 1,25(OH)2D
66 pg/ml (18-78); PTH-rP <0.2 and normal SPEP.
Parathyroid scan and thyroid U/S showed an adenoma
near the right lower pole of the thyroid. Pre-operative
management included calcitonin, pamidronate and cinacalcet. She then underwent right hemithyroidectomy and
right inferior parathyroidectomy – en bloc resection with
sacrifice of the involved recurrent laryngeal nerve and
ipsilateral lymph nodes. Intra-op PTH level decreased
from 1500 to 50 pg/ml. Histology of the 6 cm, 12 g specimen revealed perineural, capsular and vascular invasion
indicating parathyroid carcinoma. Hospital course was
complicated by hypocalcemia requiring IV calcium infusions and calcitriol. She subsequently underwent bilateral
hip repair. Germline DNA testing was positive for HRPT2
mutation in exon 7.
Discussion: PC is a rare disease encompassing <1-5%
of primary hyperparathyroidism (HPT) cases. Prevalence
of germline or acquired HRPT2 mutations is 77% in PC vs
0.8% in adenomas, with increased risk of malignancy in all
4 glands when germline-positive i.e. in the hyperparathyroidism-jaw tumor syndrome, associated with ossifying
jaw fibromas, various renal lesions, and uterine tumors.
Clinical manifestations of PC are related to severe hypercalcemia. Local recurrence rate is 50%, with late metastases to cervical nodes, lung and liver. Calcimimetics and
bisphosphonates can be used to control hypercalcemia.
Conclusion: This case represents unusual presentation of PC at young age with dramatic onset of bilateral
hip fractures. She was positive for HRPT2 mutation,
which puts her at increased risk for malignancy in all 4
– 76 –
parathyroid glands and emphasizes the need to screen
family members. Pre-operative suspicion and intra-operative recognition are of great importance in the management of these patients.
Abstract #506
AN UNUSUAL CASE OF TUMOR INDUCED
HYPOPHOSPHATEMIC OSTEOMALACIA
(TIO) AND NORMOCALCEMIC PRIMARY
HYPERPARATHYROIDISM (PHPT):
A COINCIDENCE OR ASSOCIATION?
been taking for several months before surgery. Because
of the elevated PTH a parathyroid scan was performed,
which showed a left superior parathyroid adenoma. We
are following him closely for HPT and are contemplating
parathyroidectomy.
Conclusion: Although hypercalcemic HPT is a well
known complication of long term phosphate therapy, coexistent primary HPT has not been reported with TIO.
Hypercalcemia in our patient may have been masked
because of severe osteomalacia. Reason(s) for the coexistence remains unclear.
Abstract #507
Kevin L. Borst, DO, Sudhaker Rao, MD, FACE
Objective: Although hypercalcemic HPT is a well
known complication of long-term oral phosphate therapy
in patients with TIO or hypophosphatemic rickets and
osteomalacia, co-existent PHPT has not been reported. We
report a case of TIO that resolved following tumor resection despite the presence of normocalcemic PHPT.
Case Presentation: A 57-year-old man was referred
for evaluation of “Paget’s disease” because of progressive rise in serum alkaline phosphatase (AP) and diffuse
bone pain. He noticed severe pain beginning in his feet,
ultimately progressing to ribs and back over 2 years.
He developed severe lower extremity muscle weakness,
waddling gait, and fatigue, which became debilitating.
Extensive biochemical testing and imaging studies were
done at an outside facility prior to referral. At presentation, he had a profound symmetrical proximal muscle
weakness and waddling gait. Neurological examination
was otherwise normal. Biochemical data showed a normal serum calcium and creatinine, but high serum AP of
370 IU/L (with a bone specific AP 165 IU/L). Both serum
25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were
normal. However, serum PTH was elevated at 239 pg/ml
with concomitant albumin adjusted calcium of 9.5 mg/
dl and phosphorus of 1.5 mg/dl. Maximum tubular reabsorption of phosphorus was very low at 0.48 mg/dL GFR
(2.48-4.15 mg/dL GFR), indicating severe phosphate
wasting. A serum FGF-23 was elevated at 218 RU/ml.
Bone scan revealed multiple rib fractures and an octreotide
scan showed focal uptake in the left supraclavicular fossa
consistent with possible tumor. CT of the upper extremity
displayed 3.2 x 2.0 x 2.0 cm lesion behind the left clavicle.
A transiliac bone biopsy after in vivo double tetracycline
labeling confirmed severe osteomalcia. Patholgic examination of the resected sub-clavicular tumor was consistent
with mesenchymal tumor – mixed connective tissue variant. Following resection of the tumor serum P normalized
despite high PTH levels. His bone pain and muscle weakness resolved over a period of a few months and he no longer required phosphorus or calcitriol therapy, which he had
IS THE PREVALENCE OF PRIMARY
HYPERPARATHYROIDISM (PHPT) INCREASED
IN MORBIDLY OBESE INDIVIDUALS?
IMPLICATIONS FOR PATHOGENESIS OF PHPT
Kevin L. Borst, DO, Sudhaker Rao, MD, FACE,
Arti Bhan, MD
Objective: To determine if the prevalence of PHPT is
increased in morbidly obese patients, since an increased
BMI has been reported in patients with PHPT.
Methods: Retrospective chart review for the presence of PHPT in morbidly obese patients seeking bariatric
surgery.
Results: 1,472 obese patients sought bariatric surgery between 2002 and 2008 at our institution. PHPT was
defined as ≥3 consecutive albumin adjusted serum calcium
(Ca) >10.2 mg/dl with elevated or non-suppressed PTH
and normal renal function (serum creatinine <1.5 mg/dl).
The necessary biochemical data to unambiguously diagnose PHPT was available in the Bone & Mineral Research
Laboratory computerized database in 875 (59%) patients.
Of these, 127 had serum Ca >10.2 mg/dl, but only 15
patients had PHPT as defined. The mean (SD) serum Ca
and PTH in these 15 cases were: 10.5 (0.4) mg/dl and
105 (57) pg/ml respectively. This resulted in an estimated
PHPT prevalence of 1.7 %, or 1 in 59 patients. Assuming
that none of the remaining 597 patients, in whom complete data was unavailable, did not have PHPT, the estimated prevalence is still 1% or 1 in 98 patients. This is a
2-10 fold higher prevalence of PHPT depending upon the
population studied.
Discussion: A recent meta-analysis has demonstrated
an association between PHPT and obesity. Proposed mechanisms for this association include: the effects of increased
intracellular Ca leading to insulin resistance, inhibition of
lipolysis, and direct effects of PTH on adipocyte differentiation. If the two conditions are “truly related”, we hypothesized that there would be a higher prevalence of PHPT in
patients with obesity, just as higher BMI in patients with
– 77 –
PHPT. Our findings confirm the hypothesis that obesity
and PHPT might be pathogenetically linked. An inverse
relationship between serum 25-hydroxyvitamin D level,
the best available index of vitamin D nutrition, and BMI is
well established. Prolonged stimulation of PTH secretion
due to chronic vitamin D depletion might lead to clonal
tumors arising in the setting of hyperplasia, resulting in
hypercalcemic PHPT. Alternatively, obese patients may
have susceptible vitamin D receptor gene polymorphisms,
which have been implicated in parathyroid tumorigenesis.
Conclusion: Our preliminary results suggest, for the
first time, an increased prevalence of PHPT in morbidly
obese patents, and are consistent with the recent metaanalysis showing increased BMI in PHPT. Further studies
are needed to determine the pathophysiologic mechanisms
responsible for this association.
Abstract #508
FIBROUS DYSPLASIA AND MCCUNE-ALBRIGHT
SYNDROME: AN AUDIT FROM A TERTIARY
CARE CENTRE
Sambit Das, MBBS, MD, Sanjay Bhadada, Anil Bhansali
Objective: Fibrous dysplasia (FD) is a rare metabolic
bone disease and reported as anecdotal case reports. We
describe the clinical profile and therapeutic outcome of 25
patients with FD observed over 14 years.
Case Presentation: The diagnosis of fibrous dysplasia was based on either classical radiological features
and/or histological evidence on bone biopsy. Associated
endocrinopathies if any were evaluated. The diagnosis of
McCune Albright syndrome was established by two of the
following abnormalities: fibrous dysplasia, Café au lait
macules and endocrinopathies. The clinical presentation,
biochemical parameters and imaging were analyzed. A
total of seven patients received bisphosphonate therapy.
The final outcome and side effects were noted. Age of the
studied patients ranged from 7 to 48 years (mean + SD,
24.2 + 11.4 yrs) with lag time ranging from 1 to 20 years
(mean ± SD, 6.6 ± 6.2 years). The mean duration of follow up was 3.5±2.1 years. Eighteen (72%) patients had
polyostotic disease while rest had monostotic FD. Eight
patients had endocrinopathies: five had acromegaly, one
each had gonadotropin independent precocious puberty
(GIPP), hyperthyroidism and hypophosphatemic rickets. One child with GIPP later developed hyperthyroidism. McCune Albright Syndrome (MAS) was observed
in 10 (40%) patients. Majority of the patients (23 out of
25) received various minor and major surgical procedures
and seven patients received bisphosphonates for recurrent pathological fractures. Bone pain was reduced in all
bisphosphonate treated patients with remarkable decrease
in subsequent fractures.
Discussion: This study describes the varying presentation of fibrous dysplasia with various endocrinopathies
and successful use of bisphosphonates in these patients.
The diagnosis of FD is based on classical radiological
findings substantiated with bone scans and characteristic pathological findings on histopathology. Most common endocrine abnormality documented in our series was
hypersomatotropism (20%), followed by hyperthyroidism
(8%) hyperprolactinemia (20%), hypophosphatemia(4%)
and precocious puberty (4%). However, in one of the pediatric series of fibrous dysplasia, asymptomatic hypophosphatemia was the most common endocrine abnormality
(38.5%) followed by sexual precocity (16.5%). The acromegaly associated with MAS differs from classical acromegaly by its presentation at younger age, facial asymmetry, hyperprolactinemia and lack of demonstratable
adenoma on imaging in majority of patients, however 4 out
of 5 patients with acromegaly had pituitary adenoma and
all had hyperprolactinemia in our series. Hyperthyroidism
associated with MAS is due to autonomous thyroid nodule with constitutive activation of GS alpha subunit of
TSH receptor. Ablative therapy is the treatment of choice
as was done in our patients. Patient who had precocious
puberty was gonadotropin independent as described in
literature and later developed hyperthyroidism emphasizing the fact that these patients need constant follow up for
evolving endocrinopathies. Patients with FD may present with manifestation of rickets and osteomalacia during childhood and adolescence. Hypophosphatemia is the
characteristic abnormality and is attributable to increased
secretion of FGF23 (fibroblast growth factor 23), a phosphatonin secreted from dysplastic bone lesions, hence
leading to phosphaturia. Only one of our patients had low
serum phosphate and florid features of hypophosphatemic
rickets in contrast to the findings of others. Till recently the
treatment of FD was only restricted to symptomatic orthopedic management. Various medical therapies like calcitonin and mithramycin have been tried with poor outcome.
The use of bisphosphonate (intravenous pamidronate ) as
a potential therapy for FD came with a great success with
many studies showing 60-70% improvement in bone pain
and up to 50% radiological improvement. Similar effects
were later shown by oral alendronate and intravenous
potent bisphosphonates like palmidronate and, zoledronate. The possible mechanism of action of bisphosphonates in FD is related to suppressed osteoclastic activation
which are activated in FD due to constitutive activation
of GS alpha subunit in the bone tissue. All had marked
symptomatic improvement in bone pain and reduction of
fracture incidence, although there was no improvement in
bony deformities, a finding similar to other studies.
– 78 –
Conclusion: Fibrous dysplasia is a rare disease with
varying presentations and usually requires combined
medical and surgical treatment. Medical treatment with
bisphosphonates is potentially rewarding.
A PUZZLING CASE OF HYPERCALCEMIA
was made postmortem. In our case the diagnosis, albeit
late, was made antemortem.
Conclusion: In an elderly patient with unexplained
hypercalcemia, suppressed PTH and 1,25-di(OH)vitamin
D and a negative SPEP and UPEP with immunofixation,
the possibility of NSM should be considered. Serum FLC
are a facile and rapid noninvasive test that can then be
ordered.
Ranjani Ramanathan, MD, Dwight Towler, MD
Abstract #510
Objective: To describe a case of non-secretory
myeloma (NSM) whose sole presenting feature was
hypercalcemia for almost ten years.
Case Presentation: An 88-year-old man was admitted
with recurrent hypercalcemia of 13-14 mg/dl. Historical
laboratory data revealed elevated serum calcium of 11.2
mg/dl first noted in 1999. An extensive work up during
2 prior admissions had been unrevealing. The work up
revealed a normal 25-(OH)vitamin D level of 30 ng/ml,
PTH suppressed at 6 pg/ml, normal bone scan and CT
scan of the chest, abdomen and pelvis, negative SPEP and
UPEP with immunofixation, normal TSH, PTHrp, 24 hr
urine Ca, PSA and ACE level and low 1, 25-di(OH)vitamin D. Long bone plain radiographs were unrevealing.
ESR was elevated at 54 mm/hr and CRP at 10.8 mg/l. ANA
was negative. Peripheral smear was normal. No associated
drugs were implicated. A cosyntropin stimulation test was
abnormal with a 30 minute cortisol of 12.9 mcg/dl. The
hypercalcemia was thus attributed to adrenal insufficiency
and the patient was discharged on prednisone. However
he did not improve and we saw him during his third
admission. In this setting, with suppressed PTH AND
1,25-di(OH)vitamin D, elevated ESR yet normal SPEP
and UPEP on immunofixation, malignancy remained the
primary consideration. However, long-standing hypercalcemia is not characteristic of most malignancies, although
described for multiple myeloma. A simple and rapid
serum test, the serum free light chain (FLC) assay, was
performed to look for rare NSM. This was indeed abnormal with a κ/λ FLC ratio of 47.27 (normal-0.26 - 1.65), κ
FLC 52.00 (normal-0.33 - 1.94 mg/dl), λ FLC 1.10 (normal-0.57 - 2.63 mg/dl). β -2-Microglobulin was elevated
at 6.9 (normal-0.7 - 3.4 mg/L). A bone marrow biopsy
confirmed the diagnosis. The patient had a rapidly downhill course and expired shortly thereafter.
Discussion: NSM was first described in 1958 and a
large review suggested that < 1% do not secrete immunoglobulin in serum or urine. Screening elderly patients with
hypercalcemia using only SPEP and UPEP is occasionally
fallible, even with immunofixation. Bone scans are insensitive for myeloma, and skeletal surveys can miss small
lesions. We found only one case report of NSM presenting
with hypercalcemia alone and in that report the diagnosis
ORBITAL INFLAMMATORY DISEASE IN A
PATIENT TREATED WITH ZOLEDRONATE
Abstract #509
Harpreet Kaur, MD, Christopher Bruno, MD,
Jennifer Kelly, MD, Nicolas Uzcategui, MD,
Timothy Riccardi, MD, Arnold Moses, MD
Objective: To report a rare complication of treatment
with a bisphosphonate.
Case Presentation: A 57-year-old postmenopausal
female with a history of esophageal, breast and lung cancer, currently in remission for 3 years, who has been followed for postmenopausal osteoporosis, was treated with
IV ibandronate every 3 months for a total of 6 doses. No
adverse effects were reported. Recently, she received a
5mg infusion of zoledronate in the morning and that night
she developed a painful, swollen left eye with photophobia. Ophthalmologic exam revealed intraocular pressures
of 18 mm Hg in the right eye and 45 mmHg in the left eye.
Her visual acuity was 20/25 without correction in both
eyes. There was 3+ edema of the left upper lid. On slit
lamp examination, she had 2-3 + conjuctival infection in
the left eye. The remainder of the exam was normal. An
orbit CT scan showed a hazy, increased density of the fat
in the left orbital, preseptal and retroseptal spaces along
with thickening of the globe wall indicative of inflammation. A diagnosis of orbital inflammatory disease was made
and she was started on oral prednisone 20 mg daily and
azithromycin. The orbital and eyelid swelling responded
partially to treatment but dull ache and photophobia persisted. She was then started on two Medrol dose packs on
the 9th day after the initial episode, and the swelling and
erythema of the left eye disappeared completely over a
period of next 2 weeks. She has remained symptom free
since then. Follow up CT will be repeated at 3 months.
Upon questioning the patient after the recent episode, she
recalled having mild edema of the left eye after the prior 2
infusions of ibandronate. She did not seek medical help.
Discussion: Zoledronate is a bisphosphonate which is
widely used for treatment of osteoporosis and Paget’s disease. Rarely, ocular inflammation including uveitis, scleritis, conjunctivitis, episcleritis, and photophobia has been
reported after use of this medication as well as with oral
– 79 –
bisphosphonates. Onset may occur immediately, weeks or
even months after therapy. To our knowledge, only 3 cases
of diffuse orbital inflammatory disease have been reported
following use of zoledronate. The mechanism is unknown
but may be due to the release of acute-phase reactants and
cytokines.
Conclusion: Physicians should be aware of this rare
complication of zoledronate and it should be used with
caution in patients with either a positive or even negative
history of inflammatory eye disease, or even, as in our
case, mild ocular symptoms following use of a different
bisphosphonate.
Abstract #511
THE PREVALENCE OF VITAMIN D
INSUFFICIENCY AND SECONDARY
HYPERPARATHYROIDISM IN OBESE
MALE VETERANS
Terri Washington, MD, Joel Brooks,
Valeriu Neagu, MD, Olga Cherepanova,
Lipi Sekhadia Patel, Elena Barengolts, MD
was a negative association between BMI and 25OHD for
OB AAMV (r = -0.16) and CAMV (r = -0.16) groups. There
was also a negative association between 25OHD and PTH
(AAMV: r= -0.16; CAMV: r= -0.24).
Discussion: Our study is one of a few studies evaluating relationship of vitamin D insufficiency and obesity
to include a large group of AA males with detailed health
habits. Similar to previous observation, our data shows a
higher overall prevalence of vitamin D insufficiency in
AA compared with CA males. Contrary to the previous
data, our results show similar prevalence of vitamin D
insufficiency and dietary vitamin D intake for obese AA
and CA males. Our data shows similar level of PTH in
AAMV and CAMV despite differences in 25OHD levels.
This observation is different from the majority of previous
studies and remains poorly understood although magnesium deficiency may be a contributing factor.
Conclusion: Vitamin D insufficiency is highly prevalent in both obese AAMV and CAMV. The negative association of 25OHD to BMI and PTH is similar in obese
veterans of both races.
Abstract #512
Objective: In a prospective cohort study we examined
the relationship between obesity and prevalence of vitamin D insufficiency (25-hydroxyvitamin D [25OHD] < 30
ng/ml) in males.
Methods: Male veterans (n=878) were recruited at
VA Medical Center in Chicago. Serum levels of 25OHD
and parathyroid hormone (PTH) were obtained. Surveys
and chart reviews were completed. Subjects with body
mass index (BMI) < 35 and ≥ 35 kg/m2 were considered
non-moderately obese (non-OB) and moderately obese
(OB), respectively. Vitamin D insufficiency was defined as
25OHD < 30ng/ml. Data is presented as mean (Standard
Deviation) or number (%).
Results: Overall African-American male veterans
(AAMV) (n=629) and Caucasian-American Male Veterans
(CAMV) (n=249) were of similar age and BMI [61 (11) vs
63 (13) years and 29 (6) vs 29 (6) kg/m2, respectively] and
similar proportion of AAMV (17%) and CAMV (17%)
had BMI ≥ 35 kg/m2. The overall prevalence of 25OHD
insufficiency was 86% in AAMV and 71% in CAMV,
while it was 90% and 85% in OB and non-OB AAMV and
93% and 66% in OB and non-OB CAMV, respectively.
Obese AAMV (n=104) compared with obese CAMV
(n=43) had lower 25OHD level, 16.0 (9.1) vs 20.1 (8.9)
ng/ml, and lower calcium 256 (194) vs 368 (306) mg/day,
but not vitamin D dietary intake [98 (80) vs 104 (111) IU/
day, respectively]. Similar results were seen in non-OB
males but dietary vitamin D intake was lower in AAMV
vs CAMV. PTH level was similar in AAMV and CAMV
[66.6 (47.8) and 67.6 (43.0) pg/ml, respectively]. There
RENAL FUNCTION IN PRIMARY
HYPERPARATHYROIDISM
Giorgio Borretta, MD, Chiara Giulia Croce, MD,
Laura Gianotti, Valentina Borretta, MD,
Flora Cesario, MD, Claudia Baffoni, MD,
Ignazio Emmolo, MD, Micaela Pellegrino, MD,
Francesco Tassone, MD
Objective: Renal insufficiency (RI) is a complication of the primary hyperparathyroidism (PHPT) and it
can negatively affect the clinical presentation of PHPT
and increase the risk of mortality. In asymptomatic PHPT
a Glomerular Filtration Rate (GFR) less than 60 ml/min
represents the precise level below which surgery is recommended; however the prevalence of renal insufficiency
(RI) in asymptomatic PHPT is unknown. Thus we sought
to investigate the prevalence of RI in a large case series of
PHPT patients mostly asymptomatic.
Methods: In 294 consecutive PHPT patients (M/F
= 76/218; asymptomatic/symptomatic = 151/143; age =
59.1 ± 13.7 yrs; BMI = 25.5 ± 4.9kg/m2; PTH = 215.3 ±
221.1pg/ml; ionized calcium = 1.46 ± 0.17mmol/l; serum
creatinine = 0.88 ± 0.3mg/dl) renal function estimated by
means of MDRD (Modification of Diet in Renal Disease)
equation was evaluated. A GFR <60ml/min represent the
threshold of moderate-to-severe RI definition.
Results: In the whole group mean (±S.D.) GFR
was 92.3±31.6ml/min, with a RI prevalence of 17.4 %.
Patients were subdivided according to their median age
– 80 –
(i.e. 60 years): younger patients showed higher GFR than
older ones (98.7±32.1 vs 85.5±29.6 ml/min, respectively,
p<0.0003) with a RI prevalence of 11.2% vs 23.9 %
(p<0.00001). Asymptomatic patients compared to symptomatic did not differ both for mean GFR (92.1±31.3 vs
92.5±31.9ml/min, respectively, p=n.s.) and for RI prevalence (14.7% vs 17.9 % , p=n.s.). Patients with kidney
stones, also, did not differ from those without kidney
stones in terms of GFR (93.1±31.3 vs 91.5±31.7m l/min,
p=n.s.) and for RI prevalence (16.7% vs 17.9 %, p=n.s.).
Male patients showed a lower GFR compared to females
(59.4±17.4 vs 103.8±27.0 ml/min, p<0.001), and also
higher RI prevalence (56.6 % vs 3.7 %, p<0.00001). These
findings persisted also adjusting the statistical tests for age,
serum calcium and PTH levels. In the whole group GFR
was negatively associated with age (R=-0.25, p<0.00002)
and with ionized serum calcium levels (R=-0.13, p<0.04).
Conclusion: In a large contemporary PHPT case
series a lower than previously reported prevalence of
moderate to severe renal insufficiency was observed. No
significant differences were found between asymptomatic
and symptomatic patients and also between patients with
kidney stones and those without. A sharp difference of RI
prevalence was found between sexes (independently of
the activity of the disease). Finally, the negative relationship of GFR with serum calcium would confirm the pathogenetic link between PHPT and RI.
Abstract #513
OSTEITIS FIBROSA CYSTICA IN A PATIENT
WITH SEVERE HYPERCALCEMIA
1.54 mg/dL (0.6-1.2 mg/dL), Phosphorus 2.5 mg/dL (2.55.0 mg/dL) and Alkaline Phosphatase 2154 U/L (34-104
U/L). Radiographs showed “salt and pepper” appearance,
bone cysts and brown tumors on bones. Neck ultrasound
revealed a 2.6 cm parathyroid adenoma. Primary hyperparathyroidism was considered as the etiology. Intact
Parathyroid Hormone levels were ordered and results
were 1634 pg/mL (10-65 pg/mL). Patient was taken to
surgery for parathyroid adenoma resection.
Discussion: Osteitis fibrosa cystica was first described
in the 19th century. Before 1950 around half of patients
diagnosed with hyperparathyroidism in the United States
presented with it. Today, it appears in only 2% of individuals diagnosed with primary hyperparathyroidism.
It usually results from an overproduction of parathyroid
hormone that causes increase in bone turnover. Symptoms
are the consequences of both the general softening of the
bones and the excess calcium. It is characterized by bone
pain and radiographically by subperiosteal bone resorption on the radial aspect of the middle phalanges, tapering
of the distal clavicles, and a “salt and pepper” appearance
of the skull, bone cysts, and brown tumors of the long
bones. Brown tumors result from excess osteoclast activity and consist of collections of osteoclasts intermixed
with fibrous tissue and poorly mineralized woven bone.
The usual route of treatment is parathyroidectomy.
Conclusion: Although Osteitis fibrosa cystica has
long been a rare disease it still can be seen on patients
with unchecked primary hyperparathyroidism.
Abstract #514
AN UNUSUAL CASE OF ZOLEDRONIC ACID
INDUCED SEVERE HYPOCALCEMIA IN A
TRANSITIONAL BLADDER CANCER PATIENT
WITH OSTEOBLASTIC METASTASES
Jorge Rohena, MD,
Myriam Allende, MD, MBA, FACP, FACE,
Maragarita Ramirez, MD, Marielba Agosto, MD,
Meliza Martinez, MD
Objective: Describe a patient with osteitis fibrosa cystica, a now very rare in the United States manifestation of
primary hyperparathyroidism.
Case Presentation: A 42-year-old female with past
medical history of hypertension and hypercalcemia first
noticed 2 years ago. She was hospitalized due to a femoral
fracture and consulted to endocrinology for hypercalcemia. Fracture was found after she experienced left thigh
pain while sitting in a chair at her house, without trauma.
She also had acute renal insufficiency. Two years prior
she was told of elevated calcium levels but she did not to
seek further evaluation. She also complained of nausea,
abdominal pain, constipation, polyuria and polydipsia. No
history of nephrolithiasis, bone pain prior to the fracture,
confusion or renal insufficiency. Laboratories showed
calcium at 17.4 mg/dL (8-10 mg/dL), serum creatinine
Sanjit S. Bindra, MBBS, Walaa A. Ayoub, MD, PhD
Objective: To report the first case of transitional bladder cancer and extensive osteoblastic metastases with
zoledronate induced severe hypocalcemia and to discusses
precautions and potential serious implications following
zoledronate therapy.
Case Presentation: A 64-year-old female with bladder cancer and extensive osteoblastic metastases admitted
with excruciating left femoral pain after left femoral neck
fracture status post surgical repair. One day before the surgery, she received 4 mg of zoledronate for bone pains and
prevention of further skeletal complications with calcium
of 8.1 mg/dL (nl.8.5-10.4) prior to IV zoledronate therapy.
Two days later, the patient was found to have calcium of
4.9 with feet parasethesia but no perioral parathesia or
tetany. Patient had vitamin D deficiency on vitamin D and
– 81 –
calcium therapy, normal magnesium and creatinine, and
no history of parathyroid disease. Intact PTH elevated at
1167 and 25- hydroxyvitamin D was low at 20.8 ng/mL (nl
30-70). Patient received IV and oral calcium and vitamin
D with calcium of 8.6 gm/dl corrected for albumin after
2 weeks. Patient was maintained on therapeutic doses of
vitamin D and calcium supplementation.
Discussion: Zoledronate is a highly potent bisphosphonate shown to reduce skeletal-related events in cancer patients with bone metastases. Severe hypocalcemia
requiring IV calcium therapy is increasingly seen with
wider adoption of bisphosphonate therapy. Several reports
of severe zoledronate induced hypocalcemia have been
published among cancer patients with osteoblastic metastases particularly advanced prostate, and rarely among
breast and gastric cancers. However, upon careful review
of the literature, we report the first case of zoledronate
induced severe hypocalcemia in a patient with bladder
cancer with osteoblastic metastases. Hyplacemia in our
case is likely due to unopposed osteoblastic activity with
a preexisting vitamin D deficiency. This case underscores
the need for calcium and vitamin D monitoring and adequate supplementation prior to bisphosphonate therapy to
avoid severe hypocalcemia particularly among patients
with osteoblastic metastatses which could alone cause or
at least aggravate hypocalcemia secondary to Zoledronate
therapy.
Conclusion: Our case buttresses the current literature
concerning severe hypocalcemia as a potential adverse
outcome of zoledronate therapy. We report the first case
of severe Zoledronic acid induced hypocalcemia in bladder cancer patient with osteoblastic metastasis. Our case
highlights the need for greater awareness and precautionary measures prior to the institution of IV zoledronate to
prevent potentially life threatening hypocalcemia.
Abstract #515
PAGET’S DISEASE OF THE ULNA: A RARE
LOCATION OF MONOSTOTIC DISEASE
Blake Elkins, MD, Sarah Fackler, MD
Objective: To describe a rare presentation of Paget’s
disease in the ulna of a 52 year old female.
Case Presentation: The patient is a 52-year-old,
white female of Irish descent who presented to her primary care doctor with a nine month history of left wrist
pain and swelling without history of trauma. The pain was
described as intermittent, then progressed to a chronic
ache worse with activity and alleviated by aspirin and rest.
The patient endorsed symptoms of weakness but maintained full range of motion. Physical exam demonstrated
swelling and tenderness to palpation of the ulnar aspect of
the left wrist but did not demonstrate tenosynovitis. She
was started on ibuprofen and wrist splints and followed up
after three weeks without resolution of symptoms. On follow up, the possibility of a ganglion cyst was entertained,
and the patient was referred to orthopedic hand surgery
for evaluation. X-rays of the wrist obtained prior to this
appointment showed sclerosis of the ulnar head with
lucency in the ulnar corner of the lunate. The exam by the
orthopedist was positive for ulnar compression and “ulnocarpal impaction syndrome” was diagnosed. An MRI was
ordered for evaluation prior to surgical correction and confirmed ulnocarpal impaction, but also showed underlying
bony changes of the distal ulna. The radiologist recommended a bone scan for further evaluation. The bone scan
showed increased homogenous uptake throughout the
enlarged left ulna, which was pathognomonic for Paget’s
disease. Surprisingly Bone Specific Alkaline Phosphatase
obtained at the time of diagnosis was within normal limits
at 17.2 and thought to be secondary to the localized nature
of the disease and possibly low disease activity at that
time. There were no prior Alkaline Phosphatase labs available for comparison. The patient started treatment with
Zoledronic Acid to ease pain and reduce risks of bleeding
secondary to increased bone vascularity prior to surgical
correction of ulnocarpal impaction.
Discussion: Paget’s disease of the bone, also known
as osteitis deformans, is a localized bone disorder that
affects the skeleton through increased bone remodeling.
Paget’s disease is typically diagnosed during the evaluation of pain in the weight baring bones of the axial skeleton or after discovery of abnormally elevated alkaline
phosphatase. Paget’s disease primarily affects the axial
skeleton, pelvis, and skull with proximal long bones frequently involved. Paget’s disease is predominately a polystotic process rather than involving only one bone. Our
case is unique, as Paget’s disease is not typically found in
the upper limbs or as a monostotic process. The presentation of Paget’s in the forearm is exceedingly rare with very
few cases cited in the literature.
Conclusion: Paget’s disease of the bone is a metabolic disease of abnormal bone turnover characterized by
increased osteoclastic activity and disorganized bone formation. It generally affects the axial skeleton and weight
bearing long bones. Here we presented a case of monostotic disease of the ulna, a rare location for Paget’s disease of the bone.
– 82 –
Abstract #516
Conclusion: Due to lack of renal lymphoid tissue, the
existence of a primary renal NHL has been questioned.
This presentation emphasizes its inclusion in the work
up of a patient presenting with hypercalcemia and a renal
mass.
HYPERCALCEMIA AND RENAL MASS
RECOGNIZING AN UNUSUAL DIAGNOSIS
Shuchi Gulati, MD, Harris Taylor, MD, Hamed Daw, MD
Objective: Hypercalcemia, an unusual complication
of Non Hodgkin Lymphoma (NHL) usually occurs late
in the course of the disease. We discuss an unusual case
of primary renal NHL presenting with hypercalcemia and
acute renal failure.
Case Presentation: A 66-year-old male presented
with a six week history of progressively worsening gait
instability, fatigue, unintentional weight loss of 20 lbs and
abdominal discomfort. Physical examination revealed no
lymphadenopathy or hepatosplenomegaly. Total and ionized serum calcium were 15.5mg/dL and 1.73mmol/L
respectively (nl.8-10mg/dL and 1.15-1.35mmol/L). BUN
and creatinine were 38 and 3.3mg/dL, respectively. PTH
was suppressed to 12pg/mL (nl.14-72 pg/mL) and PTHrP
was 1.8pmol/L (nl.<2 pmol/L). Calcitriol was not drawn
on admission. Serum LDH was 399U/L (nl.100-220U/L).
Abdominal CT revealed a heterogeneous hyper-dense
right renal mass measuring 15x16x20 cm. with normal
spleen, liver and left kidney. CT/PET/bone scan ruled out
involvement of other extra renal organs including lymph
nodes. IV hydration, furosemide and bisphosphonates
normalized serum calcium to 9.5mg/dl. Nephrectomy
was aborted due to excessive bleeding. Biopsy, however,
revealed a diffuse large B-cell lymphoma, non germinal
cell type. Immunohistochemical stains for CD 20, bcl-6
and MUM-1 were positive; those for bcl-2, cyclin D1 and
TDT were negative. Bone marrow aspirate was normocellular. The international prognostic index of 5 put him
at high risk of CNS involvement. Chemotherapy was
therefore started with intrathecal methotrexate along with
CHOP and Rituxan. One year later repeat PET/CT showed
no evidence of recurrence. Serum calcium was 9.6mg/dL.
Discussion: NHL may cause and can manifest solely
as severe and symptomatic hypercalcemia. It is mediated
by an increased serum concentration of PTHrP or calcitriol. Since calcitriol level was not measured and PTHrP
was close to the upper limit of normal it is not possible
to determine the relative contributions of each to hypercalcemia. Primary renal NHL is an unusual malignancy
accounting for 0.7% of all extranodal lymphomas in North
America and for 3% of all renal masses. Lesions which
lack the typical radiologic features of the more common
renal cell carcinoma should be considered for CT guided
percutaneous biopsy. This may prevent unnecessary
nephrectomy since treatment of NHL is primarily systemic chemotherapy.
– 83 –
Abstract #517
OSTEOGENESIS IMPERFECTA IN A
PREPUBERTAL GIRL TREATED WITH
PAMIDRONATE - CASE PRESENTATION
Otilia Marginean, MD, Dana Bucuras, MD, Pavel
Ecaterina, Ioan Simedrea MD, Maria Florea MD
Objective: Osteogenesis imperfecta (OI) is a congenital disorder of bone fragility caused by mutations in genes
that code for type I procollagen. Osteogenesis is an inherited disorder with severe damage of bone structure.
Case Presentation: We present a case of a 14 years
old female patient, L.V. transferred in July 2007 (at
age 12 years) in our service from the Pediatric Surgery
Department in a good and stabile state of health but with
a full immobility, being incapable to walk because of terrible muscular and bone pain and because she felt anxiety being afraid of a new fracture. She was usually carried by her mother or she used a wheel chair. Anamnesis
reveals 3 fractures of the right thighbone and 2 fractures
of the right tibia with approximately 4 cm shortness of the
right foot, a mild postural ciphosis, toracal scoliosis, and
hiperlordosis. L.V. is the second child of a non-consanguineous couple, burst weight were 3100g, height 51cm,
APGAR is not known. Even from her first month of life
the patient was registered in the Children Surgery Clinic
right hip dislocation. In our clinic the physical examination reveal short stature 143 cm (under percentile 5), bone
pain, anxiety, incapable to walk. The lab analysis reveals
normal Calcium metabolism, (Ca, Ca++, alkaline phosphatases, calciuria, fosphaturia, PTH) were normal. The
arms X-Ray detected fragility and poor bone quality and
the legs’ X-Ray showed the deforming of the thighbone’s
axe on both sides, deforming of the Coxa Vara, callous
vicious, in the inferior third part of the thighbone diaphysis and in the half part of tibia and the right fibula, diffuse
osteoporosis. The initial spine Dual X-Ray reveal spine
T score -4.7 and Z score -2.9, and hip t score -3.9. The
patient received i.v. treatment with Aredia in a dose of
0.5 mg/kg for 2 consecutive days. The cure treatment was
repeated every three months, when the patient returns to
the hospital. Between the pamidronate administrations the
girl received Calcium and Vitamin D daily. The control
spine Dual X-ray (after 1 year of treatment) reveals a T
score of -2.9 and Z score -2.3; on hip the T score were
-3.3.
The clinical evolution was good L.V. can walk and go to
school alone.
Conclusion: Osteogenesis Imperfecta is a disease
underdiagnosed in our country. Careful following the case
history, clinical and imagistic exams can sustain the diagnostic but it is necessary to have a national registry for this
disease. It is imperative necessary to have a high standard
level genetic laboratory in order to establish the exact type
of this disorder. Bisphosphonates therapy that slows dawn
bone resorption is well tolerated by children.
Abstract #518
HYPOGONADISM - AN ADDITIONAL RISK
FACTOR FOR BONE LOSS, IN CASES WITH
SECONDARY RENAL HYPERPARATHYROIDISM
difference is more important at lumbar spine level. In the
36 month follow-up period, the hypogonadal patients had
higher bone loss at spine level: 8,47 ± 6,8% as compared
with eugonadal cases: -5.71 ± 5,51%. The risk of having
bone demineralization is higher in hypogonadal patients,
at spine level (OR = 1,038) or osteoporosis (OR = 3,98),
compared with hip level (osteopenia: OR = 1,3, osteoporosis OR = 1,904).
Conclusion: Physiological or secondary hypogonadism impairs BMD in patients with secondary hyperparathyroidism. The effect is independent of age of the subject,
BMI, or lengths of hemodialysis.
Abstract #519
PARATHYROID FUNCTION IN TUMORINDUCED OSTEOMALACIA (TIO)
Otilia Marginean, MD, Dana Bucuras, MD,
Simedrea Ioan, Pavel Ecaterina, MD,
Dragsineantu Daiana, MD
Zinnia San Juan, MD, Raymond Grenfell, III, MD,
Brandy Panunti, MD, Allan Burshell, MD
Objective: Hypogonadism is associated with low bone
mass, in men and women. ESRD associates multifactorial
hypogonadism due to uremia, chronic illness, hyperprolactinemia or dialysis process. We studied the relationship
between hypogonadism - BMD - bone turnover and bone
loss in patients with secondary hyperparathyroidism.
Methods: The study group comprised of patients
diagnosed with secondary hyperparathyroidism form
all of the chronic hemodialised patients treated in the
Haemodialysis and Renal Transplantation Center form
the County Hospital nr.1. We diagnosed secondary
hyperparathyroidism by means of repeated iPTH values
(> 3xUNL), increased bone turnover markers. We also
measured LH, FSH, PRL, Total testosterone and estradiol
levels. Gynecological and urological evaluations were
also done. BMD was measured with DXA (anteroposterior technique, Delphi W device, Hologic Inc.).
Results: From the total of 131 (66 men, 65 women)
cases with secondary hyperparathyroidism, with a mean
age 44,32 years, being in the hemodialisis treatment for a
period of 49,6 ± 43,72 months, 61 (46,5%) had hypononadism. 39,4% of men had secondary partial testosterone
deficiency, 27,7% of the females had secondary amenoreea due to hyperprolactinemia and uremia, and 9 women
were in natural menopause. We observed significant difference both in initial bone mass and bone loss speed, in
the hypogonadal group as compared with the eugonadal
group. There were no significant differences regarding
age, length of disease, type of disease, coexisting risk
factors, BMI between the two subgroups. Initial BMD at
spine level was 0,811 ± 0,117 g/cm2 versus 0,918 ± 0,154,
T score = -4,298, p = 0,00006, total hip: 0,720 ± 0,13 versus 0,844 ± 0,113, T = -4,101, p=0,00011. Fig 1 and 2. The
Objective: To describe serum phosphorus response to
hyperparathyroidism and hypoparathyroidism in TIO.
Case Presentation: A 76-year-old female initially
presented in 1976 with osteopenia with a previous history of hip fracture, persistently low phosphorus (1.1-2.3
mg/dl; normal 2.7-4.5 mg/dl), renal phosphate wasting
(TmPO4/GFR 1.2), undetectable 1,25-OH vitamin D3
and elevated PTH (1600-1900 pg/ml; normal 12-72 pg/
ml). Medical treatment with calcitriol and phosphate supplements was ineffective, hypophosphatemia worsened
and she developed hypercalcemia. At parathyroid surgery, three glands appeared abnormal and were removed,
except for 50 mg of the left lower gland. Following surgery, PTH, phosphorus and calcium levels normalized. In
1998 she again presented with hyperparathyroidism and
underwent a second surgery which revealed growth of
the remnant gland to 900 mg as well as fifth parathyroid
gland in the left carotid sheath, which were both resected.
She then developed hungry bone syndrome (undetectable
PTH, calcium of 6.2 mg/dl, phosphorus of 1 mg/dl, elevated alkaline phosphatase) and then hypoparathyroidism
(undetectable PTH, calcium of 8 mg/dl, phosphorus of 3.7
mg/dl). TIO was suspected, an octreotide scan was positive, and MRI of the head confirmed two right-sided extracranial masses, consistent with meningiomas. Fibroblast
growth factor-23 (FGF23) was elevated at 4850 RU/mL
(0-180). The patient refused neurosurgery. PTH gradually
increased and phosphorus declined.
Discussion: TIO is a rare syndrome characterized by
hypophosphatemia due to renal phosphate wasting, low
serum 1,25-OH D3 levels, and osteomalacia. The proposed
mechanism is paraneoplastic secretion of phosphatonins,
such as FGF23, which inhibits phosphate transport and
– 84 –
reduces calcitriol production in the renal tubule usually
from mesenchymal or mixed connective tissue tumors.
It may present with secondary and even tertiary hyperparathyroidism and tumor resection has been reported to
be curative. This is the 3rd case of TIO with a radiologic
diagnosis of a meningioma. Tertiary hyperparathyroidism developed on at least two occasions which may be
related to the low calcitriol and phosphate replacements.
On both occasions parathyroidectomy led to improvement
in serum phosphorus.
Conclusion: TIO may be associated with tertiary
hyperparathyroidism. Induction of hypoparathyroidism
improves the phosphorus levels in FGF23-mediated TIO.
Parathyroid function modulates phosphate levels in TIO.
MILK-ALKALI SYNDROME IS A MAJOR
CAUSE OF SEVERE HYPERCALCEMIA
and malignancy. Among patients with severe hypercalcemia (calcium level>14mg/dL) it is more common than
malignancy. It consists of a triad: hypercalcemia, renal
failure and metabolic alkalosis. The “modern version”
was described in the setting of greater awareness of osteoporosis and increased availability of over the counter
calcium carbonate supplements for prevention. Daily elemental calcium intake of no more than 2 g/d is considered
safe, but lower doses should be recommended for those
patients who have predisposing factors for hypercalcemia.
The treatment for milk-alkali syndrome implies limiting calcium and alkali ingestion and volume expansion.
Bisphosphonates contribute to hypocalcaemia.
Conclusion: This case illustrates that milk-alkali syndrome is also seen in patients self-treated for dyspepsia.
Its recognition remains very important for patient care. We
emphasize the importance of a good history taking, including over the counter medications and other remedies in
order to make an accurate diagnosis and treat accordingly.
Mona Shimshi, MD, FACE, Ramona Dadu, MD
Abstract #521
Objective: To increase awareness of the milk-alkali
syndrome as a major cause of severe hypercalcemia and to
stress the importance of inquiring about over the counter
medication use.
Case Presentation: We present a 59-year-old white
male who was admitted to our hospital for acute encephalopathy, severe hypercalcemia, metabolic alkalosis and
acute on chronic renal failure. The patient had two hospitalizations in the previous year for severe hypercalcemia of unknown etiology, although extensive workup has
been performed. His past medical history was significant
for HTN, CKD, GERD, nephrolithiasis s/p JJ stent, but
no nephrocalcinosis, and chronic alcoholism. Laboratory
data revealed macrocytic anemia, serum bicarbonate=32 mmol/L, BUN=41 mg/dL, creatinine=3.35 mg/
dL, GFR=19, Ca=15.4 mg/dL, Phoshorus=3.4 mg/dL,
Alb=4.5 g/dL. A review of old records demonstrated an
elevated calcium level, low-normal phosphorus level, a
suppressed PTH and low 25 vitamin D and 1,25 vitamin
D levels. Vitamin A, PTHrP, ACE, SPEP/UPEP, TSH, 24
h urine calcium levels were all within normal range. The
patient also had a normal skeletal survey, a 4 mm lung
nodule on CT chest and a 7 mm non-obstructive left kidney calculus. He underwent aggressive hydration, natriuresis and biphosphonate treatment. By day 4 of hospitalization his calcium level was 10.4 mg/dL, bicarbonate
level was 22 mmol/L and serum BUN/creatinine steadily
trended down to 16/1.81 mg/dL. On further questioning
he did admit to taking over the counter antacids for severe
dyspepsia.
Discussion: Milk-alkali syndrome is the third leading
cause of hypercalcemia after primary hyperparathyroidism
PRIMARY HYPERPARATHYROIDISM (PHP)
WITH NEURASTHENIC DEBUT
Abstract #520
Cristina Iuliana Bejnariu, MD, Pavel Suciu, MD, PhD
Objective: To highlight the significance of parathyroids scintigraphy for every case with PHP.
Case Presentation: A 46-year-old woman with no
family history of MEN, monthly menstruation, no history of cervical irradiation presented with: asthenia, nausea, arrhytmia, depression, hypertension, polyuria and
polydipsia. The symptoms had appeared 6 months ago.
Laboratory: persistent elevated total and ionized calcium,
hypercalciuria, hypophosphatemia, elevation of the alkaline phosphatase, helicobacter pylori positive, euthyroidism, ATPO negative which leaded to PHP diagnose confirmed by the elevated PTH level. Radiology: salt and
pepper skull; subperiostal resorption of index finger; bone
cysts. Cervical ultrasonography (US): mixt nodule in the
lower pole of right thyroid lobe confirmed also by the
computed tomography (CT). DXA: osteoporosis. Were
performed right thyroid lobectomy and right parathyroidectomy (RP). Final pathology revealed lymphocytic
thyroiditis and one huge solid/cystic right inferior parathyroid mass. Post-op the symptoms persisted beside the
hypercalcemia (HC) and elevated PTH level. Thyroid US:
nodule hypoechogen in the lower pole of left thyroid lobe.
An FNA biopsy was nondiagnostic. Because a parathyroid
adenoma (PA) was suspected in this location, PTH was
measured in the aspirate. The decrease level of PTH in
the aspirate of remaining nodule from the left thyroid lobe
post right thyroid lobectomy infirmed source of PTH at
– 85 –
this level and we indicated a technetium Tc 99m sestamibi
parathyroid scan (TPS) which was negative. The patient
refused other surgery. We initiated treatment with cinacalcet 30mg/day.
Discussion: The debut of PHP was atypical with
neuropsychic, cardiovascular and gastrointestinal disturbances (GID) at a middle - aged woman. DXA modifications are characteristic for PHP especially at forearm, the
favorite situs in PHP. Even the US and CT were typical for
PA, the evolution after RP put in appearance parathyroid
hyperplasia. The cinacalcet decreased the HC but a few
initially symptoms are still persistent after one month of
treatment the PTH level is still high which means that a
part of PHP symptoms are induced by the excess of PTH
not by HC.
Conclusion: Each US and CT has a sensitivity of
60-70% and can mislead the localization of PA. TPS is
the most successful procedure for a sensitive localization (sensitivity 80%) for parathyroids. The GID of PHP
can be indistinct or superpose with GID induced by the
cinacalcet. For low doses and in the initially stages of the
treatment with cinacalcet the decrease of HC cannot be
accompanied by the decrease of PTH level.
Abstract #522
49 mg/dL (6-22 mg/dL), creatinine of 2.5 mg/dL (0.8-1.4
mg/dL), and albumin of 4.8 g/dL (3.5-5.0 g/dL). Her acute
renal failure and hypercalcemia improved with hydration.
Further work up for the etiology of the hypercalcemia
revealed a parathyroid hormone concentration of 22 pg/
mL (10-55 pg/mL) and a vitamin D concentration of 338
ng/mL (32-100 ng/mL) (D2 component was 331.6 ng/mL).
The patient stated that vitamin D therapy had been started
6 months earlier during her rehabilitation following her
pacemaker placement. Closer examination of the vitamin
D pill bottle revealed a dose of 50 international units (IU)
twice daily for maintenance therapy which was filled by
the pharmacy as 50,000 IU twice a day. The patient had
been taking this dose of ergocalciferol for approximately
six months. The vitamin D was held and hydrocortisone
10 mg twice a day was started. Over the next four days the
patient’s calcium concentration normalized.
Conclusion: Medication errors are the most frequent
type of medical error associated with poor clinical events.
More practitioners are checking vitamin D in their patients,
and errors in vitamin D prescriptions can lead to serious
adverse outcomes. Restricting the number of refills, and
communication and sharing of information between the
physician, community pharmacists and patient remain an
important safeguard for preventing such errors.
MEDICATION ERROR- RISE OR FALL
Abstract #523
Harkesh Arora, MBBS, David C. Lieb, MD,
Joseph A. Aloi, MD
COEXISTANCE OF PRIMARY
HYPERPARATHYROIDISM AND ACROMEGALY
ASSOCIATED WITH EMPTY SELLA SYNDROME
Objective: To describe the events that resulted in a
case of vitamin D toxicity.
Case Presentation: 82-year-old Caucasian female
presented to her primary care physician after an acute episode of nausea and vomiting. She reported two weeks of
worsening anorexia, decreased energy and polyuria. She
denied any mental status changes, fever, chills, dyspnea,
abdominal pain or constipation. Past medical history was
significant for mild congestive heart failure secondary
to an arrhythmia that was treated seven months earlier
with atrioventricular junction ablation and pacemaker
placement. This necessitated a prolonged hospitalization
and rehabilitation. The patient’s primary care physician
ordered a basic metabolic panel that revealed a calcium
concentration of 14.1 mg/dL (8.4-10.5 mg/dL). Repeat testing showed persistent hypercalcemia (15mg/dL). She was
admitted to the hospital and aggressive intravenous fluids
were given. Her medications included warfarin, aspirin,
calcium, vitamin D, simvastatin, metoprolol, ibandronate,
furosemide and a daily multivitamin. Physical examination revealed a normal neurological exam. The remainder
of her metabolic panel was significant for hyponatremia
at 132 mmol/L (136-145 mmol/L), blood urea nitrogen of
Objective: To describe the case of hypercalcemia
(HC) diagnosed with primary hyperparathyroidism (PHP)
and acromegaly associated with empty sella (ES).
Case Presentation: This is the case of a 59-year-old
black female with type 2 diabetes and stage III chronic
kidney disease (CKD) who was referred for evaluation
of persistent HC, despite discontinuation of hydrochlorothiazide. She had been diagnosed with PHP18 months
earlier, with calcium (Ca) of 11.1 mg/dL (normal, 8.410.2), parathyroid hormone (PTH) of 166 pg/mL (normal,
17.3-72.9), 1,25-di-hydroxy vitamin D [1,25(OH)D] of
56.8 pg/mL (normal, 15.9-55.6), and 25-hydroxy vitamin D [25(OH)D] of 9.6 ng/mL. As treatment of HC, she
had been given cinacalcet. At our evaluation, she noted
bone pain, myalgias, fatigue, and poor glycemic control.
Physical exam demonstrated mildly coarsened features
and a nodular goiter. Neck sonography confirmed heterogenous multinodular goiter and probable parathyroid
adenoma. Laboratory investigation revealed an elevated
insulin-like growth factor-I (IGF-I) of 316 ng/mL [age/
– 86 –
sex-matched reference range 81-225] and was elevated
at 510 ng/mL upon repeat testing. Glucose tolerance
testing did not appropriately suppress growth hormone
(GH). Magnetic resonance imaging (MRI) of the pituitary
discovered ES, with no evidence of pituitary adenoma.
Prolactin was normal. Based upon these clinical data, a
diagnosis of acromegaly was made.
Discussion: In our case, HC was mediated by a combination of PHP and acromegaly. PTH induces increased
Ca entry from the intestine and kidney via increase in
the production of 1,25(OH)D at the proximal convoluted tubule. GH also activates 25(OH)D conversion to
1,25(OH)D at the site of the renal tubules, leading to
concomitant increase in serum Ca. Our patient had intrinsic elevation in PTH and GH, but only minor elevation
in 1,25(OH)D (accounting for vitamin D deficiency and
CKD); despite this, the combined effects of PTH and GH
excess resulted in HC. Coexistence of acromegaly and
ES is another interesting facet of this case. Acromegaly
is most commonly caused by a GH-secreting pituitary
adenoma and its association with ES is rare. It is likely
that the ES resulted from clinically silent infarction of a
pituitary adenoma.
Conclusion: HC has numerous causes. One should
pursue specific etiology, considering acromegaly. While
coexistence of PHP and acromegaly has been described
(notably in multiple endocrine neoplasia type 1), to our
knowledge this is the first case description of PHP in the
setting of acromegaly, diagnosed without pituitary adenoma, but with ES.
Abstract #524
HIGH PREVALENCE OF HYPOVITAMINOSIS D
IN YOUNG, GESTATIONAL DIABETICS LIVING
IN THE SOUTH
the lowest recorded level being 10.7 ng/mL. Another 15
patients were classified as insufficient. In total, 24 of the
29 (82.7%) were deficient or insufficient in vitamin D.
All Hispanic and African American patients were insufficient or deficient, with the lowest levels seen in these
populations.
Discussion: DVD has recently been recognized as a
contributor to beta cell dysfunction and decreased insulin sensitivity in type 2 diabetes.2 It has also been linked
to an increased risk of GDM.3 The prevalence of DVD
among pregnant women in the North has been previously
reported.4 We wished to describe the prevalence of vitamin D deficiency among young women with GDM living
in the sunny climate of coastal North Carolina (latitude
34.22 N). Although we were expecting a good percentage
of our patients to have DVD, we were surprised to find
that 82.7% are vitamin D deficient/insufficient. DVD in
this population is problematic, with profound implications
for both the mother and the newborn. Since a newborn’s
25(OH)D concentration is approximately half that of its
mother’s5, it is not surprising that there is an increasing
frequency of childhood rickets and other autoimmune
disease. Although a single-center, small cohort study, the
high prevalence of DVD in this population may help raise
awareness among endocrinologists seeing young patients
with GDM. Whether the degree of DVD has confounding
effects on glycemic control, complications of pregnancy,
development of other autoimmune pathology, or effect on
the vitamin D status of the breastfeeding infant is subject
for further research.
Conclusion: At our coastal North Carolina practice,
82.7% of our GDM cohort seen between August 2008 and
December 2009 were vitamin D deficient, despite sunny
weather and supplementation with prenatal vitamins.
Abstract #525
Objective: To characterize the prevalence of vitamin
D deficiency (DVD) in a cohort of women with gestational diabetes (GDM) living in the southern US.
Case Presentation: Retrospective chart review of
all patients with GDM referred to our practice August
2008-December 2009. Those with co-morbid conditions
predisposing to DVD, including sprue, history of gastric
bypass surgery, malabsorption syndromes, chronic kidney
disease, or liver disease were excluded. All patients were
taking prenatal vitamins (400 IU vitamin D3). Sufficient
25-hydroxyvitamin D (25(OH)D) levels were characterized as > 32 ng/mL, insufficient levels were classified as
20-31 ng/mL, and deficient levels were < 20 ng/mL.1
Results: Twenty-nine patients met inclusion criteria, and of these, 9 were vitamin D deficient (31%) with
SEVERE HYPERCALCEMIA IN A YOUNG
PATIENT WITH “THYROIDALIZED”
PARATHYROID ADENOMA
Shadi Barakat, MD, Stephen Brietzke, MD
Objective: Parathyroid adenoma is the most common cause of Primary hyperparathyroidism. Most patients
with primary hyperparathyroidism presents with mild, if
any, symptoms of hypercalcemia because they usually
present with modest increase with serum calcium level.
Conversely, severe symptomatic hypercalcemia, especially in a young patient, should raise concern for parathyroid carcinoma.
Case Presentation: A 23-year-old, otherwise healthy,
Caucasian male, sought medical attention for evaluation of
severe abdominal pain. On one occasion, it was associated
– 87 –
with vomiting of a blood clot, and two episodes of melena.
Laboratory tests revealed elevated alkaline phosphatase of
242U/L, and calcium of 14.2 mg/dl. He was treated with
intravenous normal saline infusion, calcium remained
elevated and iPTH was 407 pg/ml. An ultrasound of the
neck revealed a 1.9 x 1.2 x 1.4 cm hypoechoic nodule
with internal vascularity inferior to the left thyroid lobe,
and a Sestamibi scan showed increased uptake in the same
region. The patient was taken to the operating room for
parathyroidectomy with limited neck exploration. The
endocrine surgeon found a large pale colored lesion adherent to the inferior pole of the thyroid. An excision of 5
lymph nodes, parathyroidectomy and left thyroid lobectomy was performed, and an intra-operative iPTH level
dropped from 329 pg/ml to 45.8 pg/ml. Patient recovered
well after the surgery with calcium level of 9.5 mg/dl on
post-op day #1. Gross pathology was normal appearing
thyroid with parathyroid tissue. The microscopic evaluation showed 5 out of 5 benign lymph nodes, parathyroid
adenoma without evidence of carcinoma, and nodular
hyperplasia of the thyroid with one microscopic focus of
parathyroid tissue.
Conclusion: Sporadic primary hyperparathyroidism
is usually caused by parathyroid adenomas. Ectopic and
super numeracy parathyroid glands are common. Entirely
thyroidal parathyroid adenomas have been described.
Severe hypercalcemia (≥ 14 mg/dl) was found in 65 –
75 % of the cases of parathyroid carcinoma and should
always prompt diligent search to exclude this probability.
The histopathological distinction between an adenoma
and a carcinoma is sometimes challenging and usually is
based on the basis of local invasion of contiguous structures, or lymph nodes or distant metastasis. The coincidence of a thyroid adenoma with non-invasive intra-thyroidal parathyroid island without pathological evidence of
malignancy is a unique aspect of this case.
phlebotomy with varying compliance. His father & two
sisters also suffered from hemochromatosis. Laboratory
studies showed calcium of 12.5 mg/dL (normal 8.6-10.2)
with intact PTH value of 32.5 (normal 10-65) pg/mL, cholesterol 254 mg/dL, LDL 184 mg/dL, TSH 1.0 uU/mL.
US of the thyroid revealed normal sized thyroid with a
4mm right nodule. A DEXA scan was compatible with
osteopenia. The patient underwent a Minimally Invasive
Radioguided Parathyroidectomy of a left upper adenoma.
The procedure involved a high resolution sestamabi scan
on the morning of surgery. In the OR, a hand held gamma
radiation detecting probe was used to map radioactivity in
all quadrants of the neck and detected a left upper parathyroid adenoma. PTH production was found to be 320 (nl
30-80) units and was diagnostic of parathyroid adenoma.
The other glands were anatomically normal & physiologically dormant. The patient’s calcium level was 9.5 with
PTH of 5 a month after surgery.
Discussion: The endocrine manifestations of hemochromatosis usually lead to hypofunction of different
endocrine glands including pancreas, gonads and thyroid.
Primary hyperparathyroidism in a patient with hemochromatosis has not been reported in the literature, to the best
of our knowledge. One of the most common confusion
areas in the diagnosis of primary hyperparathyroidism is
hypercalcemia with a “normal” PTH. Normal parathyroid
glands should stop production of PTH in a setting of nonPTH mediated hypercalcemia. Review of literature suggests that about 15% of cases of primary hyperparathyroidism show “normal” PTH levels.
Conclusion: Primary hyperparathyroidism in a patient
with hemochromatosis is extremely rare. Detectable PTH
in the face of hypercalcemia should be considered primary
hyperparathyroidism until proven otherwise.
Abstract #526
FUNCTIONAL HYPOPARATHYROIDISM AND
TETANY IN CELIAC DISEASE
PRIMARY HYPERPARATHYROIDISM
IN A PATIENT WITH HERIDITARY
HEMOCHROMATOSIS
Abstract #527
Nagashree Gundu Rao, MD, Ricardo Balestra, MD
Richard W. Pinsker, MD, FACE,
Neil Pathak, Mohan Sharma, MD
Objective: To describe an unusual occurrence of primary hyperparathyroidism in a patient with hereditary
hemochromatosis. To describe a ‘normal’ PTH level in a
patient with primary hyperparathyroidism.
Case Presentation: A 37-year-old male with a history of hemochromatosis, hyperlipidemia, and GERD,
presented for a routine visit. His hemochromatosis was
diagnosed several years ago and was treated with regular
Objective: To recognize the etiology of hypocalcemia
and functional hypoparathyroidism in celiac disease.
Case Presentation: A 39-year-old African-American
woman with a history of recently diagnosed celiac disease and pernicious anemia, presented with sudden onset
of painful muscle spasms involving the hands, feet and
face with symptoms of jaw locking. Physical examination
revealed hypertension (no prior history of hypertension)
and a positive Trousseau’s sign. She was found to have
serum calcium of 5.5 mg/dl (8.5-10.6), ionized calcium of
0.73 mmol/l (1.1-1.4) and magnesium level of 0.3 mg/dl
(1.7-2.8) Additional laboratory tests showed phosphorus
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of 3.6 mg/dl (2.5-4.5), low 25-hydroxy-vitamin D of
<7 ng/ml (35-55), low 1,25-dihydroxy-vitamin D of 10
pg/ml (15.9-55.6) and normal thyroid function tests. The
intact parathyroid hormone (iPTH) level of 36 ng/dl (1265) was inappropriately low for her calcium. The patient’s
symptoms of tetany and hypertension resolved with intravenous repletion of calcium and magnesium. With the
correction of hypomagnesemia, iPTH increased to 111 ng/
dl. The corresponding calcium was 8.2 mg/dl. The patient
was then started on oral magnesium, calcium and vitamin
D supplements. Her low magnesium levels were likely
related to her gastrointestinal losses secondary to underlying celiac disease
Discussion: Hypocalcemia in celiac disease can be
caused by vitamin D deficiency, autoimmune hypoparathyroidism or concomitant hypomagnesemia. Vitamin
D deficiency however, is characterized by low phosphorus and elevated PTH. The classic sign of severe hypomagnesemia (<1.2 mg/dl) is hypocalcemia. One-third of
the dietary magnesium is absorbed in the small bowel.
Hypomagnesemia and hypocalcemia are seen in celiac
disease due to gastrointestinal losses and malabsorptive
state. There is an intricate interplay between calcium and
magnesium metabolism. Hypomagnesemia is known to
cause hypocalcemia by decreasing the secretion of PTH,
inducing end-organ resistance to PTH and impaired
1-hydroxylation of 25-hydroxy vitamin D. This explains
the blunted response of PTH to the low vitamin D and low
calcium in this patient. Further, the increase in iPTH after
the correction of hypomagnesemia goes against autoimmune hypoparathyroidism. Interestingly, hypomagnesemia has also been implicated in the pathogenesis of hypertension by potentiating vasoconstriction. This is supported
by the resolution of hypertension with the correction of
hypomagnesemia, as seen in this patient.
Conclusion: Functional hypoparathyroidism can lead
to lethal complications, unless promptly recognized and
treated.
Abstract #528
PARATHYROID HORMONE RELATED
PROTEIN: AN UNUSUAL MECHANISM FOR
HYPERCALCEMIA IN SARCOIDOSIS
Armand Ara Krikorian, MD, Sapna S. Shah, MD,
Jay K. Wasman, MD, Abdallah Kamouh, MD
Case Presentation: A 56-year-old male with abdominal pain and nausea was found to have serum a calcium of
14.2 mg/d (albumin 3.7g/dL) with an appropriately suppressed parathyroid hormone (<3 pg/mL), a low 25-OH
Vitamin D (26 ng/mL) and normal 1,25-(OH)2D3 (57
pg/mL). Twenty-four hour urine collection revealed the
presence of calciuria. SPEP and UPEP were negative
for monoclonal gammopathy. An elevated PTHrP of 3.6
pmol/L prompted a work up for malignancy. CT scan of
the chest revealed numerous pulmonary parenchymal
nodules bilaterally and marked diffuse lymphadenopathy.
An excisional biopsy of a large right axillary lymph node
demonstrated non-necrotizing granulomatous inflammation consistent with sarcoidosis with no evidence of
malignancy. Histochemical stains for fungal organisms
and acid-fast bacilli were negative. Immunohistochemical
testing for PTHrP within the granulomatous tissue was
positive. After treatment with IV hydration and steroids,
the hypercalcemia resolved and PTHrP levels were found
to have normalized to 0.5 pmol/L.
Discussion: Hypercalcemia is a well established metabolic abnormality associated with sarcoidosis. The commonly accepted mechanism of hypercalcemia in sarcoidosis involves elevated levels of hydroxylated vitamin D
from sarcoid activated macrophages. Only two case reports
have previously noted immunohistochemical detection of
PTHrP antigen in sarcoid granulomata. PTHrP has been
shown to stimulate renal 1-α hydroxylase resulting in
increased production of 1-25(OH)2D3. Increased levels
of PTHrP in sarcoid tissue suggest a possible additional
source for vitamin D hydroxylation and hypercalcemia.
Although the source of PTHrP in sarcoidosis is unclear,
it has been shown that PTHrP production in human squamous cell lung cancer is stimulated by tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6. Elevated levels
of TNF-α and IL-6 have been demonstrated in bronchoalveolar lavage fluid in sarcoidosis, suggesting a possible
mechanism of elevated PTHrP. Furthermore, it has been
demonstrated that glucocorticoid use inhibits PTHrP
expression in vitro which could explain the sustained resolution of hypercalcemia and elevated PTHrP after steroid
therapy.
Conclusion: PTHrP may be a possible mediator of
hypercalcemia in sarcoidosis. The differential diagnosis of
PTHrP-induced hypercalcemia should include sarcoidosis
and further research is needed to establish the incidence
and source of PTHrP in sarcoidosis.
Objective: To describe parathyroid hormone related
protein (PTHrP) as a mediator of hypercalcemia in
sarcoidosis.
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Abstract #529
and can be used as an initial screening tool. These are
simple to use and can help identify which patients should
undergo DXA scans.
SCREENING FOR OSTEOPOROSIS IN
MALE VETERANS: PERFORMANCE OF
OSTEOPOROSIS SCREENING TOOLS
Abstract #530
Soe Naing, MD, MRCP, Tin Tin Kyaw, MD,
Jian Huang, MD
Objective: To determine whether the Osteoporosis
Self -assessment Tool (OST) and Men Osteoporosis Risk
Estimation Score (MORES) can be used as initial screening tools to predict osteoporosis in male veterans.
Methods: This study is a retrospective cross sectional
study. Male veterans who underwent dual x-ray absorptiometry (DXA) scan from 12/01/2004 to 11/30/2006 were
studied. They were considered to have at least one risk
factor for osteoporosis when they were selected for bone
density scan. OST index and MORE scores were calculated in these patients. General Electrics, Lunar Prodigy
Advance DXA scan was used to measure bone density in
all patients. Osteoporosis was defined as a DXA T score
of –2.5 or less in the spine, total hip, or femoral neck. OST
index was calculated as 0.2x (weight in Kg-age in years).
The MORES included 3 variables—age, weight, and history of chronic obstructive pulmonary disease.
Results: 132 (31%) of 421 men, with a mean age
of 71.3 years (26-91) and a mean weight of 85.0 kg (47154), had osteoporosis. 316 (75%) were White, 57(13.5%)
Hispanic, and 20(4.8%) African-American. The OST
index ranged from –8 to 20. Using an OST cutoff index
of 3, we predicted osteoporosis with a sensitivity of 80%,
a specificity of 45% and the area under the curve (AUC)
of 67%. The MORE scores ranged from 0 to 13. Using a
MORE cutoff score of 6, we predicted osteoporosis with a
sensitivity of 75%, a specificity of 55% and the area under
the curve of 70%. Using both OST cutoff index of 3 and
MORE cutoff score of 6, sensitivity improved to 89%,
specificity to 61% and the area under the curve to 89%.
Discussion: Several screening tools have been studied to help clinicians determine the risk of osteoporosis
in women. Relatively few screening tools have however
been suggested in men. Simple and effective tools are
needed to identify men at risk for osteoporosis. OST and
MORES have been proposed as initial screening tools for
men but there were very limited information on their performance in male veterans. Their sensitivity, specificity
and the area under the curve in our study were lower than
that was reported in other studies. However these results
significantly improved when both OST and MORES criteria were applied.
Conclusion: Combined use of OST and MORES
improves the prediction of osteoporosis in male veterans
MULTI-FACTORIAL RESISTANT
HYPOCALCEMIA IN AN ONCOLOGY PATIENT
BEING TREATED FOR BONE METASTASIS:
WHEN BISPHOSPHONATE USE AND VITAMIN D
DEFICIENCY MEET GLUCOCORTICOIDS
Isabelle Zamfirescu, MD, Harold E. Carlson, MD,
Herman Katz, MD
Objective: This case illustrates the potential danger of
hypocalcemia occurring in routine treatment for oncologic
complications of bone metastasis.
Case Presentation: Oncology patients with metastatic bone lesions commonly receive frequent bisphosphonate administration in treatment of bone metastasis
and at times require high dose glucocorticoids for spinal
cord compression. As with many chronic illnesses, oncologic patients also have high rates of vitamin D deficiency.
We present a case of resistant hypocalcemia in a patient
with unrecognized vitamin D deficiency who had been
receiving monthly bisphosphonate infusions for treatment
of metastatic colon cancer in whom the hypocalcemia
began after initiation of high dose glucocorticoids for cord
compression. Treatment with high doses of oral calcium,
calcitriol and ergocalciferol had little effect in correction
of hypocalcemia in the patient who required intravenous
calcium for several days. Ultimately the hypocalcemia
improved as glucocorticoids were reduced and continued
therapy with high doses of calcium and vitamin D.
Discussion: This case demonstrates resistant hypocalcemia caused by multiple factors in combination. We
hypothesize that there were three main interrelated causes
for the patient’s hypocalcemia. First, the patient had
received treatment with intravenous bisphosphonate on a
monthly basis. Several cases of hypocalcemia associated
with bisphosphonate use have been reported in oncology
patients due to suppression of bone resorption by osteoclasts and a resulting inability to respond to hypocalcemia
by liberation of skeletal calcium. In the current patient,
the hypocalcemia began shortly after the initiation of
high dose glucocorticoid therapy for treatment of cord
compression symptoms and improved only as the glucocorticoids were tapered, thus indicating a critical role for
glucocorticoids in the development and persistence of the
hypocalcemia. While glucocorticoids are known to lead to
negative calcium balance they rarely cause hypocalcemia
when given alone. Finally, our patient was also found to
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be profoundly vitamin D deficient and this proved difficult
to correct. This vitamin D deficiency may have impacted
skeletal bone resorption. It is also possible that high doses
of glucocorticoids also led to decreased vitamin D absorption or metabolism and ultimately decreased intestinal calcium absorption. We explore the causes of hypocalcemia
in this patient based on current literature.
Conclusion: Glucocorticoid use for spinal cord compression in this patient with a history of bisphosphonate
use and vitamin D deficiency led to the development and
persistence of a dangerous degree of hypocalcemia.
Abstract #531
FUNCTIONING MEDIASTINAL
PARATHYROID CYST
Janna Cohen-Lehman, MD, Stuart Weinerman, MD,
Ageliki Valsamis, DO
Discussion: Little over 100 cases of mediastinal parathyroid cysts have been reported with some detail in the
literature. Parathyroid cysts are quite rare, representing
0.6% of all parathyroid and thyroid lesions. Only 10%
of all parathyroid cysts are found in the mediastinum.
Parathyroid cysts associated with raised serum intact PTH
and calcium and low phosphate are classified as functional
cysts. It remains unknown how cystic PTH enters the circulation to raise serum PTH. Confirming elevated PTH
levels on FNA can make the preoperative diagnosis of a
parathyroid cyst. Surgical resection is the treatment of
choice for functional mediastinal parathyroid cysts.
Conclusion: Functioning mediastinal parathyroid
cysts are a rare cause of hypercalcemia. In order to avoid
unnecessary surgery, it is important to include ectopic
sources of parathyroid hormone in the differential diagnosis of hypercalcemia.
Abstract #532
Objective: Hypercalcemia due to a functioning parathyroid cyst is rare, and when located in the mediastinum
can present a diagnostic challenge to the treating physicians. We describe the case of a 79-year-old female who
presented with hypercalcemia due to a functioning mediastinal parathyroid cyst, the identification of which was
elusive.
to another institution with altered mental status. She was
diagnosed with primary hyperparathyroidism with serum
calcium of 18.2 mg/dL (8.4 – 10.5 mg/dL) and parathyroid
hormone (PTH) level of 2115 pg/mL (15 – 65 pg/mL), and
right superior parathyroidectomy was performed. Calcium
and PTH levels remained elevated postoperatively, and
the patient was transferred to our institution. A computed
tomographic (CT) scan of the chest revealed a simple cystic structure in the anterior mediastinum measuring 6.9 x
4.0 cm, which was thought to represent either a thymic or
pericardial cyst. Sestamibi scintigraphy suggested a possible single parathyroid lesion extending posteriorly from
the lower pole of the left thyroid lobe. It also demonstrated
a nonspecific large photopenic area with a thin irregular
rim of activity in the anterior mediastinum corresponding to the simple cystic structure identified on CT scan.
She underwent cervical re-exploration, which was again
unsuccessful at localizing the source of PTH. The patient
finally underwent fine needle aspiration (FNA) of the
mediastinal cyst, which resulted in a PTH of 364,800 pg/
mL. Median sternotomy was performed, and the pathology was consistent with a parathyroid cyst. Calcium and
PTH levels normalized, and her calcium levels remain
stable 5 months after surgery.
HYPERCALCIURIA ASSCOCIATED
OSTEOPOROSIS: ARE WE MISSING THE BOAT?
Sunil Asnani, MD, FACE, Romil Patel, Reema Salat,
Ushir Patel, MD, Neena Penagaluru, MD
Objective: To present a case of severe pre-menopausal
osteoporosis in a young woman.
Case Presentation: A woman in her 40s was evaluated for back pain and loss of 2 inches in height. She
denied depression and was menstruating regularly. She
had a history of primary hypothyroidism and nephrolithiasis. Family history was remarkable in that her mother had
severe osteoporosis. Physical examination was unremarkable; she was lean. Bone densitometry (DEXA) revealed
T and Z scores of -3.2 and -3.1 respectively at the lumbar spine, and -1.5 and -1.2 respectively at the right hip.
Pertinent labs: Serum Calcium 10.1 mg/dl (8.5-10.6);
25(OH) Vitamin D 36.2 ng/ml (32-100); intact PTH 38 pg/
ml (15-65); and TSH 2.6 µIU/ml (0.45-4.5); Endomysial
Antibody IgA was negative. The 24-hour-urine calcium
excretion was elevated at 618.8 mg (100-300); a repeat
24-hour study confirmed the elevated excretion at 537.5
mg (100-300). A diagnosis of Idiopathic Hypercalciuria
was made and treatment with hydrochlorothiazide was
initiated. Follow-up assessment has documented improvement in hypercalciuria.
Discussion: A case series of osteoporotic, premenopausal women found that 56% had idiopathic osteoporosis
and 44% had secondary osteoporosis. Almost 30% of these
women had vertebral fractures. Hypercalciuria was seen in
nearly 40% of patients with idiopathic osteoporosis. It has
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been suggested that idiopathic hypercalciuria is transmitted as an autosomal dominant trait with gene defects localized to chromosomal areas 9q33.2-q34.2 and 1q23-q24. It
is likely that the common form of hypercalciuria is a complex genetic disorder that is influenced by environmental
factors such as dietary intake. A family history of osteoporosis is frequently associated with this disorder. Patients
with idiopathic hypercalciuria should be advised to adhere
to a low calcium diet; hydrochlorothiazide is the treatment
of choice if there is evidence of bone demineralization or
recurrent renal stones despite dietary modification.
Conclusion: It is critical to identify patients with this
condition as a distinct, treatable subset of idiopathic osteoporosis given both the potential for renal dysfunction due
to recurrent nephrolithiasis and the potential for bone disease due to worsening mineralization.
malnutrition, infusion of iron dextran, use of vitamin D
and calcium based phosphate binders and insulin use in
patients with diabetes mellitus. All these are very common in patients with ESRD; obesity and diabetes are
other common co-morbidities. Our patient was interesting due to her lean habitus, normoglycemia and normal
calcium, phosphate and PTH levels, a scenario that has
been reported with increasing frequency of late and which
raises the possibility that other unknown abnormalities of
mineralization could also be involved in the development
of calciphylaxis in ESRD patients.
Conclusion: Elevated levels of parathyroid hormone
(PTH) and a high calcium-phosphorous product were
initially thought to be pivotal in the pathogenesis of calciphylaxis. The case described herein demonstrates that
such laboratory abnormalities are not invariably present.
Abstract #533
Abstract #534
NORMOCALCEMIC CALCIPHYLAXIS: A NEED
TO REEXAMINE THE PATHOGENESIS OF
UREMIC ARTERIOLOPATHY
OSTEOPOROSIS SCREENING IN WOMEN
ABOVE THE AGE OF 65 YEARS IN A
TEACHING PRACTICE
Sunil Asnani, MD, FACE, Ezinne Nwotite, MD,
Nduche Onyeaso, MD, Elizabeth Onyeaso, MD,
Swaleha Mahpara, MD
Abeer W. Anabtawi, MD, Mohammad Titi, MD,
Leela Mathew, MD
Objective: To describe a case of normocalcemic
calciphylaxis.
Case Presentation: A 70-year-old woman with endstage renal disease on hemodialysis for 5 years presented
with extremely tender skin lesions, distributed all over the
lower abdomen and lower extremities. The lesions were
2-5 cm extremely tender ischemic/necrotic ulcers with
eschars. Laboratory evaluation showed corrected calcium
of 9.7 mg/dl (8.5-10.5), phosphate 2.7 mg/dl (2.5-4.6) and
PTH 54.5 pg/ml (14-72). She had been on prophylaxis
against hypercalcemia and secondary hyperparathyroidism with paricalcitol and cinacalcet. A clinical diagnosis
of calciphylaxis was made and was confirmed by punch
biopsy of the skin. She was treated with high dose sodium
thiosulfate.
Discussion: Calciphylaxis, also known as calcific
uremic arteriolopathy, is a rare but serious disorder of
vascular calcification that leads to ischemia and necrosis of skin and soft tissue, and occurs in about 1-4% of
ESRD patients. The pathophysiology of calciphylaxis is
poorly understood. Putative mechanisms of pathogenesis
include abnormalities in coagulation, defects in inhibitors of mineralization (Fetuin-A and Matrix Gla protein)
and an increased calcium-phosphate product (hypercalcemia, hyperphosphatemia and secondary hyperparathyroidism). Associated trigger factors include weight loss,
Objective: Study aims at evaluating compliance rate
of primary care physicians in a teaching clinic based with
osteoporosis screening based on United States Preventive
Services Task Force (USPSTF) guidelines for screening
females above the age of 65 years for osteoporosis using
DEXA scan.
Methods: A retrospective review of electronic medical records (EMR) of all females between the age of 65
and 75 years who were followed for at least 1 year or more
by one of seven primary care physicians (PCP). Multiple
categories were reviewed including physician recommendation for osteoporosis screening with DEXA scan; notation that DEXA is inappropriate based on co-morbidities;
patient refusal of screening; documentation of osteoporosis screening in the health care maintenance sections by
scanning DEXA scan results in the EMR.
Results: The records of 143 female patients were analyzed. A total of 104 patients had their risk for osteoporosis
and the need for screening addressed by their PCP [overall 73% (range 56-82%)]. DEXA scan was performed on
98 patients while 6 patients refused. Twenty five patients
had a DEXA scan, but there was no documentation at the
Health Care Maintenance (HCM) section in the EMR
(24%).
Discussion: Little and variable data are available on
the national compliance rate for osteoporosis screening in
a primary care setting. A recent study estimated the mean
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compliance rate to be 56% [1]. Comparatively, our study
shows improved compliance rate of 73%. However, our
study was based on USPSTF guidelines, newer guidelines of the National Osteoporosis Foundation advocates
screening to include males above the age of 70 years, all
postmenopausal females and males above the age of 50
years with risk factors for osteoporosis.
Conclusion: Since morbidity, mortality and health
care cost of osteoporosis are rising; prevention, detection
and treatment of osteoporosis should be a mandate for primary care offices. More emphasis on the importance of
adequate patient education and physician documentation
is needed.
Abstract #535
MILK ALKALI SYNDROME:
OLD DISEASE, MODERN VERSION
volume depletion may worsen the hypercalcemia. PTH is
further suppressed by hypercalcemia. This cyclic pathophysiology maintains hypercalcemia and alkalosis as long
as calcium and alkali are taken in by mouth.
Conclusion: MAS is making a resurgence. A complete history remains the key to the diagnosis. Restoration
of normal renal function depends on the duration of hypercalcemia with acute cases having a better prognosis. If
unrecognized and left untreated, MAS can lead to metastatic calcification and renal failure.
Abstract #536
INADEQUEATE VITAMIN D LEVELS IN
AN OSTEOPOROTIC WOMAN WITH
CELIAC DISEASE
Jose Guillemo Jiménez-Montero, MD, FACE,
Alexandra Rosabal-Arce
Danielle Erin Lann, MD, Sunil Asnani, MD,
Anup Ohri, MD
Objective: To describe Milk Alkali Syndrome (MAS)
as a re-emerging etiology of hypercalcemia
with altered mental status, nausea and vomiting. She had
thyroidectomy 2 weeks prior to admission for a multinodular goiter with compressive symptoms. She was discharged home on tapering doses of Tums. However, she
continued to take high dose calcium, and also increased
her dietary calcium intake with milk and yogurt daily.
Admission calcium was 16.8 mg/dl (8.5-10.5), phosphorus 3.9 mg/dl (2.5-4.6), parathyroid hormone (PTH)
<1pg/ml (12-88), creatinine 1.8 mg/dl (0.44-1.00).
Calcium supplements were immediately discontinued and
the patient was hydrated aggressively with intravenous
normal saline. Her mental status markedly improved and
her serum calcium level normalized over the next 3 days.
Phosphorus decreased from 3.9 mg/dl to 2.1 mg/dl. She
was discharged in stable condition.
Discussion: MAS is caused by the ingestion of more
than 2 grams per day of elemental calcium with absorbable
alkali. Inability to suppress calcitriol and impaired calcium excretion increase susceptibility to the development
of this syndrome and likely play a pathophysiological role.
Avid absorption of large doses may lead to suppression of
PTH, which then produces enhanced bicarbonate retention by the kidney. Continuing ingestion of calcium carbonate and bicarbonate retention leads to alkalosis, which
causes increased calcium resorption in the distal collecting system of the kidney. Also, hypercalcemia produces a
renal concentrating defect that can be considered a form of
nephrogenic diabetes insipidus. Resultant dehydration and
Objective: To present a case of secondary osteoporosis in a middle age woman due to with celiac disease and
chronic steroid treatment.
Case Presentation: A 51-year-old female patient
with past history of myalgias, lumbar pain, and fatigue
was referred because of osteoporosis. She was treated
with analgesics and steroids during the last 5 years without relieve of her skeletal symptoms. The patient had no
thyroid, hepatic or renal dysfunction. For many years she
had suffered of abdominal discomfort, chronic diarrhoea
presumable due to lactose intolerance. At age 42, estrogens replacement therapy was initiated because of premature menopause. In 2007 a bone mineral density showed
osteopenia; alendronate was prescribed, but the patient
discontinued the medication because of gastrointestinal
intolerance. When she was seen in the endocrine clinic, in
September 2009, she complained of muscle aches, fatigue
and flatulence. At physical examination, she appeared
depressed, was pale, weighted 50 kg, her height was 157
cm, and the blood pressure was 100/80 mmHg. The abdomen was soft, no masses were palpated; pain was elicited
in the sacral region on palpation; the rest of the physical examination was unremarkable. Laboratory test were:
haemoglobin 11.5 g/dl; hematocrit 36.4 %; serum calcium
9.7 mg/dl; phosphorous 3.5 mg/dl; magnesium 3.5 mg/
dl; parathyroid hormone 32.7 pg/ml (15-68.3 reference
range); vitamin D3 levels 27 nmol/L (80-374 reference
range). Antitransglutaminase and endomyseal antibodies
were negative. In a new bone densitometry performed in
August 2009 osteoporosis was found. A small intestine
biopsy showed lymphocytic infiltrate (MARSH 1). A gluten free diet, vitamin D and calcium supplements were
initiated; three months later the patient had had no muscle
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pain, does not have fatigue and the abdominal symptoms
disappeared. However, she still complains of mild sacral
pain.
Discussion: The clinical manifestations, laboratory
and histological findings were consistent with celiac disease. Vitamin D insufficiency or deficiency can occur
in this condition and can cause metabolic bone disease.
Nonspecific musculoskeletal symptoms associated with
inadequate vitamin D levels lead other physicians treat
this patient with steroids, which in turn, increased the risk
of osteoporosis.
Conclusion: Premature menopause, chronic use
of steroids and vitamin D insufficiency, associated with
celiac disease, were the main causes associated with the
development of osteoporosis in this middle aged woman.
Conclusion: Five cases of iatrogenic hypercalcemia
or vitamin D intoxication are described. This experience
casts doubt on the conclusion that doses of vitamin D
which greatly exceed RDA are safe in most persons.
Abstract #537
Objective: To report a case of end-stage PHPT caused
by supernumerary parathyroid glands in a man with previous amputation of a suspected brown tumor.
Case Presentation: A 41-year-old Hispanic male
admitted with acute pancreatitis. The patient had h/o
RUE amputation secondary to “giant cell osteosarcoma”
in Cuba in 2006. In 2008 he had a left pathologic femur
fracture. On admission he had abdominal pain, vomit,
extreme fatigue, and inability to stand. Imaging studies
including CT-scan of the abdomen and skeletal survey
demonstrated: acute pancreatitis and diffuse lytic lesions
in the iliac bones as well as multiple lytic rib lesions and
punched-out lytic calvarial and vertebral lesions respectively. Biochemical studies showed severe hypercalcemia
(corrected calcium: 15 mg/dL) and markedly elevated
PTHi: 2,381 (5-65 pg/mL). SPEP and UPEP showed no
monoclonal band. PTH-RP <2.1 pmol/L. Sestamibi scan
showed abnormal accumulation below the lower pole of
the left lobe of the thyroid gland, as low as within the
thymus gland. The patient was taken to surgery where
six hyperplastic parathyroid glands and a left mediastinal
mass consistent with parathyroid tissue were found. Five
and a half glands and the mediastinal mass were resected.
Post-op evolution was remarkable for hungry bone syndrome that resolved. The patient was discharged in good
condition and is followed up as outpatient. Current PTHi:
32 pg/mL.
Discussion: PHPT is a disease which has evolved
from its classic presentation to a one quite different and
now most patients have few symptoms and mild hypercalcemia. Skeletal manifestations of PHPT are rare nowadays since the early detection of the disease has been possible by the introduction of serum calcium determination
in the routine biochemical screening. In some countries,
however, overt manifestations of PHPT including osteitis fibrosa cystica are still present. This case describes
IATROGENIC HYPERCALCEMIA AND
HYPERVITAMINOSIS D IN
MIDDLE-AGED WOMEN
John David Faichney, MD
Objective: To describe an experience in which commonly prescribed doses of vitamin D and calcium were
associated with hypercalcemia or hypervitaminosis D.
Case Presentation: Five women, middle-aged or
older, menopausal and with another endocrine diagnosis: Addison’s, thyroiditis or diabetes mellitus. All were
receiving doses of vitamin D which greatly exceeded
(RDA) of 400 IU, calcium supplementation. Vitamin
D dose range: 1600-4400 IU/day. Calcium supplement
range: 1000-2400 mg/day. Significant hypercalcemia
(10.8-12.3 mg/dl) observed in 4 of 5 cases. Significant
hypervitaminosis D (154, 214 ng/ml) observed in 2 of 5
cases. Detectable but low PTH (23 pg/ml, 31 pg/ml) in 2
cases when hypercalcemic. One woman did not manifest
hypercalcemia despite persistent hypervitaminosis D.
Discussion: These women shared some common
demographic features (age, gender, menopause, endocrine
disease) and all received generous vitamin D and calcium
supplements with physician blessing. For diverse reasons,
all became either hypercalcemic or vitamin D intoxicated.
The two women with vitamin D intoxication could have
been exposed to toxic concentrations of D in supplements.
A discordance between vitamin D levels and hypercalcemia was also observed and as well relatively low parathyroid hormone levels, though detectable, in 2 with normal
vitamin D and high calcium. The safety of high dose vitamin D and calcium therapy without monitoring must be
questioned.
Abstract #538
A CASE OF END-STAGE PRIMARY
HYPERPARATHYROIDISM (PHPT) WITH
MARKEDLY ELEVATED PARATHYROID
HORMONE LEVELS DUE TO
SUPERNUMERARY PARATHYROID GLANDS
Andrea Marcela Sosa Melo, MD,
Ana Cecilia Apaza-Concha, Hermes Florez
– 94 –
perfectly the complications associated with PHPT when is
misdiagnosed: this patient suffered of repeated attacks of
pancreatitis most likely secondary to chronic hypercalcemia. He underwent amputation of his RUE with a pathology report consistent with “giant cell osteosarcoma,” considered the main differential diagnosis of brown tumor
(BT).
Conclusion: BTs are pathognomonic of end-stage
PHPT. The fact that they are very rarely observed make
their diagnosis challenging to the physician. Histologically,
BT may be indistinguishable from giant cell tumors of the
bone and the diagnosis requires clinical, biochemical and
radiological correlation.
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ABSTRACTS – Obesity
OBESITY
This study shows improvements in health-related quality
of life, both in the physical and mental components, at 4
and 12 weeks, in obese patients participating in a multidisciplinary weight management program while using a
VLCD, behavior therapy and nutrition counseling.
Abstract #600
EFFECT OF MULTIDISCIPLINARY SUPERVISED
WEIGHT LOSS ON QUALITY OF LIFE
Abstract #601
Christopher Case, MD
Objective: The purpose of this study is to evaluate the
changes in health-related quality of life in obese individuals utilizing a very low-calorie diet (VLCD) with multidisciplinary supervision, behavior therapy, and nutrition
counseling.
Methods: Consecutive obese individuals (n=65)
enrolling in a weight loss program were asked to complete
the SF-36 version 2TM Health Survey form at baseline
prior to weight loss and at 4 weeks and 12 weeks after
starting the VLCD to evaluate health-related quality of
life. Weight reduction was supervised weekly by physicians, dietitians, and behaviorists in both a clinic setting
and group classes. All participants had a body mass index
(BMI) greater than 30 at baseline. The diet was an individually prescribed protein-sparing VLCD (average 800
kcal) with meal replacement products. No supplements
or medications were prescribed, and participants were
advised to begin physical activity (less than 45 minutes
weekly) after 4 weeks. Norm-based scores were calculated using QualityMetric Health OutcomesTM scoring
software. Paired t-tests were used to compare the eight
domains of the SF-36, as well as mental and physical
composite summaries, from baseline to 4 and 12 weeks.
Patients and the investigator were not aware of calculated
scores during active weight loss.
Results: At baseline, participants had SF-36 scores in
all domains below the general population norm. Scores
improved in all eight domains of health-related quality of
life at 4 and 12 weeks compared to baseline (all P<0.001),
and in both the physical and mental composite summaries. All domains showed improvements to greater than
the mean.
Discussion: Obesity can have a significant impact
on the mental and physical aspects of quality of life.
Unfortunately, very few treatments in medicine objectively improve health-related quality of life. VLCDs may
lead to significant and rapid weight loss, which often
results in many improvements in the metabolic abnormalities associated with obesity. The findings in this
study show that the medical treatment of obesity through
a coordinated clinic can also robustly improve quality of
life, providing endocrinologists, bariatrians, and patients
important options.
Conclusion: Individuals enrolling in multispecialty
weight loss centers have low health-related quality of life.
THE PATTERN OF OBESITY IN HIV
POSITIVE PATIENTS ON HIGHLY ACTIVE
ANTIRETROVIRAL THERAPY
Ayoola Olukunmi Oladejo, MBBS,
Jokotade Oluremilekun Adeleye, MBBS, FWACP,
Yetunde A. Aken’ova, MBBS, FWACP, FMCpath
Objective: To determine the pattern of Obesity in
HIV positive patients on highly active antiretroviral therapy (HAART) and to compare with the pattern seen in
HAART naïve HIV positive patients.
Methods: One hundred and eighty HIV positive
patients were selected by systematic random sampling.
Ninety-two were on highly active antiretroviral therapy
while eighty-eight were HAART naïve. Anthropometric
measurements such as the weight, height, body mass
index (BMI) and waist circumference were all done by
standard methods. Obesity was defined as BMI greater
than 30Kg/m2 and abdominal obesity was defined by the
cut off value for Europeans as defined by the International
Diabetes Federation criteria for the diagnosis of the metabolic syndrome. The fasting plasma glucose and the lipid
profile were also assayed.
Results: The mean ages of the HAART and the
HAART naïve group were 40.1± 9.5 and 37.7± 9.3 respectively (p= 0.081). The mean BMI in the HAART group
and the HAART naïve group was 26.3± 11.0 and 23.1±
4.2 respectively, p=0.012. The mean waist-circumference
between the HAART group and the HAART naïve group
was 86.8± 10.4 and 80.0± 9.5 respectively, p= 0.0001. The
overall prevalence of generalized obesity was 12.8% being
19.6% in the HAART group and 5.7% in the HAART naïve
group, p=0.002 while the overall prevalence of abdominal
obesity was 46.1% being 54.3% in the HAART group and
37.5% in the HAART naïve group, p< 0.05.
Discussion: The human immunodeficiency virus is
the etiologic agent for human immunodeficiency virus
infection and acquired immunodeficiency syndrome
(AIDS) which is the end of the spectrum of HIV infection.
AIDS is characterized by profound immune-suppression
with increased susceptibility to opportunistic infections
and certain malignancies. Individuals with advanced
disease suffer from the wasting syndrome which has a
multifactorial pathogenetic factors such has anorexia,
malabsorption states and cytokine induced cachexia. The
– 96 –
advent of HAART has revolutionized the management of
HIV infection with a dramatic reduction in morbidity and
mortality frequently associated with untreated advanced
disease and improvement in the general well being of
patients. However, this therapy is often associated with
some untoward metabolic complications which may
increase the risk of cardiovascular disease. These metabolic complications such as systemic hypertension, dysglycemia, dyslipidemia and lipodystrophy syndrome have
all been described in various studies.
Conclusion: This study has shown a higher prevalence of both generalized obesity and abdominal obesity in HIV positive on HAART therapy than the HAART
naïve group. Both generalized and abdominal obesities
have been strongly linked with increased insulin resistance and increased risk of type 2 diabetes and atherosclerotic cardiovascular disease.
Abstract #602
TO STUDY THE ROLE OF LEPTIN,
RESISTIN, AND ADIPONECTIN IN AN
ADOLESCENT OBESE GROUP
Sanjay Ganesh Godbole, MD, Chinmay Godbole,
Bhagyashri Shah, Sujata Mahadik
Objective: Global epidemic of obesity is well
described in the adult population but not much data is
available regarding the prevalence of childhood obesity
in developing countries. Adipose tissue derived adipocytokines attract an increasing attention due to the important
role they play in the pathogenesis of obesity and diabetes.
Hence in this study we have determined the prevalence
of adolescent obesity in urban population, and studied the
role of adipocytokines like leptin, resistin and adiponectin
in adolescent obesity.
Methods: A total of 50 overweight and obese subjects were recruited in this study. Fasting insulin, leptin,
resistin and adiponectin levels were measured by RIA &
ELISA method. Insulin Resistance index was calculated
by the Homeostasis Model Assessment (HOMA-IR). The
relation between these variables was studied by univariate
regression analysis.
Results: Overall Prevalence of obesity is 7.7% in
our study population. Main findings of the present study
were high prevalence of obesity in girls compared to
boys. In addition girls exhibited higher fasting plasma
glucose, serum insulin, HOMA-IR and leptin levels compared to boys. In linear regression analysis we found that
among the Adipocytokines leptin is a strong predictor of
HOMA-IR in our adolescent obese group.
Discussion: Elevated leptin levels and its association with insulin resistance support the role of leptin in
the etiopathogenesis of adolescent obesity. Thus with the
strong association between obesity and insulin resistance,
prevention and treatment of adolescent obesity appears to
be essential to prevent the development of insulin resistance and the associated complications.
Abstract #603
ENDOGENOUS CUSHING SYNDROME IN
SEVERELY OBESE POPULATION
Simona Vasilica Fica, MD, PhD, FACE, Anca Sirbu, MD,
Sorina Martin, MD, Carmen Barbu, MD, PhD,
Catalina Poiana, MD, PhD, FACE, Suzana Florea,
Claudia Lenghen, MD
Objective: To evaluate the prevalence of Cushing syndrome in severely obese patients before bariatric surgery.
Methods: In a prospective study that we have conducted in the last 2 years, we exhaustively evaluated (personal and heredocollateral history, psychological parameters and eating behavior disturbances, clinical exam,
biochemistry: inflammation, lipid profile, glycemia, oral
glucose tolerance test, insulinemia, hormonal tests: stress
hormones profile, ghrellin, leptin and other adipocitokines plasma level) a total of 176 obese subjects (65.3%
female), aged 18-67 (mean 40.29), with BMI 36-74.20
Kg/m2 (mean 48.38) and indication for bariatric surgery.
They all completed 1 mg overnight dexamethasone suppression test ( DST) (cut-off level<1.8 μg/dl). If any result
was abnormal, tests were repeated and completed with
other tests (high-dose dexamthasone suppression test,
ACTH)
Results: 14.2% (25 patients) had falsely abnormal
1 mg overnight DST, but 4 patients were diagnosed with
Cushing syndrome (3 Cushing diseases, 1 adrenal cortisol secreting adenoma), rendering the prevalence of
the endogenous syndrome to 2.27%. We compared the
patients with falsely elevated cortisol after 1 mg dexamethasone overnight with the others with suppressible
cortisol. The obese patients with falsely elevated cortisol
>1.8μg/dl after 1 mg overnight DST were older (p=0.047),
had higher basal glycemia (p=0.008) and higher morning
basal cortisol (p=0.002), but there was not statistical significant difference in BMI, waist, HOMA-IR or cholesterol, triglycerides. In this group neither basal morning
plasma cortisol nor cortisol after 1 mg DST correlated
with age, BMI, waist, basal glycemia or HOMA-IR. The
prevalence of previous known hypertension, diabetes mellitus, ischemic heart disease and dyslipidemia was not different in those two groups.
Discussion: Classic endogenous syndrome is a rare
disease with an estimated incidence of 10 cases/million
person/year. Recent reports suggest a higher prevalence
– 97 –
(1–5%) of Cushing syndrome in certain patient populations (e.g., uncontrolled diabetes and/or hypertension), but
the prevalence in an obese population is not known. We
evaluated severely obese patients with BMI > 40kg/m2 or
BMI ≥ 35kg/m2 and one or more severe comorbidities,
who were referred to the endocrinologist with indication
for bariatric surgery, without specific clinical suspicion
of Cushing’s syndrome, and found a high prevalence of
endogenous Cushing’s syndrome (2.27%).
Conclusion: Although current bariatric surgery
guidelines do not consider cost-effective and neither
recommend routine laboratory testing to screen for rare
causes of obesity, our data support screening for Cushing’s
syndrome in this category of obese patients, before bariatric surgery.
Abstract #604
PRIOR GASTRIC BYPASS SURGERY
COMPLICATING TOTAL THYROIDECTOMY
hyperparathyroidism. The pouch created to serve as a
stomach in RYGB produces less acid than a normal stomach, thus calcium citrate is the recommended calcium
preparation to be used in these patients (1). Relatively
large doses of calcium citrate, calcitriol and vitamin D
may be required to treat hypocalcemia in RYGB patients.
Conclusion: Bariatric surgery patients undergoing
thyroid surgery are at increased risk of hypocalcemia and
require aggressive supplementation to maintain normal
serum calcium levels. Preoperative supplementation with
calcium and vitamin D is recommended. Intra-operative
PTH measurements should be considered.
Abstract #605
ATTIVA, A NOVEL SUPERABSORBENT
BIODEGRADABLE HYDROGEL, INCREASES
THE FEELING OF SATIETY IN HUMANS
Hassan Massoud Heshmati, MD, Roberto Tacchino, MD,
Eyal Ron, PhD, Alessandro Sannino, PhD, Yishai Zohar
Bianca Alfonso, MD, Michael Via, MD
Objective: To describe a case of profound hypocalcemia occurring after total thyroidectomy in a patient with a
prior gastric bypass surgery.
Case Presentation: A 58-year-old female with a history of Roux-en-Y gastric bypass surgery (RYGB) presented with dysphagia secondary to multinodular goiter.
She underwent total thyroidectomy. All parathyroid glands
were identified and preserved. The patient’s baseline calcium was 8.4 mg/dL, creatinine 0.6 mg/dL, albumin 4.2 g/
dL, parathyroid hormone (PTH) 72.9 pg/mL and thyroid
stimulating hormone (TSH) 1.99 mIU/L. PTH decreased
intra-operatively to 7.1 pg/mL and subsequently became
undetectable. Postoperatively, she developed symptomatic hypocalcemia that required large doses of intravenous
calcium gluconate (2 g daily), oral calcium carbonate (7.5
g daily), calcium citrate (2 g daily), calcitriol (up to 4 g
daily) and ergocalciferol (50,000 IU daily). Serum calcium levels remained normal on this regimen after hospital discharge despite persistent hypoparathyroidism.
Discussion: Bariatric surgery drastically and positively changes the lives of obese individuals. Despite
significant improvements in obesity associated conditions and mortality, there are potential complications
and numerous metabolic and dietary sequelae associated
with RYGB. Manipulation of the parathyroid glands during thyroidectomy can result in transient or permanent
hypoparathyroidism. Bariatric surgery patients are at high
risk of severe hypocalcemia following thyroidectomy
due to diminished intestinal calcium absorption, longstanding vitamin D deficiency and prolonged secondary
Objective: To assess the effect of single administration of Attiva, a novel superabsorbent biodegradable
hydrogel obtained from cellulose derivatives, on satiety in
humans.
Methods: Ninety-five subjects (73 females, 22 males)
with a mean age ± standard deviation (SD) of 41 ± 12
years (range, 19-67 years) and a mean body mass index
(BMI) ± SD of 31.1 ± 7.5 (range, 18.0-55.9) were studied.
Twenty-one subjects had normal (or subnormal) BMI, 22
were overweight, and 52 were obese. Subjects received
2 g of Attiva (5 oral capsules) versus placebo before
breakfast, lunch, and dinner, in a double-blind, cross-over
fashion. There was a 3-day interval between each administration of Attiva to the same subject. Meals consisted
of habitual intake of each subject and were consumed
at home. Satiety was assessed using a self-administered
questionnaire immediately, and 30 and 60 minutes after
meal. The questionnaire included 5 options to score the
feeling of satiety: not at all (score 0), a little (score 1),
enough (score 2), very (score 3), and very much (score 4).
Statistical analysis was performed with a paired t-test.
Results: Attiva significantly increased the feeling of
satiety at 30 minutes after breakfast and dinner, and at 60
minutes after lunch and dinner. The mean ± SD for the
satiety scores with Attiva versus placebo at 30 minutes
were 1.85 ± 0.93 versus 1.63 ± 0.95 (P = 0.037), 1.84 ±
1.14 versus 1.66 ± 0.87 (P = 0.071), and 1.98 ± 0.97 versus 1.70 ± 1.01 (P = 0.004), for breakfast, lunch, and dinner, respectively. The mean ± SD for the satiety scores
with Attiva versus placebo at 60 minutes were 2.13 ± 1.00
versus 2.12 ± 0.83 (P = 0.960), 2.35 ± 1.06 versus 2.07 ±
– 98 –
0.86 (P = 0.007), and 2.46 ± 1.12 versus 2.15 ± 0.99 (P =
0.006), for breakfast, lunch, and dinner, respectively. The
administration of Attiva was safe and well tolerated.
Discussion: Attiva is able to swell in the stomach in
the presence of water and gastric fluids. By occupying the
gastric and intestinal cavities, Attiva can induce a feeling of satiety that lasts until the hydrogel is degraded in
the colon and expelled in the feces. The overall results of
this study demonstrating increased feeling of satiety with
Attiva are in agreement with the physical properties of
Attiva.
Conclusion: Single administration of Attiva, a
novel superabsorbent biodegradable hydrogel, to humans
increases the post-meal feeling of satiety. The treatment is
well tolerated. This effect of Attiva on satiety, if confirmed
by long-term studies, will support Attiva as a potential
anti-obesity product.
Abstract #606
PREVALENCE AND RISK FACTORS OF
METABOLIC SYNDROME IN NIGERIANS
WITH TYPE 2 DIABETES MELLITUS
Rosemary Temidayo Ikem, MD, David Soyoye, MD,
Adebayo Joseph Olorunfemi, MD,
Babatope A. Kolawole, MD
Objective: The clustering of metabolic abnormalities
in people with metabolic syndrome confers substantial
and additional cardiovascular risk over and above the sum
of the risks associated with each abnormality. For nondiabetics with metabolic syndrome, the risk for developing type 2 DM is increased five times. The inclusion of
type 2 DM as part of the definition of MS thus seems to
overwhelm other risk factors in some populations since
DM by itself is a strong CVD risk factor. To determine
the prevalence of MS using IDF criteria and to compare
the Anthropometric and Metabolic (Lipids) features of
patients Type 2 DM with and without metabolic syndrome.
Methods: All type 2 DM patients attending out patient
diabetic clinic of Obafemi Awolowo University Teaching
Hospital Complex Ile-Ife were recruited. This study was
carried out over a three month period. Their demographic
and metabolic parameters were noted and analysed.
Results: One hundred and thirty four subject with type
2 diabetes were seen, 62(46.3%) males and 72 (53.7%)
females. Their mean age was 57.65 ± 10.0 years with a
range of 31 – 90 years. The mean BMI was 26.13 ± 4.3 Kg/
M2. The prevalence of metabolic syndrome was 44.8% i.e.
60/134 M: F = 18 (30%): 42 (70%). Comparison of demographic and metabolic parameters in patients that exhibited feature of met syndrome and those without showed
that, waist circumference, blood pressure; HDL and LDL
cholesterol showed a statistical significance difference in
both groups.
Conclusion: Metabolic syndrome serves a useful
purpose in that it draws attention to the fact that some
CVD risk factors tend to cluster in predisposed patients.
The essential point in this study is that the identification of
one risk variables in a patient should prompt a search for
others.
Abstract #607
VISFATIN, ADIPONECTIN, LEPTIN AND
MACROPHAGE MIGRATION INHIBITORY
FACTOR (MIF) IN SEVERE OBESE WOMEN
WITH NORMAL AND IMPAIRED
GLUCOSE TOLERANCE
Mirjana Sumarac-Dumanovic, MD, PhD,
Micic Dragan, MD, PhD,
Stamenkovic-Pejkovic Danica, MD
Objective: Hyperglycemia could increase plasma
visfatin in patients with T2DM. This increase gets more
prominent as the glucose intolerance worsens. Macrophage
Migration Inhibitory Factor (MIF) is elevated in obesity
and it was shown that metformin suppresses plasma MIF
in the obese. The aim of the study was to determine level
of plasma visfatin, adiponectin and leptin as well as MIF
in severely obese women with normal and impaired glucose tolerance.
Methods: Ten obese women (age: 35.46±2.21yrs;
BMI 34.11±0.75 kg/m2) with normal glucose tolerance
(NGT) and 10 age and BMI matched obese women (age:
35.80±2.54 yrs; BMI 36.98±1.66 kg/m2) with normal
fasting and impaired glucose tolerance (OGTT-75 gr of
glucose) (IGT) were included in the study. Fasting plasma
visfatin (EIA Phoenix, ng/ml), adiponectin (Linco RIA,
ng/ml), leptin (Linco RIA, ng/ml) and insulin (RIA Inep,
mU/l), MIF (ELISA, ng/l) were measured. Insulin sensitivity (M index: mg/kgBW/min) was determined using
euglycemic 2hr clamp.
Results: There was no difference in fasting visfatin between NGT and IGT (72.66±4.11 vs. 69.80±5.55,
p>0.05), fasting leptin (33.53±2.98vs.30.70±3.88, p>0.05)
fasting adiponectin (8.84±1.61vs.9.65±4.59, p>0.05) and
plasma MIF (2456.75±428.91 vs. 2344.80±481.80, p
>0.05). Insulin senstitivity was reduced in obese women
with IGT (6.55±0.51vs.2.74±0.38, p<0.05).
Discussion: There were no significant correlations
among investigated parameters neither with insulin sensitivity index. No significant difference among investigated
adipocytokines was found in women with IGT in comparisson with women with NGT.
– 99 –
Conclusion: In conclusion, our data suggest that
impairment in insulin sensitivity precede change in adipocytokines and MIF during development of type 2 diabetes in obesity.
Abstract #608
THE EFFECT OF EXENTIDE ON BODY WEIGHT
AND GLYCEMIC CONTROL IN A PATIENT WITH
HYPOTHALAMIC SYNDROME UNDERGOING
BARIATRIC SURGERY
Ibrahim Mamoun Ibrahim, MD, Jeevan Mettayil, MD
Objective: The anorectic gut hormones GLP-1 (glucagon-like peptide 1) and co-secreted peptides such as
Oxyntomodulin and Peptide YY are among prime candidates for manipulation in the development of new therapies for obesity. We report the effect of Exenatide on body
weight and blood glucose control in a morbidly obese
patient with hypothalamic syndrome.
Case Presentation: A 37-year-old male with a history
of type 2 diabetes mellitus on insulin for five years and
a background of midline cerebral angioma, treated with
stereotactic high dose radiotherapy, complicated with
panhypopituitarism and hypothalamic state. He also had
obstructive sleep apnoea, deep vein thrombosis (DVT),
depression and morbid obesity. He had evidence of severe
insulin resistance, needing more than 300 units of insulin
per day. He was maintained on insulin and Pioglitazone.
However his insulin requirements were going up with a
BMI of 55 and he was subsequently referred for bariatric surgery. Three months before his surgery we decided
to add in GLP-1 analogue based therapy (Exenatide) to
help him lose some weight before the surgery. On the
initiation of Exenatide he lost a total of 16 kilograms in
weight, came off Pioglitazone and NovoRapid and was
maintained only on 18 units of Glargine. Gastric banding
was the bariatric surgery of choice because he had had a
recent DVT. Following the gastric banding, Exenatide was
stopped and he was discharged on 10 units of Glargine per
day. However, four months following the surgery he only
had very minimal weight loss of about 3 kilograms and his
blood glucose levels had deteriorated significantly and he
needed more basal and meal insulin. Exenatide (Byetta)
was restarted in addition to basal insulin and his blood
glucose levels responded very well to this, but it is still too
early to comment on any further weight reduction.
Discussion: This case report highlights emerging data
that GLP-1 is in fact both a gut hormone and a cerebral
neuropeptide with a very limited site of production in the
brain. It is produced by alpha cells of the pancreas, L cells
of the gut as well as by neurons chiefly located in the caudal section of the nucleus of the solitary tract (NST). Both
GLP-1 and its co-synthesized partner, Oxyntomodulin, are
quite potent anorexigenic peptides through both peripheral and central actions. Hypothalamic, dorsomedial and
paraventricular nuclei are also sites of GLP-1 action.
Activation of these areas leads to production of anorexigenic precursors like Pro-opiomelanocortin (POMC).
By far the highest brain levels of GLP-1 are found in the
hypothalamus, where it is present in nerve endings and the
NST acts as an important relay and amplification site for
GLP-1 signals.
Conclusion: The dramatic weight loss that we report
in this case of hypothalamic obesity is a clear pointer to
the potential of using the anorectic actions of gut hormones in the management of obesity.
Abstract #609
DEXA MORE ACCURATELY PREDICTS
OBESITY COMPARED TO BMI UTILIZING
AMERICAN BARIATRIC SOCIETY CRITERIA
FOR OBESITY IN 1,234 ADULTS IN A PRIMARY
CARE OUT-PATIENT FACILITY.
Eric Braverman, MD, Mallory Kerner, Stanley Huang,
Stella Savarimuthu, Uma Damle, Jennifer Quon,
Kenneth Blum, PhD, Nirav R. Shah, MD, MPH
Objective: Obesity has been recognized as an epidemic in the United States with approximately 23% of
Americans determined to be obese by the commonly
used body mass index (BMI). However, a direct measurement of adiposity by dual X-ray absorptiometry (DEXA)
is a more precise body fat indicator than BMI. To date,
no large-scale comparison has been made between BMI
and DEXA to directly measure percentage body fat. As
the prevalence of overweight and obesity is increasing
and resulting in a larger burden to society, this study has
important implications for policymakers, clinicians, and
patients.To investigate and compare the differences and
descriptive properties of obese classification by BMI measurement and percentage body fat as measured by DEXA.
Methods: In a retrospective study, we reviewed
medical records from 2003 to 2009 to obtain BMI (from
height and weight) and percentage body fat (from Hologic
DEXA). Subjects were classified as obese or non-obese,
using the American Bariatric Society’s classification
(BMI: 30+, Body Fat %: 25%+ males, 30%+ females).
The 1,234 patients from a private outpatient medical practice were of age 18+ with BMI and DEXA data available.
All subjects provided approved IRB written informed
consent form, and this study was approved by the PATH
Institutional Review Board.
Results: Using BMI, 20% (n = 249) were classified
as obese. Of these 249: 95% (n = 237) were obese based
– 100 –
on body fat percentage while 5% (n = 12) were non-obese.
Using body fat percentage, 56% (n = 689) were classified
as obese. Of these 689: 34% (n = 237) were obese based
on BMI while 66% (n = 452) were non-obese. The percent identified as obese by BMI (20%) compared to that
by DEXA (56%) was highly divergent (P < 0.01). 37%
(452/1234) of patients were misclassified by BMI.
Discussion: Our measurement of obesity with BMI
was nearly equal to the national percentage. However, we
have shown that BMI is a highly insensitive measure of
obesity and under-diagnoses. Extrapolating our data on a
global scale, it is very likely that obesity is a much bigger
epidemic than is currently acknowledged.
Conclusion: In light of the importance of the global
obesity epidemic, the use of BMI should be greatly curtailed, and direct measure of adiposity should be used
on large subgroups of patients often misclassified by this
measure. Further analysis should help to identify which
patients may need DEXA analysis in addition to standard
BMI measurement, and which patients may be mislabeled
as obese when using BMI. We urge additional studies to
confirm these important results especially to more accurately determine the true nature of the global obesity
epidemic.
Abstract #610
GENDER AND AGE DIFFERENCES IN THE
PREVALENCE OF NONALCOHOLIC FATTY
LIVER DISEASE IN OBESE CHILDREN
Rishi Gupta, MD, Nicole A.V. Matthews, MD,
Amrit Bhangoo, MD, Henry Anhalt, DO,
Gracilla Wetzler, MD, Shivinder Narwal, MD,
Svetlana Ten, MD
Objective: Alanine aminotransferase (ALT) elevations are considered a surrogate marker of NAFLD. Aim
of present study is to evaluate the prevalence of elevated
ALT (>40 IU/L) levels in obese children and to study
the correlation between their ALT levels and metabolic
profile.
Methods: We studied 156 obese (BMI >95% for
age and sex) children (86 girls and 70 boys) in a clinic
based study with an age range of 5-20 years. The subjects
were divided into two groups based on their ALT levels
(ALT>40 IU/L was defined as elevated).
Results: Out of total 156 children, 56 were less than
11 years old and remaining were between 11-20 years.
The mean BMI of the group was 34.3±7.7. The prevalence
of elevated ALT was 19% in the overall group, higher in
boys (27%) than in girls (13%). The frequency of ALT
elevation increased with age in boys, 13.4% at 5-10 years
of age, 15 % at 11-15 years and 53 % at 16-20 years of
age. But inverse trend was noted in girls with increasing
age (15.1%, 14.7%, 7.1% at 5-10, 11-15 and 16-20 years
age group respectively). TG levels correlated positively
(r=0.39, P< 0.001) while HDL correlated negatively with
ALT levels (r= - 0.29, p < 0.001). Ratio of TG/HDL correlated positively with ALT (r= 0.37, p < 0.001) and AST
(r=0.27, p< 0.001). No significant difference was seen in
fasting blood glucose, fasting insulin, homeostatic model
assessment of insulin resistance (HOMA-IR), blood pressure, BMI or age between the groups with normal and
elevated ALT levels.
Discussion: NAFLD is highly prevalent in obese
children based on elevated ALT levels. To our knowledge, this is the first study which looks at the variation in
prevalence of NAFLD in children according to different
age groups in both the genders. The explanation for higher
prevalence of NAFLD in boys and specially with increasing age could be related to higher visceral fat in males.
Also puberty in boys is associated with increase in insulin
resistance whereas high estrogen levels in girls could be
protective. No difference in HOMA-IR was seen between
the two groups. But HOMA-IR is a marker of peripheral
insulin resistance, so it might not represent the insulin sensitivity at the level of liver and portal circulation. A high
TG/HDL ratio can also be used as an additional marker
for detection of NAFLD along with elevated ALT in obese
children.
Conclusion: These findings have implications for
increased NAFLD and metabolic profile screening in
obese children, especially boys so that we can prevent the
long term complications of NAFLD such as liver failure in
the beginning.
– 101 –
ABSTRACTS – Other
OTHER
Abstract #700
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
CONTRIBUTION TO RACIAL DIFFERENCES
IN CARDIOVASCULAR RISK IN
NORMOTENSIVE ADOLESCENTS
Prashanth Chandra Sekhar, MD,
Jennifer Pedersen-White, DO, Greg Harshfield, PhD
Background/Objective: To evaluate RAAS (reninangiotensin-aldosterone system) contribution to racial differences in blood pressure (BP) in normotensive adolescents. Hypertension (HTN) in adults is more prevalent in
African Americans (AA) than in Caucasians (CA) and is
a major public health problem. The prevalence of “adult”
diseases in children is increasing; an estimated 4.5% of
children are hypertensive, also with a greater prevalence
in AA than CA. Little is known about the mechanism(s)
underlying racial differences in HTN in children and adolescents. Methods: We examined 84 normotensive adolescents, age 15–18 years (47 AA, 37 CA). After 3 days on
a controlled sodium diet (4000 mg/day), resting BP was
measured (an average of BP taken by Dynamap every 15
minutes for two hours). Urinary sodium excretion (UnaV),
plasma renin activity (PRA), plasma angiotensin-II (Ang
II) and plasma aldosterone (Aldo) were collected after two
hours of rest. A 2-D echocardiogram was performed on all
subjects to calculate left ventricular mass (LVM).
Results: In CA subjects, systolic BP (SBP) correlated negatively with Ang II (r = -0.389, p = 0.017) and
positively with UnaV (r = 0.384, p = 0.019), indicating
appropriate RAAS suppression and pressure natriuresis.
In AA subjects, SBP was not associated with Ang II suppression (r = 0.090, p = 0.548) and correlated negatively
with UnaV (r = -0.309, p = 0.034), indicating a lack of
RAAS suppression and inappropriate pressure natriuresis.
Overall, SBP correlated positively with LVM (r = 0.380,
p = 0.000), a correlation which was accounted for by a
highly significant relationship seen in AA subjects only
(r = 0.449, p = 0.002).
Discussion: It is well known that BP contributes to
the development of LVM. Twenty percent of the variance
of LVM in our AA subjects was accounted for by SBP. Our
data supports that the lack of Ang II suppression (which
can affect BP through arteriolar constriction, enhanced
tubular sodium retention and augmentation of sympathetic activity) and inappropriate pressure natriuresis both
affect BP and contribute to early target organ damage in
AA adolescents.
Conclusion: Dysregulation of RAAS influences the
development of increased LVM in normotensive AA adolescents. Our findings suggest that non suppressible Ang
II levels in AA may contribute directly and/or indirectly to
increased LVM and earlier cardiovascular damage.
Abstract #701
THE BEST APPROACH FOR MANAGEMENT
OF A CASE WITH COMPLETE ANDROGEN
INSENSITIVITY SYNDROME
Ali Hasan Dhari Al-Jumaili, MD
Objective: To discuss the best approach of a child
with complete androgen insensitivity syndrome (CAIS)
and to drop light on increase of the incidence of pediatric
endocrinology disorders that demand more attention from
the high health authorities.
Case Presentation: 2.5-year-old female baby
appeared normal at birth, during childhood growth was
normal and the karyotypic incongruity remained unsuspected until an inguinal lump had been discovered to be
a testis during surgical repair of an inguinal hernia at
age of 8 months for that the surgeon referred her to our
clinic before 2 months. The pregnancy and delivery were
unremarkable. She is the only child for the family with
deceased mother consanguinity positive. The grandmother
mentioned that two married women relative to the father
are sterile with amenorrhea. O/E: she is 13 kg weight and
92 cm height with female external genitalia (clitoris, labia,
vaginal opening and urethral orifice) with big Rt. inguinal
hernia and a scar in the left inguinal region for previous
herniotomy and palpable testis. The rest of her examination is unremarkable. Ultrasound shows shallow vagina
(20mm length), bilateral testes in the Inguinal canals
confirmed by biopsy, no uterus nor ovaries. Bone age 3
years. Karyotype 46 XY, Photos, FSH 2.6 mIU/ml (control 1.o14.0) for male, LH 2.1mIU/ml (control 0.7-7.40 for
male, Testosterone 0.03ng/ml (female 0.2-0.9,male 3-10),
Estradiol less than 9.0 pg/ml (control less 62) for male,
Serum Electrolytes normal, Serum cortisol normal.
Discussion: From the history, physical examination,
and investigations, this is a case of complete androgen
insensitivity syndrome (CAIS) confirmed by 46XY karotype, shallow vagina, testes with no cervix, ovaries nor
uterus. Gonadotropin results are uninterruptable/ irrelevant as the child is 2.5 years old. The incidence of (AIS)
is 1:20,000-1:64000. A person with (CAIS) has a female
external appearance despite a 46XY karyotype and undescended testes. The Androgen Insensitivity Syndrome
is x-liked recessive condition. Management of this case
and other DSD require an experienced multidisciplinary
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ABSTRACTS – Other
team, which is generally found in tertiary care centers.
The team should develop a plan for clinical management
with respect to diagnosis, gender assignment, and treatment options before making any recommendation. For
that I include my colleagues in the hospital and in the U.K
and U.S.A, who are members of BSPED & AACE, for the
best plan to manage this case as team work the decision
for all is (no benefit in keeping the testes as there good
hormone replacements available for the child to be given
in a pubertal age rather than retaining a hernia/malignancy
potential, etc., so it is better to remove the testes. Family
made aware that the child will need estrogen supplements
from age of 12 years, sterile, may need vaginal dilators
in puberty/later due to small vagina (with psychological
support for the family), so arrangement with pediatric surgeon about that has been done.
Conclusion: It is clear that management of DSD
requires an experienced multidisciplinary team, which is
generally found in the tertiary care centers, which is not
applied in our hospitals for that and due to the increase
in the no. of pediatric endocrinology disorders (pituitary,
hypothyroidism, adrenal, puberty, intersex, type 1 diabetes….etc.) that exceed thousands registered in the pediatric endocrinology clinic with diabetes in Central Teaching
Hospital for Children with discovering more rare cases
related to intersex (six cases during the past few months).
So the need for a specialized centre supplied with all laboratory facilities, trained staff, and therapy has become
an urgent demand to be a centre for teaching, research
studies, consultation and promotion of the health services
qualitatively and quantitatively, especially there is no
such a centre in the country. In this direction, a project to
develop the pediatric endocrinology with diabetes clinic
in Central Teaching Hospital to a center including all the
current and future vision had been sent through the hospital and the Al Karkh directorate to Iraqi MOH and also had
been presented in the MOH. We hope the Minister and all
in the high health authorities will support that.
Abstract #702
OBESITY AND SOCIO-DEMOGRAPHIC
VARIABLES OF HEALTH WORKERS IN A
TERTIARY INSTITUTION IN LAGOS, NIGERIA
Ofem Egbe Enang, MBBCh,
Augustine Ohwovoriole, MBBS, FMCP, FWACP, FNSEM
Objective: To assess the prevalence of obesity in an
urban Nigerian population from different ethnic groups,
and to identify lifestyle risk factors for obesity.
Methods: This was a cross-sectional study using
an opportunity sample of health workers who make up
an ethnically mixed group from a tertiary health facility
in Lagos, Nigeria. Heights, weights and waist girths for
each subject were determined using standard techniques.
Adiposity was classified using the body mass index (BMI)
and waist circumference (WC). Socio- demographic variables were obtained using a modified WHO steps questionnaire. The questionnaire was also used to determine
previous diabetes diagnosis, family history of diabetes,
smoking habits, and alcohol consumption.
Results: Mean BMI and waist circumference were
23.1 kg/m2 and 79.6 cm, respectively, for men and 23.5
kg/m2 and 77.2 cm, respectively, for women. The overall
prevalence of obesity was 9.8% and the prevalence was
higher in females (15.7%) than in males (4.4%) and the
difference was statistically significant (P<0.05). The overall prevalence of overweight and obesity was 38.1%. The
prevalence of central obesity was 4.6% in men and 20% in
women. Subjects who took salted meals were three times
more likely to be obese (Odds Ratio =3.479, P=0.001) and
those with hypertension were four times more likely to
be obese (Odds Ratio =4.308, P=0.001). Lifestyle factors
were the most important risk factors to explain the differences in overweight and central obesity between males
and females. Among females, lifestyle, occupation and
diet were the most important risk factors to explain the
differences whereas lifestyle and diet were all important
among men.
Conclusion: The prevalence of obesity is high among
health workers, and more so in females than males.
Abstract #703
A CASE OF GIANT INSULINOMA IN A PATIENT
WITH TYPE 2 DIABETES
Seshadrinathan Pramodh, MD, Dominic Parsons, MBBS,
Alex Bickerton, MBBS, DPhil
Objective: To demonstrate that hypoglycemia in type 2
diabetes outside of insulin, sulphonylurea and metiglinide
analogue use is unusual and needs to be investigated.
Case Presentation: An 81-year-old man with a past
history of diet controlled type 2 diabetes was investigated
in our hospital as an inpatient for chest pain. Whilst in hospital he had frequent episodes of hypoglycemia. He gave
a 12 month history of episodes of drowsiness, disorientation and palpitations, which occurred whenever he went
for over 3 hours without food, and resolved with carbohydrate intake. He had gained 12 kg in weight over the preceding 2 years. He was diagnosed with Impaired Glucose
Tolerance in 2003 on the basis of a 75g oral glucose tolerance test (oGTT) in 2003 (fasting glucose 70 mg/dL, 2
hour post glucose 164 mg/dL). A repeat 75g oGTT in 2006
confirmed type 2 diabetes (fasting 59mg/dL; 2 hour post
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ABSTRACTS – Other
glucose 205 mg/dL). He was managed with dietary regulations alone, and achieved HbA1c levels between 5.9 and
6.6% over the subsequent 3 years. Blood tests performed
on 2 occasions during episodes of hypoglycemia (27mg/
dL & 29mg/dl) in hospital demonstrated very high levels of insulin (81.7 & 92.2 µU/mL) and C-peptide (5793
pmol/L & 5793 pmol/L). CT scan revealed a 10cm tumor
of the pancreas, confirming insulinoma. He was treated
with diazoxide and octreotide, which stabilized the hypoglycemic episodes. Unfortunately he died from an acute
MI while awaiting surgery. Post-mortem examination confirmed the presence of a pancreatic tumour 98mm in size,
with histology confirming neuroendocrine differentiation.
The mitotic count was <2/hpf, with no marked nuclear
pleomorphism and the Ki67 index was <5%. There was
evidence of local vascular invasion, but no evidence of
local or distant metastasis.
Discussion: Insulinomas are the most common type
of tumors affecting the endocrine pancreas, usually under
20mm in size at diagnosis. There have been very few
reports of benign giant insulinomas (>9cm diameter).
The coincidental occurrence of type 2 diabetes and insulinomas is well recognized, but rare. We report an unusual
case of a benign giant insulinoma in association with type
2 diabetes, which, to our knowledge, is unique. It is likely
that the coincidental insulin resistance from type 2 diabetes masked the clinical features of hyperinsulinemia for a
considerable length of time and promoted tumor growth.
Conclusion: It is important to look for other causes of
hypoglycemia in type 2 diabetes, especially if not on medications that are associated with hypoglycemia. Insulinoma
is well recognized but rare cause of hypoglycemia in both
type 1 and type 2 diabetes.
Abstract #704
THE ROLE OF 18F-FDOPA PET SCAN IN A
CHALLENGING CASE OF PARAGANGLIOMA
Georges Chehade Elhomsy, MD, Brian E. Michael, MD,
Karel Pacak MD, PhD
and OctreoScan, did not localize the tumor. A 3, 4-dihydroxy-6-18F-fluoro-phenylalanine (18F-FDOPA).
PET scan showed the presence of a small tumor adherent to the right side of the bladder that was removed surgically. Genetic testing was negative. The patient showed no
evidence of pheochromocytoma three years after his last
surgery.
Discussion: Pheochromocytoma and paraganglioma
are a catecholamine-secreting tumor arising from the
adrenal glands and the sympathetic ganglia respectively.
About 25% of tumors harbor a gene mutation predisposing to an inherited condition. Confirming pheochromocytoma by biochemical testing, then localizing the tumor
using imaging is the best strategy. Several imaging types
are available, some (CT, MRI) are sensitive but not specific while other (MIBG imaging) are specific but less sensitive, only PET scan with 18F-FDOPA shown high sensitivity and specificity; beside, 18F-FDOPA PET scan does
not interfere with the medications and is less time consuming when compared with the MIBG imaging. Genetic
testing is indicated in the presence of paraganglioma,
bilateral adrenal pheochromocytoma, unilateral adrenal
pheochromocytoma with positive family history or with
age of onset < 20 years, presence of pheochromocytomaassociated syndrome, and an asymptomatic person with
positive family history with identified genetic mutation.
Conclusion: The optimal approach for catecholamine-secreting tumors is debatable. The lack of guidelines and the evolution of the biochemical, radiological,
and genetic testing are making the diagnosis expensive,
clear guidelines are needed to make such diagnosis less
expensive. 18F-FDOPA PET scan is not widely available
yet, but it seems to improve the localizing accuracy, in
patients with small tumors, that are not localized with
the conventional techniques. When available, we recommend considering an 18F-FDOPA PET scan if an MRI or
CT scan of the abdomen and an I123MIBG scintigraphy
fail to localize the tumor with a biochemically-confirmed
diagnosis.
Abstract #705
Objective: Describe pheochromocytoma and the new
diagnostic modalities.
Case Presentation: A 59-year-old man with asynchronous bilateral adrenal pheochromocytoma treated
with bilateral adrenalectomy presented with recurrent
episodes of diaphoresis, paroxysmal hypertension, and
palpitations of several months duration. He had a positive
family history of pheochromocytoma. Physical exam was
normal. Serum metanephrines and 24-hour urine metanephrines and urine catecholamines confirmed the diagnosis of recurrent pheochromocytoma. A work-up, including abdominal MRI and CT scan, I123MIBG scintigraphy,
POSTPRANDIAL HYPOGLYCEMIA AFTER
LAPROSCOPIC NISSEN FUNDOPLICATION
IN ADULTS
Pooja Singal, MD, Amale A. Lteif, MD,
Melissa K. Cavaghan, MD
Objective: To describe two cases of postprandial hypoglycemia following Laparoscopic Nissen Fundoplication
(LNF) in adults.
with postprandial hypoglycemia occurring weeks after
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ABSTRACTS – Other
LNF procedure for prolonged GERD. Following an episode of mild confusion 3 hours after eating at work in a
medical office, she had an Accucheck of 52mg/dL. A venipuncture revealed a blood glucose of 43 mg/dL with an
insulin level of 76 IU/ml (normal range 4 - 30mcU/ml) and
C-peptide of 12.6mg/dl (0.8-4.2 mg/ml). A 72-hour fast
was normal. She responded well to a low glycemic index
diet. Our second case was a 35 year-old male presenting
with similar episodes two hours after meals occurring a
month after LNF. His symptoms were associated with
blood glucose readings as low as 50mg/dl. Gastric emptying was noted to be accelerated. A 72-hour fast and mixed
meal tolerance test was normal. He had poor response to
diet changes; medications such as dicyclomine, octreotide
and acarbose as well as revision of his fundoplication.
Repeat gastric emptying studies were normal; however,
there was only marginal relief of his symptoms.
Discussion: Postprandial hypoglycemia following
LNF may be explained by accelerated gastric emptying
resulting in early hyperglycemia and increased release
of incretin hormones (GLP-1, GIP), which may result in
augmented insulin release as well as reduced glucagon
response in these patients. Miholic et al. Surg Endosc.
2007; 21:309-314 studied the relationship of gastric emptying and plasma concentration of gut hormones such
as GLP-1, GIP and Peptide-YY in 10 adults, before and
after fundoplication and showed greater and earlier rise in
GLP-1 and GIP secretion with accelerated gastric emptying in the first 30 minutes after meal ingestion 3 months
following fundoplication. In our first patient, the diagnosis
of postprandial hypoglycemia was made following documentation of a low serum blood glucose level associated
with increased insulin and C-peptide levels 3 hours following routine meal ingestion. An oral glucose tolerance
test was performed only in our second patient with inconclusive results despite having documented delayed gastric
emptying.
Conclusion: Postprandial hypoglycemia has been
described following LNF mostly in the pediatric population with only two case reports in adults. A proposed
mechanism for this disorder is increased insulin surge in
response to hyperglycemia in the immediate postprandial
period due to accelerated gastric emptying. An important
component of this pathophysiology is the dysregulated
secretion of incretin hormones.
Abstract #706
DAILY PHYSICAL ACTIVITY, FASTING
GLUCOSE, URIC ACID AND BODY MASS
INDEX ARE INDEPENDENT FACTORS
ASSOCIATED WITH SERUM FIBROBLAST
GROWTH FACTOR 21 LEVELS
Daniel Cuevas-Ramos, MD,
Paloma Almeda-Valdes, MD,
Francisco J. Gomez-Perez, MD, FACE,
Clara Elena Meza-Arana, Ivette Cruz-Bautista, MD,
Olimpia Arellano-Campos, Mariana Navarrate-López,
Carlos A. Aguilar-Salinas, MD
Objective: FGF21 have been linked with beneficial effects on glucose and lipid metabolism in animals.
Recently, it has been found elevated in humans with metabolic syndrome. This study aimed to investigate independent factors associated with serum FGF21 levels.
Methods: This was a cross-sectional study. A clinical
and biochemical evaluation was done to detect the metabolic syndrome in a never-treated cohort. A total of 210
individuals with (n=81) and without (n=129) metabolic
syndrome were included.
Results: Serum FGF21 levels correlated positively
with body mass index (BMI) (r=0.23, P=0.001) and age
(r=0.17, P=0.01). After adjusting for these parameters and
gender, FGF21 correlated positively with fasting glucose
(r=0.19, P=0.04), uric acid (r=0.29, P=0.04) and physical
activity (r=0.18, P=0.01). In addition, FGF21 also correlates negatively with RBP4 (r=-0.35, P=0.02), total (r=0.23, P=0.01) and HMW adiponectin (r=-0.34, P=0.03).
A multiple linear regression model analysis identified that
BMI (standardized beta (SB) = 0.247; P=0.008), glucose
(SB=0.226; P=0.003), uric acid (SB=0.191; P=0.04)
and physical activity (SB=0.223; P=0.004) are independent factors influencing serum FGF21 levels (F=10.05,
r2=0.19, P<0.001). In addition, fasting hyperglycemia
≥100mg/dl, excess body weight with BMI ≥25 kg/m2,
and uric acid ≥5.5 mg/dl predicted higher serum FGF21
levels in comparison of subjects without the abnormality.
Moreover, a further increment in serum FGF21 levels was
observed when the clinical or biochemical abnormality
coexisted with higher intensity of daily physical activity
(F=5.9, r2=0.26; P=0.001).
Conclusion: Serum FGF21 levels are influenced by
BMI, fasting glycemia, uric acid and physical activity.
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ABSTRACTS – Other
Abstract #707
RELATIONSHIP BETWEEN TWO-HOUR
ORAL GLUCOSE TOLERANCE TEST PLASMA
GLUCOSE AND URINALYSIS AS SCREENING
METHOD FOR DIABETES IN HYPERTENSIVE
PATIENTS
Abdullah Ndaman Adamu, MBBS
Objective: To evaluate random urine samples a
screening test for type 2 diabetes mellitus among people
with systemic hypertension.
Methods: Between January and May 2004, screening
for type 2 diabetes was conducted among people known to
have systemic hypertension and who were regular attendees of medical out-patient clinic of the Lagos University
Teaching Hospital. Screening was done using random
urine sample. Oral glucose tolerance test was carried out
on all the subjects as the standard for the diagnosis of diabetes. Subjects were classified as screen positive if the
urinalysis result is positive, World Health Organisation
(WHO) criteria is used to interpret the OGTT result.
Results: We recruited 206 persons to give room for
attrition, out of which 131 (participation rate of 63.41%)
of them had OGTT and urinalysis done; 87 were females
constituting 65.64% while males were 44 in number
constituting 34.35%. A sensitivity of 25%, specificity of
97.19%, positive predictive value of 66.66%, negative
predictive value of 85.24% was reported. The correlation of random urinalysis to two-hour plasma glucose of
OGTT was 0.55 and the r2 was 30%.
Conclusion: Urinalysis is a poor screening tool for
type 2 diabetes mellitus among people with systemic
hypertension.
Abstract #708
INTERESTING CASE OF MULTIPLE
ENDOCRINE NEOPLASIA (MEN) 2A WITH
MARFANOID HABITUS AND MULTIPLE
AUTOIMMUNE DISORDERS
attacks. 24 hour urine metanephrine and catecholamine as
well as plasma free metanephrine levels were significantly
elevated, CT scan imaging revealed bilateral adrenal mass,
consistent with adrenal pheochromocytoma. Laparoscopic
bilateral adrenalectomy for pheochromocytoma was performed which resulted in normalization of metanephrine
levels and improvement of symptoms. Genetic testing for
RET Protooncogen showed mutation of 634 codon TGC
to CTC consistent with MEN 2A. She was diagnosed with
type 1 diabetes mellitus at age 43. Her c-peptide level is
undetectable and GAD -65 antibody is elevated at 27 U/
mL. She is currently being treated with multiple daily
doses of insulin, but reports frequent hypoglycemic and
hyperglycemic episodes. At age 47 she developed symptoms of diplopia and was diagnosed with ocular myasthenia gravis. Her HLA genotype is consistent with A1, A25,
B8, B17, DR3, DR4, compatible with myasthenia gravis
and type 1 diabetes mellitus. Of special interest, she has
typical marfanoid habitus with high arched palate and arm
span exceeding height.
Discussion: MEN 2 A is characterized by medullary thyroid carcinoma, pheochromocytoma and primary
hyperparathyroidism. Mutation at codon 634 is strongly
associated with pheochromocytoma and hyperparathyroidism (1). In our case even though genetic mutation is in
codon 634 suggestive of MEN 2A, she has classic phenotypic feature of MEN 2B- marfanoid habitus. In addition
presence of autoimmune diseases, type 1 diabetes mellitus
and myasthenia gravis with MEN2A has not been reported
in the literature. If this specific mutation in codon 634 is
related to increased autoimmunity or this is just coexistence remains unclear.
Conclusion: MEN 2A can be associated with
Marfanoid features, and clinicians should be vigilant to
look for other hallmark clinical features and confirmatory diagnosis with genetic testing. Association of other
autoimmune diseases, type 1 diabetes mellitus and
myasthenia gravis can exist with MEN2A.
Abstract #709
MALE HYPOGONADISM AND TRANSDERMAL
TESTOSTERONE REPLACEMENT THERAPY PERSONAL EXPERIENCE
Grishma Parikh, MD, Augustin Busta, MD
Objective: To describe an interesting case of Multiple
Endocrine Neoplasia (MEN) 2A presenting with features
of MEN 2B, type 1 diabetes mellitus and myasthenia
gravis.
Case Presentation: A 64-year-old female with a
known history of medullary thyroid carcinoma diagnosed
at age 24, underwent a total thyroidectomy. At age 36, she
was diagnosed with HTN, two years later her hypertension
worsened, associated with increased anxiety and panic
Corina H. Galesanu, MD, PhD, Luminita Apostu,
Petronela Iovita
Objective: Male hypogonadism is usual associated
with sexual dysfunction, particularly diminished libido, as
well as mood disturbances, reduced lean body mass and
increased adipose - tissue mass. The aim of Testosterone
Replacement Therapy (TRT) is to restore serum testosterone (T) to eugonadal levels and minimize signs and
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ABSTRACTS – Other
symptoms of hypogonadism. Hydroalcoholic T-gel (1%)
(AndroGel)have been approved for male hypogonadism.
Methods: Eleven men with primary or secondary
hypogonadism aged 18-68 years were treated with T-gel
50 mg/daily. Six patients had primary hypogonadism and
five had secondary hypogonadism. The limits of serum
total T for establishing the diagnosis of hypogonadism in
our clinic are 8-12 nmol/L. Our study was a clinical, open
label, non randomized trial, screening examinations had
been completed before the first application of T-gel. Wellbeing and sexuality were investigated by standardized
questionnaires. Serum concentrations of FSH, LH, SHBG,
prolactin, PSA were analyzed by immunofluorometric
assays. Serum testosterone was measured by enzyme
- linked immunosorbent assay. Free T (FT) was calculated with Vermeulen formula. Biochemical parameters
were: glucose, alkaline phosphatase, creatinine, uric acid,
sodium, potassium, aspartate amino transferase (ASAT)
alanine amino transferase (ALAT), lipids. Hematological
parameters: hematocrit values and hemoglobin. Prostate
examinations included determination of volume, by digital rectal examination (DRE). Monitoring are required to
evaluate the efficacy by TT and FT and safety by PSA,
hemoglobin, hematocrit, serum lipid panel ALAT, ASAT,
prostate related symptom, sleep apnea, before the treatment at six and at twelve months.
Results: During T-gel applications body weight
increased slightly with 2.3% (from 72.3±3.5 to 74±3.8 kg)
after one year. TT levels increased from 5.16±0.7 nmol/L
to 7.8±0.3 nmol/L (6 months) and to 22.22±2.4 nmol/L
(12 months). Calculated FT levels who were 74.83±8.1
pmol/L at the beginning, increased to 171.6±36.5 pmol/L
at six months and to 326.6±39.6 pmol/L after a year of
treatment (Normal FT >250 pmol/L). Biochemical parameters: glucose, creatinine, uric acid, alkaline phosphatase,
sodium, potasium, ASAT; ALAT remained unchanged
during the treatment. No statistically significant changes
for hemoglobin and hematocrit. Compared with baseline a small increased with 6.2% of hemoglobin (13.65
to 14.5 ng/dL) and hematocrit increased with 7.4% (40.3
to 43.3%) after one year treatment. The lipid parameters
did not change during the treatment compared with baseline levels; a slight decrease in HDL-C (4.1%) and LDL-C
(3%) were observed. No changes in prostate volume or
significant changes of PSA; a slight increase in PSA was
observed but insignificant 0.8±0.5 ng/L before the treatment to 1.9±0.6 ngL at the end of first year of treatment.
Conclusion: Male hypogonadism is associated
with potentially distressing symptoms and signs, many
of which are reversible under TRT. Serum T levels ≥ 12
nmol/L and FT levels ≥ 250 pmol/L reduced symptoms
of hypogonadism. In our study normal levels of TT and
FT were obtained after one year of treatment with T-gel
1%, 50 mg/daily. Larger number of patients treated longer periods of time may help to evaluate the efficacy, tolerability and safety profiles of transdermal testosterone
treatment.
Abstract #710
TOTAL AND HIGH MOLECULAR WEIGHT
ADIPONECTIN HAVE SIMILAR UTILITY FOR
THE IDENTIFICATION OF
METABOLIC ABNORMALITIES
Paloma Almeda Valdes, MD,
Daniel Cuevas-Ramos, MD, Roopa Metha, MD,
Francisco J. Gomez-Perez, MD, FACE,
Ivette Cruz-Bautista, MD, Olimpia Arellano-Campos,
Mariana Navarrete-Lopez,
Carlos A. Aguilar-Salinas, MD
Objective: To evaluate and compare the utility of total
and HMWA for the identification of insulin resistance (IR)
and related metabolic conditions.
Methods: A cross-sectional analysis was performed
in a group of ambulatory subjects, aged 20 to 70 years, in
Mexico City. Area under the receiver operator characteristic (ROC) curve for total and HMWA were plotted for the
identification of metabolic disturbances. Sensitivity and
specificity, positive and negative predictive values and
accuracy for the identification of IR were calculated.
Results: The study included 101 men and 168 women.
The areas under the ROC curve for total and HMWA for
the identification of IR (0.664 vs. 0.669, P = 0.74), obesity
(0.592 vs. 0.610, P = 0.32), hypertriglyceridemia (0.661
vs. 0.671, P = 0.50) and hypoalphalipoproteinemia (0.624
vs. 0.633, P = 0.58) were similar. A total adiponectin level
of 8.03 μg/ml was associated with a sensitivity of 57.6%,
a specificity of 65.9%, a positive predictive value 50.0%,
a negative predictive value 72.4% and accuracy of 62.7%
for the diagnosis of IR. The corresponding figures for a
HMWA level of 4.25 μg/dl were 59.6%, 67.1%, 51.8%,
73.7% and 64.2%.
Discussion: IR and related metabolic disturbances
are characterized by low levels of adiponectin. HMWA
is considered the active form of adiponectin and a better
marker of IR than total adiponectin. IR is a treatable precursor of diabetes; its identification is therefore desirable
in clinical practice. Established direct methods to quantify
insulin sensitivity, such as the hyperinsulinemic euglycemic clamp, are relatively complex and time consuming.
Surrogate indexes are available but there are no universal
cutoff points to define IR. For this reason we attempted
to estimate an adiponectin threshold for the identification of IR. The cutoff points identified had a reasonable
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ABSTRACTS – Other
sensitivity and specificity. At present one of the disadvantages of adiponectin is that the assay for its measurement
is not widely available and is expensive.
Conclusion: Adiponectin may be a useful marker for
IR. Total adiponectin and HMWA had similar utility for
the identification of IR and metabolic disturbances.
Abstract #711
CENTRAL PONTINE MYELINOLYSIS IN
SPITE OF GRADUAL CORRECTION OF
HYPONATREMIA: 2 CASE REPORTS
Mukhyaprana M. Prabhu, MD,
Masdhusdhan Sangar, MD, Vishwanathan S., MD,
Abdul Razak MD, Balasubramanian R., MD
Objective: Central pontine myelinolysis (CPM) is
a demyelination disease of pons often associated with
the demyelination of extrapontine areas of central nervous system. Although the etiology and pathogenesis are
unclear, CPM is usually associated with hyponatremia or
its rapid correction, and chronic alcoholism is also a common underlying condition. We describe here 2 cases of
CPM occurring in non alcoholic ladies in spite of gradual
correction of hyponatremia
Case Presentation: Case 1: A 54 year-old non alcoholic lady presented with a 10 day history of abdominal
pain, dysuria with altered sensorium. Her vitals were stable and Glasgow Coma Scale (GCS) was 4/15 on presentation. At admission her serum sodium was 101mEq/l. A
diagnosis of hyponatremic encephalopathy with Syndrome
of Inappropriate Anti Diuretic Hormone (SIADH) was
made. 1.6% saline was infused and a gradual correction of
serum was done. On the 2nd hospital day, 1.6% saline was
replaced with normal saline as her sensorium improved
and she became fully conscious and oriented. 3rd day, she
was again found to be drowsier with papillary asymmetry
was intubated and hyperventilated in view of possible coning. 4th hospital day, she was comatose with no response
to painful stimuli and no spontaneous breaths. Magnetic
resonance Imaging (MRI) scan was normal. Patient continued to be comatose. Repeat MRI done later showed
features of central pontine and extrapontine myelinolysis
(EPM). She remained in vegetative state until death on the
40th post admission day.
Case 2: A 70-year-old hypertensive, non-alcoholic
woman was brought to emergency department in altered
sensorium. She was diagnosed to have hyponatremia
due to SIADH. At presentation her serum sodium was
110mEq/l. 1.6% saline was started and her sodium levels
were frequently monitored. A gradual correction of hyponatremia was done. 2nd day she was started on dextrose
normal saline as her sensorium improved. She developed
tremors and rigidity over the next few days and EPM was
suspected. An MRI scan confirmed the same.
Discussion: Osmotic Demyelination Syndrome
(ODS) is a life threatening complication that manifests
several days after aggressive therapy of hyponatremia. In
CPM there is dissolution of myelin sheaths within the central aspect of basis pontis. CPM and EPM are usually the
complications of rapidly corrected hyponatremia, especially in chronically debilitated and bed ridden patients,
but there are always exceptions to the rule. ODS may
occur when serum sodium levels are normal or high and
even if serum sodium levels are corrected within “safe”
limits Laureno and Karp et al study, 21% of patients in
study group developed myelinolysis after correction of
hyponatremia with so-called safe guidelines. There is
enough evidence to say that chronicity of hyponatremia is
the precipitating factor to myelinolysis. The initial intensity of hyponatremia and also absolute increase in serum
sodium levels has a vital role in this dramatic condition.
Conclusion: Medical literature recommendations for
management of hyponatremia are controversial. Both of
our cases were treated gradually as per “safe” guidelines
but still developed ODS. So further research is still required
regarding the question how much to correct and how slow
to correct and till then carefulness and close monitoring is
warranted to prevent this dreaded complication
Abstract #712
SEX STEROID-DEPENDENT INHIBITION OF
HYPERGLYCEMIA-INDUCED ENDOPLASMIC
RETICULUM STRESS IN ENDOTHELIAL CELLS
Mae Sheikh-Ali, MD, Prafull Raheja, MD,
Michael J. Haas, PhD, Arshag D. Mooradian, MD
Background: Elevated plasma glucose levels induce
endoplasmic reticulum stress (ER stress) in endothelial
cells. As a result, changes in endothelial cell function may
promote atherogenesis and increase vascular permeability. Estradiol regulates vascular tone by enhancing nitric
oxide-dependent vasodilation of the endothelium. It is
not clear however if estradiol or other sex steroids influence other aspects of endothelial cell function, such as ER
stress. Therefore, we measured the effects of sex steroids
on hyperglycemia-induced ER stress.
Methods: To determine if sex steroids inhibit ER
stress, we measured ER-stress in endothelial cells, a cell
type that is prone to damage and is important in atherosclerosis and cardiovascular disease. Human umbilical
vein endothelial cells (HUVEC) were treated with physiological (5 mM) or supra-physiological (27.5 mM) dextrose
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ABSTRACTS – Other
concentrations in the presence or absence of 100 nM estradiol (E), 100 nM testosterone (T), 100 nM dihydrotestosterone (DHT), and 100 nM 5-methyl-testosterone (meT).
Results: After 24 hours, ER stress was determined
by measuring secreted alkaline phosphatase activity with
a chemiluminescent substrate. Supra-physiological dextrose concentrations increased ER stress, however, in the
presence of E or T, ER stress was significantly reduced.
However, in contrast to T-treated cells, DHT and meT
were ineffective at alleviating ER stress. Since DHT and
meT cannot be metabolized to E by endogenous aromatase activity, we hypothesize that E is the primary sex steroid possessing ER stress normalizing activity.
Conclusion: These results indicate that hyperglycemia-induced ER stress is alleviated by E and T (possibly after conversion to E by aromatase). These observations suggest that sex differences, menopause, and the
age-related decline in T levels in males may have roles in
regulating ER stress in vascular cells, enhancing the risk
of cardiovascular disease.
Abstract #713
MULTIPLE ENDOCRINE NEOPLASIA TYPE 2.
EXPERIENCE IN A REFERENCE CENTER IN
MEXICO CITY
and three had persistence of medullary carcinoma.
Discussion: MEN is a rare autosomal dominant disease caused by activating mutations in the RET protooncogene. It is characterized by thyroid, adrenal and parathyroid tumors. In this case series we were able to identify
the causal mutations, in agreement with the literature all
the MEN 2B cases were due to a mutation in codon 918.
With regard to MEN 2A, the most frequent mutation was
in codon 634 as expected.
Conclusion: Appropriate diagnosis of MEN and
identification of the causal mutations are essential. A
search for affected family members is mandatory, with
prophylactic thyroidectomy and appropriate screening of
other manifestations.
Abstract #714
PREVALENCE AND METABOLIC
CHARACTERISTICS OF LIPOATROPHY
IN PATIENTS ON HIGHLY ACTIVE
ANTIRETROVIRAL THERAPY IN A
NIGERIAN OUTPATIENTS HIV CLINIC
Sandra Omozehio Iwuala, MBBS,
Olufunmilayo Lesi, FMCP
Edgar Avendaño Vazquez, MD,
Alfredo Reza-Albarran, MD,
Paloma Almeda-Valdes, MD,
Daniel Cuevas-Ramos, MD, Roopa Mehta, MD,
Francisco Gomez-Perez, MD, Juan Rull, MD
Objective: To describe the clinical characteristics,
evolution and treatment of patients with multiple endocrine neoplasia type 2 (MEN 2).
Methods: We analyzed the clinical records of all
patients with diagnosis of MEN 2 in the Instituto Nacional
de Ciencias Medicas y Nutricion Salvador Zubiran in
Mexico City from 1987 to 2008.
Results: We identified seven cases with MEN 2B and
thirteen with MEN 2A. The mean age at diagnosis was
13.5 years (6-63). Medullary thyroid carcinoma was present in all patients. MEN 2B cases had marfanoid appearance and neuro-dermatological tumors. In addition, three
(42.8%) had pheochromocytoma, of which two were bilateral. A mutation of codon 918 in the RET proto-oncogene
was identified in 5 patients, three of which appeared to be
de novo mutations. Three patients died during follow-up.
With regards to MEN 2A cases, three patients had hyperparathyroidism and five pheochromocytoma. In seven
cases a mutation in codon 634 of the RET proto-oncogene
was detected, and in four a mutation in codon 620 was
observed. At follow-up, ten patients were free of disease
Background: Lipoatrophy is an adverse effect of
highly active antiretroviral therapy (HAART). It has the
potential of influencing long term adherence to medication. As part of the lipodystrophy syndrome in HIV infection, it can be associated with metabolic abnormalities,
potentially increasing morbidity and mortality in HIV
infection. Nucleotide reverse transcriptase inhibitors
(NRTI) which often form the backbone of HAART in
resource poor settings are frequently implicated in its causation. This study set out to determine the prevalence of
lipoatrophy in patients on HAART attending an outpatient
HIV clinic in a tertiary health care centre in Nigeria.
Methods: HAART experienced patients (6 months)
were recruited for the study. The study protocol involved
administration of a questionnaire, physical examination
(including anthropometric indices and skin fold thickness), bioelectrical impedance analysis measurements
and biochemical investigations (fasting plasma glucose,
lipogram and serum insulin. Lipoatrophy was defined
clinically (patients report on questioning supported by
findings on physical examination. The case notes were
also reviewed for drug history and retrieval of recent CD4
count and viral load values.
Results: There were 145 patients studied, comprising 84 (57.9%) females and 61 (42.1%) males. The mean
(SD) age of the study population was 40.3 (8.9) years.
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Lipoatrophy was present in 48 (33.1%) HAART experienced patients. It was associated with significantly lower
body circumferences, skin fold thickness and lower body
fat (p< 0.05) but with preservation of skeletal muscle
mass. Clinical lipoatrophy was not associated with glucose intolerance or dyslipidemia or insulin resistance (p>
0.05).
Conclusion: Lipoatrophy is a frequently encountered
adverse effect of HAART in Nigerian HAART treated
patients. Its characteristics in this cohort of patients are
similar to those observed elsewhere.
Abstract #715
A CASE OF NESIDIOBLASTOSIS ASSOCIATED
WITH NONINSULINOMA PANCREATOGENOUS
HYPOGLYCEMIA SYNDROME (NIPHS) IN AN
ADULT FEMALE
Yanira Ivelisse Marrero Mcfaline, MD,
Margarita Ramirez, MD,
Myriam Allende, MD, MBA, FACP, FACE,
Meliza Martinez, MD, Marielba Agosto, MD,
Alejandra Santiago, MD
Discussion: Nesidioblastosis is the most common
cause of persistent hypoglycemia in infancy, but is rare
in adults accounting for 0.5-7% of all cases of hyperinsulinemia and tends to be more common in adult males
than in females. These patients experience predominantly
postprandial hypoglycemia and have nesidioblastosis with
islet cell hypertrophy in close contact with acinar ducts,
findings different from those in patients with insulinomas.
During episodes of hypoglycemia, patients with NIPHS
have biochemical findings similar to those of insulinoma,
including elevated plasma insulin, C-peptide, and proinsulin concentrations, low plasma beta-hydroxybutyrate,
and a negative sulfonylurea screen. Our patient’s history and findings were compatible with a diagnosis of
nesidioblastosis.
Conclusion: Nesidioblastosis is a very rare condition in adults overall and even more rare in females, but it
should be considered as a differential diagnosis in patients
presenting with hyperinsulinemic hypoglycemia. In the
majority of these patients partial pancreatectomy relieves
hypoglycemic symptoms.
Abstract #716
Objective: To describe a case of nesidioblastosis in an
adult female patient in Puerto Rico.
Case Presentation: A 38-year-old female with history diabetes mellitus type 2 and high blood pressure was
referred to our institution due to three months history of
hypoglycemia despite no use of oral hypoglycemics and/
or insulin. Patient refers that since three months ago, had
been experiencing weight gain, dizziness, and blurred
vision, which were relieved with carbohydrate ingestion.
The episodes of hypoglycemia occurred both at fasting
and postprandial. Medical history was negative for peptic
ulcer disease or gastrointestinal surgical procedures and
family history was negative for endocrine tumors. Physical
examination was unremarkable. Fasting blood sugar was
36 mg/dL (60-100 mg/dL), with concomitant insulin levels in 19.28 uIU/L (3-28 uIU/L), C-peptide 2.79 ng/mL
(0.81-3.85 ng/mL), proinsulin levels 21.2 pmol/L (1.818 pmol/L), beta-hydroxybutyrate 0.17 mmol/L (> 2.7
mmol/L), and negative sulfonylurea screen. Abdominal
sonogram and computed tomography with pancreatic protocol were negative. In exploratory laparotomy a lesion
in distal pancreas was found by palpation and distal pancreatectomy was done. A fragment of pancreas of 4 x 3.7
x 1.5 cm was removed and sent to pathology. Pathology
report revealed findings consistent with adult form of
nesidioblastosis. One month after surgery patient continues with stable blood glucose between 130 and 150 mg/
dL.
WATER INTOXICATION WITH DESMOPRESSIN
USED FOR NOCTURNAL POLYURIA.
Harsha Karanchi, MD, Eric J. Mueller, MD,
Jose A. Perez, Jr., MD
Objective: Desmopressin is a synthetic analog of
arginine vasopressin. Water intoxication and severe water
retention is a rare but alarming side effect of this drug and
it is important to educate patients regarding restriction of
fluid intake when taking this medication.
Case Presentation: The patient is a seventy-nine year
old Hispanic man with history of hypertension and benign
prostatic hyperplasia treated three years previously with
a transurethral resection of prostate. Three weeks prior to
admission the patient was prescribed oral desmopressin for
progressively worsening nocturnal polyuria by his urologist. The patient presented with a two week history of progressive bilateral leg edema and a weight gain of twenty
pounds. Two days prior to admission, the patient developed progressive dyspnea and palpitations. On physical
examination, irregularly irregular muffled heart sounds
and bilateral symmetric pitting leg edema was noted.
The electrocardiogram showed arterial fibrillation with
rapid ventricular response and low voltage. Chest radiograph demonstrated bilateral massive pleural effusions.
Laboratory testing showed mild hyponatremia and normal
cardiac enzymes. An echocardiogram was consistent with
pericardial tamponade showing a moderate anterior and
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ABSTRACTS – Other
posterior pericardial effusion with RV diastolic collapse
and normal LV function. A pericardiocentesis was done
and drain left in place for two days. Desmopressin was
stopped and the patient treated with furosemide. Pleural
and pericardial effusions and arterial fibrillation resolved
and the patient improved symptomatically. On further
questioning, the patient revealed that he habitually drank
large amounts of fluid in an effort to cleanse his body and
continued this practice while on the desmopressin.
Discussion: Several cases of severe hyponatremia
and associated seizures have been reported with desmopressin use, particularly in the pediatric population and
especially with the intranasal formulation previously
used for primary nocturnal enuresis. However, the severe
volume overload seen in this case has not been reported.
Desmopressin use for nocturnal polyuria in adults is nonFDA approved.
Conclusion: Caution should be used when prescribing desmopressin and it is prudent to educate patients
especially pediatric and geriatric populations to avoid
excessive fluid intake when taking desmopressin to prevent this life threatening but preventable complication.
Abstract #717
and 31.08% had triple vessel disease. CAG positive subjects, 62.1% had waist circumference above normal, and
about 90% have dyslipidemia and dysglycemia (DM/IGT/
IFG). In the group undergone CAG 83.9 % of diabetic and
69.76% of non diabetic had positive angiographic finding.
Results: It was observed that hypertriglyceridemia,
waist circumference, hypertension (metabolic parameters)
are significantly related with positive angiographic finding. Among the demographic parameters aging, male sex,
smoking habit and family history of cardiovascular disease
is related to angiographic positivity. Peripheral vascular
disease (PVD) as measured by low ankle brachial index
(ABI) (<0.9) (palpatory method is applied for assessing
peripheral vascular disease) is not significantly higher in
CAG positive subjects and it was also not evident that
metabolic syndrome is influencing the occurrence of PVD
in association of CAD.
Conclusion: Using the IDF criteria waist circumference, hypertension and hypertriglyceridemia are significantly predicting cardiovascular event in this study
subjects and presence of metabolic syndrome does not
influencing the relationship between cardiovascular and
peripheral vascular disease.
Abstract #718
CHARACTERISTICS OF DIFFERENT
PARAMETERS OF METABOLIC SYNDROME
IN SUBJECTS UNDERGOING CORONARY
ANGIOGRAM AND THEIR ASSOCIATION WITH
PERIPHERAL VASCULAR DISEASE
RARE INTERVENTION TO DEAL WITH
A RARE DISEASE- INSULINOMA
Khurshid Ahmad Khan, MD
Faria Afsana, MBBS
Objective: Metabolic syndrome (MetS) is associated
with an increased risk of cardiovascular disease events.
The present study was undertaken to identify the predicting parameters of metabolic syndrome that can associate
with cardiovascular and peripheral vascular disease.
Methods: A total of 360 subjects were selected purposively in this study. Two hundred and sixty subjects
(group1) were selected from Ibrahim Cardiac Hospital and
Research Institute (ICHRI), who reported for coronary
angiogram (CAG) for the first time having either a cardiac event in the past or enough clinical or investigational
evidence of coronary artery disease. One hundred subjects
were selected from outpatient department of, BIRDEM
coming for routine follow up with no past history, document/evidence of CAD or of CAG. About two thirds of the
subjects of both the groups had MetS (64.6% in group 1
and 66% in group 2). In group 1, 79.2% had positive angiographic finding and 20.8 % had normal CAG indicating
that a good percentage of subjects who were suspected to
have CAD had normal coronary arteries. Among the CAG
positive subjects 38.83% had single, 30.09% had double
Objective: To describe non-conventional treatment of
insulinoma in a patient who was poor candidate for surgical treatment based on co-morbidities.
Case Presentation: An 85-year-old female presented
with episodic complaints of sweating, palpitations, generalized weakness and confusion for last one month mostly
around early morning in a fasting state. She was admitted
to the hospital for work up. Next morning in fasting state
she had similar symptoms; blood glucose was 48 mg/dl.
Her blood was also drawn for C-peptide, proinsulin and
insulin levels. She was given IV dextrose and symptoms
subsided with that. Test results came back as insulin 10
µU/ml, C-peptide 6 pg/ml and proinsulin 21pmol/L.
Abdominal CT showed 2 cm mass in head of the pancreas. A diagnosis of insulinoma was made. Other tests
were done and possibility of multiple endocrine neoplasia (MEN 1) was ruled out. Patient did have history of
CAD, HTN and CHF with EF of 20%. Based on her age
and co-morbidities she was considered poor candidate
for surgery. Trial of oral diazoxide failed to control her
symptoms. As a last resort decision to do selective embolization of tumor was made. She was treated by repeated
embolization using spherical polyvinyl alcohol particles,
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ABSTRACTS – Other
resulting in shrinkage of the tumor leading to cure of her
hypoglycemic events and improvement of quality of life.
Discussion: Insulinoma is a rare neuroendocrine
tumor, most commonly originating from the pancreas,
which is either sporadic or familial as a component of
MEN1. It is characterized by inappropriately increased
insulin secretion leading to hypoglycemia. For localization purposes transabdominal ultrasonography and CT
abdomen are preferred initial tests, followed by endoscopic ultrasonography or arterial stimulation with hepatic
venous sampling. Surgical removal is considered the treatment of choice, with limited side effects and relatively low
morbidity and mortality. For patients whose insulinoma
cannot be located during pancreatic exploration or those
who are not candidates for or refuse surgery, diazoxide therapy for the medical management of hypoglycemia
is another option. Some rarely used treatment options for
these patients include embolization, chemoembolization,
RFA, and cryoablation.
Conclusion: Embolization as an alternative treatment
of insulinoma in a patient, who was poor surgical candidate and had failed medical treatment with diazoxide, was
very effective in improving hypoglycemic episodes as
well as quality of life.
Abstract #719
TACROLIMUS-INDUCED DKA IN A PATIENT
WITH RENAL TRANSPLANTATION AND
LAURENCE-MOON-BIEDL SYNDROME
Muhammad Qamar Masood, MD,
Madiha Rabbani, MBBS
Objective: To determine if there is a relationship
between the admitting blood glucose (ABG) and the types
of stroke in patients with stroke.
Methods: Fifty-one subjects admitted into the emergency ward of a tertiary hospital in Lagos, Nigeria, for
acute stroke, confirmed with brain computerized tomography (CT) scan were studied over a year period. Subjects’
clinical history and blood glucose were recorded at admission and analyzed.
Results: Mean age (and standard deviation, SD) of
study subjects was 60 (12) years, ranging between 28 and
85 years. The male-female ratio was 1:1. No statistically
significant difference in the ages of the male and female
subjects (p=0.20). Nine (18%) of the subjects were had
prior history of diabetes mellitus (DM) with a mean duration (SD) of 7(6) years. Most subjects (65%) had prior
history of systemic hypertension with an average duration
(SD) of 8 (7) years. The mean ABG was 134 (58)mg/dl,
ranging between 37 and 320mg/dl. While 32 (63%) of the
subjects had infarctive stroke, 16 (31%) had hemorrhagic
stroke and 3 (6%) had both. All the subjects with ABG
200mg/dl or more had an infarctive stroke. However, of
those with ABG less than 200mg/dl, 36% had hemorrhagic
stroke, 58% had infarctive stroke while 7% had both. No
statistically significant relationship between the ABG and
stroke types (p=0.13). Also, mean ABG was higher in
infarctive than in hemorrhagic stroke (138 Vs 130mg/dl)
but difference is not statistically significant (p=0.064).
Conclusion: Patients with ABG ≥200mg/dl are more
likely to have an infarctive stroke.
Abstract #720
A COMPARATIVE STUDY OF TIGHT GLYCEMIC
PROTOCOLS AND THEIR RISK OF INDUCING
HYPOGLYCEMIA IN CRITICALLY ILL
PATIENTS
Abeer W. Anabtawi, MD, Margaret Hurst, RN,
Umarshanker Doss, MD, Shashi Patel,
Carlos Palacio, MD, Krishna Kumar Rajamani, MD
Objective: Comparison of the incidence of hypoglycemia among the different tight glycemic control (TGC)
protocols is a crucial aspect that has not been addressed
in previous trials. This study compared the incidence of
hypoglycemia using three TGC protocols in critically ill
patients.
Methods: In this 18 months prospective study; 420
patients were divided into three groups by TGC protocol: A (Modified Leuven Protocol), B (Georgia Hospital
Association (GHA) Protocol, target Blood glucose (BG)
80-110 mg/dl), and C (Modified GHA Protocol, target BG
90-140 mg/dl). Groups were similar in age, gender, diabetes history, body mass index, admission type, and ICU
length of stay. End points included differences in the incidence of hypoglycemia (BG ≤ 60 mg/dl), severe hypoglycemia (BG ≤ 40 mg/dl), and hyperglycemia (BG ≥ 180
mg/dl). BGs are presented as mg/dl.
Results: A total of 34,497 BG samples were analyzed
[A: 11,202 (32.47%), B: 9,627 (27.91%), and C: 13,668
(39.62%)]. Hypoglycemia was significantly more frequent
in group A [348 episodes (3.11%)] compared to B [209
episodes (2.17%)] [OR 1.45, 95% CI 1.25-1.172, p=0.001]
and C [266 episodes (1.95%)] [OR 1.66, 95% CI 1.37-1.89,
p=0.001]. Severe hypoglycemia was significantly more
frequent in group A [131 episodes (1.17%)] compared
to B [62 episodes (0.64%)] [OR 1.83, 95%CI 1.22-1.72,
p=0.001] and C [58 episodes (0.42%)] [OR 2.77, 95%CI
2.04-3.79, p=0.001]. No significant differences in hypoglycemia and severe hypoglycemia when group B and C
were compared (p=0.10 and p=0.06). Hyperglycemia was
significantly more common in group A [2,175 episodes
(19.42%)] compared to B [1,333 episodes (13.83%)] [OR
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ABSTRACTS – Other
1.49, 95% CI 1.39-1.62, p=0.001], although it was not
significantly more frequent when A was compared to C
[2,560 episodes (18.73%), p=0.17]. Group B had a significantly lower incidence of hyperglycemia compared to
C [OR 0.69, 95% CI 0.65-0.75, p=0.001].
Discussion: Although the optimum intensity of BG
control in critically ill patients remains controversial, the
avoidance of hypoglycemia appears to be of significant
importance to obtain the maximum benefit of TGC protocols. This study shows that TGC protocols vary significantly in their efficacy and risk of inducing hypoglycemia.
Both protocols B and C significantly lowered incidence
of hypoglycemia compared to A. Using columnar insulin
dosing charts in both protocols may contribute to these
findings.
Conclusion: TGC protocols vary in their risk of
inducing hypoglycemia and this should be a key factor
when selecting a specific protocol. Future studies may
determine if these variations result in differences in clinical outcome such as mortality or adverse effects.
Abstract #721
METABOLIC SYNDROME IN EGYPTIAN
PATIENTS WITH SYSTEMIC LUPUS
ERYTHEMATOSUS
Aziza Abdel Moez Hammad, MD,
Mohamad Salah Eldin Abdel-Baky, MD,
Dalia Abdel-Mohsen, MD, Eman Ahmed Hafez, MD,
Noran Osama El-Aziz, MD
Measure (SLAM) score and Systemic Lupus International
Collaborating Clinics Damage Index (SLICC/ACR) were
used for assessment of disease activity and organ damage.
Results: The metabolic syndrome was present in 51.4
% of SLE patients and in 16.7 % of controls (p<0.05)
using the WHO definition that requires direct determination of insulin resistance, and in 38.6 % of patients and
in 10 % of controls (p<0.05) using the NCEP definition.
WHO definition has higher sensitivity, while NCEP definition has higher specificity. Among patients with SLE, both
definitions were significantly associated with higher insulin resistance, higher concentrations of C reactive protein
(CRP), higher triglycerides levels, and lower high density
lipoproteins (HDL)levels (p<0.05). Disease duration and
type of medication used were not associated with the metabolic syndrome (p>0.05), while SLE disease activity and
damage scores were associated with the metabolic syndrome (p<0.05). Patients with metabolic syndrome had
higher levels of proteinuria and more aggressive nephritis
(p <0.05).
Conclusion: Patients with SLE have a higher prevalence of insulin resistance and metabolic syndrome than
controls. In patients with SLE, the metabolic syndrome
is associated with higher levels of C reactive protein,
higher disease activity and damage scores. The metabolic
syndrome may provide a link between inflammation and
increased cardiovascular risk.
Abstract #722
Background/Objective: To study the prevalence of
the metabolic syndrome in Egyptian patients with SLE
and compare with the controls, and to evaluate its association with cardiovascular risk factors and disease characteristics. Patients with systemic lupus erythematosus
(SLE) have accelerated atherosclerosis but the causes are
not clear. The metabolic syndrome is an independent risk
factor for ischaemic heart disease. SLE provides a unique
model to identify mechanisms that are common to both
inflammation and cardiovascular disease; however there
are no controlled studies of the metabolic syndrome in
Egyptian patients with SLE.
Methods: Seventy patients with SLE who satisfied
the American College of Rheumatology (ACR) criteria,
aged ≥16 years and had disease duration ≥ 1 year and
thirty age and sex matched healthy controls were studied.
The prevalence of the metabolic syndrome was compared
in patients and controls using the National Cholesterol
Education Program Adult Treatment Panel III (NCEP)
and the World Health Organization (WHO) definitions.
Associations with cardiovascular risk factors and SLE
disease characteristics were examined. Lupus Activity
THE VALUE OF INSULINE-LIKE GROWTH
FACTOR 1 LEVEL IN PREDICTING RESPONSE
TO LEVOSIMENDAN TREATMENT IN PATIENTS
WITH SEVERE HEART FAILURE
Serhat Isik, MD, Mustafa Cetin, MD,
Hulya Cicekcioglu, MD, Ozgul Ucar, MD,
Zehra Guven Cetin, MD, Ufuk Ozuguz, MD,
Fatih Bakir, MD, Dilek Berker, MD, Serdar Guler
Objective: In spite of entire improvements achieved
in treatment, heart failure (HF) has still had high rate of
mortality. Levosimendan has positive inotropic, antistunning and cardioprotective effects during episodes of acute
HF. Among the studies on the treatment of HF, those based
on growth hormone (GH) are of interest. Besides, clinical studies of patients with HF have demonstrated that
insulin-like growth factor 1 (IGF-I) levels were low and
correlate with the severity of HF. In the present study, we
aimed to investigate the usefulness of basal IGF-I levels in
levosimendan treatment.
Methods: Thirty patients under standard HF treatment who presented with functional capacity NYHA class
III-IV and left ventricular ejection fraction (LVEF) less
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ABSTRACTS – Other
than 35% were enrolled in the study. The patients were
initiated on infusion of levosimendan loading dose of 12
µg/kg/min for 10 minutes and subsequently, infusion of
0.1 µg/kg/min 24 hours was administered as maintenance
dose. Pre- and post-treatment symptoms of patients (72
hours after the completion of infusion) echocardiographic
parameters were evaluated and blood samples were
collected.
Results: The mean age of patients was 62.6 ±10.1
years, 83.3% of patients were male and 16.7% were
female. Mean basal IGF-I level was 106.9± 47.0 µg/L.
A statistically significant improvement was detected in
NYHA class, brain natriuretic peptide (BNP) levels and
average LVEF levels of patients following the treatment
when compared to those of pre-treatment. However, no
significant difference was observed in IGF-I levels. There
was no correlation between pre-treatment IGF-I levels and
LVEF, BNP levels and NYHA classes of patients. On the
other hand, post-treatment changes in IGF-I and BNP levels and baseline IGF-I levels were found to be correlated.
Discussion: In the present study, we detected an
improvement in HF symptom scores and LVEF measurements and a decrease in BNP levels with levosimendan
treatment. This is a predictable finding consistent with
previous studies. In individuals with HF, high amount
of GH/IGF-I deficiency and diminished renal clearance
of BNP due to decreased renal perfusion in heart failure may contribute to increased BNP levels in patients
with decompansated HF. Both increased renal clearance
of BNP and decreased ventricular wall tension may be
uncovering direct suppressive effect of GH/IGF-I system
on BNP. Therefore, individuals with high basal IGF-I levels may show a greater decrease in BNP after levosimendan treatment.
Conclusion: Basal IGF-I levels may be used to predict responses of hospitalized patients with decompensated HF to levosimendan treatment.
Abstract #723
MEDIUM CHAIN ACYL-COA DEHYDROGENASE
DEFICIENCY WITH SECONDARY CARNITINE
DEFICIENCY
Jaya Reddy Kothapally, MD, Andjela Drincic, MD
Objective: To study the need of carnitine supplementation in adult patients with MCADD and secondary carnitine deficiency.
Case Presentation: We saw a 19-year-old female,
with a history of MCADD and secondary carnitine
deficiency transitioning from pediatric to adult endocrine clinic. She was diagnosed with MCADD at two
years of age. She presented with severe hypoglycemia,
dehydration, seizures and hepatic encephalopathy during
a Rotavirus infection. Metabolic workup showed evidence
of medium chain dicarboxylic acids in the urine. Plasma
acylcarnitine profile disclosed a large peak for octanoylcarnitine and elevations of C6, C8, and C10. Her carnitine
level was low and was started on carnitine supplementation and an appropriate diet and did well. Genetic testing
confirmed MCCAD. In our office, she was asymptomatic.
Her total Carnitine was 25umol/L (31-78). We discontinued the supplementation and two months later she continued to be asymptomatic. However, there was a drop in her
Free Carnitine to 4 umol/L (22-63) and total Carnitine to
7umol/L. We decided to restart carnitine supplementation
in the patient.
Discussion: MCADD is a mitochondrial fatty acid
oxidation (FAO) disorder that results from inactivity or
deficiency of the medium chain acyl-COA dehydrogenase protein, coded by the ACADM gene on chromosome
1p31. Fasting or stress in MCADD can lead to hypoketotic hypoglycemia, hypotonia, seizures, encephalopathy,
coma and death due to accumulation of toxic metabolites.
Frequent carbohydrate rich meals and avoidance of fasting
prevents the accumulation of FAO intermediates and their
COA esters. Carnitine plays an essential role in the transfer of fatty acids into mitochondria for beta-oxidation.
Biologic effects of low carnitine levels may not be clinically significant until they reach less than 10-20% of normal. Although MCADD patients may exhibit secondary
carnitine deficiency, routine supplementation in MCADD
is controversial. Upon reviewing literature we found, that
there was increase in FAO and carnitine biosynthesis during exercise.
Conclusion: MCADD patients transitioning to adulthood typically do not need carnitine supplementation. If a
decision to stop supplementation is made, it is important
to follow up carnitine levels to identify small subset of
patients with extremely low levels. Given relatively low
cost and lack of significant side effects, carnitine replacement can be considered in this subset of patients.
Abstract #724
CASE OF SUCCESSFUL PREGNANCY
AND BIRTH OF A NEWBORN IN A
WOMAN WITH AUTOSOMAL DOMINANT
PSEUDOHYPOALDOSTERONISM TYPE 1
Rishi Anand, MD, Chandana Konduru, MD,
Rosemaria Alappat, DO, Monica Schwarcz, MD
Objective: To describe a successful pregnancy and
birth of a newborn in a woman with autosomal dominant pseudohypoaldosteronism type 1 (adPHA1 or Renal
PHA1).
– 114 –
ABSTRACTS – Other
Case Presentation: A 26-year-old female G2P0100,
was referred to our endocrine clinic at 17 weeks gestation for management of pseudohypoaldosteronism type 1
and hypothyroidism. The patient, diagnosed with adPHA1
as infant, required aggressive sodium (NaCl) supplementation and cation exchange resins during childhood, and
was maintained only on cation exchange resins during
her adult life to maintain normokalemia. She reported a
prior intra uterine fetal death at 31 weeks of gestation secondary to heart defect. Family history is significant and a
brother is also affected with adPHA1. The patient’s pregnancy progressed without complication during the first
and second trimester with close monitoring of electrolytes. During the third trimester when serum sodium persisted below 130mg/dl, NaCl supplementation was added
to cation exchange resin regimen. The patient delivered a
preterm male infant at 34 weeks gestation, despite documented electrolytes within normal range. The newborn
baby had transient hyponatremia on day 1of life, which
subsequently normalized in 24 hours.
Discussion: Aldosterone, by acting on the mineralocorticoid receptor in the distal nephron, plays a crucial
role in regulation of volume and electrolyte homeostasis.
Pseudohypoaldosteronism type 1 is a rare inherited condition that is characterized by renal insensitivity to the
action of mineralocorticoids. Patients manifest neonatal
salt wasting, hypotension, hyperkalemia and metabolic
acidosis despite elevated aldosterone levels. The disorder
may be inherited by autosomal recessive or autosomal
dominant forms via either epithelial Na channel mutation or mineralocorticoid receptor mutation respectively.
Analysis of few extended adPHA1 pedigrees suggest no
obvious impairment of fertility or failure to transmit the
disease allele but the impaired reproductive fitness and
disease transmission is most likely due to high infant mortality who were at risk for adPHA1.
Conclusion: Pregnancy and infancy are periods characterized by intrinsic aldosterone resistance and patients
with adPHA1 may be at risk for further electrolyte imbalance during these two phases, so careful monitoring and
treatment is crucial for good outcomes. This is the first
reported case of pregnancy resulting in a live birth to a
mother with adPHA1.
Abstract #725
ESTIMATION OF TOTAL BODY FAT AND
CORRELATION WITH PERIPHERAL INSULIN
RESISTANCE: DOES THE METHODOLOGY
MATTER?
Donna Lawson, MD, Csava Kovesdy, MD,
Barbara Dunn, PA, Ali Iranmanesh, MD
Objective: Dual-energy X-ray absorptiometry (DXA)
is a validated method for the assessment of body composition. With fat mass as the prime objective, more accessible and less expensive methods have been used, but
there is concern about their level of sensitivity, accuracy
and reproducibility. Such concerns become more relevant,
when the study population is heterogeneous, as it relates
to age, physical fitness and muscle mass. In the present
study, measures of body fat estimated by skin fold thickness, bioelectrical impedance analysis (BIA), and nearinfrared interactance (NIR) techniques were compared to
the values obtained by DXA.
Methods: Study population consisted of 29 healthy
men ranging in age (19-78 yrs), BMI (21-38 kg/m2), and
Appendicular Muscle Mass Index (AMMI: 7.2-12 kg/m2).
To correct for height, Fat Mass Index (FMI: Kg/m2) was
used for statistical analysis. SF, BIA and NIR were compared to DEXA by performing receiver operator curve
(ROC) analyses and by calculating Pearson correlation
coefficients (r; a measure of precision), bias correction
factors (C_b; a measure of accuracy) and concordance
correlation coefficients (rho_c; the product of r and C_b).
Bland-Altman plot analysis, Pitman’s variance ratio tests
and the F test of equality of means and variances between
DEXA and each of the other three methods were used for
the comparative analysis between methods.
Results: Mean (± SD) of FMI for SF (6.33±3.07), BIA
(5.60±2.57), and NIR (5.46±2.45) were not significantly
different from DXA (5.56±2.82), and were highly correlated with R of 0.93 (SF), 0.93 (BIA), and 0.90 (NIR). Bias
correction factors (C_b) and concordance correlation coefficients (rho_c) were 0.96 (SF), 0.99 (BIA), 0.99 (NIR),
and 0.89 (SF), 0.92 (BIA), & 0.90 (NIR). Concordance
correlation coefficients for all three methods were similar,
but the paired differences vs. DEXA (SF: -0.744±1, BIA:
-0.043±1.004, NIR: -0.043±1.004) and F test for equality (p values: SF=0.003, BIA=0.42, NIR=0.87) indicated
better concordance for BIA and NIR. FMI obtained by all
methods were significantly and similarly correlated with
measures of peripheral insulin resistance (HOMA-IR).
– 115 –
ABSTRACTS – Other
Conclusion: In healthy men skin fold, bioelectrical
impedance, and infra-red methods provide accurate estimates of total body fat, which is highly correlated with the
DXA findings. Considering the cost and technical skills,
these methods, namely skin fold measurement or BIA can
be of significant value in clinical studies of body fat measurement, particularly involving large number of participants. Applicability of these methods for body fat measurement to female and non-healthy subjects and reproducibility after intervention require future investigation.
Abstract #726
THE CARCINOID OF APPENDICLE IN A YOUNG
PREGNANT WOMAN – CASE REPORT
Raluca-Alexandra Trifanescu, MD,
Mara Carsote, MD, Corina Chirita, MD,
Dana Terzea, MD, Cristina Ene, MD,
Ramona Samoila, MD, Adina Croitoru, MD,
Catalina Poiana, MD, FACE
Objective: We report the case of a young female
diagnosed with appendicle carcinoid tumor related to
pregnancy.
Case Presentation: A 27-year-old female patient suffered an emergency appendectomy. There were no symptoms suggestive for a carcinoid syndrome prior to surgery,
so neuroendocrine markers were not assessed. Pathology
exam revealed a tumor of less than 1 cm in diameter, at
the top of the appendix, with neither base nor middle portion invasion, or into the lymph nodes. These suggested
a carcinoid tumor. The immunochemistry revealed positive reaction for chromogranin A and synaptophysin, with
undetectable Ki-67 levels. One month after the surgery,
pregnancy was confirmed. Based on the low aggressive
type of the tumor the patient was not at any risk. But the
patient did not choose to keep the pregnancy. Soon after
surgery (3 months later), the neuroendocrine markers
were normal: chromogranin A= 40 pg/mL (normal values:
40 -100), serotonin= 186 ng/mL (normal values: 40-200),
the urinary 5-hydroxy indol-acetic acid= 5.2 mg/24h (normal values: 2-9). The neuronal specific enolase was also in
normal ranges: 3.5µg/dl (normal value< 18.3). According
to the patient’s option, because no guide indicates it, the
111 Indium Octreotide scan was performed and it was negative. 6 months later, the serum markers were still normal
(chromogranin A= 36 ng/mL, serotonin= 183 ng/mL). No
colonoscopy or computed tomography scan was necessary
up to this point. A long time follow-up by measurement of
serum neuroendocrine markers is planned in this case.
Discussion: The appendicle carcinoid tumor is a frequent type of carcinoid with a good prognostic in many
cases. Frequently, it is an incidental finding during surgery. There are few cases related to pregnancy. The issues
in these cases are the therapy during pregnancy, if the
pregnancy should continue and if there is any fetal risk.
The acute appendicitis picture caused by the tumor needs
to be differentiated by a complicated or uncomplicated
pregnancy. A retrospective diagnosis of carcinoid tumor
as revealed by the histological exam does not necessarily complicate a pregnancy prognosis because of the low
aggressive profile. The pathological exam brings out the
major aspects regarding the spreading potential, and the
future necessary procedures. The interaction between carcinoid tumor of the appendix and pregnancy is not yet elucidated. Serial tests of the neuroendocrine markers are the
most useful tool in follow-up and imaging scans are not
necessary.
Conclusion: The case shows the important role of differential diagnosis of acute abdominal pain in women of
childbearing age, considering this rare pregnancy-related
appendicle pathology.
Abstract #727
AN UNUSUAL PRESENTATION OF PAPILLARY
THYROID CANCER AND PARATHYROID
CARCINOMA
Leila Chaychi, MD, Allan Golding, Kathleen Belbruno
Objective: To describe a rare presentation of parathyroid carcinoma in association with papillary thyroid
carcinoma.
Methods: We describe the clinical history, physical
examination findings, laboratory values, imaging findings,
and pathologic findings of a woman with two previously
palpable thyroid nodules and mild hypercalcemia in line
with the pertinent literature review.
Results: The patient is a 79-year old woman who presented for reevaluation of two thyroid nodules and long
standing parathyroid adenoma that was initially evaluated
six years ago with the intact parathyroid hormone (iPTH)
level of 89 pg/ml (10-69) and calcium of 10.4 mg/dl (8.510.6) in the setting of normal alkaline phosphatase, creatinine and 25(OH)2 D3. She was found to have a 2.5 and 1.8
cm papillary thyroid cancer in the right thyroid lobe, upper
and lower poles respectively as well as 4.9 cm parathyroid
carcinoma in the left side.
Conclusion: Synchronous parathyroid and thyroid
carcinomas are extremely rare. To our knowledge, our
case is the first patient with parathyroid carcinoma with
clinical presentation of long standing mild adenoma in
addition to synchronous papillary thyroid carcinoma.
– 116 –
ABSTRACTS – Other
Abstract #728
diagnostic. It is often associated with increased hepatic
glycogen stores.
Conclusion: Hypoglycemia should be considered in
differential diagnosis of altered mental status in patient
with cerebral palsy. NICTH, though rare, should be
included in the differential for intractable hypoglycemia.
AN UNUSUAL CASE OF NON-ISLET CELL
TUMOR INDUCED HYPOGLYCEMIA IN A
PATIENT WITH CEREBRAL PALSY
Deepti Rawal, MD, Ajay Varanasi, MD,
Sandeep Dhindsa, MD, Teekam Lohano, MD,
Ajay Chaudhuri, MD, Paresh Dandona, MD
Abstract #729
Objective: We report an unusual case of non-islet
cell tumor-induced hypoglycemia (NICTH) presenting as
hypoglycemia in a patient with cerebral palsy.
Case Presentation: A 36-year-old female with history of cerebral palsy with limited communication abilities, group home resident was admitted to the hospital
after she had recurrent episodes of confusion, blank stare
and slurred speech in early morning hours. She would get
back to her normal self after drinking orange juice. During
several of these episodes her blood sugar was found to
be below 40. This was confirmed on lab tests. She was
then hospitalized for further investigation. During her
hospital stay she continued to have early morning hypoglycemia. During hypoglycemia her insulin level was <2,
c-peptide<0.1 on two separate occasions. Proinsulin level
was 6.8 pmol/L (<18.9), β-hydroxybutyrate β-OH (B)
0.11mmol/L (< 0.29 mmol/L), cortisol 19.5 mcg/dl and
GH 0.2 ng/ml (>10 ng/ml). Sulfonylurea screen was negative. TSH was 1.22 (0.4-5) and Free T4 was 0.78 (0.81.8). Cortisol stimulation test was normal. Hypoglycemia
responded to 1 mg glucagon by an increase in blood
glucose by more than 100 mg/dl. Serum IGF-l level was
28 ng/ml (109-284 ng/ml), and serum IGF-ll level was
1134 ng/mL (460-1240 ng/mL), Insulin receptor antibody <0.2. Pt was given a trial of prednisone and octeotide which failed to resolve hypoglycemia. Pituitary MRI
was normal. CT of the abdomen showed a solid pelvic
mass 15 cm in transverse dimension. She continued to
have hypoglycemic episodes in spite of dextrose infusion.
Hypoglycemia resolved after surgical resection of the
tumor. Histopathology of the tumor demonstrated a high
grade endometrial sarcoma.
Discussion: An uncommon cause of hypoglycemia is
the secretion of partially processed precursors of IGF-II
by sarcomatous tumors, also known as non islet cell tumor
hypoglycemia (NICTH). NICTH is associated with insulin secretion, lipolysis and ketogenesis, leading to a low
C-peptide, and inappropriately low GH and β-OH(B) concentrations in the circulation. The diagnosis of NICTH
can be confirmed by a combination of suppressed serum
insulin, c-peptide and suppressed GH levels in setting
of hypoglycemia along with elevated IGF-ll levels. An
IGF-ll/ IGF-l ratio of greater than 10 is believed to be
NEW-ONSET DIABETES AND HYPERTENSION
ATTRIBUTABLE TO ECTOPIC CUSHING’S
SYNDROME SECONDARY TO METASTATIC
PANCREATIC NEUROENDOCRINE TUMOR
Haidee David Zamora, MD, Delia Stefan, MD,
Debra Simmons, MD
Objective: To report a case of metastatic pancreatic
neuroendocrine tumor presenting as new-onset diabetes
and hypertension.
Case Presentation: 60-year-old white female with
new-onset diabetes and hypertension presents with poorly
controlled diabetes. She was fairly healthy, until 11/08,
when she was found to have hypertension. Three months
later, she was diagnosed with diabetes. She had no signs
and symptoms of diabetes, no history of Gestational DM
or a macrosomic baby. She had easy bruising and easy
fatigability. Positive family history of hypertension and
diabetes, and no history of cancer. Physical examination revealed a thin woman, with no cushingoid characteristics. Labs showed hypokalemia, in the absence of a
potassium-wasting medication. Initial work-up demonstrated absence of autoimmune antibodies to beta cells,
no evidence of primary hyperaldosteronism; however,
24-hr urine free cortisol was elevated. Overnight 1-mg
oral Dexamethasone suppression test showed an elevated
cortisol. Eight-milligram dexamethasone suppression test
revealed a non-suppressed ACTH consistent with an ectopic source. CRH test was likewise consistent with ectopic
source of hypercortisolism. CT scan showed a mass lesion
involving the neck and proximal body of the pancreas and
a solitary mass within hepatic segment VI/VII. Octreotide
scan findings correlated with the CT scan. Liver mass
biopsy showed neoplastic cells, with neuroendocrine differentiation, which stained for synaptophysin, but negative for ACTH and Chromogranin A. KI-67 was positive
in 20% of the neoplastic cells. Patient subsequently had
partial pancreatectomy and right hepatectomy.
Discussion: Pancreatic neuroendocrine tumors have
been reported to be the cause of ectopic ACTH syndrome
in up to 16% of patients. The ectopic ACTH syndrome can
follow an acute or chronic course. The acute syndrome
is associated with rapid onset of hypertension, weakness,
– 117 –
ABSTRACTS – Other
edema, hypokalemia, glucose intolerance, anorexia
and weight loss, all of which except for the edema, our
patient had at presentation. The chronic syndrome is often
clinically indistinguishable from pituitary-dependent
hypercortisolism. Hassan et al., observed an association
between recent-onset diabetes and pancreatic neuroendocrine tumors (PNET), in 55% of the patients, but longterm diabetes were unrelated to PNET.
Conclusion: This case demonstrates the association
between new-onset diabetes and hypertension and the
diagnosis of pancreatic neuroendocrine tumor, underscoring the importance of determining temporal relationships
between disease entities.
Abstract #730
GASTRIC CARCINOID TUMOR COMPLICATING
AUTOIMMUNE GASTRITIS IN A YOUNG ADULT
WITH TYPE 1 DIABETES MELLITUS
Rachanon Murathanun, MD,
Charles Berkelhammer, MD, FACG,
Tahira Yasmeen, MD, FACE
Objective: To describe a rare case of a type 1 gastric
carcinoid tumor complicating autoimmune gastritis in a
young adult with type 1 diabetes mellitus.
Case Presentation: A 26-year-old female with type1
diabetes mellitus was found to have a 1 cm hypervascular gastric mass as an incidental finding on CT scanning
to evaluate unrelated symptoms. The gastric mass was
asymptomatic. She denied gastrointestinal symptoms,
flushing, diarrhea, wheezing, melena, hematochezia, or
weight loss. Physical examination revealed no hepatomegaly, skin lesions, or signs of right-sided heart failure.
Stool was negative for occult blood. Liver biochemistry
was normal. An upper endoscopy revealed gastric atrophy
and a 1 cm submucosal gastric polyp in the mid body of
the stomach. Endoscopic polypectomy was performed.
Pathology revealed a 1.1 cm carcinoid tumor with positive margins. Tumor stain was strongly positive for chromogranin and synaptophysin, but negative for serotonin
and gastrin. 24-hour urine for 5- Hydroxyindoleacetic acid
(5-HIAA) was normal. Plasma chromogranin A level was
140 ng/ml (0-50 ng/ml). Plasma gastrin level was 866 pg/
ml (0-100 pg/ml). Antibody to intrinsic factor was positive. Serum vitamin B12 was normal. T he patient underwent partial gastrectomy. No intraoperative spread was
found. Surgical pathology revealed a focus of residual
gastric carcinoid tumor and severe autoimmune chronic
atrophic gastritis.
Discussion: The prevalence of autoimmune gastritis
in type 1 diabetes mellitus is 5-10%, compared with 2% in
the general population, a 3 to 5 fold increase. Type 1 gastric
carcinoid tumors are strongly associated with chronic
atrophic gastritis, as can occur in autoimmune gastritis.
Enterochromaffin-like (ECL) cells of the stomach are part
of the gastric neuroendocrine cell system. Condition causing loss of parietal cells, as in atrophic gastritis, results in
reduced gastric acid secretion, and ultimately, achlorhydria. Achlorhydria leads to hypergastrinemia due to negative feedback inhibition. Gastrin is trophic to ECL cells.
Hypergastrinemia can lead to ECL hyperplasia and ultimately gastric carcinoid tumor. The average age of type 1
gastric carcinoid is between 50-60 years. Our patient with
type 1 diabetes mellitus developed a 1.1 cm gastric carcinoid tumor complicating autoimmune gastritis at the age
of 26. The high prevalence of autoimmune gastritis in type
1 diabetes, and the occurrence of gastric carcinoid tumors
in such patients, even in young adults, provides rationale
for enhanced awareness, and possibly even screening in
such patients.
Conclusion: Autoimmune gastritis is associated
with type 1 diabetes mellitus and can predispose to type
1 gastric carcinoid tumors. T ype 1 diabetic patients may
develop gastric carcinoid tumor even as a young adult.
Abstract #731
A RARE CASE OF INSULINOMA WITH LOW
C-PEPTIDE CONCENTRATIONS.
Mehul Ratilal Vora, MBBS, Sandeep Dhindsa, MD,
Paresh Dandona, MD, Teekam Lohano, MD,
Ajay Chaudhuri, MD
Objective: To describe a case diagnosed with insulinoma with low C-peptide concentrations.
Case Presentation: A 48-year-old Caucasian female
with no significant past medical history was referred to our
clinic for low blood glucose of 29mg/dl on routine blood
work. Her blood glucose during the clinic visit was 31.
She was asymptomatic and denied any symptoms of hypoglycemia. Laboratory blood revealed blood glucose of
45mg/dl, HgA1c 4.6%, insulin concentration 22mc Unit/
ml (2-20), c-peptide 0.7ng/ml (0.8-6), Plasma Proinsulin
26.9 pmol/L (<18.9), Sulfonylurea screen Negative,
Glucagon <50pg/ml (<61pg/ml), Beta-Hydroxybutyrate
0.17 mmol/L (<0.29mmol/L) Growth Hormone 2.3 ng/
ml (>10), IGF-1 121 ng/ml (94-252), cortisol 20.9 mcg/
dl (5-25) TSH 1.890 mcUnit/ml ( 0.5-5) Free T4 0.85ng/
dl (0.8 -1.8), insulin autoantibody Negative. Our patient’s
chemistry was consistent with insulinoma, except a low
C-peptide level. She had a CT-scan of the abdomen and
pelvis, which showed 3 enhancing lesions in the tail of
the pancreas in close proximity to each other measuring
from 0.5cm to 2cm in diameter. An MRI of the abdomen
also confirmed them. She had an octreoscan for tumor
– 118 –
ABSTRACTS – Other
localization and was found to have lesion distally at the
tail of the pancreas corresponding to the abnormality seen
in the CT scan. The patient continued to monitor her blood
glucose at home and had low blood glucose frequently but
remained asymptomatic. She underwent distal pancreatectomy. Two well differentiated endocrine neoplasms 1.2cm
and 0.8cm in greatest dimensions and multiple endocrine microadenomas limited to pancreas were found.
All stained positive for insulin and chromogranin A. Her
blood sugars were elevated post-operatively but became
normal a month after surgery.
Discussion: Our patient with insulinoma showed low
c-peptide levels, compared to the proinsulin and insulin
levels. Both insulin and c-peptide are normally produced
by cleavage of the proinsulin in equimolar amounts.
Exogenous insulin and insulin antibodies both affect the
insulin levels but the c-peptide levels are not affected by
them. Our case demonstrates a low c-peptide level, which
is generally considered inconsistent with insulinoma. One
previous case report and a few in-vitro studies in rats and
humans have shown low c-peptide levels due to enhanced
intracellular protein degradation by cathapsin B a cyseine
proteinase, in insulinoma cells.
Conclusion: In summary our case demonstrates a
rare case of insulinoma with decreased c-peptide concentrations presumably due to enhanced c-peptide degradation. Thus careful interpretation of blood tests and clinical
features in needed in a case of hypoglycemia to rule out
insulinoma.
Abstract #732
A RARE CASE OF NON ISLET CELL
TUMOR HYPOGLYCEMIA
(288-736), Insulin antibody 4.1uU/ml (0-5), Beta hydroxybutyrate: 0.4, Glucagon stimulation test increased blood
sugar from 46 mg/dl to 106mg/dl. Abdomen/ pelvic CT
showed very large and heterogeneous pelvic mass. Patient
was started on stress dose of I/V steroids and responded
favorably. PPN and I/V synthroid were discontinued.
Hypoglycemia reappeared when steroids were tapered
down to physiological dose. Patient was maintained without hypoglycemia on prednisone 40 mg daily and underwent surgery for pelvic mass. Pathology revealed multiple
large cellular leiomyomatas, largest weighing 2896 grams
and measuring 22x20x14cm. Hypoglycemia completely
resolved after surgery.
Discussion: Hypoglycemia can be caused by several
tumors including islet and non islet cell tumors (NICTH).
NICTH is usually associated with tumors of mesenchymal, vascular or epithelial cell types. Most common cause
of NICTH is tumoral overproduction of incompletely processed IGF2 (Big IGF2) resulting in stimulation of insulin
receptors and increased glucose utilization. Other possible
causes include insulin receptor antibodies and tumor infiltration of liver or adrenal glands. Our case clearly demonstrates the correlation of the massive leiomyomatas, IGF2
and recurrent hypoglycemia. In contrast to insulinoma, C
peptide and insulin levels are low. Beta hydroxybutyrate
level is also low and glucagon stimulation test is normal
or near normal. Treatment includes complete removal of
tumor. When it is not possible, medical therapy includes
use of steroids, diazoxide or long term glucagon infusion.
Conclusion: Though rare, NICTH associated with
increase production of IGF2 can be the cause of recurrent
hypoglycemia in the presence of a tumor.
Abstract #733
Faiza Aziz, MD, Zewge Shiferaw, MD
Objective: To demonstrate rare association of hypoglycemia with tumoral production of IGF2
Case Presentation: Our patient is an 80-year-old
female with history of diabetes mellitus (not on any hypoglycemic agents), HTN, hypothyroidism and history of
progressively growing mass in abdomen for last one year.
She presented in ER with history of fall and feeling dizzy
for last few weeks. Blood sugar in ER was found to be 26
mg/dl. She was started on Dextrose 10% infusion and was
consuming about 2/3rd of her meals but continued to have
recurrent episodes of symptomatic hypoglycemia. Patient
was transferred to ICU and started on PPN and I/V synthroid for severe hypothyroidism. Lab results are as follows TSH: 47, FT4:0.42. Concomitant with blood sugar of
36, C-peptide: 0.1ng/ml (0.8-3.85), Insulin level: <2uIU/
ml (0-24.9). Cosyntropin test revealed adequate adrenal response. IGF1:72ng/ml (59-177), IGF2: 782ng/ml
METABOLIC SYNDROME:
GAMMA-GLUTAMYLTRANSFERASE VS.
ALT/AST?
Maria del Pilar Serra, MD, Mercedes Pineyro, MD,
Gabriela Sosa, MD, Maria Zeballos, MD,
Cristina Belzarena, MD
Background/Objective: To evaluate the hypothesis
that ggt alterations are more prevalent in the metabolic
syndrome than those of alt or ast. Studies have reported
ggt levels in association with oxidative stress, also suggesting a relationship with metabolic syndrome and cardiovascular risk factors. High levels of this enzyme have
been linked with increased risk of diabetes and metabolic
syndrome (ms). Some studies have shown the previous to
be true for ggt but not for alt or ast. Liver enzymes have
been linked to metabolic syndrome variables in large representative samples of the general population.
– 119 –
ABSTRACTS – Other
Methods: A retrospective case-controls study was
performed. We identified 86 patients with ms (group 1)
and 84 patients without ms (group 2) followed in our
department. Patients without liver function tests, reported
excess alcohol drinking, or known liver disease of any etiology were excluded. Metabolic syndrome was defined in
accordance with atpiii criteria as the occurrence of three or
more of the following risk factors: (1) waist circumference
(wc) ≥102 cm. In men and ≥88 in women; (2) blood pressure (bp) ≥130/85 mmhg; (3) triglycerides (tg) ≥150 mg/
dl; (4) hdl cholesterol < 40 mg/dl (men) and < 50 mg/dl
(women) and (5) fasting plasma glucose ≥100 mg/dl. Data
on last year lfts was obtained.
Results: patients with ms were significantly older than
those without ms (62.13±12.38 (n=83) vs. 56.91±17.78
(n=47) p=0.001). There was no difference in sex ratio
between groups. No significant differences in diet and exercise between groups 1 and 2 was seen (61.3% _vs._ 61.5%
_p=0.983_y_34.3% _vs. 35._3%_p=0.919,respectively).
Median ggt levels were significantly higher in g1 compared to g2 (24.0 (7,699) vs. 20 (6,162) (n = 131)
p=0.014)); in contrast, there were no differences in ast (22
(8,75) vs. 23 (4,103) (n = 134) p=0.206) or alt levels (17.5
(6,125) vs.16 (6,191) (n = 134) p=0.200). Linear regression analysis showed that glycemia ≥100 mg/dl and bmi
were significantly associated with higher levels of ggt (r 2)
(0.13 p = 0. 023), with no other ms components entering
the model.
Conclusion: Levels of ggt are significantly higher
in patients with Ms. However, no differences in ast or alt
were found. Conversely, in multivariate analysis ggt elevations were significantly linked only with bmi and glycemia. It may be cost-effective to measure only ggt instead
of all liver enzymes to assess patients with ms.
low urine and serum osmolarities. The hyponatremia was
corrected with fluid restriction and dextrose solution 5%
was used to slow the correction rate of Na levels. Once
Na returned to a level of 122mmol/Lt the patient became
responsive again and was easily extubated. The history
revealed the presence of significant polydipsia for the few
days prior to presentation, with a daily intake of water
around 4 gallons, that the patient attributed to the newly
started psychotropic medications. All the laboratory evaluation for seizures came back normal apart from the above
mentioned values and the diagnosis of psychogenic polydipsia was confirmed. The patient’s regimen was changed
and the patient has stayed asymptomatic on follow-up.
Discussion: Psychogenic polydipsia is a syndrome
caused by the interaction of several psychotropic medications with the brain osmostat, leading to a derangement
of the thirst mechanism. The clinical effect of that, is a
feeling of excessive thirst and increased water intake,
which in turn leads to electrolytes and fluid imbalances.
The water intake could be increased to such an extent that
could cause an acute drop of serum Na levels and lead to
acute hyponatremia symptoms, sometimes severe enough
to warrant clinical investigation.
Conclusion: Our case demonstrates the wide spectrum of symptoms that could be attributed to this clinical
entity and points to the well-known problem of polypharmacy as a major risk factor for serious and potentially
lethal effects.
Abstract #734
Sunil Asnani, MD, FACE, Reema Salat, MD,
Abdel Alsharif, MD, Neena Penagaluru, MD
A CASE OF NEW ONSET SEIZURES
Rodis Paparodis, MD, Dimitra Bantouna, MD,
Renee Schickler, MD
Objective: Review the pathogenesis and the spectrum
of clinical manifestations of psychogenic polydipsia.
female, resident of a psychiatric long term care facility
that presented with seizures. Her medications were started
a few days prior to presentation and were valproate, chlorpromazine, quetiapine and haloperidol. She was found to
have generalized seizures, after which she was minimally
responsive and was intubated for airway protection. The
laboratory evaluation revealed a significant hyponatremia of 107mmol/Lt with undetectable urine Na and very
Abstract #735
PANCOAST TUMOR: AN UNSUALLY
AGGRESSIVE PRESENTATION OF A
NEUROENDOCRINE TUMOR
Objective: To present an unusually aggressive and
metastatic case of bronchial carcinoid with further atypical presentation.
Case Presentation: A 70-year-old male with 55-packyears smoking history was admitted with loss of sensation below the nipples, and falls. This had been progressive over the last one week. He denied any bowel/bladder
complaint. On exam, he had a sensory level at T4 dermatome; there was no motor deficit. Systems review revealed
upper back pain for the last year, treated with NSAIDs.
Chest X-ray revealed a right upper lobe mass, and chest
CT showed a 7.4 x 5.1 cm irregular mass with invasion
of right posterior second rib and T2 vertebral body with
direct extension into the spinal canal, cord compression, and multiple parenchymal lung nodules. Bone scan
– 120 –
ABSTRACTS – Other
showed abnormal tracer activity in T3, T4 and multiple
posterior ribs. Pathology revealed intermediate grade neuroendocrine carcinoma (atypical carcinoid).
Discussion: Bronchial carcinoid tumors are a rare
group of pulmonary neoplasms characterized by neuroendocrine differentiation and relatively indolent clinical behavior. They account for 1-2% of lung malignancies in adults and 20-30% of carcinoid tumors. Typical
carcinoids are low-grade, slowly-growing and rarely
metastasize. High-grade, typical for small cell lung cancers, behave aggressively with rapid tumor growth and
early dissemination. Atypical carcinoids are intermediate.
Immunohistochemical identification is the most reliable
method to confirm neuroendocrine differentiation. They
are thought to arise from specialized bronchial cell (the
Kulchitsky cell) and have low serotonin content. Typical
bronchial carcinoids have excellent prognosis with fiveyear survival rates of 87-100%. Despite their low malignant potential, long-term follow-up is warranted because
local or distant recurrence may occur years after initial
treatment. Further, it is uncommon for carcinoids to present as a pancoast tumor. Lastly, spinal canal invasion and
compression is another rarity of this case. Treatment is
typically surgical resection or debulking with radiation.
Conclusion: Our patient is interesting for presenting with an atypical carcinoid. Physicians must always
keep this diagnosis in the differential given its superior
prognosis.
Abstract #736
SUDDEN WHITENING OF HAIR ASSOCIATED
WITH HYPOGONADISM AND LOW IGF-I
follicle stimulating hormone (FSH) 2.6 mIU/mL, prolactin 7.3 ng/mL, IGF-I 56 ng/mL (age and sex-matched reference range 81-225). Overnight polysomnography was
diagnostic of obstructive sleep apnea (OSA). Continuous
positive airway pressure (CPAP) therapy was provided.
Intramuscular testosterone was delivered biweekly, with
favorable levels achieved (trough testosterone 632.0, peak
testosterone 734.4.). He had 35 pounds weight loss after
dietary and exercise interventions. IGF-I increased (98
ng/mL). Physical examination 12 months following onset
of whitening of hair demonstrated darkening at the base
of the white hairs on his scalp, as well as new growth of
dark hairs on his arms and legs. Visual images of hair are
shown.
Discussion: Sudden whitening of hair may involve
simultaneous lengthening of white hair or selective loss of
dark hair. Androgens exhibit a moderate effect on extremity hair, with a stronger effect noted on facial and parietal hair. Increased growth of androgen-dependent hair
likely occurred as a consequence of testosterone therapy,
and as such a repopulation by dark hairs may have been
manifested as resolution of whitened hair. A low level of
IGF-I in obesity has been characterized and may relate to
OSA syndrome. IGF-I accelerates growth of hair and hair
follicles. It is interesting that improvement in IGF-I following weight loss and appropriate treatment of OSA has
occurred in concert with resolution of hair whitening.
Conclusion: While sudden whitening of hair has
been described in vitiligo, and alopecia areata, a strong
association with hypogonadism or low IGF-I has not been
described, per se. Apparent resolution of our patient’s
findings raises the possibility of the ameliorating contribution of eugonadism and normalization of IGF-I.
Abstract #737
John Charles Parker, MD, FACE,
Brittany Noel Bohinc, MD,
Paul Caldwell Whitesides, Jr., MD
Objective: To describe a case of rapid-onset of hair
whitening with newly-diagnosed hypogonadism and
decreased insulin-like growth factor-I (IGF-I), with subsequent resolution within 12 months.
Case Presentation: A 57-year-old white male noted
fatigue, labile hypertension, headaches, and rapid-onset
whitening of his hair occurring over approximately
8 weeks time. He also had lighter beard growth and
had lost hairs on his arms and legs. Physical examination demonstrated androgenic alopecia (which had been
long-standing), but the remaining scalp hairs were white.
Moustache was white. Eyelashes appeared normal. No
vitiligo. Investigations for thyroid dysfunction and adrenal insufficiency were unrevealing. Additional evaluation
included total testosterone of 276 ng/dL, free testosterone 7.8 pg/mL, luteinizing hormone (LH) 4.5 mIU/mL,
METASTATIC NEUROENDOCRINE TUMOR
WITH PRIMARY ALDOSTERONISM
Muthukrishnan Jayaraman, MD
Objective: To describe a case of refractory hypokalemia in a patient with neuroendocrine tumor.
Case Presentation: A woman with severe refractory
hypokalemia was evaluated. Arterial blood pH, bicarbonate and spot urinary potassium was done. Plasma aldosterone and renin were done at baseline and after IV saline
suppression. Serum cortisol was estimated after overnight
dexamethasone suppression. A liver tissue sample was
evaluated for histopathology and immunohistochemistry
for Chromogranin A and Neuron Specific Enolase was
done. Metabolic alkalosis with high urinary potassium
and high plasma Aldosterone to Renin ratio, which was
non suppressible with Isotonic Saline infusion was noted.
– 121 –
ABSTRACTS – Other
Serum cortisol was normally suppressible after overnight
dexamethasone suppression test. Ultrasonography and a
computerized tomogaphic scan of her abdomen showed
multiple hepatic space occupying lesions but were negative for an adenoma in the adrenal glands or a tumor
elsewhere in the abdomen. On histopathology of liver
tissue, metastases were detected, which were positive for
Chromogranin A and Neuron Specific Enolase.
Discussion: Aldosterone excess in the setting of a
neuroendocrine tumor may be due to renin secreting
tumors causing hyperreninemic hyperaldosteronism or
rarely ACTH secreting tumors which may lead to aldosterone excess with low renin and present as Cushing’s
syndrome (ectopic ACTH secretion). We documented
aldosterone excess with low renin and cortisol, which
ruled out these two possibilities.
Conclusion: Primary aldosterone excess was documented in this patient with metastatic neuroendocrine
tumor, which we presume was the likely source of
aldosterone.
Discussion: The suggestive clinical characteristics of
hyperandrogenism are very common problems in women
and have been related with excessive androgen production
from ovaries, suprarenal glands or both. The most common identifiable cause of androgen excess is the polycystic
ovary syndrome. The virilizing tumors are rare. Ovarian
steroid cell tumors secrete great quantities of testosterone
or androstenedione and differ from Leydig cell tumors in
that they lack crystals of Reinke. Usually, they are benign,
but 20% of malignancy has been reported. They can produce different substances.
Conclusion: Ovarian steroid cell tumors are rare.
Diagnosis depends on androgens levels. The election
treatment is oophorectomy. Androgens levels are normalized after surgery.
Abstract #738
OVARIAN STEROID CELL TUMOR
Edith Jacqueline Luque Cuba, MD,
Freddy García Ramos, MD
Objective: To describe the behavior and features of an
ovarian steroid cell tumor in a post menopausal woman.
Case Presentation: We report the case of a postmenopausal woman with virilizing signs and a left anexial
mass. Testosterone 4.3ng/mL (0.2-0.95); DHEAS 56ug/
dL (35-430); androstenedione: 10ng/ml (0.4-2.7); Cortisol
16ug/dL. Testosterone post dexamethasone suppression
test 3.5ng/mL. An oophorectomy was performed in this
patient. Androgen levels were normalized after surgery.
– 122 –
ABSTRACTS – Pituitary Disorders
PITUITARY DISORDERS
Abstract #800
EFFICACY OF GROWTH HORMONE THERAPY
ON PATIENTS WITH GROWTH HORMONE
DEFICIENCY TREATED WITH RECOMBINANT
GROWTH HORMONE
Ali Hasan Dhari Al-Jumaili, MD, Qasim Rahi
Objective: This study was conducted to determine
the growth velocity response to recombinant growth hormone (rGH) therapy in growth hormone deficient children
(GHD). The effects of factors such as age, gender, birth
weight and chronological bone age were also evaluated in
these patients.
Methods: A prospective study was conducted in 160
patients (age range 3-12 years). These growth deficient
patients were selected from a cohort of 1400 patients
originally presented for evaluation of short stature. All
subjects underwent complete history and physical examination including measurements of height and weight.
In all patients mid parental heights were calculated to
exclude normal short stature (genetic and constitutional).
Following this patients were screened to exclude systemic causes of short stature (celiac disease, renal failure). Patients were also screened for genetic disorders and
also underwent a detailed evaluation for hypothyroidism,
Cushing’s syndrome and growth hormone deficiency.
After confirming growth hormone deficiency patients were
treated with growth hormone. A control group, matched
for sex distribution, age and other variables (n=160) were
also included in this study.
Results: The patients with growth hormone deficiency
included 160 patients with 112 males and 48 females.
Control group consisted of 76 male and 84 female children. The incidence of consanguinity was 40/120 in the
study group in comparison to 61/99 in control group. The
type of delivery (normal vaginal vs cesarean section) was
24/136 in the patients and 34/126 in control group. The
birth weights were adjusted according to gestational age
divided as* normal for gestational age (NGA), *small for
gestational age (SGA) and *small with unknown gestational age. The result was 126.21 and 13 in patients group
and 130, 18, and 12 in control group. Height velocity
increased from 3.5±1.2 cm/year before treatment to 8.5
±3.6 cm/year after 6 months of treatment with significant
P value. This significant increment in height velocity was
compared in different age group (range 3-12 y) ,different
bone age (range 1-10 y) , and different degree in delay
of bone age (range 2-8) ,degree of GHD either partial or
complete and the degree of response in relation to birth
weight correlated with gestational. The result shows
no significant difference regarding the response to GH
therapy between sex difference (male/female ratio range
in GHD patients range 2.3:1 & in control group 1:1.03
respectively), consanguinity (3:1 among patients group&
1:1.63 in control group respectively), delay in bone age
and degree of GHD respectively.
Discussion: It is obvious from this study that there is
a significant response in the linear growth after treatment
with recombinant GH therapy in patients with GHD by
increment of height velocity from 3.5 ± 1.2/year before
treatment to 8.5 ± 3.6 cm/year after 6 months of treatment. This response is approximately similar to those
reported previously. The majority of patients included in
this study with GHD 79% (126 from 160) were considered
normal for gestational (NGA) and because birth weight
has been shown to have a great influence on the response
of growth hormone therapy in this study (P value 0.007)
which is similar to the study of Lassare C. et al 1991. The
explanation is that children with SGA could be relatively
insensitive to the action of either endogenous GH or to
IGf-1. The percentage of small for gestational age to normal for gestational age 13% to 79% respectively approximately similar to John C. et al 1998 result were 19% to
81% respectively and similar to control group. Reference
to the criteria of this study the significant response to the
therapy was achieved by 85% (136 from 160) and 15%
(24 from 160) fail to achieve adequate response. This may
be explained as: SGA patients need higher doses of GH
0.48mg/kg/week in divided doses (1,2,3), The patients
may not follow the proper instructions regarding the dose,
frequency or the cooling chain. Wrong diagnosis because
lack of many hormonal assay e.g.: IGF-1, GHBP, etc.
Intercurrent illnesses during therapy period might interfere with the response.
Conclusion: This study indicates a significant
response in linear growth in patients with GHD after treatment with recombinant GH with positive relationship with
birth weight so effort & resources needed to achieve availability of the drug, related equipments, laboratory tests &
trained personnel. This study is a preliminary one and we
hope for further expanded studies in this.
Abstract #801
ANEURYSMAL SUBARACHNOID HEMORRHAGE
COMPLICATING TRANS-SPHENOIDAL
SURGERY FOR A PITUITARY ADENOMA
Subramanian Kannan, MD, Tarun Rustagi, MD,
Patrick Senatus
Objective: To emphasize the vascular complications
of pituitary surgery with special emphasis on aneurysmal
bleeding.
– 123 –
Case Presentation: 39-year-old male presented with
headache, intermittent photophobia and left sided visual
field defect of 3 month duration. Physical exam was significant for bitemporal hemianopia. Subsequently, MRI of
the brain revealed a contrast enhancing macroadenoma of
size 3.5 x 3 x 3 cm extending from the sella into the suprasellar region causing a mild mass effect on the optic chiasm with no invasion into the carotids. A CT-angiogram
did not reveal any intracranial aneurysm. His endocrine
evaluation was suggestive of a non-secretory adenoma.
A transcranial craniotomy and tumor debulking was performed. A post operative CT showed reduction in size of
tumor to 1.8cm. Immunochemical stains were negative
for functionality. Post-operative anterior pituitary evaluation was normal. A follow up MRI with MRA showed
a residual tumor with no evidence of aneurysm. A transsphenoidal surgery was performed for removal of the
residual tumor. There was a significant intra-operative
epistaxis. Despite achieving adequate hemostasis, patient
did not recover post-operatively. CT scan of head showed
intraventricular hemorrhage with hydrocephalus. A cerebral CT angiogram showed a 6mm anterior communicating artery aneurysm which was successfully embolized.
Patient was closely monitored in the ICU, but his mental
status never improved and he underwent a tracheostomy
and a feeding tube placement. Post-operatively he developed Diabetes insipidus, hypothyroidism, and hypoadrenalism for which he was started on hormone replacement
therapy.
Discussion: Arterial bleeding during transsphenoidal surgery for pituitary adenoma usually happens due to
rupture of intracavernous carotid or carotico-cavernous
fistula and/or pseudoaneurysm. A large series failed to
demonstrate any link between aneurysm formation and
pituitary tumors. Pituitary apoplexy and fatal epistaxis
have also been reported. In this poster we present a patient
with a non functioning pituitary macroadenoma and anterior communicating artery aneurysm, which caused significant hemorrhage during the surgery. Retrospective analysis of MRI and CT angiograms revealed no evidence of
aneurysm. We presume that the initial bleeding was from
the internal carotid artery with subsequent formation of
pseudoaneurysm.
Conclusion: A thorough evaluation for intracranial
vascular malformation should be undertaken before surgery for pituitary macroadenomas and invasive pituitary
tumors with special precautions in patients who have had
prior surgeries in the sellar region.
Abstract #802
POSTPARTUM GRANULOMATOUS
HYPOPHYSITIS WITH SPHENOID SINUS
INVOLVEMENT: A CASE STUDY
Charalambos Demetri, DO, Kamal Shoukri, MD,
Sherry Taylor, MD, J. Enrique Silva, MD
Objective: To report an unusual case of granulomatous hypophysitis with sphenoid sinus involvement in a
woman presenting with headaches and visual field deficits
2 weeks after a normal delivery.
with headache and visual disturbances 11 days postpartum. MRI revealed a sellar mass with suprasellar extension, invasion of cavernous sinuses and optic chiasm,
along with sinus mucosal thickening. A subtotal resection was performed via transphenoidal route. Histology
demonstrated extensive non vasculitic granulomatous tissue in pituitary and sphenoid mucosa samples. Serology
for infectious causes and autoimmunity were negative.
Fungal, bacterial, and tuberculosis staining and culture
were all negative as well. She required desmopressin and
thyroxine replacement after surgery. The patient’s headaches and visual field defects resolved rapidly. Sequential
follow up revealed spontaneous resolution of the residual
mass in 5 months without further intervention.
Discussion: Hypophysitis is an inflammatory condition of the pituitary gland that can be difficult to distinguish from other pituitary lesions. There are 3 histopathological categories of hypophysitis, namely granulomatous,
lymphocytic, and xanthomatous. The granulomatous
form has been described in the setting of tuberculosis,
syphilis, Takayasu’s disease, Crohn’s disease, Wegener’s
granulomatosis, sarcoidosis, Langerhans’ histiocytosis,
rheumatoid arthritis and Rathke’s cleft cyst rupture. The
term primary granulomatous hypophysitis is reserved to
those cases where the investigation fails to reveal a cause.
Primary granulomatous hypophysitis was first described
by Simmonds in 1917 who reviewed 2000 pituitary glands
at autopsy. We feel our case represents a primary granulomatous process given the absence of any associated
systemic or infectious granulomatosis. It remains unclear
whether the lesion was primarily hypophyseal or due to
local extension from the adjoining sphenoidal sinusitis.
Conclusion: Unique features of this case include the
simultaneous presence of granulomatous lesions in the
pituitary and sphenoidal sinus, its presentation in early
postpartum period, as well as the spontaneous resolution
of the residual granulomatous lesions in both the sphenoid
– 124 –
sinus and sella turcica. Our case demonstrates that complete resolution of granulomatous hypophysitis can occur
in a postpartum patient without the use of glucocorticoids.
Abstract #803
Abstract #804
A CASE OF REVERSIBLE VALVULOPATHY
ASSOCIATED WITH CABERGOLINE THERAPY
Troy Dillard, MD, Maria Fleseriu, MD,
Kevin S. Wei, MD, Chris Yedinak, NP
SEVERE HYPONATREMIA INDUCED BY
INTRANASAL DDAVP
Rakhi Shah, MD, Fariba Rahnema, MD,
Mrinalini Kulkarni-Date, MD
Objective: Central diabetes insipidus is recognized by
inability to secrete ADH in response to high plasma osmolality. This leads to polyuria with compensatory polydipsia, if thirst mechanism is intact, resulting in euvolemic
state. Some patient smay have detectable plasma vasopressin level, which represents partial form of the disorder.
Case Presentation: A 50-year-old female with history
of partial diabetes insipidus (DI) was admitted after MVA.
Pt was diagnosed with partial DI at age 12 and records
from past could not be obtained. Patient reported having
headaches associated with low serum Na. After starting on
her home dose of DDAVP of 2 nasal spray (10mcg) bid,
her serum Na was decreased to 115mmol/l, with serum
osmolality 240 and urine osmolality 357. When DDAVP
was held Na increased to 132mmol/l, with serum osmolality 280 and urine osmolality 75. Decreasing DDAVP
to1 spray bid Na dropped to 125mmol/l, with serum
osmolality 253 and urine osmolality 510. MRI brain was
unremarkable. TSH, LH, FSH levels and her cosyntropin stimulation test were normal. Her DDAVP dose was
titrated based on her urine output and serum Na. Serum Na
remained stable when 0.1mg DDAVP was given if urine
output >300ml/hr x 3 hrs. Patient was discharged with oral
DDAVP at dose of 0.1mg in morning and 0.1mg at around
5pm if her urine output is high. With this dose of DDAVP
patient’s Na remained stable and headaches resolved.
Discussion: Patients with DI are treated with DDAVP
in doses to normalize urine osmolality and flow. After
urine output normalizes, it produces increase in total body
water and subsequent decrease in plasma osmolality and
Na concentration. Eventually water balance is maintained
and hyponatremia does not develop. But in some patients
abnormal thirst persists and they develop hyponatremia.
In these patients, administering DDAVP based on UOP
(>300ml/hr x 3hrs.) may be an optimal way of treating.
Conclusion: In DI, after initiation of therapy with
DDAVP serum Na should be monitored closely. In some
patients, DDAVP dose should be adjusted depending on
urine output to prevent rare complication of hyponatremia.
Objective: To highlight reversibility of valvulopathy
associated with high dose cabergoline (CAB) therapy.
with delayed puberty and headache. Hormonal evaluation
revealed hyperprolactinemia (PRL=1000) and hypopituitarism. MRI showed a 2.2 cm pituitary tumor. CAB was
titrated to 6 mg/wk over 4 years without normalization
of prolactin or adequate tumor shrinkage. His hypopituitarism was appropriately replaced. After a total cumulative dose of 814 mg, an echocardiogram (echo) revealed
normal LV function, mild apical displacement, and mild
non-coaptation of the mitral leaflets with associated mild
mitral regurgitation. CAB was discontinued and replaced
with bromocriptine. Repeat echo (reviewed by same cardiologist) 8 months later showed resolution of all prior
abnormal findings. Clinical exam, including vitals signs
was unchanged between these two visits.
Discussion: While high cumulative doses of CAB are
a clear risk factor for valvulopathy in Parkinson’s patients,
the true risk of valvulopathy at doses used in prolactinomas is unknown and studies show conflicting results. In
our patient, a definitive causal relationship between CAB
use and valvulopathy could not be established without a
true baseline echo. However, causality is likely since no
other etiology for his valvular abnormalities were identified and cessation of CAB resulted in complete resolution
of these findings. There were no hemodynamic changes
between echo’s to explain this resolution. This implies
that, in specific cases, CAB may induce valvulopathy at
much lower doses than previously thought. It is possible
that higher doses in the first 2 years of treatment at a relatively young age, rather than total cumulative dose, played
a role in the development of valvulopathy in this patient.
While reversible dopamine agonist-induced valvulopathy
is documented in only a few patients with Parkinson’s disease, this is the first case described in a patient treated for
a prolactinoma.
Conclusion: Increased risk of valvulopathy should
be considered in patients requiring higher cumulative
CAB doses. Echocardiography should be performed in
these high-risk patients, drug holidays implemented and
patients withdrawn from these agents if possible. This case
highlights the potential reversibility of mild valvulopathy
– 125 –
associated with CAB therapy if treatment is discontinued
before the onset of the severe structural abnormalities.
Prospective studies are required to better characterize the
clinical significance of these valvulopathies, their natural
history and the potential for reversibility.
Abstract #805
HYPERPROLACTINEMIA WITH
GALACTORRHEA DUE TO
SUBCLINICAL HYPERTHYROIDISM
Issac Sachmechi, MD, FACP, FACE,
Hammad Bhatti, MD, David Reich, MD, FACE,
Paul Kim, MD, FACE
Objective: Hyperprolactinemia is a common finding
in primary hypothyroidism but increased prolactin in the
setting of subclinical hypothyroidism has been scarcely
reported in the literature.
Case Presentation: We describe a case of a 48-yearold female. Her past medical history was significant for
hypertension and sciatica. Because of her positive PPD
status in June of 2006, she was started on isoniazid (INH)
and vitamin B6. However, the patient only took her
medication for a few months and was lost to follow-up.
Subsequently, her INH treatment had to be restarted again
in January of 2007. She presented with painful galactorrhea for two to three weeks. Her last menstrual period was
3 weeks prior to her presentation, and the patient denied
any use of tobacco, marijuana, alcohol, illicit drugs, over
the counter medications, or prescription medications
with the exception of her anti-hypertension medications
(HCTZ 25MG daily and losartan 50mg daily) as well as
INH and B6. Her physical examination was within normal limits, except for diffuse non-tender enlargement of
her thyroid gland which has remained unchanged over
the past one year. Her breasts were tender to palpation
with milky yellow discharge bilaterally. The visual field
exam was normal. Labs showed: negative pregnancy test,
TSH level 5.63 (0.7-5mIU/ml), free thyroxine (free T4)
0.75 ng/dL (0.58-1.64 ng/dL), total T4 6.96 mcg/dL (6.0912.2mcg/dL), total triiodothyronine (T3) 91.4 ng/dL (87178 ng/dL) and prolactin 55.42 (3.34-26.74 ng/ml). Her
mammogram was normal and an MRI failed to show any
pituitary disease. The patient finished her course of INH
and she was started on levothyroxine 50mcg daily. Three
months later her galactorrhea and breast pain was relieved
and labs showed TSH level of 1.4 mIU/ml and prolactin
level of 13.44ng/mL.
Discussion: This is a rare case of hyperprolactinemia
due to subclinical hypothyroidism that resolved with thyroid hormone replacement therapy. The patient was not on
any medications known to cause hyperprolactinemia. INH
therapy not reported causing subclinical hypothyroidism
and hyperprolactinemia. Only three cases of galactorrhea
associated with subclinical hypothyroidism have been
reported. Similar to the reported cases in the literature, our
patient’s TSH and prolactin levels returned to normal with
levothyroxine therapy. A case of sterility associated with
increased prolactin and subclinical hypothyroidism have
been reported.
Conclusion: Hyperprolactinemia with galactorrhea
can occur in subclinical hypothyroidism. Treatment of
subclinical hypothyroidism and follow up of prolactin
level should be done in order to avoid ordering an unnecessary MRI of the sella tursica.
Abstract #806
XANTHOMA DISSEMINATUM:
A CASE REPORT
Miguel E. Pinto, MD, FACE, Glenda Escalaya, MD,
María E. Escalaya, MD, Jose L. Pinto, MD
Objective: To report a case of a young normolipemic woman with cutaneous and mucosal xanthomas who
developed neurogenic diabetes insipidus and hyperprolactinemia because of inflammatory pituitary stalk lesion.
with nine months history of polydipsia, polyuria, galactorrhea, secondary amenorrhea, and weight gain. Her previous medical history included chronic anemia, and widespread cutaneous and mucosal xanthomas. Laboratory
tests showed hyperprolactinemia, but serum electrolytes
and lipid profile were normal. The water deprivation test
was compatible with neurogenic diabetes insipidus. The
cerebral magnetic resonance imaging showed pituitary
stalk enlargement. Histologic examination of a skin biopsy
showed diffuse infiltration of the dermis with histiocytes,
which exhibited central nuclei and clear, vacuolated cytoplasm. Biopsy results were consistent with xanthoma disseminatum. Treatment was started with cabergoline, nasal
desmopressin, and dermabrasion for skin lesions.
Conclusion: Xanthoma disseminatum is a rare,
benign proliferative disorder in children and adults characterized by disseminated xanthomatous lesions in normolipemic patients. Central nervous system involvement
is rare and usually occurs in the systemic variety. Pituitary
stalk disease commonly causes hyperprolactinemia, diabetes insipidus, and varying degrees of hypopituitarism.
Natural history of xanthoma disseminatum usually is
benign, but lesions in critical anatomical locations may
result in morbidity and mortality.
– 126 –
Abstract #807
assist in defining extent of disease. Molecular profiling,
and possible treatment with tyrosine kinase inhibitors, are
areas needing further study.
METASTATIC PROLACTINOMA; DIAGNOSIS,
AND TREATMENT WITH TYROSINE
KINASE INHIBITORS
Abstract #808
Stanley Edward Von Hofe, MD, FACE,
Jeff Edenfield, MD
Objective: To report a case of man with pituitary carcinoma with metastatic disease.
Case Presentation: A 37-year-old man presented with
hypopituitarism and a prolactin of 1727 ng/dl. Pituitary
MRI revealed a 2.5 x 2.0 x 2.8 cm intrasellar mass.
Bromocriptine (up to 10 mg orally tid), followed by transsphenoidal surgery (TSS), yielded a post-op prolactin of
153 ng/dl. Therapy was changed to pergolide, and over the
next 4 years prolactin decreased to 33, and MRI revealed
no obvious tumor. The prolactin rose to >200, and there
was regrowth of pituitary tumor (MRI) to 2.2 x 2.2 x 1.8
cm over the next four years, and pergolide was changed to
cabergoline and a second TSS performed. Prolactin was
29 post-op, and the patient had radiation therapy to the
pituitary. The prolactin rose over the next year to 1622,
despite a change from cabergoline to quinagolide. MRI
showed questionable tumor recurrence within the sella
and clivus, and a third TSS was performed, but no tumor
tissue was found. Spine MRI suggested wide-spread metastatic disease, and PET scan revealed diffuse uptake in
the liver and multiple bony lesions. The prolactin level
was now 20,517. Liver biopsy confirmed metastatic
neuroendocrine carcinoma with positive immunostains
for prolactin. Molecular profiling (Molecular Profiling
Institute, Phoenix, Arizona) demonstrated up-regulation
of c-kit, epidermal growth factor receptor, and plateletderived growth factor, among other gene targets(all tyrosine kinase-driven processes). Treatment was begun with
sunitinib 50 mg qd and high dose cabergoline (5 mg bid)
continued. Over 7 months PET scan showed progression
of metastatic disease, and sunitinib and cabergoline were
discontinued and dasatinib (70 mg bid) begun. One week
later the prolactin level was 228,000, and the patient was
hospitalized with acute renal failure, thought possibly due
to tumor lysis syndrome. Within 6 weeks of starting dasatinib the prolactin had decreased to 12.7, and it remained
in the normal range thereafter. The patient, however, experienced much bone pain and progression of disease (PET/
CT) and died from metastatic disease 13 months after
starting dasatinib and 16 ½ years after his initial diagnosis.
Discussion: Pituitary carcinoma with metastatic disease is rare, about 140 cases, with only 47 being prolactinomas, reported prior to 2006. Typically patients demonstrate escape from dopamine agonist therapy during the
course of their disease. Imaging with MRI and PET may
RATHKE CLEFT CYST AND PITUITARY
DYSFUNCTION: MEDICAL AND SURGICAL
TREATMENT OPTIONS
Simona Ioja, MD, Victor Ciofoaia, MD, Rob Sandhu, MD, MPH
Mark Kulaga, MD, Nancy J. Rennert, MD, FACE, FACP
Objective: We present two cases of Rathke cleft cysts
(RCC) with pituitary dysfunction and we review the natural history and management of this disorder.
with headache and bradycardia and was found to be hyponatremic, normokalemic, hypothermic and hypoglycemic.
Lab evaluation revealed panhypopituitarism [cortisol 0.9
ug/dl, ACTH 49 pg/ml (nl.7-50), TSH 3.35uU/ml (nl.0.494.67), FT4 0.44 ng/dl (nl 0.71-1.85), Total Testosterone
20 ng/ml (nl260-1000), Free Testosterone 1.1pg/ml(nl
50-210), FSH/LH 3.7/1.4 mIU/ml (nl), Prolactin 4.8nh/ml
(nl)]. MRI showed a 14 x7.5 x5.2 mm non-enhancing pituitary cyst, projecting the pituitary upwards into the anterior aspect of the suprasellar cistern. He had no visual field
deficits. He was treated with hydrocortisone with normalization of sodium level, levothyroxine and testosterone.
A 25 year old female presented with intermittent headaches and 6 months of secondary amenorrhea. Prolactin
level was elevated at 207 ng/ml (nl 6-29.9), however TSH,
gonadotropins, and cortisol were all within normal ranges.
MRI showed a 1 cm cyst with mildly deviated pituitary
stalk. She had no visual field deficits. The patient wanted
to preserve future fertility if possible.
Discussion: RCC are fairly common non-neoplastic epithelial cysts derived from remnants of the Rathke
pouch, found in 20% of pituitaries at autopsy. Rarely,
RCCs can result in pituitary dysfunction. A spectrum of
endocrine dysfunction has been reported in a large case
series: 57% presenting with hypocortisolism, 43% with
hypogonadism, 39% with hyperprolactinemia, 35% with
hypothyroidism, 35% with GH deficiency, 13% with GH
excess and 9% with diabetes insipidus. Accurate diagnosis and differentiation from craniopharyngiomas is
important for both treatment selection and outcome prediction. Management of RCCs with endocrine dysfunction should be individualized. Treatment options include
medicine, surgical drainage, alcohol injection and radiation (gamma knife) and will be discussed in detail with
attention to risks, benefits and outcomes as documented
in the literature. In our first case, the patient was offered
surgery but declined and is being monitored. In the second
– 127 –
case, medical therapy was given, but surgery is being
contemplated.
Conclusion: RCCs can be associated with variable
pituitary dysfunction. Treatment should be individualized to address the specific endocrine dysfunctions with
consideration of risks and benefits, including postsurgical
recurrence rates that are close to 20%.
Abstract #809
HYPOPITUITARISM SECONDARY TO
INTRASELLAR ANEURYSM
not correct even after surgery. Our patient had a very rare
presentation of secondary hypothyroidism, growth hormone deficiency which corrected post surgery and possibly diabetes insipidus at presentation.
Conclusion: Anterior communicating artery aneurysms causing hypopituitarism are rare and this should
be considered in the differential diagnosis of any patient
who present with hypopituitarism and/or persistent headache. In this modern age with CT scan technology early
detection and treatment of this condition can be life saving
without significant neuroendocrine sequelae.
Abstract #810
Sailatha Padmanabhan, MD, Allison Galloway, DO,
Mary Zoe Baker, MD
Objective: To describe a young patient with anterior
communicating artery aneurysm causing hypopituitarism.
to the emergency department with progressively worsening headache, nausea, vomiting and double vision. She had
had polyuria, polydypsia, fatigue and alopecia for several
weeks prior to presentation. On physical exam, she had
weakness of her left third cranial nerve. Her laboratory
studies were as follows: Sodium 128meq/L (134-144),
TSH 0.072 μ IU/mL (0.350-4.940), free T4 0.5 ng/dL (071.5), random cortisol 27 mcg/dL (6.0-30.0), LH 0.2 mIU/
mL (1.6-70), FSH 1.07 mIU/mL (0.9-16) (she had taken
depot medroxy progesterone injection 4 months ago),
prolactin 21.70 ng/mL (1.2-29.9), and IGF1-104 ng/mL (116-358). A CT scan of the brain and a CT angiogram
confirmed the presence of a 1.6 x 1.5 x 1.5 cm bilobed
saccular aneurysm emerging from the inferior margin of
the junction of distal right A1 and anterior communicating
artery with subarachnoid hemorrhage. She subsequently
underwent microsurgical dissection and clipping of the
anterior communicating artery aneurysm. She tolerated
the procedure well except for postoperative diabetes insipidus. She was discharged on desmopressin and levothyroxine. A cosyntropin (0.25mg) test one-month post surgery showed a baseline cortisol level of 9.2 mcg/dL, 19.7
mcg/dL at 30 min and 24.9mcg/dL at 60 min. A repeat
IGF1 was 211 ng/ml.
Discussion: Intrasellar aneurysms are a rare, but recognizable cause of hypopituitarism accounting for 0.17%
cases of hypopituitarism, with anterior communicating
artery aneurysms being much less common than those
arising from the internal carotid artery. At least one pituitary hormone deficiency seems to occur more commonly
than previously thought after a year from subarachnoid
hemorrhage related to aneurysms. Adrenal, thyroid and
gonadal deficiencies were the deficiencies in the order of
decreasing frequency in a Mayo Clinic retrospective study
of hypopituitarism and intrasellar aneurysms. They may
TEMOZOLOMIDE FOR CORTICOTROPH
ADENOMAS REFRACTORY TO SURGERY
AND RADIATION: A CASE OF RAPID
TUMOR REGRESSION
Troy Dillard, MD, Maria Fleseriu, MD,
Johnny B. Delashaw, MD, Edward A. Neuwelt, MD,
Chris Yedinak, NP
Objective: To highlight the potential for temozolomide (TMZ) to induce rapid tumor regression in patients
with aggressive corticotroph adenomas (CA) refractory to
surgery and radiation therapy.
Case Presentation: We present a case of a 56-yearold male with a 3 cm CA diagnosed in 1996, treated with
transphenoidal surgery (TSS) and radiotherapy. His disease recurred 11 yrs later with rapid tumor growth to 4.2
x 2.5 cm, multiple Cushing’s symptoms and he underwent
2nd TSS. His tumor recurred after 6 mos, this time without
florid Cushing’s symptoms but with ophthalmoplegia. He
required, over 16 mos, an additional 3 surgeries (2 TSS, 1
craniotomy) and repeat radiation therapy to control hypercortisolemia. The highest ACTH during this interval was
306 pg/mL. Ki67 staining index on his surgical specimens
was 5-6%. Due to large residual tumor and visual defects,
the patient was started on TMZ at 150mg/m2, titrated to
190mg/m2 per dose taken 5 days monthly. The only significant side effect was moderate nausea. After only 10
weeks of TMZ, the patient’s tumor showed a remarkable
60% regression in size with objective improvement in
ophthalmoplegia.
Discussion: Treatment of aggressive CAs represents
a therapeutic challenge. They are often invasive, incompletely resected and recurrence is common. Conventional
treatment options (surgical debulking and radiation) are of
limited success and few options remain. TMZ is an oral
alkylating agent. Tumors that express O-6-methyluanineDNA methyltransferase (MGMT) are resistant to its effects.
Thus, low expression of MGMT predicts responsiveness.
A series of 88 pituitary adenomas revealed low levels of
– 128 –
MGMT expression in 13% of tumors. Prolactinomas were
most likely to have low MGMT, but there was no difference between invasive and noninvasive or recurrent and
non-recurrent tumors. Small series suggest that aggressive
CAs (especially Crooke’s cell variants) have low MGMT
expression. Only a few cases of CAs responsive to TMZ
have been reported. Our case is the only case reported
with such a rapid and robust response in tumor size. It is
unclear if radiation pre-treatment may have enhanced our
patient’s response to TMZ.
Conclusion: TMZ shows significant promise in the
treatment of aggressive pituitary adenomas. Our case
highlights its potential effectiveness even after multiple
surgical interventions and radiation therapy. After only 10
weeks of TMZ, a 60% decrease in tumor size was noted
with improvement in ophthalmoplegia. Further clinical
trials of TMZ in the treatment of aggressive pituitary adenomas are warranted.
Abstract #811
ACROMEGALY AS A CAUSE OF CALCITRIOLDEPENDENT HYPERCALCEMIA
Reshma Shah, MD, Angelo Licata, MD, PhD,
Nelson M. Oyesiku MD, PhD, FACS,
Adriana G. Ioachimescu MD, PhD
levels ranged between 9.8-10.7 mg/dL, PTH 23 pg/mL,
and calcitriol remained high of 81.3 pg/mL.
Discussion: Approximately 10% of acromegalic
patients were reported to have hypercalciuria and nephrolithiasis, but hypercalcemia without elevated PTH in acromegaly has never been reported. Proposed mechanisms of
hypercalciuria include parathyroid hyperplasia, increased
Ca absorption, renal tubular acidosis or calcitriol overproduction. Normalization of IGF-1 with GH receptor antagonist reduces urinary Ca clearance and calcitriol level.
Alternatively, GH replacement has been shown to increase
serum Ca level from baseline. We present 2 cases of calcitriol-dependent hypercalcemia correlating with acromegaly activity. Biochemical remission of acromegaly
resulted in normalization of Ca and calcitriol levels, while
incomplete resection was associated with persistent calcitriol-dependent hypercalcemia. GH may activate renal
1-α-hydroxylase resulting in increased calcitriol production and subsequent hypercalcemia and hypercalciuria,
but further studies are needed to clarify the mechanism.
Conclusion: Hypercalcemia rarely occurs in patients
with acromegaly, likely due to increased calcitriol levels
by GH, either by increased synthesis or decreased clearance of the vitamin.
Abstract #812
Objective: We describe 2 cases of calcitriol dependent
hypercalcemia associated with growth hormone excess.
Case Presentation: A 50-year-old female with 1
year h/o hypercalcemia presented with features of acromegaly. Serum calcium (Ca) was 10.9 mg/dL (8.610.2), parathyroid hormone (PTH) 20 pg/mL (10-65),
25-hydroxyvitamin D 33 ng/mL (20-100), urine Ca 388
mg/day, PTH-related peptide undetectable, and calcitriol
(1,25-(OH)2 vit D) 119 pg/mL (15-75). She had negative PPD, chest x-ray, ACE level, and gadolinium scan.
Insulin-like growth factor-1 (IGF-1) was 911 ng/mL (49292) and growth hormone (GH) 14.5 ng/mL (0.03-10), not
suppressed after OGTT. MRI showed a 1.7 cm pituitary
tumor. Transsphenoidal adenomectomy (TSA) resulted
in normalization of IGF-1 (197 ng/mL), GH (1.4 ng/mL),
Ca (10.0 mg/dL), and calcitriol (50 pg/mL). At 3 months,
GH suppressed after OGTT and MRI showed complete
tumor resection, while Ca remained normal. A 52 y/o F
was diagnosed with visual field deficits on routine exam.
MRI showed a 3 cm pituitary macroademona. IGF-1 was
416 ng/mL and GH 75.8 ng/mL. Incidentally, she was
found with Ca of 10.8 mg/dL associated with PTH 19 pg/
mL and calcitriol 66 pg/mL. TSA resulted in immediate
reduction of GH (18.6 ng/mL), IGF-1 (246 ng/mL), & Ca
(8.4 mg/dL). At 3 months, IGF-1 was 440 ng/mL, GH 9.9
ng/mL, while MRI showed parasellar tumor residue. Ca
DIABETES INSIPIDUS IN A PATIENT WITH
METASTATIC SMALL CELL LUNG CANCER
Alina Khan-ghany, MD, Vitor Pastorini, MD,
Seth Sclair, MD, Reyan Ghany, MD,
Bresta Miranda-Palma, MD
Objective: To report a case of diabetes insipidus
(DI) in a patient with metastatic Small Cell Lung Cancer
(SCLC) to the pituitary stalk.
Case Presentation: A 49-year-old male smoker, with
recently diagnosed SCLC, presented to the ER with a postobstructive pneumonia. Radiographic staging showed
metastases to the mediastinum; bone; and pituitary stalk,
which was a well-defined enhancing 6 x 6 mm lesion on
brain MRI. On day 8 of hospitalization, he developed
superior vena cava syndrome and received emergent radiation and chemotherapy with etoposide and carboplatin.
The day after chemotherapy, he was noted to have a urine
output of 12 L with an oral intake of 7 L. A history of icecravings and the urge to wake up at night to drink cold
water was elicited. He denied symptoms of orthostasis,
headaches, or visual changes. Laboratory data revealed
a urine osmolality of 123 mOsm/kg with corresponding serum sodium of 140 mmol/L. The patient remained
eunatremic despite polyuria so a water deprivation test
was performed. After 4 hours of water deprivation, serum
– 129 –
sodium increased from 142 to 148 mmol/L with a urine
osmolality that remained hypotonic (88 -118 mOsm/kg).
During hour 5 of water deprivation, a desmopressin challenge produced an increase in the urine osmolality to 363
mOsm/kg, confirming the diagnosis of central DI. The
patient was subsequently started on intranasal desmopressin with improved polyuria and polydipsia. Anterior
pituitary function was normal as assessed by ACTH, LH,
FSH, testosterone and IGF-1 levels. Prolactin was 18 ng/
ml. TSH, free T4, anti-TPO antibody were 11 uIU/ml, 0.8
ng/dl and 431 IU/mL, respectively, consistent with primary autoimmune hypothyroidism.
Discussion: Pituitary metastases (PM) occur in 1-4
% of patients with malignancy on autopsy with non-small
cell lung cancer as one of the leading causes. There are
few reports of metastatic SCLC to the pituitary gland in
the literature. PM are typically asymptomatic, however,
when they are symptomatic, 60-70 % of patients present
with DI. It is hypothesized that since the posterior pituitary
receives its blood supply from the systemic circulation,
the probability of metastatic seeding is greater than seeding to the anterior pituitary, which receives its blood supply from the portal system. Treatment modalities include
chemotherapy, surgery, and radiation therapy. In our case,
the patient received whole brain radiation.
Conclusion: DI is a rare complication of metastatic
SCLC. DI often is unrecognized, but once identified and
treated, quality of life is improved. Mean survival rates of
metastatic SCLC range from 6 to 22 months independent
of treatment strategy.
Abstract #813
BREAST CANCER WITH NEUROENDOCRINE
PHENOTYPE: THE ROLE OF PITUITARY
TUMOR INDUCED HYPERPROLACTINEMIA
Catalina I. Poiana, MD, PhD, FACE,
Mara Carsote, MD, Madalina Musat, MD, PhD,
Dana Terzea, MD, Corina Chirita, MD,
Dan Hortopan, MD, PhD, Anda Dumitrascu, MD, PhD
one more month after. Pregnancy was confirmed. Based
on high dimensions of the macroprolactinoma, estrogen
stimulus associated with pregnancy was considered to
be dangerous, so early pregnancy termination was performed. Six months later, the CT scan of pituitary showed
an important shrinkage of the tumor to 2.1 by 1.2 cm, with
prolactin level of 30.13ng/mL. During the following 3 yrs,
bromocriptine was progressively reduced while normalization of the visual field and shrinkage of the pituitary
adenoma to 1.3/0.9 cm (prolactin: 4.02 ng/mL). Low dose
bromocriptine (7.5 mg/day) was continued for 2 yrs when
the tumor became a microadenoma (of 0.87/0.71 cm) and
remained so till present. At the age of 45, the breast exam
revealed a nodule in the upper-outer quadrant of the left
breast associated with orange like skin. The ultrasound
showed a nodule of 1.5 cm. The surgical approach of the
nodule was recommended and intra-operator pathological
exam revealed a mammary carcinoma. Total mastectomy
and axillary lymph nodes excision was performed. There
was a T1G1N0, mucinoid carcinoma. The immunohistochemistry was positive for estrogen and prolactin receptors. External irradiation and total histerectomy with bilateral anexectomy were performed. Further chemotherapy
or immunotherapy is under consideration.
Discussion: The prolactin induces changes at the
level of the mammary gland, regardless of normal or
pathological context. Hyperprolactinemia in women with
breast cancer is of poor prognosis for the breast disease,
probably by a direct autocrine production by cancer cells
themselves. The prolactin receptors in the tumor in a
long standing case of hyperprolactinemia due to a pituitary macroadenoma may be responsible of tumor growth.
Controlled prospective studies would be useful to determine the risk of breast cancer (if any) for women with
chronic high prolactin.
Conclusion: The mucinoid breast cancer may gain a
neuroendocrine profile, with a more rapid growth induced
by prolactin receptors in a context of hyperprolactinemia.
Abstract #814
Objective: We report a case of macroprolactinoma
diagnosed with breast cancer at age of 45.
Case Presentation: Woman of 47 has a 6 year history
of prolactinoma. At diagnosis, she had hypo-menorrhea
and intense headaches. Prolactin levels were very high:
>1000 ng/mL (normal < 20ng/mL) with low FSH and LH
levels. The pituitary CT scan revealed a macroadenoma
of 4 /4.45/ 4.25 cm, with suprasellar extension and invasion into the left cavernous sinus and left temporal lobe.
High dose therapy with dopamine agonist, (bromocriptine 30 mg/day) was started. Three months later prolactin decreased to 52.29 ng/mL, but the menses stopped
AN UNUSUAL CASE OF HYPOGLYCEMIA IN
TYPE 1 DIABETES
Seshadrinathan Pramodh, MD, Dominic Parsons, MBBS,
Alex Bickerton, MBBS, D. Phil
Objective: To demonstrate the possible multi-factorial
potentially reversible causes of hypoglycaemia in Type 1
Diabetes, aside exogenous insulin.
Case Presentation: A 55-year-old woman with a 40
year history of Type I DM, primary hypothyroidism and
a 2 year history of severe hypoglycemic episodes and
weight loss, presented following hypoglycemic collapse
– 130 –
to our hospital. She had 1-2 episodes of severe hypoglycemia a week, with minimal warning symptoms, requiring
frequent glucagon administration. She exercises heavily,
cycling 6 miles a day, whilst consuming handfuls of glucose tablets to avoid hypoglycemia. She also has a history of anorexia in the past and continues to be heavily
obsessed about her weight. She was on multiple daily
doses of insulin with Glargine and Aspart. Admission
plasma glucose level was 25.2 mg/dL. She received 80
g of glucose intravenously over 3 hours before eventual
recovery and achieving euglycemia. She was investigated
for adrenal insufficiency and was found to have a low
morning cortisol (6.74 µg/dL) and inadequate response
to 250 µg ACTH stimulation (17.6 µg/dL at 30 mins).
An ACTH of 26 pg/mL (NR 0-40) and renin of 18 mu/L
(NR 2-30) excluded primary adrenal insufficiency. An
insulin stress test confirmed secondary hypoadrenalism
(peak cortisol of 14 µg/dL). Appropriate GH response on
insulin stress test (peak GH rise of 12 µg/L), and normal
post-menopausal levels of LH (33.9 U/L) and FSH (52.0
U/L) and prolactin (22.35ng/mL) confirmed normal function of other anterior pituitary hormones. She was slightly
over replaced with Thyroxine (TSH 0.03mu/L; fT4 23.5
pmol/L). A pituitary MRI scan was normal leading to a
diagnosis of isolated ACTH deficiency. She was started
on steroid replacement and the dosage of Thyroxine was
reduced. This reduced the episodes of severe hypoglycemia, but not mild and moderate episodes.
Discussion: Isolated ACTH deficiency is an unusual,
but well-recognized cause of hypoglycemia in Type 1
Diabetes characterized by low cortisol production, normal secretion of pituitary hormones other than ACTH. It
is usually autoimmune in origin In this case, there were
several factors contributing to hypoglycemia including
exercise, anorexia and hypoglycemia unawareness. The
prolonged episode of severe hypoglycaemia prompted
investigation for cortisol insufficiency.
Conclusion: It is important to look for unusual and
reversible causes of hypoglycemia in Type 1 Diabetes.
Adreno-cortical insufficiency must always be considered
as a possible cause of hypoglycemia, prompting appropriate investigation.
Abstract #815
ACUTE INCREASED INTRACELLAR PRESSURE
SHORTLY AFTER RECEIVING GNRH AGONIST
& ANDROGEN RECPTOR ANTAGONIST FOR
PROSTATE CANCER TREATMENT
Lee Hong, MD, Nasrin Azad, MD
Objective: To describe a case of acute increased
intrasellar pressure shortly after receiving GnRH agonist
(goserelin) and androgen receptor antagonist (flutamide)
for prostate cancer treatment.
Case Presentation: A 68-year-old man developed
excruciating right sided headache and diplopia one week
after receiving goserelin and flutamide. Physical exam
showed third nerve palsy and bitemporal hemianopsia.
Magnetic resonance imaging (MRI) of the brain showed a
large sellar mass (2.6 cm x1.9 cm) compressing the optic
chiasm and extending to right cavernous sinus without
hemorrhage. Initial assessment revealed FSH 104(1-18
mIU/ml), LH 10 (1-9 mIU/ml), α subunit 51.3 (<0.6ng/
mL), TSH 0.19 (0.35-5.50 uIU/mL), Free T4 0.73 (0.891.80ng/dL), Free T3 1.7 (2.3-4.2 pg/mL), total testosterone (TT) 591 (241-827 ng/dL), free testosterone (FT)
133.3 (35.0-155.0 pg/mL), somatomedinC 230 (71-290
ng/mL), GH 1.4 (0-10 ng/mL), ACTH 8 (7-50 pg/mL),
cortisol 9.94 (4.30-22.40 mcg/dL) and prolactin 20 (2-18
ng/ml). A repeat MRI four weeks later showed no interval
changes but visual field defect worsened. He then underwent transsphenoidal debulking of the tumor. Post-op MRI
showed decreased pituitary tumor size and decompression
of the optic chiasm. FSH&LH levels decreased to 42&3
respectively. His visual field improved within the next
six months. Immunohistochemical staining of tumor was
strongly positive for LH. No tissue necrosis was noted. He
had prostectomy two weeks later and flutamide was discontinued. No more goserelin was given. Five years later,
LH/FSH/TT/FT were 12/32/366/38.5 and no changes on
MRI.
Discussion: We are presenting a case of gonadotropin producing tumor with sudden growth coincide with
the administration of goserelin and flutamide. While continuous GnRH agonist therapy is known to decrease LH
and FSH in normal pituitary, it may have acute stimulatory effect on gonadotropin adenoma, resulting in sudden
enlargement of tumor. Pituitary apoplexy after GnRH agonist therapy had been reported before. But, no hemorrhage
or necrosis noted on imaging or pathology in our patient.
His symptoms occurred a week after receiving GnRH agonist fit the time window for cell proliferation to generate
a significant growth of the pituitary adenoma. This is the
fourth reported case of increased intrasellar pressure without pituitary apoplexy following GnRH agonist therapy.
In the last three cases, patients’ symptoms occurred at
10, 12 and 7 days after GnRH agonist administration. In
addition, our patient received flutamide which is known to
increase LH and FSH production. It may also contribute to
the growth of the pituitary adenoma.
Conclusion: We reported a patient with sudden
symptoms of increased intrasellar pressure shortly after
receiving goserelin and flutamide without any evidence
of pituitary apoplexy. We hypothesize the acute growth of
the adenoma was due to the administration of goserelin
and possibly flutamide.
– 131 –
Abstract #816
Coexistence of hypogonadism as in this case is well
described in literature.
Conclusion: The management of pituitary adenoma
in Nigeria is challenging for myriad of reasons. Recurrent
tumors are very likely if surgery alone (not first line of
treatment) is used for treatment.
RECALCITRANT PITUITARY ADENOMA
PRESENTING AS ACROMEGALY AND
HYPOGONADISM IN A NIGERIAN MALE
Andrew Enemako Uloko, MD, Fabian H. Puepet, MD,
FMCP, Shehu M. Yusuf, FWACP,
Ayekame Tini Uloko, BPharm
Abstract #817
Objective: Reports of recurrent pituitary adenoma
in Nigeria remain scanty probably due to diagnostic and
therapeutic challenges. Our objective is to report a case
of recalcitrant pituitary adenoma with Acromegaly and
hypogonadism in a Nigerian male.
Methods: The case records of a 32-year-old Nigerian
male with suspected Acromegaly and hypogonadism was
reviewed. Hormonal assays, screening for diabetes mellitus, neuro-imaging were performed and review of relevant
literature undertaken.
Case Presentation: A 32-year-old male referred
from the urology clinic to the endocrine clinic of AKTH
in April 2009 had a 3-year history of excessive body
growth, recurrent headaches, impaired vision, loss of
libido and erectile weakness. He had trans-frontal pituitary adenomectomy 15 months earlier at a Saudi hospital
with initial improvements. His clinical features however
recurred 10 months ago mainly with progressive body
growth, difficulties with appropriate shoe and cap sizes,
bilateral gynecomastia, greasy/oily skin, hyperpigmentation, recurrent headaches and impaired vision (blindness
left eye, cataract right). Laboratory evaluation revealed
normal fasting plasma glucose and OGTT. Hormonal
assays: FSH 1.7IU/L (1.0-19.0IU/L), LH 1.1IU/L (1.0-9.0
IU/L), Prolactin 3.8 ng/ml (2.6-13.1ng/ml), Testosterone
0.76nmol/l (9.5-35 nmol/l). Thyroid function tests (Free
T3, T4, TSH) were normal. Basal growth hormone (GH)
assay > 96µIU/ml (normal up to 13.5 Μiu/ml) and failure to suppress GH after a 2-hour 75g OGTT (>96 µIU/
ml 30mins, >96 µIU/ml 60mins, >96 µIU/ml 90mins, >96
µIU/ml 120mins and >96 µIU/ml 180mins). Recent brain
CT scan showed a huge pituitary macroadenoma with
some frontal lobe infarcts. A diagnosis of Recalcitrant
Pituitary Adenoma with Acromegaly and Hypogonadism
was made. He is yet to commence medical treatment for
the adenoma due to logistic and social constraints.
Discussion: The main treatment for pituitary macroadenoma is by use of drugs depending on the tumor
type and the predominant hormone secreted. Surgery is
considered when medical therapy is not successful or
when pressure symptoms are very prominent due to tumor
size. As in this case, there is high chance of recurrence of
tumor growth if surgery alone is used in the treatment.
OUTCOME STUDY OF TRANSSPHENOIDAL
SURGERY FOR ACROMEGALY:
UNIVERSITY EXPERIENCE
Adriana Gabriela Ioachimescu, MD, PhD,
Diana M. Pimentel, Vaninder S. Chhabra,
Nelson M. Oyesiku, MD, PhD
Objective: To determine the biochemical outcome
of acromegaly patients treated by transsphenoidal adenomectomy (TSA).
Methods: We reviewed all acromegaly cases (N=61)
of TSA by a single neurosurgeon between 1998 and 2009.
We excluded 8 patients with follow-up < 3 months and 5
patients with prior pituitary surgery by a different surgeon.
Criteria for remission were: normalized age- and gendermatched IGF-1 and fasting growth hormone (GH) < 2.5
ng/mL (or GH <1 ng/mL during OGTT).
Results: Twenty two men and 26 women, age
45.7±11.9 were followed for a median of 1.5 years after
TSA (0.33-8 years). At 3 months postoperatively, the
remission rate was 70% in patients with non-invasive
(N=23) and 16% for invasive tumors (N=25). The remission rate was 77% for microadenomas (N=13) and 31.4%
for macroadenomas (N=35). In the remission group, the
tumor size was smaller (1.4±1.0 cm) vs. no-remission
group (2.2±1.0 cm, p 0.007). Although preoperative GH
and IGF1 were lower in the remission group, there was no
significant difference vs. no-remission group. GH on postoperative days 1-5 was lower in the remission (1.6±1.7)
vs. non-remssion group (53±197, p=0.1). Immediate postoperative GH was <3 ng/mL in 90% of patients in remission group and in 37% of patients who did not achieve
postoperative remission. MRI at 3 months postoperatively
showed tumor residue in 9.5% of patients in the remission
group and 81.5% of patients who did not achieve remission. Thirty three patients were followed for more than
1 year (median 2.5). Recurrence occurred in one patient
(3%) at 8 months post TSA. Among the 19 who did not
achieve postoperative remission, 5 (26%) normalized
IGF1 and GH during somatostatin analog therapy and 5
(26%) after radiation therapy while taking medical treatment. The median time from radiation to remission was 2
years (1 to 5).
– 132 –
Discussion: Remission rate for acromegaly varies
greatly among studies due to different remission criteria,
changes in hormonal assays and surgeon’s experience.
Proposed predictors of postoperative biochemical remission include tumor size and invasiveness, incomplete
tumor resection and preoperative GH levels. Our study
supports the predictive value of tumor size, invasiveness
and incomplete tumor resection. Some studies suggested
that low GH immediately after TSA is a predictor of longterm remission. However, we found that 37% patients
who did not achieve remission had GH < 3 ng/mL in the
first few days after surgery.
Conclusion: Tumor size, dural invasion and incomplete resection are important prognostic factors of surgical outcome in acromegaly. Immediate postoperative GH
levels should not be used alone to predict long-term biochemical remission.
Abstract #818
LANGERHANS CELL HISTIOCYTOSIS IN AN
ADULT PATIENT MANIFESTED AS DIABETES
INSIPIDUS AND HYPOTHALAMIC LESION
found in systemic LCH. Chemotherapy was started.
Discussion: LCH is a rare entity that results from
pathological proliferation and infiltration by Langerhans
cells, with an incidence of 3-5 cases per million per year in
pediatric population. Adults are rarely affected (1.8 cases
per million per year). It shows predilection for the HPA
leading to CDI in about 17-30% of the cases. In the presence of other pituitary deficiencies, the prevalence of CDI
can be as high as 94%. The pathogenesis has been attributed to LC-infiltration as well as scarring lesions in HPA.
MRI shows typically a thickening of the pituitary stalk or
loss of the pituitary spot. Hypothalamic masses are found
in 8-18% of cases. Biopsies from certain delicate regions
such as the hypothalamus are controversial.
Conclusion: LCH should be in the differential diagnosis of adult patients presenting with CDI, anterior pituitary hormone abnormalities and hypothalamic lesions.
Endocrinologists need to develop high clinical suspicion
of endocrine abnormalities associated with systemic diseases such as LCH. This recognition could avoid unnecessary and risky invasive procedures such as brain biopsy.
Abstract #819
Ana Cecilia Apaza Concha, MD,
Andrea Marcela Sosa-Melo, MD,
Luz Marina Prieto Sanchez, MD
EXPRESSIVE APHASIA: A RARE
MANIFESTATION OF UNTREATED
HYPOPITUITARISM
Objective: To report a case of an adult patient newly
diagnosed with Langerhans Cell Histiocytosis (LCH)
complicated with Central Diabetes Insipidus (CDI).
Case Presentation: 46-year-old Hispanic female
presented with a 6-month history of progressive confusion, memory problems and incoherent speech associated to polyuria, polydipsia. After an episode of loss of
consciousness she was admitted to a tertiary care Hospital
where a brain MRI (Magnetic Resonance Imaging)
showed a 1.6 X 3cm hypothalamic lesion. She was transferred for possible mass resection. Her mental status worsened. She developed polyuria with severe hypernatremia
of 176mmol/L and inappropriately low urine osmolality.
The patient was treated with desmopressin with good
response. Other pituitary evaluation showed central
hypothyroidism, hypogonadotrophic hypogonadism, low
IGF-1 levels and prolactin levels slightly elevated. After
stabilization, she underwent craniotomy and hypothalamic biopsy. Pathology result showed “astrocytosis and
perivascular lymphocytic infiltration”. In additional medical record review it was found that she had chronic vulvar and major labia lesions that were biopsied 5 months
prior to this episode. Pathology result was consistent with
Histiocytes and Langerhans cells with positive cD1a and
S100 stain. It was concluded that the hypothalamic lesion
was compatible with the type of pathology that can be
Richard W. Pinsker, MD, FACE, Kaushik Doshi, MD,
Kelly L. Cervellione, MA, MPh, Danny Guillen, MD,
Birju Shah, MD, Pooja Kanth, BS
Objective: To describe a case of expressive aphasia
caused by untreated hypopituitarism.
Case Presentation: A 73-year-old male with HTN,
DM and depression was admitted due to an episode of
syncope. He had been diagnosed with meningioma in
2001, and underwent a craniotomy in 2001 and again in
2004. He subsequently received gamma knife treatment
for invasion of the cavernous sinus. Since then, he had
experienced progressive weakness, lethargy, and multiple episodes of hypoglycemia and syncope. In 2008 he
became non-verbal and was diagnosed with ‘expressive
aphasia’ by neurologists, thought to be caused by ischemia from past treatments. A few weeks prior to current
hospitalization, he was admitted due to an episode of dizziness with loss of consciousness. Mild hypothyroidism
was diagnosed; l-thyroxine was started. CT scan showed
a large, hyper-dense pituitary mass invading the sella and
eroding into the sphenoid sinus. At current admission,
the patient was non-verbal and unable to walk; his BP
= 80/60 and pulse = 60bpm. He was taking l-thyroxine
50mcg/day. Due to CT results from last admission and
history of gamma knife surgery involving the cavernous
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sinus, endocrine function work-up was ordered. Results
included: Cortisol 2.72 ug/dL with post-cosyntropin of
12.6 ug/dL, prolactin 14.2 ng/mL, TSH 3.99 mlU/mL, free
T4 0.44 ng/dL (onl-thyroxine), total T3 90 ng/dL, ACTH
6.0 pg/mL, FSH 0.9 ng/mL, LH 0.1 ng/ml, total testosterone 120 ng/dL (N 260-1000 ng/dL). Hypopituitarism
was diagnosed and hydrocortisone 100 mg IV q8h was
started. On day two of steroid treatment the patient began
to respond verbally and provide information on his condition. He also began walking with assistance. He was
started on cortisone 25mg BID orally along with l-thyroxine 50 mcg daily. At one-week follow-up, the patient was
doing very well with complete resolution of his expressive
aphasia.
Discussion: Development of signs and symptoms
of hypopituitarism is sometimes insidious. Patients frequently have modest hyperprolactinemia with GH and
gonadotropin failure. TSH and ACTH deficiencies are
much less common. As in our patient, radiation therapy
eventually results in a 50%-60% incidence of pituitary
insufficiency. Once the hypopituitarism was realized and
treated, our patients expressive aphasia quickly and completely resolved, evidently due to improved adrenal status.
Conclusion: Untreated hypopituitarism can cause
numerous complications that can greatly depreciate quality
of life, including a wrong diagnosis of “expressive aphasia”. Proper endocrine replacement therapy can greatly
improve a patient’s quality of life in such circumstances.
Abstract #820
DIAGNOSTIC DILEMMA: REVISITING THE
DIAGNOSIS OF PITUITARY NEOPLASMS
The patient underwent a left pterional and subfrontal craniotomy with gross total resection of the mass. Pathology
revealed pituitary cells with intermediate mitotic activity
and positive immunostaining for MIB-1 and p53. No areas
of metastasis were identified.
Discussion: The definition, diagnosis, therapy, and
prognosis of pituitary carcinomas are controversial due to
a paucity of reports that exist in the English literature. The
case above illustrates the difficulty encountered when trying to discern between invasive pituitary macroadenoma
and primary pituitary carcinoma. Most cases of pituitary
carcinomas are believed to arise from the malignant transformation of benign macroadenomas. Differentiating
between the two has clinical significance for the patient
due to the substantial difference in the morbidity and mortality of pituitary carcinomas. The currently accepted definition of primary pituitary carcinoma requires the presence of metastatic spread at discovery. The World Health
Organization further differentiates pituitary neoplasms
with the classification of atypical adenomas: exhibiting
high mitotic activity, an increased (>3%) Ki-67% LI, and/
or p53 immunoreactivity. The goal of this subdivision is
to clarify the adenomas with the greatest likelihood of
transformation. This intermediate stage could confound
the diagnosis by suggesting that the course of an invasive
adenoma is more indolent which may lead to delays in
treatment and increased risk of metastases.
Conclusion: Dismal survival rates exist after documentation of metastatic disease. To improve the overall
response rate and stop initial progression to metastatic disease, efforts should be made to look for more conclusive
histological discernment between invasive adenomas and
carcinomas.
Abstract #821
Dana Patrick Houser, MD,
Elena A. Christofides, MD, FACE
Objective: To reexamine the difficulty that exists in
a diagnosis of pituitary neoplasm illustrated with a case
presenting as a non-metastasized lesion exhibiting intermediate histopathologic features.
Case Presentation: A 27-year-old African male with
a five-year history of intermittent periorbital headaches
presents with new-onset visual field deficits. Family
history was positive for long-standing headaches in his
mother which prompted a workup of the patient’s symptoms. The patient declined to be evaluated at that time,
but consented now due to the visual field changes. On
physical exam, visual field testing revealed bitemporal
hemianopsia and rotational nystagmus. MRI revealed a
4cm sellar mass with suprasellar extension and significant
deviation of the optic chiasm. Laboratory studies done
pre-op did not reveal any pituitary hormone abnormalities.
RAPID EFFICACY OF BROMOCRIPTINE IN A
MALE WITH MACROPROLACTINOMA AND
VISUAL LOSS
Ajay Varanasi, MD, Manav Batra, MD,
Deepti Rawal, MD, Teekam Lohano, MD,
Jody Leonardo, MD, Paresh Dandona, MD
Objective: We report an interesting case of macroprolactinoma in which we documented a dramatic reduction in prolactin levels in less than two days after starting
bromocriptine.
Case Presentation: A 63-year-old Caucasian male
with type 2 diabetes mellitus, coronary artery disease,
and hypertension presented with deterioration in vision
over a period of four months, starting with the right eye
and progressing to the left. On physical exam patient had
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bitemporal hemianopsia. Hematological and biochemical
profiles were normal. He had an elevated prolactin concentration of 1800ng/dl (0-17 ng/dl), a low testosterone of
<20ng/dl (150 – 400 ng/dl) and a low growth hormone concentration <0.1ng/ml (>10 ng/ml). MRI of brain revealed a
3.5 x 2.3 x 2.3 (cm) pituitary mass with suprasellar extension and compression of optic chiasm. He was admitted to
the neurosurgical unit for possible surgical intervention,
for deteriorating vision and large pituitary mass. While
awaiting surgery, the patient was started on bromocriptine 5 mg twice daily. Prolactin concentration fell within
36 hours and his vision improved dramatically within 48
hours of starting bromocriptine. His prolactin levels had
dropped down to 598 ng/dl at 36 hours and to 76.4 ng/
dl on day 7 of treatment. As his symptoms improved and
prolactin levels improved, plan for surgery was cancelled.
The size of tumor on MRI was reduced to 2.5 1.5 x 1.5
(cm) 3 months after initiation of bromocriptine.
Discussion: Macroroprolactinomas cause endocrinological symptoms due to hyperprolactinemia and neurologic symptoms due to space occupation and compression.
This case presented with neurological symptoms in spite
of extremely high prolactin concentrations. Bromocriptine
and other dopamine agonists are the most effective drugs
for treating both micro and macro-prolactinoma, since
they suppress prolactin secretion while also causing rapid
tumor shrinkage. The fall in serum prolactin and the
reduction in tumor size typically occur within the first two
to three weeks of such therapy. This report shows for the
first time that the reduction in prolactin concentrations can
occur within two days of bromocriptine treatment.
Conclusion: Our case re-emphasizes the fact that
bromocriptine or dopamine agonists should be tried as
first line agents in treatment of macroadenomas, even if
the patient has neurological symptoms like loss of vision
and headache, with close clinical assessment for signs of
further compression or deterioration in which case surgery
may be necessary.
Abstract #822
PITUITARY HEMORRHAGE DURING
PREGNANCY AS THE PRESENTING FEATURE
OF A PITUITARY MACRODENOMA
headache and nausea in the 36th week of her first otherwise
uneventful pregnancy. She was not hypotensive or orthostatic and there were no signs of diplopia, cranial nerve
dysfunction or papilledema. MRI brain showed recent
hemorrhage within pituitary gland and adenoma could
not be ruled out. Hormonal evaluation did not show any
pituitary dysfunction. Because of the potential worsening
of pituitary hemorrhage into apoplexy, she was treated
with oral hydrocortisone 50 mg and closely observed. She
remained clinically stable and was discharged on maintenance dose of steroids which were continued through
the rest of the pregnancy. She successfully delivered a
baby via C-Section at 40 weeks; stress dose steroids were
given at delivery. Her repeat MRI pituitary after delivery
showed a non functional macroadenoma.
Discussion: While post partum hypopituitarism
(Sheehan’s syndrome) is well known, there are not many
case reports of pituitary hemorrhage during pregnancy. It
is likely that in patients with pre existing adenomas, pituitary enlargement during pregnancy increases the risk of
pituitary hemorrhage/infarction. The presentation of pituitary hemorrhage may range from asymptomatic to catastrophic pituitary apoplexy. In its most dramatic presentation apoplexy causes the sudden onset of excruciating
headache, diplopia, and mental status changes and can be
fatal if untreated. Pituitary dysfunction is often seen with
apoplexy and pituitary hemorrhage and may be transient
or permanent. Nevertheless, once pituitary hemorrhage
is diagnosed it is imperative to treat patients with glucocorticoids because of the potential fatality from acute
adrenal insufficiency. These patients also need supportive
management, close monitoring and if necessary, surgical decompression. It is especially important to consider
the possibility of pituitary hemorrhage in pregnancy in
the right setting as it can potentially lead to apoplexy and
place both the mother and fetus at risk.
Conclusion: Clinicians need to be aware of the situ
ations where pituitary hemorrhage should be suspected
and evaluated, especially during pregnancy and the need
for emergent management with glucocorticoids in such a
scenario.
Abstract #823
A RARE CASE OF PITUITARY APOPLEXY
RESULTING FROM MICROPROLACTINOMA
EXPANSION DURING PREGNANCY
Madhuri Devabhaktuni, MD, Praveena Gandikota, MD,
Jeanine Albu, MD
Objective: To present a case of pituitary hemorrhage
during pregnancy as the presenting feature of a pituitary
macroadenoma.
Case Presentation: A 34-year-old woman with history of hemochromatosis trait was admitted with severe
Nitasha Bakhru, MD, Matthew Levine, MD, FACE
Objective: To illustrate a case highlighting the importance of detecting expanding microprolactinomas during
pregnancy.
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Case Presentation: A 25-year-old female 13 months
post-partum presented with spontaneous galactorrhea 4
months after cessation of breast-feeding. History notable
for oligomenorrhea prior to pregnancy. Prolactin level was
128 ng/mL, estradiol <28 pg/mL, FSH 1.8 mIU/mL, LH
0.7 mIU/mL, qualitative B-HCG negative. Initial MRI
Brain was unremarkable. Given suspicion of microprolactinoma unidentified on initial imaging, a focused MRI of
the sella was pursued. A 0.6cm microadenoma sparing the
optic chiasm and sphenoid sinus was found. Cabergoline
was initiated with resultant cessation of galactorrhea.
Prolactin decreased to 2 ng/mL. Patient was educated that
if she became pregnant again, she may discontinue cabergoline given a <5% chance of microadenoma expansion
during pregnancy. Unfortunately, she failed to follow-up
thereafter. In the interim, pregnancy was confirmed and
cabergoline stopped. Within months, she experienced
worsening headaches and visual impairment. MRI Brain
revealed increase in size of adenoma to 1.5cm with internal hemorrhage and encroachment on the optic chiasm.
Prolactin had risen to 93.2 ng/mL. C-section was performed at 32 wks gestation with subsequent transsphenoidal tumor resection. Post-partum, her vision improved and
prolactin decreased to 9.3 ng/mL with continued preservation of other pituitary hormones.
Discussion: Symptomatic enlargement of microprolactinomas during pregnancy has been reported in 1.6%
of cases. It is a rare phenomenon necessitating heightened
clinical suspicion. Prolactinomas are the most common
hormone-secreting pituitary tumors with incidence being
four-fold greater in women. Microadenomas are three
times more common than macroadenomas. These tumors
are an important cause of infertility. Treatment with dopamine agonist therapy results in the resumption of ovulatory menses in 80-90% of females. Bromocriptine exhibits the most clinical safety data for use during pregnancy.
Resuming bromocriptine is the treatment of choice for
pregnant patients with a microprolactinoma who develop
signs suggesting tumor expansion. The decision for continuation of the medication perinatally needs to be individualized, taking into account such factors as prenatal sellar
extension and clinical symptoms. Asymptomatic microprolactinoms do not necessitate serial imaging or prolactin
measurement during pregnancy.
Conclusion: Although enlargement of microprolactinomas during pregnancy is rare, devastating effects such
as pituitary apoplexy can occur. This case underscores the
importance of early clinical detection of such patients in
ensuring the health of the mother and fetus.
Abstract #824
CENTRAL DIABETES INSIPIDUS IN A
PATIENT WITH ACUTE MYELOID LEUKEMIA
ASSOCIATED WITH CHROMOSOME 3
INVERSION AND CHROMOSOME 7 MONOSOMY
Ana Cecilia Apaza Concha, MD,
Andrea Marcela Sosa-Melo, Maria del Pilar Solano
Objective: To report a case of Central Diabetes
Insipidus (CDI) in a 21-year-old African American male as
a complication of Acute Myeloid Leukemia (AML).
Case Presentation: 21-year-old African American
male admitted with weakness, fever, pleuritic chest pain,
CBC showed a white count of 138 000, Hemoglobin of
6.6g% and normal platelets. Bone marrow (BM) biopsy
showed AML-M1. He had a complicated hospitalization
with pericardial effusion requiring pericardial window. The
disease was refractory to induction chemotherapy. During
his admission he developed pulmonary nodules and broad
antibiotic therapy was started including liposomal amphotericin B. On day 60 of hospitalization he presented significant polyuria of 7 liters/24 hours. His metal status deteriorated, had a seizure and needed to be transferred to intensive
care unit. Serum Sodium level was 185 mmol/L, Serum
Osmolality 284 mmol/L, Urine osmolality 139mOsm/
kg. He was started on desmopressin intravenously twice a
day and dextrose 5% infusion. Antidiuretic hormone level
was 3.4pg/mL. A cytogenetic BM study showed chromosome 3 inversion (q21q26) and chromosome 7monosomy.
Brain MRI showed unremarkable hypothalamus and pituitary gland. After medical treatment, his sodium decreased
to 156mmol/L and the urine osmolality to 498 mOsm/Kg
in a period of 36 hrs. Mental status recovered completely.
Amphotericin was discontinued after an 8 week-course.
When stable, the patient was treated with salvation chemotherapy but unfortunately he failed. The patient was sent to
Hospice.
Discussion: CDI presents as a result of deficient secretion of antidiuretic hormone. It is most often idiopathic in
origin 30-50%. Other etiologies include trauma and malignancies. From the hematological neoplasias, AML and specially the one related with chromosome 3 inversion and/or
chromosome 7 monosomy is the most commonly associated with CDI. The latter can present before, during or after
the diagnosis. Pathogenesis is still unclear, but appears to
be secondary to leukemic infiltration of the posterior lobe
and pituitary stalk. Inappropriate activation of EVI-1 gene
is suspected to play a key role. Some reports did not demonstrate any gross CNS abnormality in neuroimaging as in
the case.
Conclusion: AML associated to CDI is a rare syndrome and the association with chromosome 7 monosomy
and chromosome 3 inversion carries worse prognosis.
Diabetes Insipidus is a hazardous clinical presentation that
needs to be suspected and recognized in order to be appropriately managed.
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ABSTRACTS – Reproductive Endocrinology
REPRODUCTIVE ENDOCRINOLOGY
Abstract #900
CORRELATION OF PROSTATE-SPECIFIC
ANTIGEN WITH LUTEINIZING HORMONE,
FOLLICLE-STIMULATING HORMONE,
PROLACTIN, TESTOSTERONE, INHIBIN B,
SPERM COUNT AND MOTILITY IN
NIGERIAN MALES
Abraham Adewale Osinubi, MBBS, MSc,
Godwin O. Ajayi, Prof., Sunday A. Omilabu, Prof.,
J.O. Wellington, BSc
Objective: This present study sought to investigate
the relationship between PSA and LH, FSH, prolactin,
testosterone, Inhibin B, sperm count and sperm motility in
Nigerian males.
Methods: Subjects were adult Nigerian males (30-45
years), whose wives were attending the Prenatal Diagnosis and
Therapy Centre of the College of Medicine of the University
of Lagos. Subjects with prostatic disease, chromosomal
abnormalities, undescended testes, obstructive syndromes
of the genital tract, and hypogonadism secondary to surgery,
trauma, or chemotherapy were excluded from this study.
Patients on hormones, steroids and fertility drugs were also
excluded. Serum levels of PSA, LH, FSH, prolactin, testosterone and inhibin B were evaluated concomitantly in
all the subjects using ELISA (enzyme-linked immune
assay) method. Seminal fluid analysis was carried out
using standardized laboratory protocols. The correlations
among the variables were analyzed using Pearson’s correlation coefficients (r). Statistical significance was defined as
p<0.01, except where otherwise stated.
Results: Our results show that PSA correlates positively
with inhibin B (r=+0.60; t= 3.21) and this is statistically significant (p< 0.01). In addition, there is a statistically significant (r = -0.5; p< 0.01) negative correlation between serum
PSA levels and sperm count, and a weak negative correlation between serum PSA concentration and sperm motility
(r= -0.3; p<0.1). No linear relationship could be established
between PSA and FSH level (r between the two =+0.08;
SE= 0.11; t= -0.76). The correlation coefficient between the
values of PSA and those of prolactin is -0.09 (SE= 0.11; t =
0.85), while that of PSA levels and testosterone was +0.03
(SE= 0.11; t= 2.64). Since these values are not statistically
significant, there is probably no linear relationship between
serum concentrations of PSA and prolactin and testosterone
levels.
Discussion: The results of present study showed that
serum levels of PSA correlated positively with serum
inhibin B levels. However, there was no linear relationship between serum levels of PSA and LH, FSH, prolactin
and testosterone levels. Present study also demonstrated
that serum PSA levels correlated negatively with sperm
count. The reason for our observations is not clear. In men,
inhibin B is secreted from the testis as a product of Sertoli
cells involved in the regulation of FSH secretion. Previous
studies have reported inhibin B to be positively correlated
with sperm concentration and negatively correlated with
serum FSH. Patients with a larger testicular volume also
have a higher serum inhibin B concentration. Since this
present study showed PSA to be positively correlated with
inhibin B, one would have expected PSA to be positively
correlated with sperm count. The reason for the negative
correlation between serum PSA and sperm count in our
study remains unclear. One previous study had reported
a positive correlation between seminal PSA and sperm
motility, in contrast to ours. The disparities (one of the
main reasons for bringing this study to the knowledge of
colleagues) in the results of these earlier studies and ours
could be due to the fact that we assayed the serum PSA,
while they largely assayed seminal PSA. The free PSA
molecule represents a very heterogeneous population,
including pro-PSA, cleaved (“nicked”) PSA, PSA that can
complex with α1-antichymotrypsin (ACT), and PSA that
cannot complex with ACT but complexes with α2- macroglobulin. In addition, heterogeneity in the carbohydrate
part of the PSA molecule results in several isoforms, ranging from nonglycosylated to fully glycosylated. These
variations of the free PSA molecule also affect its immunological characteristics, and for that reason, results of
comparison studies done with mixtures of free PSA from
seminal plasma do not compare favorably with results that
would be obtained with serum. Similar observations have
been made in spinal cord injury patients in whom disparities were recorded in the serum and seminal PSA levels.
A second source of disparity could be the sample studied.
Most of the other studies used subjects from the general
population while we used a selected group (i.e., husbands
of women attending a prenatal clinic). Other plausible reasons for the differences between previous studies and ours
could be racial, genetic or environmental. Clinical interpretation of PSA concentrations is further confounded by
the wide range of PSA concentrations encountered in normal men. For example, PSA ranged from 0.30 to 15.00 ng/
ml in our subjects (mean value of 2.90 ± 2.88 ng/ml), all of
whom have no history of prostatic disease.
Conclusion: Serum levels of PSA correlate positively
with serum levels of inhibin B and negatively with sperm
count in Nigerian males, whose wives are attending a prenatal clinic in Lagos, Nigeria. Present study further highlights the heterogeneity of PSA, and that interpretation of
results should be made with some caution. PSA is probably more than a tumor marker. Further studies, are necessary to further elucidate the importance, mechanism and
implication of the observed correlations, especially those
– 137 –
between PSA and inhibin B, sperm count and motility in
subjects under varying conditions.
Abstract #901
ESTROGEN PLUS PROGESTIN TREATMENT:
EFFECT OF DIFFERENT PROGESTIN
COMPONENTS ON SERUM MARKERS OF
APOPTOSIS IN HEALTHY
POSTMENOPAUSAL WOMEN
Maria Karaflou, MD, George Kaparos, PhD,
Demetrios Rizos, PhD, Emanuel Logothetis, MD,
Andreas Alexandrou, MD, Leon Aravantinos, MD, Maria
Creatsa, MD, George Christodoulakos, MD,
Irene Lambrinoudaki, MD
Objective: To investigate the effect of two hormone
therapy (HT) regimens differing only in their progestin
component on serum markers of apoptosis.
Methods: Randomized, double-blinded, clinical
study at the University Menopause Clinic, involving one
hundred healthy, naturally menopaused women, aged
44-54. Patients were randomized to either 17b-estradiol
1mg/drosperinone 2 mg (E2 /DSP) or 17b-estradiol 1mg/
norethisterone acetate 0.5 mg (E2 /NETA) for 6 months.
Serum soluble Fas (sFas), soluble Fas Ligand (sFasL) and
cytochrome-c (cyt-c) at baseline and at 6 months.
Results: Serum sFas significantly decreased in both
groups (E2 /DSP group: 6997.4 ± 681.8 pg/mL at baseline vs 5842.1 ± 1386.0 pg/mL at 6 months, p=0.021; E2 /
NETA group: 7634.3 ± 2446.6 pg/mL at baseline vs 6454.1
± 1981.7 pg/mL, p= 0.040). Serum sFasL significantly
decreased in both groups (E2 /DSP group: 62.82 ± 19.22
pg/mL at baseline vs 54.3 ± 12.99 pg/mL at 6 months, p=
0.038; E2 /NETA group: 62.25 ± 36.12 pg/mL at baseline
vs 52.79 ± 28.37 at 6 months, p= 0.010). sFas/sFasL ratios
decreased from 111 at baseline to 108 at 6 months in the
E2 /DSP group and from 123 at baseline to 122 at 6 months
in the E2 /NETA group. Serum cyt-c levels were under the
detection limit (<0.05 ng/mL) at baseline and at 6 months
in both groups. For this reason, statistical analysis on cyt-c
levels was not feasible.
Discussion: Currently, there is an increasing interest
in identifying accessible molecular markers, which may
aid in the diagnosis of various conditions and in the evaluation of therapeutic efficacy. The apoptotic products sFas,
sFasL, cyt-c may serve as useful clinical markers for the
detection of diseases whose pathophysiology involves
apoptosis. Nadal et al, Clin Cancer Res 2005; 11:47704, computed sFas/sFasL ratios and suggested that these
values were related to chemotherapy-induced apoptosis
in cancer patients. In our study sFas/sFasL ratios have
decreased in both groups from baseline to 6 months,
indicating a possible anti-apoptotic effect of the two HT
regimens investigated.
Conclusion: The decrease in sFas/sFasL ratios
among postmenopausal women receiving either E2/DSP
or E2 /NETA suggests a decrease in apoptosis associated
with the above pathway. However, cyt-c levels were not
even detected in the study groups suggesting an absence
of mitochondria-associated apoptosis. Further studies are
necessary to elucidate the effect of different progestins
included in HT regimens on apoptotic products.
Abstract #902
EFFECT OF HT AND TIBOLONE ON ADAM-8
AND CD40L
Maria Karaflou, MD, Irene Lambrinoudaki, MD, George
Kaparos, PhD, Odysseas Grogoriou, MD, Andreas
Alexandrou, MD, Constantinos Panoulis, MD, Emanuel
Logothetis, MD, Maria Creatsa, MD,
George Christodoulakos, MD, Evangelia Kouskouni, MD
Objective: The role of neutrophils and platelets in
atherothrombotic disease is well established. The aim of
our study was to investigate the effect of hormone therapy
(HT) and tibolone on the soluble markers of neutrophil
and platelet activation, a member of the disentigrin and
metalloproteinase domain family-8 (ADAM-8) and CD40
Ligand (CD40L) respectively, in healthy postmenopausal
women.
Methods: 106 healthy postmenopausal women were
randomly allocated to: estradiol plus drospirenone (E2/
DSP), estradiol hemihydrate 1mg plus norethisterone
acetate (E2/NETA) 0.5mg and tibolone 2.5 mg. Serum
ADAM-8 and CD40L were measured at baseline and at 6
months.
Results: Baseline values of ADAM-8 and CD40L
were similar between groups. No significant correlation
was revealed between ADAM-8 or CD40L and parameters related to cardiovascular risk factors in each group.
No significant changes were observed between baseline
values and values at 6 months (E2/DSP group: ADAM-8
levels: 267.4 ± 71.3 pg/mL at baseline vs 270.7 ± 42.8 pg/
mL at 6 months, p= 0.86, CD40L levels: 6.43 ± 3.13 at
baseline vs 6.79 ± 2.70 ng/mL at 6 months, p= 0.67), (E2/
NETA group: ADAM-8 levels: 308.3 ± 64.3 at baseline vs
294.7 ± 57.7 pg/mL at 6 months, p= 0.40, CD40L levels:
9.68 ± 2.81 at baseline vs 8.59 ± 5.13 ng/mL at 6 months,
p= 0.51), (tibolone group: ADAM-8 levels: 307.5 ± 87.5
at baseline vs 289 ± 48.1 pg/mL at 6 months, p=0.48,
CD40L: 9.46 ± 4.30 vs 9.26 ± 4.60 ng/mL, p= 0.99).
Discussion: ADAM-8 is a protein abundantly present in human neutrophils, which is reported to be released
into circulation during neutrophil activation. According to
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Sriraman et al, Biol Reprod 2008, 78:1038-48, ADAM-8
seemed to be hormonally regulated, under the coordinate action of progesterone and LH in ovulating follicles.
Furthermore, CD40L is considered a critical link between
inflammation, atherosclerosis and thrombosis. However,
Oviedo et al, Gynecol Endocrinol 2008, 24:354-7, have
shown that therapeutic dosages of oral or transdermal
estradiol did not modify sCD40L levels in postmenopausal women.
Conclusion: Our study did not detect an association
between HT or tibolone and serum ADAM-8 or CD40L
in healthy postmenopausal women. Despite a plausibly
important role of neutrophil and platelet activation in the
pathophysiology of atherothrombosis, pre-analytical or
analytical sources of variation may have limited the clinical application of ADAM-8 and CD40L. Larger prospective studies are needed to elucidate the effect of low-dose
HT or tibolone on serum markers of neutrophil and platelet activation.
Abstract #903
IDENTIFICATION OF A NOVEL MISSENSE
MUTATION IN THE 5-ALPHA REDUCTASE TYPE
2 GENE IN AN EXTREMELY PREMATURE 46,
XY MALE INFANT
Cayce Jehaimi, MD, Patrick G. Brosnan, MD,
Nunilo I. Rubio, MD
Objective: To describe the clinical and biochemical
features in a very premature male infant with confirmed
5-alpha reductase type 2 deficiency (SRD5A2).
Case Presentation: A 46, XY male infant born at 26
weeks of gestation presented at day of life 1 with micropenis and severe hypospadias. Family history was lacking for consanguinity or genetic diseases. At day of life 3,
Endocrine service was consulted for evaluation of ambiguous genitalia. Physical examination revealed a small
penile length measured at 1.2 cm (-2.2 SD), penoscrotal
hypospadias, bifid scrotum, cryptoorchid testes and blind
vaginal pouch. Pelvic ultrasonography confirmed bilateral
testicular structures present in the superior aspect of the
inguinal canal. No Mullerian structures were identified.
Persistently elevated testosterone to dihydrotestosterone
(T: DHT) ratio lead to direct sequencing of the SRD5A2
gene using exon specific polymerase chain reaction. DNA
comparative studies revealed a novel missense mutation
within exon 1 of the first allele, with a G>T change altering codon 69 from Alanine to Serine [Ala69Ser]. A second previously reported G>A base change was detected
in exon 4, changing the encoded amino acid Glycine to
Serine at codon 196 [p.Gly196Ser] in the other allele. Both
mutations are predicted to be functionally significant.
Discussion: SRD5A2 catalyzes the conversion of testosterone into DHT. This isoenzyme (type 2) is expressed
in high levels in the prostate and other androgen-sensitive
tissue. The SRD5A2 is located on chromosome 2, region
p23 and is comprised of five exons and four introns (Labrie
et al 1992). Various studies have demonstrated that any
single base mutation of the SRD5A2 gene may result in
reduced enzymatic activity (Andersson et al 1991) and
incomplete virilization.A second isoenzyme (SRD5A1 or
type 1) with 50% sequence identity also exists. Mutations
in the SRD5A2 gene associated with male pseudohermaphroditism were first described by Thigpen et al (1992).
At least 50 different mutations in the SRD5A2 gene have
been compiled by the Human Gene Mutation Database.
Of these reported cases, about 60% were homozygous.
Conclusion: We describe a novel missense mutation
of the SRD5A2 in an extremely premature, genetically
male infant. This mutation underscores the importance of
the stability of the gene in order to achieve full enzymatic
activity. Early identification allowed timely genetic counseling for the family in addition to providing a framework
for future care of the patient. Molecular analysis of the
SRD5A2 gene should be pursued in genetic males born
with clinical evidence of hypovirilization and abnormal T:
DHT ratio regardless of gestational age.
Abstract #904
HYPERANDROGENISM IN A
POSTMENOPAUSAL WOMAN: A DIAGNOSTIC
CHALLENGE
Vicky Cheng, MD, Krupa Doshi, MD,
Tommaso Falcone, MD, Charles Faiman, MD
Objective: To describe a postmenopausal woman with
marked hyperandrogenism in whom a dramatic response
to gonadotropin-releasing hormone agonist (GnRHa)
administration fails to delineate the source.
Case Presentation: A 53-year-old postmenopausal
woman with end-stage renal disease status-post kidney
transplant was referred because of high serum testosterone
levels. She presented with worsening acne and hirsutism
for the previous two years. She denied any deepening of
her voice or baldness. Medications included prednisone
7.5mg every other day. On examination, she was thin (BMI
14.5 kg/m2). Mild acne and facial hirsutism but no frontotemporal balding, cushingoid features, palpable masses or
clitoromegaly were noted. Lab results: total testosterone,
224 ng/dL (normal 20-70); free testosterone, 30 pg/mL
(1-9); FSH, 192 mU/mL (>20); LH, 194 mU/mL (>20);
DHEAS, 86 µg/dL (10-152); androstenedione, 7.6 ng/
mL (0.5-2.7); 17-α hydroxyprogesterone, 1.3 ng/mL (0.93). Two-day low-dose dexamethasone failed to suppress
– 139 –
testosterone levels. Transvaginal ultrasonography: right
ovary measured 5.5 cm3 with non-visualization of the left
ovary. CT scan without contrast showed a normal right
adrenal, minimal left adrenal thickening and normal ovaries. GnRHa (Depo-Lupron) 3.75mg IM administration,
after one month, resulted in a marked decline in FSH and
LH levels and testosterone became undetectable.
Discussion: The source of marked hyperandrogenism, ovarian versus adrenal, in postmenopausal women
represents a diagnostic challenge particularly if no obvious tumor is seen on diagnostic imaging. Moreover, the
inability to perform venous catheterization studies in our
patient, in whom contrast media represented an unwarranted risk, confounds the problem. Suppression of androgen levels with low-dose dexamethasone has been used to
screen for a non-tumorous adrenal source. As in the present case, this failure coupled with the fact that the patient
was on long-term prednisone points to a tumorous adrenal
or ovarian source. We reasoned that a clear response to
a GnRHa would discriminate between the two potential
sources. Regrettably, the literature has described cases
of adrenal adenomas which suppressed paradoxically
on GnRHa administration. Although our patient refused
surgery to document the source of hyperandrogenism,
GnRHa affords a favorable long-term therapeutic option.
Conclusion: The dramatic improvement in a postmenopausal woman with marked hyperandrogenism by
means of GnRHa therapy demonstrates its potential use in
poor surgical candidates without necessarily delineating
the source of androgen excess.
Abstract #905
HORMONAL AND SONOGRAPHIC EVALUATION
OF OVARIAN RESERVE IN PATIENTS WITH
Serhat Isik, MD, Hatice Nursun Ozcan, MD,
Dilek Berker, MD, Yasemin Ates Tutuncu, MD,
Ufuk Ozuguz, MD, Ayse Gul Alimli, MD,
Gulhan Akbaba, MD, Mehmet Alp Karademir, MD,
Serdar Guler, Assoc. Prof.
to determine ovarian volume, and total antral follicle
count (AFC) and their serum FSH levels were assessed on
the same day. The number of antral follicles <10 mm in
each ovary was counted.
Results: Means ± SD for the age, disease duration and
body mass index (BMI) among women in the present study
were 37.4±6.9 years, 6.0±4.6 years, and 35.9±8.9 kg/m2,
respectively. A significant difference was found in terms of
FSH values (IU/L) (Group 1: 7.8±0.9 vs 5.0±1.0; Group 2:
8.2±1.1 vs 7.2±1.8; Group 3: 9.5±3.2 vs 6.4±2.4, respectively) and AFC [Group 1: 21.1±4.8 vs 25.0±9.1; Group
2: 10.4±5.2 vs 23.0±9.5; Group 3: 6.0±3.5 vs 21.7±2.1,
respectively] between patient and control groups for each
decade group (p<0.001 for all). However, only difference
was observed in Group 1 between the groups of T2DM
and the healthy controls in terms of total ovarian volumes
(cm3) (9.7±3.0 vs 16.3±4.7, respectively) (p=0.002). A
negative correlation was determined between the values
of AFC and FSH, age, glycolized hemoglobin and fasting blood glucose levels ((r=-0.406, p<0.001; r=-0.618,
p<0.001; r=-0.505, p<0.001; r=-0.687, p<0.001, respectively). In regression analysis, it was observed that the
effects of age and FSH on AFC were continuous.
Discussion: Up to day ovarian reserve has not to
be evaluated in type 2 diabetic patients. In our study,
we detected higher FSH levels and lower AFC values
that would point to a decrease in ovarian functions when
compared to healthy individuals. We think that insulin
resistance and frequently comorbid polycystic ovary syndrome, which are involved in pathogenesis of T2DM and
which are known to cause deterioration in ovarian functions, are responsible for this difference.
Conclusion: We, for the first time, showed in this
study that ovarian reserve decreases in T2DM patients
compared to the nondiabetics at the same age group.
Attention should be paid to preventive approaches for diabetes from early ages because of both fertility problems
and the fact that early menopause may increase the risk
of cardiovascular disease, which is already elevated in
diabetics.
Abstract #906
Objective: Chronic diseases such as diabetes mellitus
(DM) may determine premature ovarian failure by various mechanisms. We studied the parameters of ovarian
reserve in women with type 2 DM (T2DM).
Methods: Eighty-nine women with T2DM and 73
healthy women were evaluated through categorization
in age groups [Group 1 (20-29): 7/18; Group 2 (30-39):
35/35; Group 3 (40-49): 47/20, T2DM/control, respectively]. On the third day of the menstrual period, fertile
women with regular monthly cycles and no history of
ovarian surgery underwent a transvaginal ultrasonography
ISOLATED LEYDIG CELL DEFICIENCY IN A
74-YEAR-OLD MAN
Hema Padmanabhan, MD, MBBS, Ali Iranmanesh, MD
Objective: To describe a case of isolated leydig cell
deficiency in a 74-year-old man.
Case Presentation: A 74-year-old married male with
history of seizure disorder, primary hypothyroidism,
osteopenia, colon cancer, type 2 diabetes mellitus and
hypertension was referred to endocrine clinic for erectile
– 140 –
dysfunction and decreased libido. He denied history of
tobacco, or illicit drug, but indicated social consumption
of alcohol. His medications included Metformin, Dilantin,
Metoprolol, Glipizide, calcium and vitamin D. Patient had
never fathered a child. He denied visual symptoms, dizziness, headache, nausea or vomiting. Rest of systemic
review and physical examination was unremarkable.
Testes were descended and measured 18 ml bilaterally
without palpable masses. Laboratory findings included
within the normal range values for estradiol (24.7 pg/
mL; normal: 7.6-42.6), inhibin-B (173.6 pg/mL; normal:
60-260), cortisol, TSH, prolactin and IGF-1, with gonadal
function over the follow-up period summarized in the following table.
Conclusion: Decreased circulating total and free testosterone concentrations associated with increased LH
levels are consistent with compromised testosterone biosynthesis. This along with normal testicular size and normal serum concentrations of FSH and inhibin-B is indicative of a primary defect in Ledig cell function. Although
unlikely, defective LH bioactivity could be an alternative
possibility.
Abstract #907
ISOLATED SEMINIFEROUS TUBULE DAMAGE
IN A 53-YEAR-OLD MAN
Hema Padmanabhan, MD, MBBS, Ali Iranmanesh, MD
Objective: To describe a 53-year-old man with isolated seminiferous tubule damage.
Case Presentation: A 53-year-old male with history
of depression, and hypertension was referred for evaluation of hypogonadism. Current medications included
Fluoxetine, clonazepam, Quetiapine and Mirtazapine. He
denied tobacco, alcohol or illicit drug use. He was not
married, has never fathered a child, and past semen analysis had shown azoospermia. No history of mumps, chemotherapy, or trauma to the groin. He had history of working
with depleted uranium in the past. Physical examination
revealed normal vital signs and normal systemic examination. Testes were descended in scrotum and were
soft, measuring 4 cm in diameter and without masses.
Circulating concentrations of TSH, ACTH, cortisol, and
IGF-1 were normal. Monitoring of gonadal function over
a period of 11 years revealed normal serum concentrations
of total testosterone (273-620 ng/dL; normal: 241-827),
and LH (6.4-15.1 µIU/mL; normal: 1.5-9.3), but increased
FSH (22.5-38 µIU/mL; normal: 0.9-15). Circulating concentration of inhibin-B was significantly decreased at 6.7
pg /mL (normal: 60-260).
Conclusion: Defective spermatogenesis associated
with increased circulating FSH and markedly decreased
inhibin-B concentrations are consistent with seminiferous
tubule damage, most probably due to radiation exposure.
Normal serum testosterone and LH concentrations over
a period of several years indicate preserved function of
Leydig cells, which are known to be more resistant to the
effect radiation.
Abstract #908
BIOLOGICAL VARIATION OF TESTOSTERONE
IN MEN, WOMEN, AND CHILDREN OF VARYING
AGES AND ETHNICITIES: A REVIEW
Vin Tangpricha, MD, PhD, FACE, Brittany E. Butler,
Julianne Cook Botelho, PhD, Hubert W. Vesper PhD
Objective: Studies have shown associations between
altered testosterone levels and a wide range of adverse
health conditions such as obesity, cardiovascular disease,
metabolic syndrome, and autism. In order to distinguish
between clinically significant pathological changes in
hormone levels and the normal fluctuations observed
in healthy individuals, it is important to understand the
biological variability of testosterone and the factors that
affect it. The aim of this research was to review the biological factors affecting testosterone levels and to identify
gaps in current knowledge.
Methods: We used Pub Med to perform a literature
search that identified scientific publications addressing
the biological variability of human testosterone levels
in the entire population, including both genders and all
ages. Studies measuring total testosterone, calculated free
testosterone, and/or bioavailable testosterone were evaluated. Initial search terms included combinations of the following words: men, women, children, testosterone levels,
pre-analytical, biological variability, and biological variation. Only studies published within the last 25 years were
considered, but most included studies that had been published within the last 20 years.
Results: Major biological factors associated with testosterone levels in men included diurnal (levels peak in the
morning and decrease by at least 43% by the evening), age
(decrease with increasing age), polymorphisms in androgen-related genes, and disease states (anemia, cardiovascular disease, diabetes, and hypertension). Findings on
seasonal variations were inconclusive. Excluding diurnal
variation, these factors were also related to testosterone
levels in women as were use of oral contraceptives (47%
decrease in levels) and oophorectomy (23% decrease in
levels).
Conclusion: The relationship between testosterone
and cardiovascular disease, diabetes, and hypertension has
not been well studied in women. Race/ethnicity seem to
affect testosterone levels with Asian and African-American
– 141 –
men having lower and higher levels, respectively, compared to Caucasian men and African-American women
having higher levels than Caucasian women. Other factors
that affect testosterone in individuals include preeclamptic pregnancies, prenatal environment, body weight, diet,
and exercise. More well designed studies are needed to
identify factors affecting testosterone in healthy people,
especially in women and children.
Abstract #909
SERUM AND SEMINAL INHIBIN B AND
ANTI-MÜLLERIAN HORMONE AS NONINVASIVE MARKERS OF PERSISTENT
SPERMATOGENESIS IN MEN WITH NONOBSTRUCTIVE AZOOSPERMIA:
A SYSTEMATIC REVIEW AND META-ANALYSIS
OF DIAGNOSTIC ACCURACY STUDIES
Konstantinos A. Toulis, MD, MSC,
Paschalia K. Iliadou, MD, MSc, Christos Tsametis, MD,
Basil C. Tarlatzis, MD, PhD, Ioannis Papadimas, MD,
PhD, Dimitrios G. Goulis, MD, PhD
Objective: A non-invasive test that could predict the
presence of sperm during a testicular sperm extraction
(TESE) procedure in men with non-obstructive azoospermia would be of profound clinical importance. Inhibin B
(Inh-B) and anti-Müllerian hormone (AMH) have been
proposed as direct markers of Sertoli cell function and
indirect markers of spermatogenesis.
Methods: A search was conducted in the electronic
databases MEDLINE, EMBASE and Cochrane Central
Register of Controlled Trials from inception through June
2009. Thirty-five different studies reported data on the
predictive value of one or more index markers (serum InhB: 31 studies, seminal Inh-B: four studies, serum AMH:
two studies, seminal AMH: three studies) were included
in the systematic review. Eight studies, which had serum
Inh-B as an index marker, met the predefined criteria and
was included in the meta-analysis.
Results: Serum Inh-B demonstrated a sensitivity of
0.67 (95% confidence interval [CI]: 0.56 – 0.76) and a
specificity of 0.84 (CI: 0.61 – 0.94) for the prediction of
the presence of sperm in TESE. The pre-test probability
of 40% was incorporated in a Fagan’s nomogram, and
resulted in a positive post-test probability of 73% and a
negative post-test probability of 21% for the presence of
sperm in TESE.
Conclusion: Inh-B cannot serve as a stand-alone
marker of persistent spermatogenesis in men with NOA.
Abstract #910
SUCCESSFUL TWIN PREGNANCY IN A WOMAN
WITH PANHYPOPITUITARISM
Praveena Gandikota, MD, Martin Ketlz, MD,
Jeanine Albu, MD
Objective: To report a case of successful pregnancy in
a patient with panhypopituitarism.
Case Presentation: A 12-year-old patient with craniopharyngioma underwent three surgical resections and
subsequently developed panhypopituitarism including
diabetes insipidus (DI). She was treated with cortef, synthroid, desmopressin and oral contraceptive pills. Human
growth hormone (GH) was added at age 15. At 34 years,
she underwent controlled ovarian hyperstimulation with
human menopausal gonadotropin (hMG) and human chorionic gonadotropin (HCG) and intrauterine insemination (COH/IUI), resulting in a triplet pregnancy that was
reduced to twins. During pregnancy GH was discontinued and cortef, synthroid, and desmopressin doses were
increased. She successfully delivered twins via C-section
at 36 weeks, with no complications or postpartum hemorrhage (PPH); stress-dose steroids were given at delivery.
Discussion: Pregnancy after loss of both anterior and
posterior pituitary function is uncommon. More cases are
now being reported using artificial reproductive techniques
(ART), though miscarriage up to 39% has been described.
We speculate that, in our patient, use of GH with hMG and
HCG played a significant role in the successful outcome
of the pregnancy. It is now recognized that GH/ IGF-1
have an active role in gametogenesis as well as follicular maturation. There are reports of successful pregnancy
after sequential co-treatment with GH and gonadotropins
after failed ovarian response to only gonadotropins. It thus
seems prudent, that women with hypopituitarism seeking pregnancy be initiated on GH replacement to aid in
improving pregnancy rate with ART. Safety of GH during pregnancy is not determined and is discontinued during pregnancy. There have been few cases where GH has
been continued until the second trimester. Pregnancies in
hypopituitary patients are high risk with high rates of both
fetal and obstetric complications [small for gestational age
(SGA), fetal malpresentation and PPH]. The hypothesis
for these complications is utero-placental dysfunction
due to deficient pituitary hormones and neuroendocrine
feedback mechanisms. Patients need stress dose steroids
during delivery and thyroid supplementation needs to be
increased during pregnancy.
Conclusion: Pregnancy in a patient with loss of both
anterior and posterior pituitary function through utilization
– 142 –
of ART is feasible but uncommon. These patients need
close antenatal as well as peri-natal monitoring due to
high risk of complications for both mother and fetus. More
research is needed regarding the role/utilization/safety of
GH prior and during pregnancy.
Abstract #911
ASSOCIATION STUDY OF CAG REPEAT
POLYMORPHISM OF THE ANDROGEN
RECEPTOR WITH POLYCYSTIC OVARY
SYNDROME (PCOS) IN THE ROMANIAN
POPULATION
Mihail Gr. Coculescu, MD, PhD, FRCP, FACE, Nicoleta
Baculescu, MD, Daniela Aflorei, MD,
Andra Caragheorgheopol, PhD, Ilinca Gussi, MD, PhD,
Florin Grigorescu, MD, PhD, Serban Radian, MD, PhD
Objective: To assess association of androgen receptor
alleles and their degree of inactivation (by DNA methylation) with PCOS and its phenotypic traits.
Methods: Case-control association study. We
recruited 112 PCOS patients (Rotterdam criteria) and 72
control subjects of Romanian descent. Androgen receptor genotyping, X-chromosome methylation analysis, and
phenotyping for PCOS were performed.
Results: Median CAG repeat numbers were 23
(range 11-30) in PCOS and 23 (range 15-30) in controls.
Biallelic means of CAG repeats did not differ significantly
between PCOS and control groups (22.73 vs. 23.07).
X-inactivation analysis was possible in 148 subjects (87
PCOS and 61 controls). No significant distribution differences were observed between PCOS and control groups,
with non-random inactivation in 52.87% vs. 54.1% and
skewed inactivation in 10, 34% vs. 16.39% of subjects,
respectively. In the non-random subset of PCOS and controls, both biallelic means (22.46 vs. 23.55, p= 0.0016)
and X-weighted biallelic means (22.46 vs. 23.43, p=0.011)
were significantly lower in PCOS. There was no evidence of preferential allele inactivation in favor of shorter
alleles in PCOS. We observed a significant positive correlation between total plasma testosterone values and AR
X-weighted biallelic means (r-square=0.18, p=0.015)
which was lost in PCOS subjects. Ferriman-Gallwey hirsutism scores were not influenced by AR alleles.
Discussion: Our results support the view that shorter
AR alleles for the CAG polymorphism are associated
with PCOS, at least in the subgroup of patients with nonrandom X-inactivation. While in normal control women,
shorter alleles are associated with lower total testosterone
values this “protective” association is not seen in PCOS
subjects.
Conclusion: We demonstrate that in Romanian
women (Eastern Europe) the CAG polymorphism of the
androgen receptor plays a role in the genetics of PCOS.
– 143 –
ABSTRACTS – Thyroid Disease
THYROID DISEASE
presented with constipation or ileus and also advice
administering levothyroxine alone on empty stomach, followed by rest of the medications an hour later.
Abstract #1000
Abstract #1001
A CASE OF MEGACOLON SECONDARY TO
SEVERE HYPOTHYROIDISM
Amitha Padmanabhuni, MD
Objective: To describe the effect of malabsorbtion
of levothyroxine leading to development of ileus and
megacolon.
Case Presentation: A 74-year-old white male with a
history of hypothyroidism, type 2 diabetes mellitus, CVA
with left hemiparesis, s/p peg tube, neurogenic bladder,
ambulatory dysfunction, was admitted to the hospital for
decrease in urine output. Apparently he had been experiencing diarrhea at home for the past four months, passing
lot of gas but no vomiting or abdominal pain. On physical examination no thyromegaly was noted, abdomen was
distended but soft and non tender with decreased bowel
sounds. Obstructive series done in the hospital showed
ileus with diffuse dilatation of the entire colon about 14
cm in size with air fluid levels. During the workup, TSH
was 108. On further history taking, although patient had
peg tube for the past four years, he started to receive oral
diet since last four months and was administering all his
medications at the same time, crushed in apple sauce.
We started him on IV levothyroxine considering malabsorption. After the first dose patient had two large bowel
movements and subsequently over the next couple of
days patient had several large solid bowel movements and
felt better. Repeat obstructive series showed decrease in
colonic dilatation and air fluid levels.
Discussion: Constipation is a problem that can be
particularly troublesome for people with hypothyroidism.
Hypothyroidism slows down many of the body’s systems,
including digestion and elimination. With lower levels
of thyroxin there is an abnormal bowel movement which
leads to chronic constipation and overtime progresses to
ileus and megacolon. In occasional patients, marked ileus
may be confused with intestinal obstruction. Though ileus
in this patient could be multifactorial the fact that patient
had several bowel movement soon after starting iv levothyroxine displays the fact that hypothyroidism played a
major role in causing chronic constipation and ileus.
Conclusion: Simple treatment of hypothyroidism in
patients with constipation can substantially improve their
quality of life and prevent complications like ileus and
megacolon. As per our case report malabsorbtion of levothyroxine might be due to fact that it was taken together
with multiple medications, drug interaction or due to
crushing in applesauce. Therefore we recommend routine
screening of hypothyroidism with TSH for all patients
REVIEW OF A SERIES OF THYROIDECTOMY
PATIENTS - PREDICTIVE VALUE OF
SONOGRAPHY AND CYTOLOGY
Nishanth Sanalkumar, MBBS, Mathew John, Ragi KV,
Aniyan Poulose
Objective: To review a series of thryroidectomy
patients with a predictive value of sonography and
cytology.
Methods: Clinical, imaging and fine needle aspiration
(FNA) biopsy data of all patients who underwent thyroidectomy over a 3 year period at a tertiary referral centre
in India was reviewed. Accuracy of FNA and other preoperative data on predicting the final histopathology was
examined.
Results: 136 patients underwent thyroidectomy over
a period of 32 months. Mean age (±SD) of this population
was 44.26 (±12.6) years. There were 105 women (77%)
and 31 men (23%). Only a minority of patients (12%)
were on levothyroxine prior to surgery. Ultra sonogram
was done in 63% of patients. Solitary thyroid nodule was
present in 31%, multi-nodular goitre in 65% and diffuse
goitre in 4%. Presence or absence of calcification was
reported in 38%, vascularity in 34%, echo characteristics in 50% and LN status in 55%. FNA data was available in 124 patients and was classified as benign (60.5%),
malignant (14.5%), indeterminate (17.7%) or inadequate
(7.3%). Majority of the patients underwent total or neartotal thyroidectomy (65%). Histopathology was benign in
70% and malignant in 30%. The malignant pathologies
were papillary carcinoma in 28% and follicular variant in
2%. The benign lesions were nodular colloid goitre (40%),
lymphocytic thyroiditis (15%), follicular neoplasm (13%)
and others. Although a STN was more likely to be malignant (59%) as compared with a MNG (32%), a malignant
lesion had almost equal probability of being reported as
STN or MNG in ultrasound. Presence of lymph nodes was
a significant predictor of malignancy (p 0.01). The FNA
result also significantly predicted the histopathology with
a good specificity (98.5%) but lower sensitivity (63%).
The positive predictive value was 94.4% and negative predictive value 87%. Of the 22 patients with indeterminate
FNA, 15 were benign and 7 were malignant.
Discussion: Ours is a retrospective review of data
from a relatively small population. Ultrasound data was
available in a limited number of patients and suffered
from inter-observer variability in reporting. FNA had good
– 144 –
specificity but less sensitivity compared with that reported
in literature. Sensitivity might be improved by doing more
ultrasound guided FNA.
Abstract #1002
VASCULITIS IN A PATIENT WITH
AMIODARONE-INDUCED THYROTOXICOSIS
TREATED WITH METHIMAZOLE
Rachanon Murathanun, MD, Mais Trabolsi, MD,
Tahira Yasmeen, MD, FACE,
Farah Hasan, MD, FRCP, FACE
Objective: To report a case of vasculitis in a patient
being treated with methimazole for amiodarone-induced
thyrotoxicosis.
Case Presentation: A 57-year-old man with a past
history of type 2 diabetes mellitus, congestive heart failure, and ventricular tachycardia presented to our clinic
for follow-up of his diabetes. He had been treated with
amiodarone for the past one year. His physical examination revealed fine tremors of the upper extremities but no
exophthalmos or thyroidomegaly. Thyroid function tests
were ordered and the results were as followed: TSH <0.01
(0.35-5.00), FT4: 2.4 (0.7-1.5), FT3: 5.9 (2.3-4.2). The
patient was diagnosed with amiodarone-induced thyrotoxicosis (AIT). Due to his poor glycemic and the type of
AIT was not yet clear, amiodarone was discontinued and
methimazole (MMI) 15 mg BID was started empirically.
Further investigations revealed TSI level of 109 (0-109)
and IL-6 level was 9.4 (≤3.6). Thyroid ultrasound demonstrated a normal thyroid with no nodules. Two weeks
later, he developed a hemorrhagic palpable purpuric rash
mainly on the trunk and lower extremities. The patient
denied fever, weight loss, hemoptysis, hematuria, myalgia
or joint pain. Due to the suspicion of vasculitis, methimazole was discontinued and further serologic investigations
were performed. ANA, myeloperoxidase (MPO), and
proteinase-3 antineutrophilic anticytoplasmic antibodies
(ANCA) were all negative. However, his serum creatinine
rose from 1.17 to 2.51 mg/dL. Urinalysis was positive
for pyuria and microscopic hematuria with 10-20 erythrocytes, 20-40 leukocytes. Skin biopsy revealed damaged
dermal blood vessels with perivascular neutrophilic infiltration, karyorrhectic debris and erythrocytes which were
consistent with leukocytoclastic vasculitis. In order to
treat AIT type 2, prednisone was started at 40 mg daily
initially and was tapered subsequently. Approximately 2
weeks later, the purpuric rash resolved and his creatinine
decreased to the baseline. The patient became euthyroid
after 2 months of treatment with prednisone.
Discussion: Vasculitis is a rare but major toxic
reaction seen with antithyroid-drug treatment, more
commonly found in connection with propylthiouracil
(PTU) than with methimazole (MMI). There are previous
reports of patients with MPO-ANCA-associated vasculitis syndromes caused by MMI and PTU. The incidence
was reported to be between 0.53 and 0.79 patients per
10,000, and the ratio of the estimated incidences for MMI
and PTU was1:39.2. The clinical features of antithyroidassociated vasculitis include myalgia, arthritis, hemoptysis, acute renal dysfunction, skin ulceration, and vasculitic rash. Although this syndrome generally resolves
after drug cessation, high-dose corticosteroid therapy or
cyclophosphamide may be needed in severe cases. By far
the previous reports of antithyroid medication associated
vasculitis were described in patients with Graves’ disease.
Our patient developed vasculitis syndrome with negative ANCA and presented with a vasculitic rash and acute
renal dysfunction while being treated with methimazole
for AIT. The absence of MPO-ANCA in our patient may
reflect a different pathogenesis.
Conclusion: Vasculitic rash in patients being treated
with antithyroid drugs could be an early sign of a serious
vasculitis syndrome and clinical awareness of this complication should be of considerable importance. To the best
of our knowledge we report the first case of vasculitis in a
patient with AIT treated with methimazole.
Abstract #1003
EVALUATION OF HEARING LOSS IN PATIENTS
WITH GRAVES’ HYPERTHYROIDISM
Dilek Berker, MD, Hayriye Karabulut, MD,
Serhat Isik, Yasemin Tutuncu, MD, Ufuk Ozuguz, MD,
Muharrem Dagli, MD, Gonul Erden, MD,
Yusuf Aydin, MD, Serdar Guler, MD
Objective: Hearing loss is commonly associated with
thyroid disorders, and during propilthiouracil treatment.
However, the relationship between hyperthyroidism and
auditory system has not been investigated. The aim of this
cross-sectional, case–control study is to investigate hearing loss in patients with Graves’ disease (GD).
Methods: Twenty-two patients with newly diagnosed
GD and 22 healthy control subjects were included. Pure
tone audiometry at 250, 500, 1000, 2000, 4000 and 8000
Hz and immittance measures, including tympanometry
and acoustic reflex tests, were performed in the patients
and controls.
Results: There were no statistically significant differences between the ages and genders of the patient
and control groups (p=0.567 and p=0.757, respectively).
No significant difference was observed between hearing threshold of right and left ears in GD and control
groups (Bonferroni corrected p>0.0042). When only one
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ear was taken into account (44 ears), hearing thresholds
of GD group were significantly higher than controls at
all frequencies (p<0.05). Although no significant effect
of thyrotoxicosis was observed on hearing loss at 250,
500, 1000 and 2000 frequencies, a significant effect was
detected at 4000 and 8000 frequencies. In GD group, odds
ratio for hearing loss at 8000 frequency was 14.97 (95%
confidence interval 4.03-55.64) compared to controls. The
pure tone average (PTA) thresholds of patients and controls were significantly different in all three PTA groups
(p<0.05). Right and left pure tone audiometric findings
were positively correlated with FT3, FT4 and negatively
correlated with TSH in GD at 8000 frequency.
Discussion: We detected a decrease in hearing ability,
particularly at high frequencies, in patients with GD. The
correlation between thyroid hormone levels and hearing
thresholds at high frequencies may suggest that increased
hearing thresholds in GD may be due to metabolic effects
of high thyroid hormones. It is known that some of the
clinical findings of hyperthyroidism result from sympathetic over-activity due to up-regulated adrenergic receptors in some tissues. Another possible mechanism for
hearing loss in patients with GD is vascular mechanism
as seen in autoimmune diseases resulting in sensorineural
hearing loss.
Conclusion: Our results revealed that hearing ability decreases, mostly at high frequencies, in patients with
GD. Further studies are needed to explain the cause and
mechanism of hearing loss in patients with GD.
Abstract #1004
A LARGE MULTICENTER CORRELATION
STUDY OF THYROID NODULE
CYTOPATHOLOGY AND HISTOPATHOLOGY
Richard Burnham Lanman, MD,
Chung-Che Charles Wang, MD,
Lyssa Friedman, RN, MPA, Giulia Kennedy, PhD,
Electron Kebebew, MD, Martha Zeiger, MD,
Juan Rosai, MD, Virginia LiVolsi, MD
samples; these results were reviewed and adjudicated by
a subset of the authors according to the Bethesda System
for Reporting Thyroid Cytopathology. Local histopathology diagnoses were obtained for 816 samples from 607
patients. Histopathology slides were over-read by 2 thyroid pathology experts without knowledge of the initial
interpretation, and results listed according to the WHO
criteria, with the addition of the recommendations from
the Chernobyl Pathologists group.
Results: 1420 FNA samples had cytopathology
results: 827 (58%) Benign (B), 350 (25%) Indeterminate
(I), 189 (13%) Malignant (M), and 54 (4%) NonDiagnostic (ND). Of the 848 prospectively collected FNA
samples, 625 (74%) were B, 110 (13%) I, 74 (9%) M, and
39 (4%) ND. 816 FNA samples had local histopathology
results: 59% B, 41% M, 0% Uncertain Malignant Potential
(UMP). 141 cases had expert over-reads with the following results: Expert 1 – 50% B, 47% M, 3% UMP; Expert
2 - 51% B, 46% M, 3% UMP. The two experts concurred
in 134 cases (96%) but reclassified the local specific histopathology diagnosis in 32% of the cases and generically
from B to M or from M to B in 9% of the cases. Malignant
histopathology rates for cytopathologically indeterminate
nodules were 36% local and 34% expert.
Discussion: Post-operatively almost 2/3 of nodules
with indeterminate cytology proved to be benign, a figure comparable to recently published retrospective FNA
series. In addition, expert histopathology over-read had a
significant 9% B to M or M to B reclassification. The prospective sub-cohort in this study is the largest prospective,
multicenter evaluation of thyroid FNA pathology to date.
Conclusion: False positive results remain a concern
in thyroid cytopathology. Molecular testing studies to
more accurately diagnose FNA results are needed, especially in the cytology indeterminate group where 66% of
cases are benign post-operatively and surgery could be
avoided. These studies should incorporate expert surgical
pathology interpretation in their study design, given local
to expert histopathology variation.
Abstract #1005
Objective: To correlate, in a large multicenter study,
indeterminate thyroid nodule fine needle aspiration (FNA)
cytopathology diagnoses with histopathology diagnoses
by local and expert histopathologists in the corresponding
surgically resected specimens.
Methods: 848 FNA samples were prospectively collected from 708 patients in clinic or pre-operatively from
16 community-based, 3 academic U.S. and 2 non-U.S.
sites. An additional 572 banked FNA samples from 444
patients were obtained from 2 academic U.S. centers.
Initial cytopathology diagnoses were obtained for all
CLINICAL CHARACTERISTICS OF PAPILLARY
THYROID MICROCARCINOMA: BASED ON THE
SIZES OF PRIMARY TUMORS
Ufuk Ozuguz, MD, Serhat Isik, MD,
Yasemin Ates Tutuncu, Gulhan Akbaba, MD,
Ayse Arduc, MD, Dilek Berker, MD, Serdar Guler
Objective: In recent years, the diagnosis of papillary
microcarcinoma (PMC) has increased with widespread
use of ultrasound-guided fine-needle aspiration biopsy,
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particularly by endocrinologists. However, consensus has
been established yet on treatment of PMC. In the present
study we aimed to assess the relationship between clinical and pathological features of PMC patients with tumor
size.
Methods: One hundred-fifteen patients diagnosed
with PMC from 2003 to 2009 were evaluated retrospectively. Papillary microcarcinoma was defined as a tumor
of 10 mm or less in greatest diameter using the histological classification criteria of thyroid tumors of WHO.
Tumor sizes, histopathologic characteristics, extrathyroidal spread, lymph node (LN) involvement, distant metastases and surgical procedures are recorded. The patients
were divided two groups according to tumor sizes (Group
1: tumor size 5 mm and above, 67 patients; Group 2:
tumor size less than 5 mm, 48 patients).
Results: One hundred-five of the patients were female
and 10 were male. The mean age was 45.6±12.3 years.
Total thyroidectomy had been performed on 107 patients,
subtotal thyroidectomy in 6 patients and lobectomy in 2
patients. Lymph node dissection had been performed on
24 patients. Tumor was multifocal in 28/115 (24.3%) and
bilateral in 13/115 (11.3%) of the patients. One patient had
vascular invasion, 7 had capsule invasion, 2 had extrathyroidal involvement, 7 had LN involvement and 1 had distant metastases. Seven of the 16 patients with tumor >0.5
mm had LN involvement while there was no LN inolvement in group 2 (p=0.026). No significant difference was
found with regard to general demographic characteristics,
multifocality, vascular invasion, capsule invasion, extrathyroidal spread and distant metastases between the two
groups.
Discussion: Papillary microcarcinomas are slowgrowing tumors that spread commonly by lymphogenous
way. The main poor-prognostic factors include tumor size,
LN involvement, advanced age, male gender, multifocality and extrathyroidal spread. However, these factors do
not suffice to predict tumor recurrence, metastases and
tumor- related deaths. On the other hand, there exists a
relationship between LN involvement and locoregional
reccurrence and distant metastases. In the present study
LN metastases were significantly higher in patients with
tumor size 5 mm and larger.
Conclusion: Papillary microcarcinoma patients with
tumor size 5 mm and larger should be evaluated in terms
of LN involvement.
Abstract #1006
PULMONARY METASTASIS IN WELL
DIFFERENTIATED THYROID TUMOR OF
UNKNOWN MALIGNANT POTENTIAL: A CASE
PRESENTATION AND REVIEW OF LITERATURE
Asma Ahmed, MBBS, Najmul Islam
Objective: To report a case of a metastatic well differentiated thyroid tumor of unknown malignant potential.
Case Presentation: We describe the case of a 40-yearold female with history of multinodular goiter. Ultrasound
revealed two large nodules in left lobe of thyroid, largest
one being 4 x 1.3 x 1.2 cm, and the right lobe had three
small nodules. Technetium scan showed a cold nodule in
the left lobe. Chest X ray revealed large soft tissue mass
in neck displacing trachea. FNAC of dominant nodules in
the left lobe was consistent with benign pathology. U/S
repeated after one year revealed complete replacement
of left lobe with large solid cum cystic nodule measuring 6.1 x 4.4 x 2.8 cm, which subsequently increased
after another year to 7.4 x 4.4 x 2.8cm. . Repeat FNAC
subsequently didn’t show any evidence of malignancy. In
view of the fact that the size of her thyroid nodule was
progressively increasing and displacement of trachea, it
was decided on clinical grounds to perform total thyroidectomy. Histopathology showed well differentiated thyroid tumor with unknown malignant potential. One month
after her thyroidectomy, TSH stimulated thyroglobulin
was 13.90ng/ml by chemiluminescence with TSH of
65.44Uiu/ml (0.27-4.2) and negative thyroglobulin antibodies. After involving multidisciplinary teams it was
decided to manage her with radioactive iodine. Her post
ablation 131I whole body scan (WBS) showed uptake in
thyroid bed with pulmonary metastasis. Subsequently, C.T
scan with contrast after WBS showed no evidence of pulmonary metastasis suggestive of iodine avid pulmonary
micrometastasis. At six months of follow-up patient was
found to be completely tumor free with TSH stimulated
thyroglobulin of 0.30ng/ml and negative neck ultrasonagraphy and low dose (2mci) I131 WBS. Patient has been
started on suppressive dose of thyroxine and is planned
for strict follow-up according to guidelines for papillary
or follicular thyroid carcinoma.
Discussion: Due to the vagueness of the clinical
behavior of these tumors, clinicians and surgeons are
often puzzled regarding the treatment of these tumors.
Moreover, there are no guidelines for the management
of these tumors. In the management of our case, we also
encountered the similar problem of treatment uncertainty
but ultimately decided to treat the patient with I131 RAI
post thyroidectomy. This clinical decision of 131 RAI
ablation, later on proved to be a sensible one, due to the
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finding of pulmonary metastasis on post RAI whole body
scan.
Conclusion: On the basis of the reported findings, it
is tempting to speculate that these new entities should be
treated with total thyroidectomy followed by RAI until
more long term data is available documenting the outcome
of these lesions.
Abstract #1007
FOLLICULAR VARIANT OF PAPILLARY
THYROID CARCINOMA PRESENTING
AS BONE METASTASIS
Asma Ahmed, MBBS, Najmul Islam, MBBS
Objective: To report a case of follicular variant of
papillary thyroid carcinoma (FVPTC) initially presenting
as spinal metastasis.
with history of pain and numbness over lateral aspect
of right thigh. MRI demonstrated a lesion involving L2
vertebra measuring approximately 3.5 ×2 cm. Bone scan
showed increased tracer uptake at L2 vertebrae & right
shoulder joint. FNA of the L2 bone lesion was suggestive of metastasis carcinoma with primary in prostate vs.
thyroid. Transrectal U/S of the prostate and PSA were
normal which ruled out prostate being the primary focus.
Further focusing on to find out primary etiology, US of
thyroid was done which was normal. C.T scan revealed
small nodules in the left lobe of thyroid gland and both
lungs. Furthermore, thyroglobulin level was found to be
extremely high at 2858ng/ml. FNAC of left thyroid nodule revealed scanty benign tissue. The patient received
radiation therapy for his bone metastasis at L2 site. In
view of extremely raised thyroglobulin levels and FNAC
of bone lesion suggestive of primary lesion possibly in
thyroid, it was decided to proceed with total thyroidectomy. Histopathology of excised thyroid gland was in
keeping with the diagnosis of FVPTC. Two weeks after
thyroidectomy, thyroglobulin levels were 5056ng/ml indicating high tumor load. Patient received 200 mci of radioactive iodine followed by I131 whole body scan showing
multiple areas of increased uptake in lumbar vertebrae,
right shoulder region and pulmonary region.
Discussion: Several subtypes of papillary thyroid
carcinoma (PTC) exist which constitute for approximately
20% of all PTCs. The follicular variant of papillary thyroid
carcinoma was first described by Lindsay and later Chen
and Rosai reported the detailed morphologic description of
this tumor. The tumor is designated as a follicular variant
of PTC when the lining cells have nuclear features characteristic of papillary thyroid carcinoma (Nuclear clearing,
overlapping and grooves) and the follicular predominance
over papillae is complete. The difference between follicular carcinoma and follicular variant of papillary thyroid
carcinoma has significant clinical implications. Follicular
carcinomas usually metastasize hematogenously, on the
other hand FVPTC behaves like usual PTC with rare
hematogenous spread and similar survival rates. There are
case reports of this entity in literature presenting as bone
metastasis, but this is not a very common feature. Our
patient didn’t have any history of thyroid lump or swelling
in neck. Since histopathology of the bone lesion suggested
thyroid or prostate being the primary, we had to search for
thyroid nodule which was ultimately found on C.T scan.
Furthermore, after thyroidectomy this patient received
RAI 131 and subsequent131I whole body scan revealed
multiple areas of increased uptake including lumbar and
pulmonary metastasis suggestive of widespread metastatic disease.
Conclusion: This case highlights the fact that
although FVPTC are very much similar to classic PTC but
a subset of it may behave as follicular carcinoma and can
also present initially with bone metastasis.
Abstract #1008
THYMIC ENLARGEMENT—A FEATURE OF
GRAVES DISEASE
Madhavi Yarlagadda, MD, Colleen Veloski, MD
Objective: To increase the awareness of the usual
benign course of thymic enlargement in patients with
Graves’ disease and recommend close radiologic observation and reevaluation after treatment of Graves as an
alternative to surgical excision.
Case Presentation: We present a case series of six
subjects seen in our practice in the past year, with Graves’
disease and an incidentally discovered enlarged thymus on
imaging studies. Among the six patients, five had active
Graves’ disease at the time of discovery of the thymic
mass, and one had a history of Graves’ disease 20 yrs
prior. Two patients had thymectomy due to suspicion for
thymoma and both histopathologic evaluations revealed
thymic hyperplasia. The other four patients were scheduled for thymectomy pending evaluation by endocrinology. Based on our recommendations, the planned thymectomies were postponed and those patients are being
followed by serial CT scans while being treated for hyperthyroidism. Thyroid stimulating immunoglobulins are
also being followed as markers of disease activity.
Discussion: Association of thymic hyperplasia
with Graves’ disease was recognized decades ago, but
was not usually detected clinically. Initially, the thymus
was thought to play a role in autoimmune hyperthyroidism, but thymectomy was found to have no effect on
– 148 –
hyperthyroidism. In 1996, a study by Mukarami et al demonstrated that thyrotropin receptors (TSH-R) were present
in normal thymus tissue suggesting that TSH-R auto antibodies may cause thymic hyperplasia in Graves’ disease
in the same manner that TSH-R auto antibodies stimulate
thyroid growth. The study also demonstrated a decrease
in thymic mass size and density along with a concomitant decrease in TSH-R antibodies following treatment for
Graves’ disease with antithyroid medications.
Conclusion: Thymic enlargement in the past was an
under recognized feature of Graves’ disease prompting
the publication of many case reports. In recent years, the
routine use of CT angiogram to rule out pulmonary embolism has led to an increase in detection and many potentially avoidable thymectomies. In most cases, Graves’
related thymic enlargement regresses with treatment of
the Graves’ disease. Often patients are not referred to
endocrinology until after surgical resection of the thymic
mass. Cardiothoracic surgeons and other physicians must
be made aware of the association between benign thymic
hyperplasia and Graves’ disease in order to avoid unnecessary surgery. We also recommend screening all patients
with thymic enlargement for hyperthyroidism prior to surgical removal.
Abstract #1009
RET CODON 618 MUTATIONS IS THE MOST
FREQUENT PHENOTYPE IN SAUDI FAMILIES
WITH MULTIPLE ENDOCRINE NEOPLASIA
TYPE 2A
Dr. Tariq Abdulrahman Nasser, Prof. Faiza Qari,
Dr. Abdulah Karawagh, Dr. Jumana AlAama
Objective: To evaluate the prevalence of the RET
mutation in Saudi families with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid
carcinoma (FMTC).
Methods: A total of 10 unrelated Saudi families with
germline mutation of the RET protooncogene and/or
immunohistochemistry diagnosis of MTC were identified.
Before undergoing genetic testing, all patients and their
family members had given their written informed consent in accordance with institutional ethic guidelines and
national regulations. The presence of pheochromocytoma
(PHEO) or hyperparathyroidism (HPT) was excluded by
extensive testing of all affected individuals and their at
risk family. Seventy-eight family members were evaluated
by medical history, physical examination and biochemical measurements of fasting serum calcium, basal plasma
calcitonin levels, plasma parathyroid hormone, 24-h urinary excretion of catecholamines and metabolites, and
DNA analysis. Genomic DNA was isolated from peripheral blood leucocytes using standard procedure. Exons 10,
11, 13, 14 and 16 of the RET proto-oncogene were analyzed by single strand conformation polymorphism analysis, direct DNA sequencing and/or restriction enzyme
analysis.
Results: Among the 78 individuals, a total of 46 individuals with hereditary MTC were enrolled in this study.
Thirty (aged 12–65 y), patients had previously y for MTC.
In addition; molecular screening identified another 16
individuals without clinical evidence of disease but at risk
because of an affected relative. From this MTC group 10
patients had been operated on for PHEO and 4 for HPT.
The diagnosis of MTC, PHEO and parathyroid hyperplasia was confirmed by pathological examination postoperatively. Among 10 families with hereditary MTC, 5
diagnosed with MEN 2A and 5 with FMTC. Two from 5
MEN 2A family’s mutation was located at codon 618 in
exon 10. The incidence of MTC, PHEO and HPT in the 25
MEN2A patients was 100%, 52% and 16%, respectively.
In our series, the most frequent phenotype was the MEN
2A syndrome with codon 618 mutations (46.6%), followed by 634 mutation 44.2%. In 1 of 10 families, screening of exons 10, 11, 13, 14 and 16 was negative for RET
mutations. Of the 5 families classified as MEN2A, three
had a mutation at codon 634, exon 11while the other two
families had a mutation at codon 618.
Discussion: Mutations that cause activation of RET
have been well characterized and several groups have
studied the disease phenotype–genotype. Differences in
the frequency of specific RET mutations in MEN 2A phenotypes have been found in series from different countries,
suggesting that the occurrence of these mutations may be
influenced by genetic background. We analyzed the RET
proto-oncogene from 79 patients from 10 unrelated Saudi
families. A total of 46 individuals with hereditary MTC
were enrolled in this study. Our study analyzed the RET
proto-oncogene from 79 patients from 10 unrelated Saudi
families. A total of 46 individuals with hereditary MTC
were enrolled in this study. The nature of the mutations in
our MEN 2A families is 618 found in 46.6% of all cases of
MEN 2A, which is interestingly different from the results
of the International RET mutation consortium analysis
Conclusion: We showed the frequency profile of
RET proto-oncogene mutations in a sample of 10 unrelated Saudi’s families with hereditary MTC. The most frequent RET proto-oncogene mutations in Saudi’s families
with MEN 2A and familial medullary thyroid carcinoma
(FMTC) is mutation in codon 618.
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Abstract #1010
Abstract #1011
THE VALUE OF ON-SITE PATHOLOGIC
ASSESSMENT FOR DETERMINING SAMPLE
ADEQUACY DURING ULTRASOUND GUIDED
BIOPSY OF THYROID NODULES
UNEXPECTED OUTCOMES OF SELF-IMPOSED
DIETARY RESTRICTIONS AND DIETARY
PREFERENCES: CASE REPORT OF IODINE
DEFICIENCY INDUCED GOITER IN CENTRAL
NEW JERSEY
Bhakti Paul, MD
Objective: The purpose of this study is to determine
whether having on site pathologic evaluation of specimens improved the adequacy rate for ultrasound guided
(US) fine needle aspiration (FNA) of thyroid nodules
Methods: Retrospective review was conducted for all
patients referred for US-FNA of thyroid nodules in our
institution since 2007. Data from 200 US guided FNAs
done in the presence of an attending pathologist (group
1) who inspected the specimen from each pass as it was
obtained for adequacy was compared with 200 US guided
FNAs done at an off-site clinic (group 2) without on-site
specimen evaluation. The number of passes made per nodule in group 1 was contingent on feedback from the pathologist. A standard of 3 passes were made for each nodule in
group 2. This group contained 37 males, 163 females with
a mean age of 53. 3 passes were made for each nodule in
group 2. This group contained 23 males, 177 females with
a mean age of 52. FNAs in both groups were performed
using 23G needles with ultrasound guidance using the
same suction method, and final interpretation was made
by the same board certified cytopathologists.
Results: 5% of FNAs performed in group 1 with on
site pathology evaluation were inadequate, compared to
13.5% in the group 2 without on site pathology. (p=0.005,
Fisher’s Exact test). Group 1 contained 37 males, 163
females with a mean age of 53. Mean nodule size was 2.4
cm. The final diagnosis was 146 benign, 38 indeterminate and 6 malignant. Group 2 contained 23 males, 177
females with a mean age of 52 with a mean nodule size as
2.8 cm.143 nodules were benign, 22 were indeterminate,
and 8 malignant. The median number of passes was equal
in both groups and was 3 with the number of passes ranging from 2 to 8 in group 1.
Discussion: Ultrasound guided Fine Needle aspiration biopsy is a standard procedure for diagnostic evaluation of thyroid nodules. Our study found that the inadequacy rate is reduced by more than half with on-site
pathology. This in turn decreases patient burden, cost of a
repeat biopsy and potentially prevents delay in treatment.
Conclusion: The presence of on-site pathology evaluation significantly improves diagnostic yield. This has to
be balanced against the costs of providing this coverage.
Amy Chow, MD, Sun Wei, MD, Xiangbing Wang, MD
Objective: Iodine deficiency induced goiters have
generally been eliminated with iodized salt in America.
However, sporadic cases of euthyroid goiter due to iodine
deficiency have been reported, even in New Jersey, a supposedly iodine-replete state. We report the cases of two
patients in central New Jersey who suffered from iodine
deficiency-induced euthyroid goiters.
Case Presentation: A 47-year-old female with hypertension presented with goiter. Examination was notable
for diffused enlarged thyroid. CBC, CMP, TSH, free T4,
total T3 and thyroid perioxidase (TPO) antibody level
were normal. Sonogram showed diffusely enlarged homogeneous-appearing thyroid gland. A 24-hour urine iodine
collection showed subnormal level of 42ug. Further discussion revealed that she refrained from consuming salt
for her hypertension and avoided seafood by choice.
She was diagnosed with goiter secondary to iodine deficiency and was advised to use iodized salt and eat seafood. Six months later, the goiter resolved. A 36-year-old
female with hypertension presented with thyroid nodules.
Examination was notable for BMI of 46 and diffused
enlarged thyroid. CBC, CMP, TSH, free T4, total T3 and
TPO were normal. She had 5 children including one year
old twins. Fine needle aspiration was negative for malignancy cells. An I123-uptake and scan showed a 24-hour
uptake of 37 % and a diffusely enlarged gland. A 24 hour
urine iodine collection revealed an iodine level of < 10ug.
She also avoided salt for hypertension, cut down dairy
products and bread for weight loss and refrained from
consuming seafood by choice. She was diagnosed with
iodine deficiency induced goiter and started on iodized
salt. Six months later, patient’s nodules resolved.
Discussion: Our cases of iodine-deficiency occurred
in an iodine-abundant environment. Given the culture and
dietary history of these patients, the possible mechanisms
of iodine deficiency includes: 1) avoidance of salt due to
medical conditions like hypertension. 2) avoidance of seafood due to personal preferences. These cases highlight
the importance of obtaining specific dietary information
on the intake of iodized salt and seafood routinely during
evaluation of patients with goiter. Measurement of urinary
– 150 –
iodine excretion is warranted in suspicious cases. If iodine
deficiency induced goiter is diagnosed, dietary iodine supplementation can have a profound antigoitrogenic effect
and lead to dramatic resolution, thereby avoiding unwarranted thyroxine suppression therapy and fine needle
aspiration.
Abstract #1012
THE CHANGING FACE OF PAPILLARY
THYROID CANCER: IS 50THE NEW 30?
either through imaging or surgery is playing an increasingly important role in the older population.
Conclusion: Patients with PTC are growing older
which has important prognostic and treatment implications. PTC tumor size is decreasing and older patients are
being treated for an increasing number of small tumors
perhaps reflecting the increased detection of these incidental thyroid nodules because of the proliferation of
imaging studies.
Abstract #1013
David T. Hughes, MD, Megan R. Haymart, MD,
Barbra S. Miller, MD, Paul G. Gauger, MD,
Gerard M. Doherty, MD
LARGE NEEDLE ASPIRATION BIOPSY FOR
PREOPERATIVE SELECTION OF HURTHLE
CELL NODULES
Objective: The incidence of papillary thyroid cancer
(PTC) is growing at a faster rate than any other malignancy, yet it is unknown what role the aging population
has on PTC incidence rates. With the goal of understanding the role of age in thyroid cancer incidence, this study
sought to analyze the changing demographics of patients
with PTC over the past three decades.
Methods: Retrospective cohort evaluation of patients
with papillary thyroid carcinoma from 1973-2006 using the
National Cancer Institute’s Surveillance, Epidemiology,
and End Results (SEER) database.
Results: From 1973-2006 the incidence of PTC has
increased for all age groups, but has escalated the most in
patients older than age 45. Over the last three decades, the
peak incidence of PTC has shifted from the 30-40 yearold age group to the 40-50 year-old age group. Until 1999
most cases of PTC were found in patients younger than
45, however in 2006 the majority (61%) are now found in
patients older than age 45. From 1988 to 2003 there has
been an increasing incidence of all sizes of PTC in all age
groups; however the largest increase has been in tumors
less than 1 cm in patients older than 45 years. Forty-three
percent of tumors in older patients are now 1cm or less,
while only 34% are 1 cm or less in younger patients. The
rates of invasion and the presence of distant metastasis
have remained relatively stable from 1988 to 2003 in both
age groups, but the relative incidence of multifocal disease has increased 10% and is now present in approximately 25% of all cases of papillary thyroid cancer.
Discussion: The demographics of patients with PTC
are evolving with the peak incidence shifting from the 3rd
decade to the 4th and 5th decades of life. Since under the
current AJCC staging system, only patients older than age
45 can be classified as stage III or IV, the increasing age
of patients with PTC will have important implications for
staging and subsequent treatment. The increasing incidence of tumors less than 1 cm in the older age groups also
leads to speculation that the incidental discovery of PTC
Angelo Carpi, MD, Giuseppe Rossi, PhD,
Jeffrey Mechanick, MD, Andrea Nicolini, MD,
Giancarlo di Coscio, PhD
Objective: We reported that large needle aspiration
biopsy (LNAB) histology distinguishes nodules with
indeterminate follicolar structure by fine needle aspiration
biopsy (FNAB) cytology into two groups: pure microfollicular nodules with increased likelihood of postoperative
malignancy and mixed micro-macrofollicular nodules
with decreased risk of postoperative malignancy.
Methods: We compared FNAB (23-22 gauge needles)
and LNAB (20-18 gauge needles) diagnostic accuracy in
Hürthle cells nodules (HCN; Hürthle cell found in >60%
of all cells examined) at FNAB which were excised following preoperative examination with FNAB and LNAB
(4 men and 20 women; nodule size range 1-4 cm).
Results: FNAB demostrated 7 benign HCN (which
were considered as negative preoperative findings), 8
HCN with atypia (positive preoperative); 7 suspected
cancers with HC (positive preoperative); and 2 cancers
with Hürthle cells (positive preoperative). LNAB showed
a microfollicular structure in 14 nodules (positive preoperative) and a mixed micro-macrofollicular feature in 10
nodules (negative preoperative). Postoperative findings
were: benign (negative) 16, carcinoma (positive) 8. The
sensitivity and specificity for FNAB were 87.5% (7/8,
95% C.I.: 64.5-100%) and 37.5% (6/16, 95% C.I.:13.7-61,
2%) respectively; and for LNAB were 87.5% (7/8, 95%
C.I.:64.5-100%) and 75.0% (12/16, 95% C.I.:53.8-96.2%),
respectively. FNAB results were significantly different
from post-operative result (McNemar’s test, Exact 2-sided
p=0.012), while LNAB results were not (McNemar’s test,
Exact 2-sided p=0.375). Youden’s index, a global measure
of accuracy, was high for LNAB (0.62, 95% C.I.: 0.310.94) but not for FNAB (0.25, 95% C.I.: -0.08-0.58).
Conclusion: These data confirm previous findings
that LNAB is more specific than FNAB and can be used
– 151 –
for preoperative selection of thyroid nodules containing
Hürthle cells.
Abstract #1014
IODINE CONTENT IN FAST FOODS:
COMPARISON BETWEEN TWO US FAST FOOD
CHAINS
Conclusion: Iodine intake from fast food restaurants,
a major source of nutrition for many Americans, may
be low unless milk shakes, iodinated bread, or fish are
consumed.
Abstract #1015
SIMULTANEOUS DIAGNOSIS OF MULTIFOCAL
METASTATIC PAPILLARY THYROID
CARCINOMA AND FOLLICULAR LYMPHOMA
Sun Lee, MD, Angela M. Leung, MD, Xuemei He, MD,
Lewis E. Braverman, MD, FACE,
Elizabeth N. Pearce, MD, MSc
Objective: To determine the iodine content in food
items from popular fast food chains in the US.
Methods: Use of iodized salt in food preparation
was determined by phone calls and emails to various
fast food chains in the US. Burger King and McDonald’s
were selected for further evaluation of food iodine content, as Burger King endorses use of iodized salt whereas
McDonald’s does not. Seven comparable items were
selected from each venue. Two restaurants for each venue
in the Boston area were selected at random, and two items
per category from each restaurant were purchased. The
iodine content of two samples of each homogenized item
was measured spectrophotometrically by the method of
Benotti et al.
Results: The average iodine content per item was as
follows: for McDonald’s; Big Mac with cheese 16.7mg,
small French Fries 2.7mg, Filet-o-Fish 69.9mg, Southern
Style Chicken Sandwich 5.3mg, Happy Meal Hamburger
4.3mg, Chicken McNuggets 3.0mg, 12-oz Vanilla Shake
163.7mg; for Burger King; Whopper with cheese 25.8mg,
small French Fries 4.3mg, BK Big Fish 43.5mg, Original
Chicken Sandwich 163.6mg, BK Kids meal hamburger
3.9mg, 4-piece Chicken tenders 2.1mg, 12-oz Vanilla
Shake 147.8mg. Further analysis of Burger King’s chicken
sandwich showed that the source of high iodine was the
bread and not the chicken patty.
Discussion: NHANES III (1988-1994) reported a
decrease in the median urinary iodine from 320 mg/L to
145 mg/L compared to NHANES I (1971-1974). Adequate
iodine intake is especially important in pregnant and
lactating women for normal fetal and neonatal neurodevelopment. Given the high consumption of fast foods in
America, two fast food chains were selected to assess
iodine content. Despite the difference in the use of iodized
salt in food preparation, the iodine contents appear to be
similar between comparable items of McDonald’s and
Burger King except for Burger King’s chicken sandwich,
most likely due to the high iodine content in the bread
from iodate used as a dough conditioner. Items containing
milk and fish had the highest iodine content.
Sandra L. Weber, MD, FACE, Christopher Woody,
John Neuffer
Objective: To describe a case of simultaneously diagnosed thyroid cancer and lymphoma.
Case Presentation: A previously healthy 55-year-old
woman with recently diagnosed osteopenia, taking calcium and Vitamin D, presented with a new palpable left
neck mass. She also complained of multiple lumps in both
breasts. She underwent left neck lymph node resection
and multiple breast biopsies. The breast biopsies were all
benign. The neck mass was diagnosed as papillary thyroid carcinoma metastatic to a lymph node. She underwent near total thyroidectomy and lymph node dissection.
Multifocal, papillary thyroid carcinoma of the thyroid was
found in both lobes. The largest focus was in the left lobe,
0.8 cm and extending into the perithyroidal soft tissue.
Nine of 39 lymph nodes were positive for metastatic papillary thyroid cancer. Some of the 16 left jugular lymph
nodes, none with evidence of metastatic papillary thyroid
cancer, showed partial effacement of architecture. Several
of the follicles were atypical showing a monotonous population of centrocytes without polarization or lingibis body
macrophages. Immunohistochemical staining showed that
the atypical follicles were positive for CD20 and CD10
(strong) and overexpressed Bcl-2. Kappa and lambda
light chain staining did not show plasmacytic differentiation. These findings are consistent with in situ localization of follicular lymphoma. She completed an evaluation
for lymphoma including Positron Emission Tomography
(PET) scan and bone marrow biopsy which did not show
any evidence of lymphoma. She underwent radioactive
iodine therapy with post treatment uptake in the thyroid
bed and neck area right of midline. There was no abnormal distant uptake. At one year after resection she is without evidence of lymphoma or papillary thyroid cancer.
Discussion: According to The National Cancer
Institute, in 2009 there were an estimated 37,200 new
cases of thyroid cancer, 27,200 in women and 74,490 new
cases of lymphoma, 33,860 in women with 29,900 identified as Non-Hodgkin lymphoma. The incidence of thyroid
cancer is 15 per 100,000 white women. The incidence
– 152 –
of lymphoma is 19.8 per 100,000 white women, 17.2
per 100,000 for Non-Hodgkin lymphoma. The incidental identification of follicular lymphoma in this woman
prompted an extensive evaluation for lymphoma in other
locations. Because the neck lymphoma overexpressed
Bcl-2, bone marrow PCR (polymerase chain reaction)
testing for Bcl-2 major break point region and microcluster region was performed. PET scanning which can distinguish metabolically more active cells like thyroid cancer
and lymphoma cells is also helpful in determining extent
of disease.
Conclusion: The simultaneous diagnosis of two cancers is distinctly unusual. As part of the therapeutic intervention of papillary thyroid cancer, lymph node dissection
is a standard process with the possibility of identifying
simultaneous lymphoma as described here.
Abstract #1016
UTILITY OF HIGH RESOLUTION ULTRASOUND
IN THE CHARACTERIZATION AND
IDENTIFICATION OF DIFFERENTIATED
THYROID CARCINOMA
goiters, 11 follicular adenomas and 5 oxifilic adenomas).
The highest sensitivity of ultrasound characteristics to
identify thyroid carcinoma were: microcalcifications
84%, hypoechogenicity 76% and irregular margins 94%.
Independent risk factors to predict thyroid carcinoma
were: microcalcifications (OR 13.24, IC 95% 5.52-27.59,
p=0.0001) irregular margins and local invasiveness (OR
3.71, IC, 95% 1.44-9.58, p=0.007). Hypoechogenicity
with microcalcifications had the greatest associated risk
(OR 12.69, p<0.0001). In addition, hypoechogenicity and
irregular margins and local invasiveness predicted also
thyroid carcinoma (OR 3.05, p<0.002).
Conclusion: Sonographic findings significantly associated with differentiated thyroid cancer were: hypoechogenicity, microcalcifications, irregular margins and invasion to adjacent tissue. The presence of hypoechogenicity
associated with microcalcifications and hypoechogenicity
associated with irregular margins and invasion were the
most useful. Sonographic characteristics of thyroid nodules are useful to suspect malignancy and help to guide
further evaluation with fine needle aspiration biopsy or
surgery.
Abstract #1017
Kenny Sofía Joya Péñate, MD,
Bernardo Pérez Enriquez, MD, Paloma Almeda, MD
Objective: To identify ultrasonographic characteristics for recognizing differentiate thyroid carcinoma from
benign lesions. Due to the high prevalence of thyroid nodules, and its association with thyroid carcinoma in about
5% of cases, it is important to develop a cost-effective
strategy for its evaluation. Neck ultrasound is a noninvasive and relatively inexpensive tool that can be useful for
evaluation of thyroid nodules.
Methods: Cross-sectional study to evaluate the utility of neck ultrasound to identify thyroid carcinoma. We
studied 147 patients whom underwent thyroid surgery
between January 2005 and December 2007. All patients,
before surgery, had neck ultrasound and fine needle aspiration biopsy performed. For each sonographic sing, we
established sensitivity, specificity, positive and negative
predictive values considering the final pathology report. In
addition, odds ratio was estimated. The ultrasound characteristics were evaluated by two blinded endocrinologists.
Also, fine needle aspiration biopsies, when performed,
were evaluated considering the final pathology diagnosis.
Results: Mean age was 42.8±14.89 years (18-77) and
129 (87.8%) cases were women. In 92 (62.6%) cases multiples nodules were found. In 81 cases final diagnosis was
papillary thyroid carcinoma, 6 of which were reported as
microcarcinomas (67 classic, 13 follicular and 1 tall-cell
type). Twelve cases were follicular thyroid carcinomas
and in 54 cases benign lesions were diagnosed (38 colloid
A GENOMIC TEST FOR ACCURATE
IDENTIFICATION OF BENIGN THYROID
NODULES
Richard Burnham Lanman, MD,
Giulia C. Kennedy, PhD, Nusrat Rabbee, PhD,
Jonathan Wilde, PhD, Hui Wang, PhD,
Darya Chudova, PhD, Eric Wang, PhD,
Camila Friedlander, PhD, Jessica Reynolds,
Ed Tom, Morita Pagan, PhD, Charles Wang, MD,
Lyssa Friedman, RN, MPA, Martha Zeiger, MD,
Electron Kebebew, MD, Juan Rosai, MD,
Virginia LiVolsi, MD
Objective: To develop a molecular test on thyroid
nodule fine needle aspirates (FNAs) that provides accurate diagnostic information on nodules with indeterminate
cytopathologic features. The literature reports that ~ 20%
of thyroid nodules aspirated by FNAs result in indeterminate cytopathology diagnoses. Due to the ambiguity of the
results, many of these patients undergo hemi- or total thyroidectomy, yet only 30% of these cases are subsequently
shown to be malignant on histopathology. More definitive
diagnostic tests performed on thyroid FNAs would be
desirable, as this would reduce the number of patients with
benign conditions subjected to surgery and its sequelae,
such as dependence on life-long thyroid hormone replacement. Many studies have used molecular analysis to try
to determine which “indeterminate” cytology samples are
– 153 –
malignant. We use a different approach, i.e., we identify
those indeterminate nodules which are benign.
Methods: We used genome-wide mRNA expression analysis to measure >247,186 transcripts including
alternatively-spliced genes in 849 thyroid nodules comprising subtypes which result in indeterminate cytopathology. Machine-learning algorithms utilizing expert surgical
pathology over-reads as the gold standard were combined to develop a multi-gene molecular classifier that
accurately distinguishes benign from malignant thyroid
lesions. We also developed improved laboratory protocols
for collection of thyroid fine-needle aspirates and subsequent extraction of nucleic acid from these specimens. We
successfully employed these protocols across 21 academic
and community-based sites in the U.S.
Results: The multi-gene classifier utilizes ~200 gene
transcripts and multi-dimensional analytical methods
to achieve an overall cross-validated accuracy of >95%
when tested on prospectively collected thyroid FNAs.
Large numbers of genes are necessary to achieve high
performance across the myriad of thyroid nodule subtypes
encountered in clinical practice. Preliminary performance
characteristics of this test show ROC curve AUC values
of 0.94, indicating reasonable sensitivity as a function
of specificity. Furthermore, the false negative rate we
observe with our molecular classifier is no greater than
that of FNAs diagnosed as benign by cytopathology.
Conclusion: Using several different classifiers we
have identified a subset of samples whose surgical pathology diagnoses are highly inconsistent with their molecular
profiles. These discordant calls are counted as classifier
errors, but in fact may be due to inadequate sampling of
the thyroid nodule during the FNA process or to ambiguous surgical pathology diagnoses.
Abstract #1018
BEWARE OF THE SPECTRUM OF AMIODARONE
INDUCED THYROTOXICOSIS (AIT)
any intervention. A 73-year-old woman with no H/O
thyroid disease developed new onset Afib with dyspnea.
Pulmonary embolism was ruled out by CT angiography.
Additionally, she needed amiodarone for controlling Afib.
TFTs showed TSH 0.19 mU/L, freeT4 2.4 ng/dL with further worsening over next few days. She was successfully
treated with both methimazole (60 mg/day) and prednisone (40 mg/day) to control thyrotoxicosis over 5 months
while amiodarone was discontinued. A 58-year-old man
with H/O cardiomyopathy (ejection fraction 20%), post
AICD on amiodarone since 2007 developed palpitations
10 days prior to admission and was found to have TSH
0.014 mU/L, freeT4 >7.7 ng/dL and freeT3 23.1 pg/dL .
Methimazole was started but symptoms persisted and he
was admitted with wide complex tachycardia (150 beats/
min). Since it was difficult to determine the type of AIT,
patient was started on both methimazole and steroids and
amiodarone was discontinued. He continued to have recurrent ventricular tachycardia (VTach) despite maximal
doses of methimazole, intravenous steroids, and multiple
anti-arrhythmics and thus, lithium and cholestyramine
were added to try and control thyrotoxic state. Despite all
efforts, he had uncontrolled VTach and died.
Discussion: The above cases highlight the spectrum
of presentation and the complexity of managing AIT.
Though radioactive iodine uptake scan, cytokines like
interleukin-6 and color flow doppler of thyroid have been
proposed to distinguish type I and II AIT, many times, it is
difficult to clearly determine the type. This prompts treatment with both thionamides and steroids. A diagnostic
modality that would clearly distinguish the 2 types would
be beneficial and more research is needed in this area.
Finally, whether amiodarone should be continued or not is
a matter of contention as well.
Conclusion: The presentation of AIT can range from
asymptomatic to severe thyrotoxicosis and is associated
with significant morbidity and potential mortality. It is
essential that amiodarone be used judiciously and when
used, thyroid status be monitored periodically.
Abstract #1019
Praveena Gandikota, MD, Sandra Foo, MD,
Lynn Allen, MD
Objective: To describe varied presentations of AIT
ranging from benign to fatal outcomes and challenges of
management.
Case Presentation: A 61-year-old woman with H/O
atrial fibrillation(Afib), aortic and mitral valve replacements, no thyroid disease, on amiodarone for >5 years
was evaluated due to abnormal thyroid function tests
(TFTs): TSH <0.03 mU/L, freeT4 3.1 ng/dL and totalT3
192 ng/dL. Since she had no symptoms/signs of thyrotoxicosis, she was closely monitored without discontinuing amiodarone. Over 3 months, TFTs normalized without
GRAVES’ DISEASE PRESENTING AS
INTRACTABLE VOMITING
Mohsen Eledrisi, MD, FACE, Fayez Bishara, MD, MRCP
Objective: To describe a patient with thyrotoxicosis
due to Graves’ disease who had an unusual presentation
with predominantly vomiting.
Case Presentation: A 20-year-old unmarried female
was evaluated for persistent vomiting for 3 months along
with unintentional weight loss of about 9 kilograms. Her
past medical history was not significant and she was not
– 154 –
taking any medications. On physical examination, she
looked cachectic, her weight was 35.5 kg, body mass index
was 14.6 kg/m2 , blood pressure was 130/80 mmHg, and
pulse was 130 beats per minutes. She had no fever. Her
thyroid was mildly enlarged with no palpable nodules or
lymph nodes. Examination of the eyes and cardiovascular,
respiratory, gastrointestinal and neurological systems was
normal. Laboratory data showed a normal hemoglobin,
electrolytes, and liver function tests. Because of intractable vomiting, the patient was admitted to the hospital
for further evaluation. An esophagogastroduodenoscopy
showed mild gastritis which did not explain the patient’s
complaints. Thyroid function tests were obtained; TSH
was < 0.01 mIU/L (normal, 0.35-4.5) and Free T4 was
77 pmol/L (normal, 9-19). A technitium99 scan showed a
homogenous increased uptake in both thyroid lobes with
a significantly increased uptake at 17 % (normal, 2-4 %).
The diagnosis of Graves’ disease was made and she was
started on Methimazole 10 mg twice daily and Propranolol
40 mg twice daily. Her condition significantly improved;
vomiting resolved and she was discharged after staying
in the hospital for 7 days. After 6 weeks, she reported no
complaints and had gained 10 kilograms. TSH was < 0.01
and Free T4 was 17.4.
Discussion: The diagnosis of thyrotoxicosis is generally suspected on clinical grounds. Typical symptoms of sympathetic overactivity are usually observed.
Gastrointestinal manifestations of thyrotoxicosis, which
are not commonly reported, have included increased frequency of stools and weight loss due to increased calorie
requirement or malabsorption. The patient we are reporting had an unusual presentation, as she presented with persistent vomiting. The diagnosis was delayed until thyroid
function tests were obtained.
Conclusion: Thyrotoxicosis should be suspected in
patients who present with prolonged and unexplained gastrointestinal symptoms such as vomiting. This will assure
timely diagnosis and treatment.
Abstract #1020
THERAPEUTIC UTILITY OF PLASMA
EXCHANGE IN AMIODARONE INDUCED
THYROTOXICOSIS TYPE II
for the last five years. He presented with complaints of
generalized weakness and weight loss of fifteen pounds
over the last three months, diarrhea and palpitations over
the last four weeks. On physical exam he was found to
be in atrial fibrillation and thyroid exam was normal. His
labs showed TSH 0.01 µIU/mL, free T4 5.6 ng/dL and
T3 421 ng/dL. An ultrasound of the thyroid was normal
without any nodules. A technetium 99M-pertechnetate
scan obtained because of inability to get an iodine uptake
due to recent use of iodinated contrast showed no detectable tracer uptake in the thyroid gland and findings consistent with thyroiditis. The patient was diagnosed with
AIT type II and was started on metoprolol and high dose
prednisone. The dose of prednisone was increased in two
weeks due to lack of response. In four weeks an empiric
trial of methimazole was used because of further increases
in free T4 and T3. Due to complaints of anxiety, insomnia and agitation the dose of prednisone was reduced.
After 8 weeks from initial diagnosis the patient had to
be readmitted to the hospital due to severe weakness and
altered mental status. His labs showed TSH < 0.01 µIU/
mL, free T4 5.2 ng/dL and T3 444 ng/dL. Iodine 123 thyroid scan showed absence of tracer uptake in the thyroid
consistent with Amiodarone induced thyroiditis. A trial
of plasma exchange was decided up on due to persistent
thyrotoxicosis with exacerbation of his comorbidities.
His labs after the first plasma exchange showed free T4
3.8 ng/dL and T3 282 ng/dL. He received a total of three
plasma exchanges over the course of the next two weeks.
His mental status improved and his free T4 at the time of
discharge was 2.2 ng/dL and T3 179 ng/dL and were stable
and not increasing.
Discussion: AIT type II is a type of destructive
inflammatory thyroiditis. It can occur any time during
amiodarone therapy or even long after discontinuation.
Glucocorticoids have been considered to be the drug
of choice. Individual case reports have shown plasma
exchange as a therapeutic option for rapid control of thyrotoxicosis due to other causes. This case demonstrates its
potential utility for acute treatment of AIT type II.
Conclusion: Plasma exchange can be a therapeutic
option in AIT type II not responding to glucocorticoids
and may achieve more rapid control.
Abstract #1021
Harsha Karanchi, MD, Christopher Leveque, MD,
Dale J. Hamilton, MD, FACP, FACE
MALIGNANT STRUMA OVARII
Objective: To describe improvement of amiodarone
induced thyrotoxicosis (AIT) type II after use of plasma
exchange.
Case Presentation: The patient is a seventy-seven
year old Caucasian man with history of Parkinson’s disease and atrial fibrillation. He had been on amiodarone
Tricia Diane Hislop-Chesnut, MD, Mary Beth Hodge, MD
Objective: Struma Ovarii (SO) is the presence of
thyroid tissue as a major cellular component in an ovarian tumor. It is nearly always present in a teratoma. It is
found most commonly between the ages of 40 and 60 and
– 155 –
patients typically present with a pelvic mass, hyperthyroidism or ascites. Malignancy in the setting of SO is rare
and the incidence is thought to be 0.1% to 0.5% of all
ovarian tumors. We present a case report of a middle aged
female with a history of a toxic multinodular goiter who
presented with recurrent abdominal pain and was found to
have malignant SO at the time of laparotomy.
Case Presentation: A 57-year-old female with a history of a right thyroid lobectomy 24 years ago for adenomatous goiter and treatment with radioactive iodine 5
years ago for a toxic left nodule presented with abdominal
pain. She had noted postprandial pain for the last several
months and she underwent a cholecystectomy for cholelithiasis. Because of persistent abdominal pain, she had
a CT scan of her abdomen and pelvis. It was remarkable
for a non-obstructing internal hernia and a 1.9 cm right
adnexal mass consistent with a benign dermoid tumor. She
underwent exploratory laparotomy, lysis of adhesions,
repair of internal hernia and right oophorectomy.
Results: The pathology revealed a cystic teratoma
with struma ovarii. Within the teratoma, there was a 5 mm
focal neoplastic thyroid tissue consistent with follicular
variant of papillary carcinoma. Her thyroid stimulating
hormone (TSH) 5 months prior was 3.4 uIU/ml (0.3-4.5).
She then underwent a completion thyroidectomy which
was consistent with an adenomatous goiter. A thyroglobulin level drawn 1 month after thyroidectomy was 0.2 ng/
ml (<33.1ng/ml) with negative antithyroglobulin antibody. A CT scan of her abdomen and pelvis repeated 6
months after her laparotomy did not show any evidence of
metastatic disease.
Conclusion: This is a case of a patient with a history of a toxic multinodular goiter status post radioactive iodine therapy, which was incidentally found to have
malignant change of struma ovarii. Her follow up has been
reassuring for surgical cure. Earlier studies suggested that
small areas of nuclear changes without evidence of invasion and/or metastases were not diagnostic of malignancy.
However, recent studies have suggested that malignant
SO should be monitored for at least 20 years, as there is
potential for metastases. Patients should be followed with
periodic imaging studies and thyroglobulin levels for any
evidence of recurrent disease. Treatment and follow up of
these patients has been variable due to the few cases identified in the literature.
Abstract #1022
THYROID STIMULATING HORMONE: A
USEFUL MARKER FOR THYROID CANCER?
Michael Pakdaman, MD, Jacques How, MB, ChB,
MRCP, MD, Rania Ywakim, MD,
Richard J. Payne, MD, FRCS(C)
Objective: Thyrotropin (TSH) is a known thyroid
growth factor. We aim (1) to compare preoperative serum
TSH among patients with documented well differentiated thyroid carcinoma versus patients with benign thyroid disease and (2) to search for a specific relationship
between TSH levels and papillary microcarcinoma (PMC)
incidence.
Methods: We reviewed 1047 patients who underwent total thyroidectomy at our university teaching
hospital between 2002 and 2008. Patients without preoperative TSH values or those outside the normal range
were excluded, as well as cases of poorly differentiated
carcinoma (n=576). Values were compared using the chisquared test.
Results: Our results yielded 223 benign cases, 346
cases of papillary carcinoma, 4 follicular carcinomas,
and 3 Hürthle cell carcinomas. The incidence of malignancy was 43.8% in patients with serum 0.4 ≤ TSH < 0.8
mIU/l (p < .001) versus 56.8% for those with 0.8 ≤ TSH
< 1.4 mIU/l (p = 0.124) and 71.3% for those with 1.4 ≤
TSH < 4.0 mIU/l (p < .001). No statistically significant
differences in the mean serum free T4 and free T3 concentrations were found between the malignant v/s benign
groups. Tumor size was not found to increase in parallel with TSH concentrations and there was no association
between the serum TSH values and the frequency of extrathyroidal extension.
Discussion: This study demonstrates that the risk of
malignancy in thyroid nodules increases in parallel with
higher serum TSH concentrations within the normal range.
Further studies are necessary to assess the predictive value
of this association and its potential clinical application.
Conclusion: Preoperative serum TSH concentrations
may serve as a predictor for thyroid malignancy.
– 156 –
Abstract #1023
Abstract #1024
TOTAL THYROIDECTOMY SECTIONING AND
YIELD OF INCIDENTAL DISEASE
ECTOPIC SITES OF NODAL METASTASIS IN
PAPILLARY THYROID CARCINOMA:
A REVIEW OF 10 CASES
Michael Pakdaman, MD, Louise Rochon, MD,
Richard J. Payne, MD
Objective: The thickness of pathologic sectioning of
the surgical thyroidectomy specimen is variable among
different institutions. Additionally, many institutions
choose only to analyze “representative sample” - sections
within the portion of the thyroid with gross disease. This
study investigates our previously reported highest incidence of papillary microcarcinoma (PMC) by (1) comparing yield of disease when serial sections are submitted intoto versus representative samples and (2) assessing for a
relationship between the number of sections-per-gram of
thyroid tissue and rates of PMC.
Methods: Pathology results were reviewed for all
consecutive total thyroidectomies between 2002 and 2008
(n=1045). All specimens were serially sectioned at 3mm.
Specimen data recorded included sample weight, number of sections, and whether all sections were assessed
“in-toto” or as a “representative sample” based on gross
inspection. Statistical significance was calculated using
chi-squared analysis.
Results: Among the 790 thyroids submitted in-toto,
PMC incidence was 53%, compared to 39% in cases where
representative samples were submitted (p < 0.01). In cases
where <=0.6 sections-per-gram were submitted, the incidence of PMC was 43% versus 56% when >0.6 sectionsper-gram were submitted (p <0.001). The total incidence
of PMC at our institution was 52.0%. By extrapolation, if
only representative samples were viewed at our institution
and all were sliced at 5mm sections, the incidence of PMC
is estimated at 28.6%.
Discussion: This indicates that thick sectioning may
decrease the yield of PMC, as can limiting pathologic
analysis to sections involving the representative sample.
These findings may explain our previously reported highest incidence of PMC.
Conclusion: This study found a higher yield of disease when increased portions of thyroid tissue were analyzed. Extrapolation to conform to conventional methodology yields results similar to previous literature.
Michael Pakdaman, MD, Dipti Kamani, MD,
Gregory W. Randolph, MD, FACS
Objective: Papillary thyroid carcinoma is commonly
known to metastasize to regional nodes in the neck, with
subsequently good prognostic outcomes. Metastases to
ectopic sites such as the parapharyngeal space and axilla
are rare and uncommonly reported. We aim to present the
rate and behavior of papillary carcinomas with ectopic
metastases at our institution.
Methods: We reviewed all consecutive cases of neck
thyroidectomy and neck dissection performed under
one surgeon from 2004 to June 2009 (1030 cases in 911
patients). Neck dissections were planned using a standardized algorithm based on preoperative CT scan. All cases
of papillary thyroid carcinoma (PTC) in the thyroid bed,
soft tissue, or lymph nodes were recorded (512 cases in
434 patients). Cases of ectopic nodal metastases were
identified.
Results: Of 368 cases with PTC in the thyroid bed,
124 had concomitant nodal disease (33.7%). 10 surgical
cases identified ectopic lymph nodes (3.8% of all cases
with positive nodal disease). Ectopic sites included the
floor of mouth, retropharynx, parapharyngeal space, lateral chest wall, axilla, and parotid gland.
Discussion: While rare, ectopic sites of nodal metastasis do occur in patients with papillary carcinoma of
the thyroid, warranting discussion on the importance of
patients with thyroid cancer undergoing preoperative CT
from the skull base to the mediastinum.
Conclusion: We report the largest series of ectopic
nodal metastases from papillary thyroid carcinoma.
Abstract #1025
POST-PARATHYROIDECTOMY THYROIDITIS
Daniel Rubin, MD, Alan Farwell, MD,
Stephanie Lee, MD, PhD
Objective: To describe a case of post-parathyroidectomy thyroiditis.
Case Presentation: A 60 year-old female with no
history of thyroid disease presented with tachycardia,
hypertension, and palpitations 11 days after undergoing a
difficult resection of a 340 mg right parathyroid adenoma
– 157 –
for primary hyperparathyroidism. Physical exam revealed
a palpable but non-tender thyroid of normal size, a mild
tremor and no Graves’ ophthalmopathy. The healing neck
scar had no signs of inflammation. Preoperative TSH was
1.90 uIU/mL (NL 0.35-5.50). On postoperative day (POD)
11, testing showed: TSH <0.01 uIU/mL, T3 269 ng/mL
(NL 60-181), T4 9.6 mcg/dL (NL 4.5-10.9), and FTI 4.1
(NL 1.0-4.0). TPO antibodies were negative. Nuclear thyroid scan on POD 15 showed a 1.8% 4-hr I-123 uptake
(NL 5-15%) with reduced visualization of the right lobe,
ipsilateral to the surgery. The patient was treated only with
a beta blocker and symptoms resolved within days. On
POD 21, thyroid tests were: TSH 0.02, T3 169, and FT4
1.11 (NL 0.89-1.80). By postop week 9, the thyroid tests
normalized to: TSH 1.55 and FT4 1.05.
Discussion: Post-parathyroidectomy thyroiditis was
first reported in 1992. Patients present within 2 weeks after
surgery with thyrotoxicosis and low radioactive iodine
thyroid uptake. Anti-thyroid medications are not indicated as the low uptake suggests that the thyroid hormone
excess is not from production but of release resulting from
thyroid manipulation during surgery. Thyroid function
tends to normalize in weeks to months. Symptomatic thyrotoxicosis has been reported in 15-35% of parathyroidectomy patients followed prospectively. Predictors of postparathyroidectomy thyroiditis are having the procedure
done in a community vs. an academic setting, bilateral
vs. unilateral exploration, lithium use, and the absence of
a concurrent thyroid lobectomy. Similar cases have been
reported in the setting of surgery for secondary and tertiary hyperparathyroidism. The present case is notable for
a nuclear thyroid scan that localizes very low uptake to the
operative site.
Conclusion: Post-parathyroidectomy thyroiditis is a
rare but possibly under-recognized cause of low uptake
thyrotoxicosis. Endocrinologists should be aware of the
risk of thyrotoxicosis after difficult parathyroid dissections. In patients at risk for complications of thyrotoxicosis, postoperative monitoring of thyroid function and
prophylactic beta blocker therapy should be considered.
Abstract #1026
GRAVES’ HYPERTHYROIDISM PRESENTING AS
A TENDER THYROID
Lyndell Cheston Horine, MD, Krishna Bhaghayath, MD,
Fred Faas, MD, Antoine Makdissi, MD
Objective: To describe 3 patients who presented with
a painful thyroid gland and hyperthyroidism secondary to
Graves disease.
Case Presentation: Three patients are described
who presented with painful thyroid goiters due to Graves
disease. In all three patients, the thyroid was diffusely
swollen and tender on examination. They all had elevated thyroxine levels and suppressed thyrotropin levels.
Painful, subacute thyroiditis was suspected. Thyroid scintigraphy was homogeneous with elevated uptake indicative of Graves’ disease in all 3 patients. Two patients had
positive serum thyrotropin receptor antibodies and inflammatory markers were absent. These were not obtained in
the third patient as it was felt that the results of her scintigraphy and thyroid function tests were sufficient to make
the diagnosis. Two patients were successfully treated with
radioactive iodine therapy, resulting in resolution of their
hyperthyroidism and goiter, while the third elected to
undergo thyroidectomy.
Discussion: Graves disease with hyperthyroidism
typically presents with a minimally or non-tender diffusely enlarged thyroid gland. It is less common for
patients with Graves to present with marked thyroid tenderness, and few cases have been reported. In contrast,
patient’s with subacute thyroiditis classically present with
a painful thyroid.
Conclusion: A painful thyroid can be a less common
way for Graves’ disease to present. In patients clinically
presenting with the signs and symptoms of thyroiditis,
including thyroid tenderness, it is important to rule out
Graves’ hyperthyroidism by performing thyroid uptake
with radioactive iodine.
Abstract #1027
NOT ALL THAT LIES IN THE TRACHEA IS
INVASIVE THYROID CANCER
Eran Alon, MD, Mark Urken, MD
Objective: To report on 5 patients with suspected primary thyroid neoplasms with tracheal invasion that ultimately proved not to be invasive thyroid cancer, and in so
doing to make clinicians aware of other tracheal pathologies that may mimic invasive thyroid carcinoma.
Case Presentation: We present a retrospective review
of 5 cases presenting with suspected thyroid malignancies with tracheal invasion. 3 patients were found to have
benign pathologies (benign tracheal scarring, recurrent
laryngeal nerve schwanoma, and benign intratracheal thyroid rest), the fourth patient was diagnosed with a chondrosarcoma of the trachea, and the fifth patient suffered
from a collision tumor with papillary thyroid carcinoma
and squamous cell carcinoma of the larynx.
Discussion: The incidence of tracheal invasion in
thyroid carcinoma is reported to be between 1% to 13%
and is a major cause of death. Imaging studies play an
important role in diagnosis, staging, treatment and surveillance of thyroid neoplasms. Ultrasonography, MRI
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or Computed Tomography can be used to diagnose and
evaluate the extent of tracheal involvement. Mapping the
extent of loco-regional disease is vital to optimal patient
consultation and surgical planning. Tracheal involvement
will alter surgical planning and may require shave resection, window resection or circumferential tracheal resection with reconstruction. However, the clinician must bare
in mind that other pathologies both benign and malignant may mimic invasive thyroid carcinoma and falsely
upstage the disease.
Conclusion: Thyroid carcinoma with tracheal invasion is a major cause of death in thyroid malignancies.
However, the clinicians, radiologists and pathologists
should keep in mind other pathologies that may mimic
tracheal invasion.
Abstract #1028
EFFECTS OF SELENIUM SUPPLEMENTATION
ON TPOAB IN ACTIVE AUTOIMMUNE
THYROIDITIS
Slavica Ciric, MD
Objective: In several prospective randomized trials it has been shown that selenium supplementation in
patients with autoimmune thyroiditis (AIT) significantly
reduces serum thyroid peroxidase antibody (TPOAb) concentrations after 3 and 6 months treatment.The effect of
selenium (Se) supplementation was more pronounced in
patients with higher TPOAb concentrations (>1200 U/
ml).The aim of our study was to investigate the effects of
Se tretmant on patient with newly developed or active AIT
and high TPOAb titers.
Methods: Forty AIT female petients(aged 23 – 56
years) with elevated plasma TPOAb above1200 U/ml and
basal TSH within the normal range were included in the
present study.All patients received 200 µg sodium selenite
per day orally over a period of 3 months.TPOAb,TSH,and
free thyroid hormones were determined by commercial
assays.All patients underwent ultrasonographical histogram analyses under standardized conditions.Mean
densities of the thyroid tissues were determined in grey
scales(GWE).
Results: No significant difference in the TPOAb levels was found after Se administration (1972 ± 1055 vs.
1953 ± 1054 U/ml; p=0.055).Also, we found no differences of thyroid echo levels (17.04 ± 2.07 GWE vs. 17.01
± 2.05 GWE; p=0.166)
Conclusion: We demonstrate that Se administration
in our AIT patients with high disease activity does not
induce significant changes of TPOAb levels and sonographic echogenicity of the thyroid gland.
Abstract #1029
THYROTOXIC PERIODIC PARALYSIS-TPP–
AN UNUSUAL CAUSE OF ACUTE
QUADRIPLEGIA IN A YOUNG PATIENT
Saima O. Farghani, MD, Jay A. Sher, MD
Objective: To describe an alarming complication of
hyperthyroidism characterized by sudden onset of muscle
paralysis in apparently young healthy patients.
Case Presentation: A 29-year-old healthy Asian
woman presented with sudden onset weakness of her legs
bilaterally. Within the next 12 hours the weakness had
progressed upwards to involve her upper extremities. Her
serum Potassium was 1.4 with urinary potassium of 90
meq/ml. She denied any history of laxative abuse or licorice intake. Detailed history did not reveal any features
related to hyperfunctioning of the thyroid gland. On physical examination no goiter was appreciated. TSH was suppressed at 0.04 and free T4 was 2.71. Patient’s potassium
was replaced intravenously as well as she was started on
Propylthoiuracil (PTU) 100 mg q6hours and Propranolol
20 mg q8 hours. Within the next 12 hours she made a
remarkable recovery with total improvement of her weakness in all four limbs. She was discharged on potassium
supplements and PTU three days later. Repeat thyroid
function tests 6 weeks later were normal.
Discussion: Thyrotoxic Periodic Paralysis (TPP)
is a potentially lethal complication of hyperthyroidism
characterized by muscle paralysis and hypokalemia. It
is a well-known complication of thyrotoxicosis in 20-40
year old Asian men. The attack is characterized by recurrent, episodes of muscle weakness that range from mild
weakness to complete flaccid paralysis. Seldom cases
of total paralysis of respiratory, bulbar and ocular muscles have been reported. Patients usually experience the
attack after a heavy carbohydrate rich meal as they have
an exaggerated insulin response during oral glucose challenge. Our patient had the episode after her carb- rich
breakfast. Serum potassium level is usually < 3.0 mmol/
liter. Hypokalemia is the consequence of a massive shift
of potassium from the extracellular into the intracellular
compartment. This is related to increased sodium-potassium-adenosine triphosphatase pump activity in patient
with TPP. The enhanced ß-adrenergic response in thyrotoxicosis further enhances this pump’s activity.
Conclusion: TPP is a rare condition in non-Asians,
and the diagnosis at presentation is often delayed because
of the subtleness of the clinical features of thyrotoxicosis
and the similarities of the paralysis with other more common conditions. It is now being seen more frequently in
the Western world with the admixture of different ethnic
populations. Early diagnosis is crucial to prevent serious
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complications. TPP is a curable disorder that resolves
when euthyroid status is achieved.
Abstract #1030
THYROID FUNCTION AND VOLUME
DISORDERS CORRELATES WITH IQ IN
MENTALLY RETARDED CHILDREN
Hamid Reza Bazrafshan, MD, S. Vahedi, Gh. Jafari,
N. Bahnampour
Objective: Goiter is still an endemic health problem in
Gorgan after a decade of universal salt iodization in Iran.
Hypothyroidism has more complications in children than
adults. Developmental disorders of CNS are so important. This study proposed to determine that prevalence of
thyroid function and volume disorders and its correlation
with the IQ of mentally retarded (MR) children.
Methods: This cross-sectional study was carried out
on 120 mentally retarded students at two rehabilitation
centers in Gorgan, north of Iran. We excluded cerebral
palsy and major metabolic disease suffering patients from
this study. Thyroid volume was measured by an ultrasonography (US) specialist. IQ was evaluated by a standard questionnaire.
Results: The mean age of the children was 11.7 years.
Goiter prevalence in physical examination was 42% but
it was 84% in the US evaluation. Mean concentration of
TSH and T4 in all cases was 3.9 and 5.7 respectively. TSH
had a reverse linear correlation with IQ but T4 was opposite of this (P<0.05). 34 cases (28.3%) had a higher level
of TSH, 45 cases had low IQ scores, 42 had moderate
scores and 33 had high IQ scores.
Conclusion: We found that serum TSH and thyroid
volume have had a reverse correlation with IQ in MR children. Thyroid enlargement and hypothyroidism is more
prevalent in mentally retarded children than others. So a
decision should be made to screen and cure thyroid disorders in this high risk population. We should also consider
evaluating the iodine intake status, thyroid autoimmunity
and other causes of goiter in this population for future
investigation.
Abstract #1031
THE ENIGMA OF STRUMA OVARII
Kishore M. Lakshman, MD, MPH,
Beatrice M. DeMoranville, MD,
Lewis E. Braverman, MD, FACE
Case Presentation: A 60-year-old female with a history of depression and GERD was referred for the evaluation of an abnormally high thyroglobulin (TG) of 1040
ng/mL that was discovered serendipitously by her PCP
at the time of ordering a thyroid panel. Her TG antibodies were undetectable. She had a normal TSH (2.4 uIU/
mL), free T4 (1.1 mg/dL) and free T3 (282 pg/dL). The
patient had multiple symptoms such as fatigue, headache, nausea and lower extremity pain present for several
months. She denied abdominal or pelvic pain. A thyroid
ultrasound showed a normally appearing thyroid with no
focal abnormalities. A whole body I-123 scan revealed
a normal 24 hr uptake of 14.5 % that was entirely concentrated in the thyroid with no extrathyroidal uptake. A
pelvic ultrasound showed a 4.8 cm right adnexal mass
containing cystic and solid components. A laproscopic
right salpingo-oophorectomy was performed. Histology
revealed a benign struma ovarii accompanying an ovarian teratoma. Immunochemistry staining for thyroglobulin
was positive. One month following surgery, her TG was
down to 48.7 ng/mL (normal range: 1-55 ng/mL) and she
reported resolution of all her presenting symptoms.
Discussion: The typical presentation of a struma
ovarii is that of abdominal pain or a palpable abdominal/
pelvic mass that leads to imaging and eventually surgery.
A whole body I-123 may not reveal the diagnosis preoperatively, as in the above patient, due to concentration
of I-123 by the thyroid gland. Other vague symptoms as
reported by the patient have been documented, but it is
unclear whether they are secondary to the high TG levels. Uncommon presentations include vaginal bleeding,
ascites and pleural effusion (pseudo-Meig’s syndrome).
Hyperthyroidism from a functional struma ovarii occurs
only in about 5-15% of the cases. Malignant transformation is reported in 0.3- 5 % of cases with papillary carcinoma being the most common. Metastatic malignant
struma ovarii have also been reported.
Conclusion: Struma ovarii are difficult to diagnose
pre-operatively. Challenging case reports include struma
ovarii coexisting with Graves’ disease, non-toxic multinodular goiter, Hashimoto’s thyroiditis, and primary thyroid cancer. Benign struma ovarii may present with ascites
and elevated CA-125 levels mimicking a malignant ovarian neoplasm. Surgical resection for benign struma ovarii
is recommended but there is no consensus on the treatment of malignant disease: chemotherapy, surgical resection, radiation and radioiodine ablation following thyroidectomy have been described.
Objective: To report a case of struma ovarii and
review its pathophysiology.
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Abstract #1032
a second neoplasm may suggest a genetic background but
an incidental finding may also be involved.
Conclusion: There are several dysfunctions of the
genes that control the cell cycle reported in the pancreatic
as well as thyroid neoplasia. Whether the thyroid would be
systematically checked once a patient with NET came to
the attention of an endocrinologist is a challenging matter
to prove for the future.
NEUROENDOCRINE TUMORS AND
THYROID NODULES
Catalina I. Poiana, MD, PhD, FACE,
Mara Carsote, MD, Corina Chirita, MD,
Andrei Goldstein, MD, Adina Croitoru, MD,
Dan Peretianu, MD, PhD, Dana Terzea MD,
Simona Fica, MD, PhD, FACE
Abstract #1033
Objective: We report a series of three cases with
patients already known with different neuroendocrine
tumors where accidentally thyroid nodules were found.
Case Presentation: A 59-year-old female has a one
year history of a pancreatectomy for a 9 cm solid tumor
of the body and the tail. The pathological report pointed
rare mitosis (2-3/10 HPF). Positive immuno-staining is for
chromogranin, synaptophysin, neuronal specific enolase.
The diagnosis is well differentiated pancreatic neuroendocrine carcinoma. Increased serotonin (twice normal)
is normalized 3 months after therapy with octreotidum
LAR 20 mg/month. Also a left thyroid node of 3 cm is
discovered with normal thyroid function and calcitonin.
Total thyroidectomy is performed. The pathological exam
revealed a micro-follicular and trabecular embryo-fetal
adenoma. A 51-year-old male had 4 years ago a right hemicolectomy with L-T ileotransverse anastomosis for a polyploidy tumor of 4 cm, at the level of ileocecal valve, with
local invasion into the wall and local lymph nodes. The
immunohistochemistry was positive for chromogranin,
NK1. The PCNA proliferation marker was increased (5060%). In the present, the clinical exam discovered a left
thyroid node of 1 cm. The fine needle aspiration biopsy
suggested papillary carcinoma. The pathological exam
after total thyroidectomy confirmed it. Thyroid suppression therapy was started. Also 100 mCi of 131I was added.
A 70-year-old female had 2 years ago total gastrectomy
for gastric cancer with local lymph nodes invasion. The
histological exam revealed a tumor of 5 cm with features
of poor differentiated carcinoma. At age of 70, a large goiter was accidentally discovered. Thyroidectomy was performed and metastasis from a neuroendocrine tumor was
diagnosed. The immuno-hystological profile was positive
for synaptophysin, chromogranin A and negative for calcitonin and thyreoglobulin. The same phenotype was retrospectively analyzed in the gastric tumor. The value of ki67
was 25%. Therapy with octreotidum LAR 20 mg monthly
was started.
Discussion: In patients with neuroendocrine tumors,
the thyroid involvement is atypical, unless metastasis is
presented (except for the cases diagnosed from the beginning with the medullar thyroid carcinoma). The finding of
DETECTION OF THYROID CANCER IN
TWO PATIENTS WITH HYPERTHYROIDISM
Arinola Ipadeola, MBBS, Temilola Akande, MBBS,
Willliams Balogun, MBBS, Jokotade Adeleye, MBBS
Objective: To report two patients with hyperthyroidism who were also discovered to have thyroid cancer.
Case Presentation: A 68-year-old lady with a background history of hypertension, presented with a three week
history of recurrent vomiting and diarrhea. Examination
findings were in keeping with congestive cardiac failure
and atrial fibrillation. During the course of her admission,
she was noted to have an enlarged asymmetric thyroid
gland, periorbital puffiness, tachycardia and fine tremors
of the hands. Thyroid function test result was in keeping
with a diagnosis of hyperthyroidism. Thyroid ultrasound
scan showed a diffusely enlarged gland. Fine needle aspiration cytology (FNAC) was reported as consistent with
papillary carcinoma. A 42-year-old lady presented with a
day’s history of fever and joint pain. There was a background history of an anterior neck swelling and increased
protrusion of both eyes of eighteen months’ duration for
which she had being receiving treatment at another health
care facility. She had lost weight (4kg) had heat intolerance as well as hyperdefaecation. Clinical examination
revealed an asymmetric thyromegaly, tachycardia, a displaced apex beat, periorbital puffiness and tremors of the
outstretched hands. An impression of Hyperthyroidism
was made. Thyroid ultrasound scan showed a diffusely
enlarged gland while the FNAC showed features thought
to be suspicious of a malignant neoplasm. Both patients
were placed on anti-thyroid medications and have been
referred to the Consultant General Surgeon for total thyroidectomy in view of the FNAC reports.
Discussion: The coexistence of hyperthyroidism and
thyroid cancer had previously been considered an infrequent event, but recent literature suggests the incidence
is increasing. FNAC in both cases was done routinely as
part of investigations in evaluating persons who present
with goitres. This case report draws attention to the association between hyperthyroidism and thyroid cancer. The
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coexistence of thyroid cancer in the hyperthyroid patient
will certainly significantly influence the treatment options
and management plan as in the two cases presented.
Conclusion: Fine needle aspiration cytology is a simple and essential tool, especially when ultrasound guided
and should be done in all patients presenting with a goiter and hyperthyroidism. Nuclear scintigraphy may also
be helpful in the investigation of hyperthyroid patients, as
the presence of “cold” nodules may suggest malignancy &
guide FNAC. The association needs to be further explored
amongst Nigerians with regards to defining the risk factors, clinicopathologic features and outcomes.
Abstract #1034
ETIOLOGY OF ENDOGENOUS
HYPERTHYROIDISM IN TWO PATIENTS WITH
LONG STANDING HYPOTHYROIDISM
FT4 1.70, FT3 2.53 and thyroglobulin 195. Thyroglobulin
AB and Anti TPO AB were negative. Thyroid stimulating
AB 412 (0-129) and thyrotropin recptor AB 2.80 (0-1.75).
Graves’ disease causing hyperthyroidism was diagnosed.
Conclusion: Endogenous hyperthyroidism can
develop in patients with long standing hypothyroidism
due to various etiologies. Non-suppressed thyroglobulin
can differentiate endogenous hyperthyroidism from exogenous hyperthyroidism due to over dose of levothyroxine.
Non functional thyroid nodules may become functional
over time and cause endogenous hyperthyroidism especially in setting of Iodine loading .In autoimmune thyroid
disease lymphocytes can switch from producing thyroid
receptor blocking to stimulating antibodies over time and
can cause endogenous hyperthyroidism after long standing hypothyroidism.
Abstract #1035
Saba Faiz, MD, Tipu Saleem, MD, MS, FACE,
Abid Yaqub, MD, FACP, Parsana Santhanam, MD
Objective: To describe etiology and diagnostic work
up of endogenous hyperthyroidism in two patients who
have long standing hypothyroidism.
Case Presentation: A 48-year-old lady admitted to
psychiatry ward with suicidal ideation. She has hypothyroidism for 20 years. She was taking synthroid 250
mcg/day for many years with normal TFTs one year ago.
She has a recent contrast enhanced CT scan of spine for
surveillance of spinal cord tumor. Physical examination
revealed pulse 101, temp 98.1, blood pressure 116/76 and
non-tender enlarged goiter with a nodule on left side. TFTs
showed TSH 0.015 (0.3-4.4) and FT4 5.38 (0.75-2.0).
Synthroid was stopped, repeat TFTs in a week showed
TSH<0.004, FT4 1.44 and FT3 2.28 (1.8-4.2). TFTs in 2
months showed TSH 0.016, FT4 1.95 and thyroglobulin
13. Anti TPO AB, anti thyroglobulin AB, thyroid stimulating AB and thyrotropin receptor AB were negative. She
had low I-123 uptake of 2.3 % at 24 hours while 24 hour
urine iodine 786 ug/spec (100-460) was high .Neck US
showed multinodular goiter. Toxicity of multinodular goiter was attributed to recent iodine loading in form of contrast material used in recent CT scan. FNAC of left sided
3 cm nodule was categorized as atypical cells and pt had
total thyroidectomy. Histopathology showed benign nodular hyperplasia. A 86-year-old lady presented with CHF
and atrial fibrillation. She had long standing hypothyroidism. She was on a stable dose of synthroid 50 mcg/day.
She denied any symptoms of hypothyroidism or hyperthyroidism. She had temp 97.9, HR 90, BP 120/60 and palpable thyroid gland without any discrete nodule or bruit.
TFT’s showed TSH .025 and FT4 2.02. Synthroid was
stopped for a week and repeat testing showed TSH 0.067,
GRAVES’ DISEASE PRESENTING AS
TAKOTSUBO CARDIOMYOPATHY IN A
YOUNG ADULT WOMAN
Theresa Adadzewa Fynn, MD, Wolali Odonkor, MD,
Gail Nunlee-Bland, MD, Vijaya Ganta MD, Suliman
Abdelwahab, MD
Objective: To describe thyrotoxicosis as a cause of
myocardial stunning in a case of Graves’ disease.
Case Presentation: A forty year-old African American
woman bus attendant, with past medical history significant for eczema, sinusitis and bronchitis was admitted
to the intensive care unit for acute onset chest pain. Pain
was located in the central chest, 8/10 in intensity, sharp,
radiating to both shoulders with associated dyspnea. She
admitted to palpitations and recurrent leg swelling in the
past few months but denied orthopnea, weight loss or heat
intolerance. She was found to have unexplained increase
in Troponins- (32ng/ml) and normal exercise tolerance,
with no coronary artery disease risk factors and negative drug screen. The EKG showed ST- T wave changes
but was inconsistent with acute ST elevation myocardial
infarction (MI). Unable to adequately explain the elevated
troponins, a cardiac catheterization was performed which
showed clean coronaries with apical hypokinesis. A thyroid panel revealed TSH-0.02 mu/ml, T3-367 ng/dl, total
T4-20.19 mc/dl, T3UP 43.5% and TSI 140% consistent
with Graves’ disease. She was managed with methimazole
and did well.
Discussion: First described in 1991, Takotsubo is
generally characterized by transient systolic dysfunction
of the apical and/or mid segments of the left ventricle
that mimics MI, but in the absence of significant coronary artery disease. The following are the proposed Mayo
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Clinic diagnostic criteria, all four of which are required for
the diagnosis: Transient hypokinesis, akinesis or dyskinesis of the left ventricular mid segments with or without
apical involvement. The regional wall motion abnormalities typically extend beyond a single epicardial coronary
distribution. Absence of obstructive coronary disease
or angiographic evidence of acute plaque rupture. New
electrocardiographic abnormalities (either ST-segment
elevation and/or T-wave inversion) or modest elevation
in cardiac tropinins. Absence of pheochromocytoma or
myocarditis. Conservative treatment with hydration and
resolution of the stressor, usually results in rapid resolution of symptoms and EKG changes. The patient met the
above criteria and her symptoms resolved after conservative treatment with hydration and treatment of the thyrotoxicosis with methimazole.
Conclusion: Reversible left ventricular dysfunction
precipitated by thyrotoxicosis has been reported and the
mechanism can be explained by exaggerated sympathetic dysfunction. In conclusion all patients presenting
with Takotsubo cardiomyopathy must be evaluated for
hyperthyroidism.
Abstract #1036
HEMOLYTIC ANEMIA ASSOCIATED WITH
METHIMAZOLE TREATMENT IN A PATIENT
WITH GRAVES’ DISEASE
Raluca-Alexandra Trifanescu, MD,
Madalina Vasilica, MD, Serban Radian, MD,
Catalina Poiana, MD, FACE
dL). Thyrotoxicosis was slightly improved (TT3=250
ng/dL, TT4=14.3 µg/dL). Methimazole was stopped and
lithium carbonate 450 to 600 mg/day was started, with
successful control of thyroid hormones levels (TT3=183
ng/dL, TT4=12 µg/dL) and without side effects (lithaemia= 0.38; 0.37 mEq/L). Intravenous corticotherapy
(Methylprednisolone 125 mg/day, 3 days) followed by
oral corticosteroids (Prednison 1 mg/kgc/day, gradually
decreasing the dose) and folic acid 5 mg/day successfully
controlled hemolytic anemia: hemoglobin increased from
13 g/dL to 14 g/dL; there was a gradual decrease up to
normalization of both total bilirubin (3.62; 1.59; 1.07 mg/
dL) and unconjugated bilirubin (2.82; 0.96; 0.75 mg/dL).
Total thyroidectomy was safely performed and the patient
had an uneventful recovery.
Discussion: TSH was measured by immunoradiometric assay, TT3, FT4, TT4 by chemiluminescence, TRAb
by MEIA. Hematological side effects of antihyroid drugs
such as agranulocytosis, aplastic anemia and thrombocytopenia are well known, but hemolytic anemia was very
seldom reported. Acquired immune hemolytic anemia
due to methimazole-dependent red blood cell antibodies
(as already been reported for carbimazole) which reacted
with all erythrocytes or concomitant autoimmune hemolytic anemia revealed by methimazole could be involved
in pathogenesis.
Conclusion: This is the first case report of hemolytic anemia associated with Methimazole in Romania. It
should be kept in mind that hemolytic anemia may be a
rare complication associated with methimazole therapy.
Abstract #1037
Objective: To present a case of hemolytic anemia
associated with Methimazole treatment in a patient with
Graves’ disease.
Case Presentation: N.L, male, 51 years, initially presented with severe Graves’ disease (TSH< 0.03 mIU/L,
FT4>100 pmol/L, TT3>500 ng/dL, TRAb=7.62 IU/L)
without significant ophthalmopathy. Hemoglobin was
14.7 g/dL and alkaline phosphatase slightly increased
(149 IU/L). Antithyroid drugs were started (Methimazole
30 mg/day). After 2 weeks Methimazole treatment, the
patient presented with pruritus, artrhalgia and urticaria,
unresponsive to the replacement of Methimazole with
Carbimazole. Clinical exam revealed scleral jaundice,
macular rash, liver enlargement without splenomegaly.
Biochemical data showed hemolytic anemia: hemoglobin
decreased from 14.7 to 13 g/dL, increased reticulocytes
(3.1%), increased total bilirubin 3.62 mg/dL with increased
unconjugated bilirubin 2.82 mg/dL. Both transaminases
were normal. Thrombocytes were normal (165,000/mm3),
coagulation tests (INR, APTT) were normal, excluding Evans’ syndrome. Sideremia was normal (85.1 µg/
PLASMAPHERESIS AND CHOLESTYRAMINE IN
THE TREATMENT OF THYROID STORM
Gregory D. Cook, MD, Diane Biskobing, MD
Objective: To describe a case where cholestyramine
and plasmapheresis were used with conventional treatment to rapidly lower thyroid hormone levels.
Case Presentation: A 25-year-old woman with
Graves’ disease presented for treatment of hyperthyroidism. Prior treatment with PTU had been stopped due to
financial difficulties. She was admitted to the hospital after
jaundice developed within weeks of resuming PTU. On
initial exam: BP 156/72, HR 148, T 102. Pertinent findings
included marked jaundice, diffusely enlarged goiter with
bruit, tachycardia, and a hyper-pigmented papular rash on
abdomen. Lab data: TSH <0.01, total T4 24.4 (4.5-12.5),
free T4 5.1 (0.8-1.8), total T3 653 (60-181), albumin
3.4, alk. phos. 260, total bilirubin 27, conj. bilirubin 20,
AST 102, ALT 45. Initial treatment with hydrocortisone
and propranolol resulted in temporary improvement. On
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day 3 her condition rapidly deteriorated and efforts were
made to prepare her for urgent thyroidectomy. Treatment
included methimazole 30mg daily, SSKI 250mg Q 8H,
hydrocortisone 100mg IV Q8h, esmolol infusion, cholestyramine 4 g Q 6h, and plasmapheresis. Prior to plasmapheresis on day 4, free T4 was 3.3. After one plasmapheresis session, free T4 decreased to 2.4. Subsequently,
free T4 decreased to 1.3 on day 6 and to 0.6 on day 8. In
spite of efforts to control her hyperthyroidism, she did not
survive. Hospital course was complicated by pulmonary
hemorrhage, fungemia, renal and liver failure.
Discussion: Thyroid storm can be life-threatening,
with a mortality rate of 20-30%. Traditional therapy
includes thionamides, inorganic iodine, beta-blockers, and
steroids. Some clinical situations require rapid lowering of
thyroid hormone levels. In hyperthyroidism the enterohepatic circulation of thyroid hormone is increased. In this
setting cholestyramine, a bile acid sequestrant, has been
shown to rapidly lower thyroid hormones by binding and
removing thyroid hormone from the enterohepatic circulation. Thyroid hormone is over 99% protein bound and
plasmapheresis lowers thyroid hormone levels by removing protein bound hormone. Additionally, as the plasma is
exchanged with fresh frozen plasma or albumin solutions,
new binding sites are available, thereby decreasing free
hormone levels. With the addition of plasmapheresis and
cholestyramine therapy in our patient, thyroid hormone
levels were rapidly decreased to normal levels in 2-3 days.
Conclusion: Cholestyramine and/or plasmapheresis
can be added to the treatment of severe hyperthyroidism to
facilitate more rapid lowering of thyroid hormone levels.
Abstract #1038
HYPERTHYROIDISM AND BIPOLAR DISORDER.
WHAT IS THE LINK?
Juan Pablo Brito, MD, Andrea Sosa, MD
Objective: Lithium has been used in the treatment of manic and hypomanic depressive disorders.
Approximately, 5 to 35% of patients receiving lithium
develop biochemical hypothyroidism. The etiology of this
condition can be explained by the inhibitory effect of this
drug on thyroid hormonal release, thyroglobulin iodidation and coupling reaction. On the other hand, only few
cases of hyperthyroidism related to lithium have been
reported in the literature and the etiology has not been
explained adequately.
Case Presentation: A 63-year-old male with prior
history of bipolar disorder under medical treatment presents to his Primary Care Doctor complaining of increasing
episodes of severe anxiety all day long for two months
beyond his baseline levels. During physical exam he was
noted to have mildly enlarged and palpable thyroid without nodules and negative exophtalmos. Further work-up
demonstrated low TSH, elevated free T4, elevated thyroglobulin and decreased 24-hour uptake. In light of the long
treatment with lithium, the diagnosis of lithium associated
thyroiditis was suggested. Lithium was discontinued and
patient was switched to Valproic acid. Thyroid function
and iodine uptake at 24 hours done 2 months later were
normal.
Discussion: This case enhances the importance of
a complete history and detailed physical exam in the
primary care setting. This case also illustrates that for
patients under lithium treatment, thyroid hormonal follow
up is essential. The main lesson, however, is the recognition of the variety of thyroid pathologies associated with
lithium ranging from hypothyroidism to hyperthyroidism.
Abstract #1039
“GREYHOUND THYROTOXICOSIS”:
COINCIDENTAL SUBACUTE THYROIDITIS IN
THE SETTING OF UNDIAGNOSED
GRAVES’ DISEASE
Objective: To present a case of thyrotoxicosis (TS)
and goiter discovered after neck trauma and outline the
course of subsequent autoimmune-mediated hypothyroidism (HT).
Case Presentation: A 59-year-old white female developed cervical swelling and right-sided tenderness after her
pet greyhound stepped on her neck. Ultrasonography (US)
demonstrated a 3.6-cm irregular mass on the right with
normal L. lobe. Laboratory testing: TSH 0.009 µIU/mL
(0.35-5.5), total T4 18.7 µg/dL (4.7-13.3), total T3-391
ng/dL (85-205). Within 21 days, the tenderness abated,
but she developed fullness on the L. side and US revealed
an inhomogenous appearance (no absent vascularity by
power Doppler (PD) examination), with reduction in
R. lobe volume (no nodularity) and increase in L. lobe
volume. TS persisted [TSH <0 .01. free T4-2 .38 ng/dL
(0.89-1.76), free T3-6.5 pg/mL (2.3-4.2)], with support
for Graves’ disease (GD) [thyroid peroxidase Ab (TPO)
Ab 243 IU/mL (0-34), TSH receptor Ab (TRAb) 26 IU/L
(0-1.75]. She was placed on methimazole at 5 mg daily,
but within 6 weeks time, she developed HT [TSH 130.79,
free T4 0.29, free T3 0.9, TPO Ab 306, TRAb 37.18,
thyroglobulin (Tg) <0 .5 ng/mL (0.5-55), Tg Ab 66 IU/
mL (0-40), thyroid-stimulating immunoglobulin (TSI)
130% (0-139)]. She was started on levothyroxine at 25
mcg daily, as HT persisted. After 4 weeks of treatment:
TSH 152.52. Free T4 0.19, TRAb 36.24, TSI 84% and US
showed decrease in thyroid volume, with no substantial
– 164 –
internal vascularity. Euthyroidism was achieved on 88
mcg daily (TSH 1.06, free T4 1.6, TRAb >40, TSI 73%).
Discussion: It is coincidental that she has had clear
evidence of GD but experienced thyroiditis (as evidenced
by absence of intense vascularity within the thyroid by
PD), possibly from the pressure on her neck by the greyhound. While profound HT developed rapidly on lowdosage of thyrostatic drug therapy (TDT), it is unlikely
that such a short duration of therapy could have induced
this remission. Subsequent testing indicated persistence
of TRAb, but without overwhelming TSI activity. It is
posited that conversion from TSH receptor stimulatory
antibodies to TSH receptor blocking antibodies occurred,
leading to HT.
Conclusion: The exact etiology for TS is often easily
discerned but in our case, the coexistence of supportive
tests for GD with US evidence to the contrary portrayed a
mixed picture. The timeframe for the subsequent HT was
neither typical for subacute thyroiditis or remission of GD
on TDT. Simultaneous measurement of TRAb and TSI
proved beneficial in clarifying the diagnosis.
evaluation of post thyroidectomy cases of differentiated
thyroid carcinoma. The presence of the unique sodium
iodide symporter (NIS) in the basolateral surface of thyroid follicular cells resulting in sodium-dependant active
transport of iodine, its organification and retention has
been successfully exploited in investigation as well as
targeted treatment of various thyroid disorders with 131I.
The thyroid and the thymus are embryologically-related
organs and thymic ectopy in the thyroid has been reported
in mice as well as adult humans with and without thyroid disease. While ectopic thyroid tissue in the thymus
could explain the 131I uptake in the mediastinum, the exact
explanation for thymic 131I uptake remains unknown.
Conclusion: Whole body 131I scans can have false
positive uptake due to thymus even at extremes of age.
While 131I uptake has been described in young patients
with thymic hyperplasia, we present here 2 cases of
elderly patients with false positive uptake in thymus. With
aging population and increasing incidence of thyroid carcinoma, physicians need to be aware of this entity to avoid
over-treatment.
Abstract #1040
Abstract #1041
THYMIC UPTAKE OF IODINE-131 IN
ANTERIOR MEDIASTINUM
PAPILLARY THYROID MICROCARCINOMA
ASSOCIATED WITH BENIGN THYROID TISSUE
IN THE DELPHIAN LYMPH NODE
Sunil Asnani, MD, FACE, Anupam Ohri, MD
Objective: To describe 2 cases of 131I uptake by
thymus.
Case Presentation: An 82-year-old man with follicular carcinoma of thyroid gland was treated with total
thyroidectomy, remnant ablation and TSH suppression.
Follow up thyroid sonogram was negative for any residual/recurrent disease in the neck. Stimulated thyroglobulin (Tg) level 1 year later was <0.5 ng/ml. Concurrent
whole body 131I scan (WBS) revealed a focus of minimal
to mildly increased tracer uptake anteriorly at the level of
superior mediastinum. Chest X ray and CT chest did not
reveal any abnormality. A 78-year-old woman with papillary thyroid carcinoma was treated with total thyroidectomy, remnant ablation and TSH suppression. Serial thyroid sonograms were negative for any residual/recurrent
disease in the neck. Stimulated thyroglobulin (Tg) level
1 year later was 0.2 ng/ml. Concurrent WBS revealed a
focus of minimally increased activity at superior mediastinum. CXR or CT chest did not reveal any lymphadenopathy. PET scan did not show any abnormal activity.
No further intervention was done. Both patients are being
monitored with serial sonogram and Tg levels; they continue to be in remission.
Discussion: WBS is a highly accurate procedure
that plays a pivotal role in clinical decision making in the
Emad Naem, MD, Mae Sheikh-Ali, MD,
Abdul-Razzak Alamir, MD
Objective: To report a case of benign thyroid tissue in
the Delphian lymph node of a patient with papillary thyroid microcarcinoma.
Methods: We present a case report, including clinical and laboratory data as well as surgical histopathology
in a women with papillary thyroid microcarcinoma and
concomitant benign thyroid tissue in the Delphian lymph
node.
Results: A 41-year-old female with family history of
thyroid cancer presented with thyroid nodules. Thyroid
US showed multiple small hypoechoic nodules in both
thyroid lobes. Her thyroid function tests were normal.
Patient underwent total thyroidectomy and prelaryngeal
lymph node dissection. Surgical pathology showed papillary microcarcinoma (0.3 cm) located in the left lobe of
thyroid. The Delphian node pathology revealed lymph
tissue with two microscopic foci of cytologically benign
appearing thyroid inclusions. The inclusions immunostaining with Thyroglobulin and TTF-1 was positive and
consistent with thyroid origin. No thyroid cancer metastasis was found in the other 2 lymph nodes that were
removed.
– 165 –
Discussion: Papillary thyroid microcarcinomas
(PTMC) generally have an excellent prognosis (Mazzaferri
et al). Lobectomy without 131I thyroid remnant ablation
is reasonable treatment for the low-risk group with unifocal PTMC smaller than 1 cm. The ATA recommends 131I
remnant ablation for all patients with TNM stage III and
IV cancer and for all patients with stage II cancer who are
younger than 45 years. The ATA also recommends 131I
remnant ablation for most patients 45 years or older with
stage II cancer and selected patients with stage I cancer,
especially those with multifocal disease, nodal metastases,
extrathyroidal or vascular invasion, and/or more aggressive histologies. The patient presented above is considered
stage one by TNM classification. She had a total thyroidectomy which seems an appropriate operation for her.
Aggressive therapy with 131I remnant ablation would not
be recommended by the ATA criteria. However, she has
ectopic benign thyroid tissue in the Delphian lymph node.
The prevalence of the incidental finding of thyroid inclusions in neck dissections ranged from the 0.6% estimated
by Gerard-Marchant10 and the 1.0% determined by Clark
et al. It does not necessarily indicate the need for aggressive therapy (Leo´n et al). Development of primary papillary thyroid carcinoma from malignant transformation
of benign intranodal thyroid inclusions has been reported
(Wang et al). The risk of malignant transformation seems
to be higher in this patient since she did have PTMC as
well as a family history of thyroid cancer. Based on that,
131I thyroid remnant ablation was recommended to this
patient.
Conclusion: Ectopic thyroid tissue in the lymph node
is a rare entity. The need for aggressive therapy is not necessarily indicated. However, in high risk patients, malignant transformation may occur and aggressive therapy
should be considered.
Abstract #1042
SELENIUM SUPPLEMENTATION IN THE
TREATMENT OF HASHIMOTO’S THYROIDITIS
Konstantinos A. Toulis, MD, MSC,
Athanasios D. Anastasilakis, MD, PhD,
Thrasivoulos G. Tzellos, MD, MSc,
Dimitrios G. Goulis, MD, PhD,
Dimitrios Kouvelas MD, PhD
Objective: Evidence suggests that selenium (Se) supplementation could be useful as an adjunctive therapy to
levothyroxine (LT4) in the treatment of Hashimoto thyroiditis (HT). However, the benefit from this supplementation in terms of clinical practice remains unclear and thus,
no evidence-based recommendation regarding Se supplementation in the treatment of HT is available yet.
Methods: Systematic review and meta-analysis of
relevant randomized, placebo-control, blinded trials.
Results: Patients with HT assigned to Se supplementation for three months demonstrated significantly lower
thyroid peroxidase autoantibodies (TPOab) titers (four
studies, random effects WMD: -271.09, 95% CI: -421.98
to -120.19, p < 10-4) and a significantly higher chance
of reporting an improvement in well-being and/or mood
(three studies, random effects RR: 2.79, 95% CI: 1.21 to
6.47, p = 0.016) as compared to controls. Natural course
of HT, demands in levothyroxine (LT4) replacement therapy and ultrasonographic thyroid morphology were found
either unaltered or underreported.
Discussion: Based on the best available evidence, Se
supplementation is associated with a significant decrease
in TPOab levels at 3-months and with improvement in
mood and/or general well-being. Evidence suggests a different pattern of response to Se supplementation in HT
relative to baseline TPOab levels that, if confirmed, could
be used to identify which patients would benefit most
from treatment.
Conclusion: An improvement in thyroid function and
morphology should be demonstrated before Se routine
supplementation could be recommended in HT.
Abstract #1043
ATROPHIC THYROIDITIS ASSOCIATED WITH
SPURIOUS CHRONIC KIDNEY DISEASE
Sandra Omozehio Iwuala, MBBS,
Ibilola A. Sanusi, MBBS,
Olufemi A. Fasanmade, MBBS, FWACP
Objective: To present a case of hypothyroidism complicated by low creatinine clearance and diagnosed with
chronic kidney disease.
with history of heavy menstrual losses of eight months
associated with facial swelling and cold intolerance both
of six months duration. A detailed history was obtained,
followed by a full physical examination. Laboratory
assessment included lipid profile, full blood count, electrolyte, urea and creatinine and thyroid function tests. The
history also revealed easy fatigability, reduced energy
drive, slowed mental activity, cold intolerance and periorbital swelling. There were no urinary symptoms. Physical
Examination revealed a woman, who looked older than
her stated age with periorbital fullness and palor. She had
no pedal edema or goiter. Her BMI was 28kg/m2 and her
waist hip ratio 0.72. Her TSH was 76.22miu/l, free T3
1.5pmol/l and free T4<1.9pmol/l. Lipid profile revealed
increased total cholesterol and LDL cholesterol while
HDL cholesterol and triglycerides were within normal
– 166 –
limits. ECG showed bradycardia and low voltages and
her PCV was 28%. Anti thyroid anti bodies were strongly
positive. Creatinine clearance was 36.2ml/min. Other lab
results were within normal limits. A diagnosis of atrophic
thyroiditis with chronic kidney disease was made. She
was placed on L-thyroxine, and after 3 months became
euthyroid and her creatinine clearance became normal.
Discussion: The causes of hypothyroidism in
Nigerian adult practice are mainly post surgery, Sheehans
syndrome and post radiotherapy. Spontaneous hypothyroidism appears to be rare in our setting. Thyroid hormones can have clinically relevant effects on the glomerular filtration rate as reflected in the serum creatinine and
creatinine clearance. Hypothyroidism has also been found
to be associated with acute renal failure. The marked
variation in serum creatinine and thus creatinine clearance
observed in the index case with her thyroid status has been
documented in literature but may not be widely known.
Conclusion: Hypothyroidism with elevated serum
creatinine may not be due to kidney disease.
Abstract #1044
INITIATION OF TREATMENT OF WELLDIFFERENTIATED THYROID CANCER
DURING PREGNANCY: A CASE REPORT
Jennifer R. Pedersen-White, DO, FACE
Objective: To report a case of well differentiated thyroid cancer in a 23-year-old pregnant female and to review
the treatment she received during and after her pregnancy.
Case Presentation: A 23-year-old female was
referred to the endocrinology clinic for evaluation of an
incidentally discovered thyroid nodule (discovered in
March of 2007 when a CT of the head was performed
after a motor vehicle accident). The nodule was reported
to be a hypodense, 3.3 cm x 3.2 cm x 3.0 cm mass which
compressed and deviated the trachea to the right. Thyroid
US performed 4/17/07 revealed a 3.0 cm x 2.3 cm x 2.9
cm heterogeneous nodule with a hypoechoic rim which
deformed and expanded the contour of the thyroid. Fine
needle aspiration biopsy (FNAB) of left thyroid nodule
on 4/25/09 revealed papillary thyroid cancer. There was
no history of radiation exposure and no family history of
thyroid cancer. The patient was scheduled to undergo total
thryoidectomy in May of 2007, but was postponed by the
patient until July of 2007. In mid-June of 2007, the patient
became pregnant. Despite this, she verbalized a strong
desire to undergo thyroidectomy during her pregnancy; at
14 weeks gestation this was performed. Surgical pathology
revealed a 3.3 cm papillary thyroid cancer, follicular variant with no nodal involvement but with evidence of vascular invasion. The patient was maintained biochemically
euthyroid on Synthroid 150 mcg daily postoperatively. In
March of 2008, the patient delivered a healthy term infant.
In April of 2008, after she had stopped breastfeeding, the
patient was admitted for inpatient I-131 ablation.
Discussion: Although this patient was not pregnant
at the time of diagnosis, it is recommended that thyroid
nodules discovered during pregnancy be evaluated in the
same manner as in non-pregnant women. FNAB can be
performed for evaluation dominant nodule(s) discovered
during pregnancy (scintiscan/radioactive isotopes, however, must be avoided). Well differentiated thyroid cancers affect approximately 1 in 1000 pregnant women.
Evidence suggests that the prognosis of differentiated
thyroid cancer in pregnancy is similar to that occurring
in non-pregnant women of similar age. Optimal timing
for thyroidectomy in a pregnant woman is controversial.
Some authors advocate surgery during pregnancy (due
to concerns that human chorionic gonadotropin release
during pregnancy can accelerate growth of thyroid carcinomas). Others advocate postponing surgery until after
delivery (citing prognosis similar to that in non-pregnant
women and concerns of potential maternal/fetal complications). Thyroidectomy can safely be performed during
the second trimester of pregnancy (thus avoiding potential
teratogenic effects of surgery performed during the first
trimester and risk of preterm labor associated with surgical procedures performed in the third trimester).
Conclusion: Treatment options for well-differentiated thyroid cancer in pregnancy include surgical resection during the second trimester or delay of surgery until
after delivery. Radioiodine scans and treatment should be
delayed until after delivery and cessation of breastfeeding.
Abstract #1045
CALCITONIN-NEGATIVE NEUROENDOCRINE
TUMOR OF THE THYROID (CNNETT):
A DISTINCT CLINCAL ENTITY
Saima O. Farghani, MD, Tomer Davidov, MD,
Ly Ma, MD, Nicola J. Bernard, MD, S. Trooskin, MD,
L.F. Amorosa, MD
Objective: Medullary thyroid carcinoma (MTC) is a
neuroendocrine tumor arising from the parafollicular cells
(C-cells) of the thyroid gland. Calcitonin is secreted from
C-cells and therefore serves as a tumor marker for medullary thyroid cancer. Here we present a case of a calcitoninnegative neuroendocrine tumor of the thyroid (CNNETT),
arising from thyroid follicular cells. The differentiation
between MTC and CNNETT is important as the management may differ.
Case Presentation: A healthy 40-year-old woman
presented with an incidental right thyroid nodule on
– 167 –
MRI of the cervical spine. Ultrasound revealed a solitary hypoechoic 2.0 cm right thyroid nodule. Fine needle
aspiration showed findings suspicious for a poorly differentiated carcinoma with neuroendocrine differentiation. Staining for calcitonin was negative, arguing against
MTC. Stains were positive for CK8, CK18, thyroglobulin,
synaptophysin and pankeratin, suggesting that the tumor
was arising from follicular cells. The serum calcitonin and
the patient’s RET-oncogene mutation assay were negative.
Calcium level was normal at 9.8, and her parathyroid hormone level was normal at 35. Urine VMA and metanephrines were negative. The patient had no family history of
any endocrine disorder. A CT of the head, chest, abdomen,
and pelvis showed no suspicious lesions. There was no
evidence of lymphadenopathy based on examination and
neck MRI. PET scan was negative. She underwent total
thyroidectomy. Final pathology showed a well differentiated 1.5cm neuroendocrine tumor confined to the thyroid
gland. No mitotic activity or vascular invasion was identified. Calcitonin staining was negative but thyroglobulin
and synaptophysin were positive. She did not receive
iodine-131 or any adjuvant treatment and is disease free
on 6 month follow-up.
Discussion: Neuroendocrine tumors (NET) arise
from the embryonic neural crest and are present in many
organs, especially the midline organs including the esophagus, stomach, pancreas, intestine, and lung. Less common sites of NET are the pituitary, adrenal, skin and thyroid (MTC). Neural crest tissue form calcitonin-producing
C-cells that migrate and fuse with the primordial thyroid
gland. These are the cells that rise to medullary carcinoma.
In our case, the NET of the thyroid was calcitonin-negative and positive for markers of follicular thyroid cells,
arguing for a NES arising from the diffuse neuroendocrine
system of the thyroid rather than from C- cells. This distinction between MTC and CNNETT is important as the
treatment and prognosis may differ.
Abstract #1046
ARE VETERANS EXPOSED TO AGENT ORANGE
MORE LIKELY TO GET GRAVES’ DISEASE?
in VA Network 2 (upstate New York). We compared the
frequency of diagnosis of thyroid cancer, nodules, hypothyroidism and Graves’ disease in Veterans classified as
exposed (n=19,709) or not exposed (n=50,913) to AO.
Between groups, differences in race, smoking history, and
diabetes mellitus (DM) were first assessed with chi-square
tests and t tests, and then with multivariate logistic regression. The odds ratios (OR), corresponding 95% confidence
intervals (CI), and p-values (with/without Bonferroni correction) were determined for each condition.
Results: All the Graves’ patients were male (annual
incidence of Graves’ disease in men has been estimated at
~5-8/100,000). Graves’ prevalence in Veterans exposed to
AO was three times that in the unexposed group. (18/19709
vs. 15/50913 in the unexposed group; OR=3.1023, 95%
CI=1.563-6.159, p=0.00128). Interestingly, if the more
conservative Bonferroni correction was not used, hypothyroidism appeared to be decreased in those exposed to
AO (597/19709 vs. 1733/50913 in the unexposed group;
OR=0.344, 95% CI=0.806-0.97, p=0.013). The prevalence of thyroid cancer or nodules between the two groups
was not statistically different. In a multivariate logistic
regression model, AO exposure was the most important
predictor of Graves’ disease, OR=3.23, 95% CI=2.883.58, p<0.001. Age, smoking and DM were not significantly associated, although smoking history was almost
universal.
Discussion: 2,3,7,8- tetrachlorodibenzo- p- dioxin
(TCDD), a contaminant in Agent Orange, binds to AhR
(aryl hydrocarbon receptor) extremely tightly, and causes
prolonged activation of genomic and non-genomic
pathways involved in development, oncogenesis and
metabolic disorders. In mice, AhR can regulate the differentiation of regulatory T cells and of T cells that produce interleukin-17, and AhR ligands like TCDD can
modulate autoimmunity (Nature 453:65-71, 2008; J.
Immunol.182:6576-6586, 2009).
Conclusion: Despite the limitations associated with
retrospective chart reviews and studying an uncommon
disease, in view of known immune modulating effects of
TCDD, the prevalence of Graves’ disease in AO exposure
warrants further investigation.
Abstract #1047
Ajay Varanasi, MD, Toufic Abdo, MD, David Kasinski,
Amy O’Donnell, MD, Stephen Spaulding, MD
Objective: Environmental factors can increase the
prevalence of autoimmune diseases.
Methodology: Most Vietnam era Veterans have been
assessed for possible Agent Orange (AO) exposure. In the
summer of 2008 we reviewed the prevalence of major thyroid diagnoses in the Veterans Administration (VA) electronic medical record database beginning in 1996 for veterans born between 1925 and 1950 who received treatment
CASE REPORT - THYROIDITIS AFTER
NECK SURGERY
Radha Andukuri, MD, Laura Armas, MD,
Andjela Drincic, MD, Shalini Bichala, MD
Objective: To discuss the possibility of thyroiditis
after neck surgery. Traumatic thyroiditis was reported after
seat belt injuries and also after vigorous thyroid palpation.
– 168 –
Post-operative thyroiditis was reported after neck exploration for parathyroidectomy and thyroidectomy. However,
it was not reported after other kinds of neck surgery.
Case Presentation: We report here a 71-year-old
Caucasian lady who presented to the hospital with atrial
fibrillation after cervical spine surgery. She has a history
of atrial fibrillation, rate-controlled on metoprolol and on
chronic anti-coagulation therapy. Thyroid function tests in
the past six months were in hypothyroid range with TSH
anywhere between 5.4 to 6.97 mIU/ml prior to surgery. She
was not started on any replacement. She had cervical diskectomy through an anterior neck approach. She presented
with atrial fibrillation about 8 days after surgery. Her TSH
was 0.06uIu/ml, free T4 was 3.55ng/dl and freeT 3 was
5pg/ml. Thyroid peroxidase antibodies, thyroid stimulating immunoglobulins were negative. Thyroid ultrasound
showed bilateral hypoechoic nodules measuring 1cm and
1.3cm with normal vascularity. Thyroid uptake and scan
was done for evaluation of hyperthyroididsm. Four hour
uptake and 24-hour uptake were low at 1.7% and 1.7%
respectively consistent with thyroiditis. Her atrial fibrillation was controlled with metoprolol and follow-up thyroid
function tests showed a gradual restoration to euthyroid
status post-operatively. Her TSH at 4 weeks after surgery
was 0.26 mIU/ml and freeT4 was 1.2ng/dl.
Conclusion: Thyroiditis can occur after a number of
neck surgeries including neuro-surgery and physicians
should be aware of this. Patients should be educated about
the symptoms of hyperthyroidism and thyroid function
tests be checked with any suspicious symptoms.
Abstract #1048
patients (55.1%) received 30 mg of antithyroid drug.
Treatment was changed to lithium carbonate in 30.4% of
patients, and to radioiodine in 69.6%. All patients were
treated with reverse isolation, and broad spectrum antibiotics. Twelve (40%) patients received granulocyte colony
stimulating factor. The mean treatment period with antithyroid drugs before agranulocytosis was 13 weeks. In
this case series, the overall mortality was 13.3%.
Discussion: Agranulocytosis caused by antithyroid
drugs was 0.58% higher than previous reports. The only
drug used in these patients was thiamazole, propilthiouracil not available in our country. Most patients are female
because the population our hospital is predominantly
women hospitalized. It was found that two patients, who
developed, developed Agranulocytosis at doses less than
20mg. The recovery is approximately 2 to 3 weeks after
the cessation of the drug, we found a recovery time of 10
days.
Conclusion: Agranulocytosis is the most feared
side effect of antithyroid drugs. In the largest series,
agranulocytosis occurred in 0.35% of patients receiving
methimazole. Most cases occur within the first 90 days
of treatment. Fever and sore throat are the most common
presenting symptoms of agranulocytosis, and the administration of G-CSF may shorten the time to recovery and
length of hospitalization in patients with agranulocytosis
due to antithyroid drug.
Abstract #1049
HURTHLE CELL THYROID CARCINOMA
Naga M. Yalla, MD,
L. Raymond Reynolds, MD, FACP, FACE,
Deepa Taneja, MD
CLINICAL CHARACTERISTICS OF PATIENTS
WITH AGRANULOCYTOSIS INDUCED BY
ANTITHYROID DRUG
Helard Andres Manrique, MD, Pedro Alberto Aro, MD,
Rubelio Enrique Cornejo, MD, Miguel Pinto, MD,
Jose Solis, MD, Angel Escalante, MD
Objective: To describe the clinical characteristics of
patients with agranulocytosis in patients treated with antithyroid drug.
Methods: We reviewed the medical charts of patients
with diagnosis of hyperthyroidism which developed
agranulocytosis between 2002 and 2008.
Results: From 5,161 hyperthyroid patients, 29
patients (0.58%) developed agranulocytosis associated
with the use of antithyroid drug (100% with thiamazole).
The 86.2% were female. The average time of disease was
14.68 ± 3.72 months. The most frequent symptoms were
fever (96.7%) and sore throat (90%). Hematologic recovery from neutropenia was 10 days (range, 5 to 21 days).16
Objective: Malignancy in autonomously functioning
thyroid nodules is extremely rare. We present an unusual
clinical scenario and a rare histo-pathological finding of
Hurthle Cell carcinoma in a patient with an autonomous
nodule.
Case Presentation: A 13-year-old white female presented with a recent history of a palpable thyroid nodule
during a primary care clinic visit. She had a suppressed
TSH of 0.01uIU/ml, high normal T4 and elevated T3
levels. Ultrasound of the thyroid revealed a 3.5 cm complex mass in the left lobe with increased central vascularity. I123 imaging of the thyroid revealed an asymmetrically enlarged thyroid gland, with focal enlargement and
homogenously hyper-intense activity in the left lobe. The
right lobe was not visualized. Twenty four hour uptake
was 27.7%. The patient underwent left lobectomy and
isthumusectomy. Pathology revealed a 5cm encapsulated
well differentiated Hurthle cell carcinoma with negative
– 169 –
margins. The non- neoplastic surrounding thyroid tissue
showed evidence of chronic lymphocytic thyroiditis. The
patient underwent subsequent completion thyroidectomy
with no evidence of residual carcinoma in the right thyroid
lobe. Post-operatively the patient had a 24-hour I-1315 mCi
whole body scan (WBS), demonstrated activity in the thyroid bed. Additionally, there was bilateral medial uptake
above the thyroid bed, consistent with either the upper
extremes of the thyroid lobe or possibly localized metastasis. She underwent radioactive iodine ablation with 153.7
mCi I-131. Subsequent I131 WBS 6 months later revealed
no regional or distant iodide-avid thyroid thyroid tissue
with complete ablation of the iodide-avid foci in the neck.
Discussion: Reports in the literature of autonomous
thyroid nodules that are malignant are exceedingly rare.
Schroder et al concluded that only 10 case descriptions
unequivocally met the criteria for malignancy manifesting
as a solitary warm or hot nodule, with virtually all cases
being described as either follicular or papillary. Hurthle
cell cancer, which is considered an oxyphilic variant of
follicular carcinoma, accounts for only 3-10% of all differentiated thyroid cancers.
Conclusion: Less than 10% of Hurthle cell neoplasms on scintigraphy show uptake of radiocative iodine.
This makes our case exceptionally rare in which we have
biochemical evidence of hyperthyroidism coupled with
anatomical and histopathological evidence of Hurthle cell
carcinoma correlating with an area of hyper-intense tracer
uptake on I123 scintigraphy.
patients with or without PHT. Nonetheless, those with
PHT had significantly higher CO, PASP, peak transmitral
early diastolic flow velocity (E), and ratio of E to early
diastolic mitral annular velocity (E1). Among the 14
hyperthyroid patients with PHT, 10 (40%) had pulmonary arterial hypertension PAH with normal E/E1, and 10
(16%) had pulmonary venous hypertension (PVH) with
elevated E/E1. These hemodynamic abnormalities of PAH
or PVH returned to normal after restoration of euthyroid
status.
Discussion: In patients with thyrotoxicosis and normal LV systolic function, asymptomatic PHT as detected
by echocardiography was observed in 56% of patients at
presentation. Although the pathogenic mechanisms are
not clearly understood and various factors have been proposed to contribute to the development of this problem,
one of the important factors is the absence of the vasodilatory response of the pulmonary vasculature to thyroid
hormones. This might not allow the pulmonary circulation
to accommodate the increased CO and thus result in an
elevated PASP, PHT resolved in all patients on achieving
euthyroid status, suggesting that thyrotoxicosis directly
contributed to the occurrence of PHT.
Conclusion: In patients with thyrotoxicosis and normal LV systolic function, up to 56% had PHT due to either
PAH with increased CO (40%) or PVH with elevated LV
filling pressure (16%). Most importantly, thyrotoxicosis
related PHT was largely asymptomatic and reversible
after restoration to euthyroid status.
Abstract #1050
Abstract #1051
THYROTOXICOSIS - A REVERSIBLE
CAUSE OF PULMONARY HYPERTENSION
PREVALENCE OF SONOGRAPHICALLY
DETECTED NODULAR THYROID DISEASE
AMONGST POST-MENOPAUSAL WOMEN IN
NORTH-EAST INDIA
Rakesh Kumar Sahay, MD, DNB, DM, FACE,
Babul Reddy H, MD, DM, Neelaveni K, MD, DM,
Jayanthi Ramesh, MD, DM
Manash Pratim Baruah, MD
Objective: To determine the prevalence and clinical course of pulmonary hypertension (PHT) related to
thyrotoxicosis.
Methods: Serial echocardiographic examination was
performed in 25 consecutive patients with thyrotoxicosis
(20 females, 5males) to estimate pulmonary arterial and
pulmonary venous pressures. This was done at baseline
& repeated once euthyroid status was achieved (mean 6
months after initiation of antithyroid treatment). Results
were compared with 15 age and sex-matched healthy
controls.
Results: All hyperthyroid patients had normal LV
systolic function, and 14 patients (56%) had PHT with
PASP of greater than 35 mm Hg. There were no significant
differences in the clinical characteristics of hyperthyroid
Objective: The increased sensitivity and wider use
of ultrasound has resulted in number of incidentally discovered lesions in the thyroid gland. Reported prevalence
of sonographically detected thyroid nodules (incidentalomas) in general population ranges from 5.2 to 67.0%, with
a distinct preponderance in female. There is complete lack
of data in this regard from the North-East region of India
which has only recently become iodine sufficient.
Methods: Thyroid ultrsonography was performed
in patients attending an awareness camp for post menopausal women with patient in supine position, with the
neck hyperextended. It was always done by the same person (MPB) using a WED 2010 real-time scanner with a
7.5 MHz linear transducer. Patients with known history of
thyroid disorder were excluded.
– 170 –
Results: There were 49 females, age ranging from
36-85years (mean±SD=58.57±9.88years, median 59years.
Mean (±SD) age at menopause was 45.91±5.03years.
Mean (±SD) body mass index (BMI) was 23.41±4.57
kg.mr-2, with a median BMI of 23.84 kg.mr-2 . Ultrasound
screening of the thyroid revealed presence of nodular thyroid disease in all total 13 out of 49(26.5%) subjects, of
which 8(16.3%) had multi-nodular goiter, and 5(10.2%)
had a solitary thyroid nodule. Within the sub-group having
nodular disease (n=13), 62% were multi-nodular and 38%
were solitary. Amongst of rest of the subjects (n=36)without any nodular disease, 22 (61.1%) had a normal looking
thyroid, , 12(33.3%) had diffusely hypo echoic gland , and
2(5.5%) subjects had diffusely hyper echoic gland.
Conclusion: Relatively high prevalence of sonographically detected nodular thyroid disease in our population is similar to other areas which had iodine deficiency till recent years. Finding of significant number of
hypoechoic glands needs further elucidation.
Abstract #1052
the thyroid in 1938. There are few reported cases of thyroid
involvement in sarcoidosis, but the incidence is reportedly
4% in some autopsy studies. The literature has described
varying associations of scarcoidosis with thyroid disease.
The relationship between the presence of sarcoid granulomas in the thyroid gland and clinical thyroid disease is
not known. There have also been conflicting reports of the
effect of sarcoid on thyroid function with some authors
reporting rare functional derangements and others reporting the incidence of overt thyroid disease about 3.6%,
most being attributed to an autoimmune process.
Conclusion: Sarcoidosis is a multisystem disease that
affects people of all racial and ethnic groups. Sarcoidal
granulomas are more commonly manifested as ocular
signs and symptoms, intrathoracic lymph-node enlargement, pulmonary involvement, skin findings, or some
combination in more than 90% of patients. This case presents a rare example of sarcoidosis involving the thyroid
with manifestation of thyroid dysfunction. Furthermore, it
illustrates that corticosteroid therapy may be beneficial in
thyroid sarcoidosis.
THYROID SARCOIDOSIS: A CASE REPORT
Abstract #1053
Dwain E. Woode, MD, Cheryl Givens, MD,
Ebenezer A. Nyenwe, MD
STERNAL METASTASIS FROM FOLLICULAR
THYROID CANCER, A RARE OCCURRENCE
Objective: To describe a rare case of sarcoid thyroiditis in a 41-year-old African American male
Case Presentation: A 41-year-old male with a history
of End-Stage Renal Disease (secondary to Sarcoidosis)
referred for management of hypothyroidism diagnosed 4
years prior. Treated with levothyroxine 50 mcg, his physical examination was remarkable for a large, firm, non-tender multinodular goiter. Biochemical evaluation showed:
TSH 12.2, free T4 0.94 ng/dl, Free T3 2.1 pg/mL; Thyroid
Peroxidase Ab 25 IU/mL, Thyroid Antithyroglobulin Ab
<20. Thyroid ultrasound demonstrated a heterogeneous
thyroid goiter. Thyroid scintigraphy revealed an enlarged
gland with inhomogeneous uptake of 44%. Cytology of
fine needle aspiration demonstrated multinucleated giant
cells and lymphohistiocytic aggregates, reported as consistent with sarcoidosis vs thyroditis. He was treated with
levothyroxine and prednisone for flare up of sarcoidosis
with subsequent regression of his goiter.
Discussion: Given the negative thyroid serology,
autoimmune thyroiditis is unlikely. Also, the presence of
multinucleated giant cells and lymphohistiocytic aggregates on cytology, in a patient with known sarcoidosis,
supports the diagnosis of sarcoid thyroiditis. Autoimmune
thyroiditis accompanying sarcoidosis is rare. Spencer and
Warren were the first to describe a sarcoid granuloma in
Jagdeesh Ullal, MD, John T. O’Brian, MD, FACP, FACE
Objective: To describe a case of follicular thyroid cancer with metastasis to the manubrium and upper sternum
treated with sternal resection and sternal reconstruction.
male with history of thyroid cancer who presented with a
sternal mass. Nine years previously he presented with a 5
cm lesion in the right lobe. He proceeded to have a right
thyroid lobectomy which revealed follicular carcinoma
with focal vascular invasion. He then had completion thyroidectomy, followed by remnant ablation a month later
with a dose of 150 mCi of I131. Two years later, during
follow up, he had a whole body radioiodine scan which
showed moderate residual uptake in the thyroid bed. He
was treated with another dose of 150 mCi of I131. One
year after the second ablation, he had another surveillance
scan that showed no activity. He was lost to follow up
for about 2 years and he re-presented with a TSH level
of 85.7, due to non-compliance, and a thyroglobulin level
of 14,536. There was a small delay in further evaluation
because of severe hypertension but he did have a technetium scan that showed uptake in the manubrium, and a
CT scan of the chest showed multiple pulmonary metastases. He was again lost to follow up, but came back for
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another I131 ablation 8 years after initial diagnosis, receiving another 200 mCi for ablation of pulmonary metastases. A year later he presented to us with a painless sternal mass, and PET CT scanning was done to identify all
metastatic foci. There was a 5.9 x 4.5 cm expansile hypermetabolic manubrial lesion in exactly the location of the
patient’s mass. There was no uptake in the pulmonary
parenchyma. He was referred for surgical removal, and
had the 1st and 2nd rib cartilages, the clavicular heads, and
the upper sternum removed, followed by reconstruction
with methyl methacyrlate and marlex mesh. His preoperative thyroglobulin level had been 60,565 ng/ml, which
dropped to 28,766 ng/ml immediately following surgery.
Histopathology of the lesion revealed prolific mitotic
activity and extensive vascular invasion, consistent with
metastatic follicular carcinoma. Further therapeutic intervention is underway.
Discussion: Follicular thyroid cancer typically
spreads via hematogenous dissemination. And distant
metastases occur in 10 to 15 percent of patients. There are
very few cases worldwide describing sternal metastases
from follicular thyroid cancer treated with resection and
sternal reconstruction. This procedure would appear to
offer better survival and outcomes compared to treatment
with radioiodine alone. One other case from Japan had
manubrial metastasis that was treated in a similar fashion
and had a good response to multimodality therapy. Sternal
metastasis cancer is uncommon. However; follicular thyroid cancer appears to metastasize more often than other
head and neck tumors, and it’s proximity to the sternum
may be a contributing factor.
Conclusion: This is a case of follicular thyroid cancer with metastasis to the manubrium. It offers a unique
perspective on the nature of follicular thyroid cancer in
its potential to spread to bone. This case had a successful
outcome through surgical intervention, both in reduction
of tumor burden, and avoidance disfiguration or disability
in the patient via reconstruction of the sternum.
Abstract #1054
MEDULLARY CARCINOMA INCORRECTLY
DIAGNOSED AS FOLLICULAR AND HURTHLE
CELL CARCINOMA ON FNA AND
SURGICAL PATHOLOGY
Richard B. Guttler, MD, FACP, FACE, John S. Abele, MD
Objective: To alert the endocrinologist to read the
whole path report. There is the need for outside second
opinions when FN, FC or HC tumors are diagnosed on
either FNA or Surgical Pathology. Although the follicular/Hurthle cells and medullary cells have some similar
pathologic findings, there are obvious differences. The 2
cases will demonstrate how the inability of general pathologists to tell them apart can lead to serious consequences
for the two patients described, and put the endocrinologist
at risk for malpractice MP.
Case Presentation: The first patient with a thyroid
nodule was diagnosed as a FN on FNA, and a FC after
lobectomy. A completion thyroidectomy was negative
for cancer. She received 300 Millicuries of RAI/131, and
several neck dissections for cancer neck nodes, before the
correct diagnosis was made 12 years later. She had metastatic disease in the liver. Clinical trials and early death is
her fate. The general pathologist had mentioned the possibility of MC on the initial FNA, but failed to order calcitonin stains. The endocrinologist did not act when MC
was mentioned in the pathology report. He never ordered
a blood calcitonin. There were other clues in the twelve
years including no detectable thyroglobulin, or no iodine
uptake on multiple body scans post I/131 therapy. The
RET oncogene was negative. The second patient had a
better result. A thyroid nodule was biopsied and the general pathologist unequivocally called the nodule a HCN.
The lobectomy path report was HCC. The same general
pathologist wrote both reports. However, before the completion thyroidectomy, and RAI/131, recommended by the
endocrinologist, the patient asked for a second opinion.
The original FNA cytology was not HCN, but MC. The
cells had classic “eccentric egg yolk nuclei”, classic salt
and pepper nuclear pattern. The lobectomy surgical block
was positive for calcitonin. The blood calcitonin, and CEA
6 weeks after the lobectomy were elevated. She had a +
ultrasound lymph node mapping and had completion thyroidectomy and modified radical neck dissection on the
side of the original cancer confirming metastatic disease.
The finding of the error early allowed the correct second
surgical intervention and avoided unnecessary radiation
therapy. The RET oncogene was negative.
Discussion: Endocrinologists need to read the whole
path report, and act on it. The general pathologists may
have a problem differentiating MC from FN, FC, HCN,
and HCC. This can be compounded when the same pathologist does the cytology, and surgical pathology.
Conclusion: The first case would not have been
missed if either the pathologist or the endocrinologist
had ordered a calcitonin. The second patient was saved
from the same fate by luck, because the patient, not the
endocrinologist asked for another opinion. First case
Endocrinologist and pathologist lost MP suit.
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Abstract #1055
of FDG in inflammatory lesions [associated with the high
density of activated macrophages] such as active granulomatous conditions, namely sarcoidosis, as in our patient.
Conclusion: Various non neopalstic disease states
must also be considered when FDG- avid skeletal lesions
are identified in patients with established papillary thyroid
cancer to avoid misinterpretation!
UNRECOGNIZED SKELETAL SARCOIDOSIS
MIMICKING METASTATIC PAPILLARY
THYROID CANCER ON FDG POSITRON
EMISSION TOMOGRAPHY
Niyati Chiniwala, MD, MPH, Intekhab Ahmed, MD,
Kevin Furlong, DO, Serge Jabbour, MD, FACP, FACE,
Monika Shirodkar, MD, Jeffrey Miller, MD
Abstract #1056
Objective: To highlight the false-positive finding of
FDG-PET scan due to non neoplastic disease states in a
patient with papillary thyroid cancer.
for evaluation of palpable right-sided cervical lymphadenopathy. She was asymptomatic and denied any significant past medical history. Physical examination revealed
a right-sided level IV lymphadenopathy without any palpable thyroid nodules. Clinical diagnosis favored a possible lymphoma, so FDG PET-CT scan was ordered and
showed a hypermetabolic right neck mass, a right thyroid nodule, thoracic lymph nodes and extensive hypermetabolic activity within bilateral humeral bones, ribs,
thoracic-lumbar spine and pelvis reported as consistent
with metastatic osseous disease. Ultrasound confirmed
a 45-mm lymph node as well as 11-mm right thyroid
nodule. FNA (fine needle aspiration) of the lymph node
showed features of reactive hyperplasia. FNA of the right
thyroid nodule revealed cytologic features suspicious for a
follicular lesion of undetermined significance. The patient
underwent total thyroidectomy with selective neck dissection. Surgical pathology revealed a 12-mm right lobe papillary thyroid cancer; the resected lymph nodes showed
only granulomatous lymphadenitis (negative AFB stain).
Withdrawal whole body I-131 scan with TSH >30 was
negative with no metastatic disease activity and undetectable thyroglobulin of < 0.1 ng/ml with negative thyroglobulin antibody. On closer directed questioning, patient
forgot that 15 years earlier she was admitted with dyspnea
and a chest x-ray then revealed hilar lymphadenopathy
probably consistent with sarcoidosis but she defaulted
from follow up. Sarcoid specialist confirmed generalized
sarcoidosis.
Discussion: Metastases from papillary thyroid carcinoma predominantly involve regional lymph nodes.
Hematogenous spread at the time of initial diagnosis is
rare (2-10%). Among such patients, 2/3rd have pulmonary
and only 1/4th have skeletal metastases. In this report, we
describe misinterpretation of FDG-PET scan as metastatic
thyroid carcinoma in a middle age female with proven
papillary thyroid cancer and unsuspected generalized sarcoidosis with skeletal involvement. FDG-PET imaging
can have false-positive findings, caused by accumulation
PAPILLARY CARCINOMA OF THE
THYROID WITH METASTASIS TO
CEREBELLUM AND MASTOID
Maria Jocelyn Capuli-Isidro, MD
Objective: Case of E.A. 56-year-old female, Filipino,
Catholic, from Sultan Kudarat, admitted due to loss of
appetite. History started 1994, patient was noted to have
enlarged thyroid right lobe, FNAB was done showed follicular adenoma, hence total thyroidectomy of the right
lobe done at a local hospital in Mindanao.
Case Presentation: In 1995, Whole body scan showed
functioning residual thyroid tissue limited to functioning
fossae. RAI 100 MCI was given. Repeat whole body scan
showed residual neck tissue with focal localization of the
right supraorbital area suggestive of functioning thyroid
metastasis. RAI 200 MCi was given both at St. Luke’s
Hospital. Repeat whole body scan a year later showed
functioning metastatic thyroid tissue in the right orbital
and possibly nasopharyngeal area. In Feb 1997, patient
first sought consult at our institution, RAI 100MCi was
given. April 1997, whole body scan showed small area of
midline radioactivity in the region of the buccal cavity,
no abnormal accumulation of radioiodine seen elsewhere
in the body. Patient was maintained on eltroxin 200MCG
before breakfast. Repeat whole body scan done in 2002
showed no detectable accumulation of radioiodine in the
anterior nor elsewhere in the body. In 2004, repeat whole
body scan showed increase accumulation of radioiodine
at right temporoparietal region, hence RAI 100 MCi was
given. However, patient was lost to follow up.
Results: July 2009, patient followed up, had a mass at
the mastoid area with purulent discharge draining from the
right ear; biopsy was done at a local hospital in Mindanao
showed metastatic papillary carcinoma. September 2009,
patient was readmitted at our institution, MRI of the head
was done showed cerebellar mass with beginning hydrocephalus. Patient was then advised to have metastasectomy of the mastoid and cerebellar mass however patient
refused and was sent home. Few days after the patient was
discharged, she was noted to have decreased appetite and
body weakness. She was admitted again at a local hospital but opted to transfer to our intitutution. Patient then
– 173 –
underwent metastasectomy of the mastoid and cerebellar
mass.
Conclusion: Post op patient was intubated due to
hypoxemia and was hooked to vasopressors due to sepsis and
unstable cardiac status. Patient subsequently had improved
hemodynamic status, and was discharged improved.
Conclusion: The prevalence of subclinical and metabolic syndrome was high in the population study. There
is no association between subclinical hypothyroidism and
components of metabolic syndrome. There is no association between subclinical hypothyroidism and overweight/
obesity.
Abstract #1057
Abstract #1058
SUBCLINICAL HYPOTHYROIDISM AND ITS
ASSOCIATION WITH METABOLIC SYNDROME
AND OBESITY IN A FEMALE POPULATION
OF LIMA
THYROTOXICOSIS-INDUCED TAKOTSUBO’S
CARDIOMYOPATHY
Kaye-Anne Newton, BS, Fredysha Mcdaniel, MD,
Theresa Fynn, MD
Juan Carlos Lizarzaburu, MD, Valery Nuñez, MD,
Victor Cornetero, MD
Objective: To determine prevalence of subclinical hypothyroidism and metabolic syndrome in a female
population of Lima. To determine the association between
subclinical hypothyroidism and components of metabolic
syndrome. To determine the association between subclinical hypothyroidism and overweight/obesity.
Methods: Descriptive study. A total of 54 women
with no past history of thyroid disease, diabetes mellitus diagnosis, cardiovascular disease, high blood pressure and stroke were studied. Exclusion criteria: pregnancy and subjects who did not accept to participate in
the study. Variables: Thyroid stimulating hormone (TSH),
free thyroxine (FT4), Body Mass Index (BMI), Metabolic
Syndrome (MS) based on the International Diabetes
Federation (IDF) definition.
Results: The mean age of the participants was 29.7
(SD ± 9.311) years and the mean BMI was 24. 62 (SD ±
3.69) kg/m². There were 24 women with overweight and
obesity (44. 4 %). The prevalence of subclinical hypothyroidism and metabolic syndrome was 13% and 38.95%,
respectively. We did not find significant differences in the
mean of metabolic syndrome components: HDL cholesterol (P=0,681), triglycerides (P=0.275), fasting glucose
(P=0.256), systolic blood pressure (P= 0.078), diastolic
blood pressure (P = 0.69), abdominal perimeter (P=0.233),
in the women with and without subclinical hypothyroidism. TSH levels mean is not significantly different between
normal weight and overweight/obese women (P=0.245),
just as the prevalence of subclinical hypothyroidism is not
grader in overweight/obese women.
Discussion: The prevalence of subclinical hypothyroidsm is more frequent in women and we found a
higher prevalence compared with the literature. There are
some reports that suggest association between subclinical
hypotirodism and metabolic syndrome and other an association with overweight/ obesity. In our study we did not
find this association.
Objective: To present an unusual case of Graves’
disease presenting as a forme fruste of Takotsubo’s
phenomena.
Case Presentation: A 40-year-old African-American
woman with no significant past medical history presented
with chest pain which awoke her from sleep. Initial EKG
was not impressive for ST/T wave changes. The initial
troponin was 0.33 ng/mL. Cardiac catherization was performed which showed normal coronary arteries. A left
ventriculogram showed an ejection fraction of 60% and
hypo- to akinetic area at the apex of right ventricle. The
patient’s chest pain continued to recur with further elevation of troponin and significant ST elevation over the
precordial leads with tomb-stoning despite standard acute
coronary syndrome protocol. Thyroid function studies
were done and revealed a TSH of 0.02 MU/ML (normal
0.4 to 4.0 MU/ML), T3 of 367 ng/dL (normal 82 to 179
ng/dL), T4 of 20.19 MC/dL (normal 4.5 to 12.5 MC/dL)
and thyroid stimulating immunoglobulin of 140. On presentation the patient had no significant eye finding but did
have a weight loss of about 15 lbs. The patient was started
on methimazole and propranolol with no further recurrence of chest pain.
Discussion: Takotsubo’s cardiomyopathy is a condition which is associated with transient systolic dysfunction of the apical and or mid segments of the left ventricle
with associated chest pain, elevated cardiac enzymes and
ECG changes. Its presentation can mimic myocardial dysfunction in the absence of significant coronary artery disease. Postulated mechanisms include acute myocarditis,
stress induced activation of adrenoreceptors, epicardial
coronary arterial spasm, increased sympathetic tone and
catecholamine excess. Thyrotoxicosis is a well described
cause of coronary artery vasospasm. It is believed that
untreated hyperthyroidism results in increased sensitivity
to norepinephrine and a blunted response to nitric oxide
mediated coronary vasodilatation, culminating conceivably in vasoconstriction.
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Conclusion: We present a case which illustrates
Graves’ thyrotoxicosis with ST elevated MI with no significant coronary artery disease. We postulate that the
recurrent episodes of chest pain are a result of coronary
artery vasospasm which failed to resolve due to untreated
hyperthyroidism, ultimately presenting as a forme fruste
of Takotsubo’s cardiomyopathy. Thus thyroid function
testing should be considered in patients with persistent or
recurrent chest pain despite standard treatment.
Abstract #1059
neurological symptoms after I-131 ablation or during thyroid hormone withdrawal for I-131 ablation. High dose
steroids have been used successfully to prevent complications from radioablation of brain metastases.
Conclusion: Brain metastasis is a rare initial presentation of PTC and is associated with significant diagnostic
and therapeutic challenges. Patient survival is typically
less than 1 year, despite multimodality therapies including
radioiodine, whole brain radiation, stereotactic radiosurgery or traditional surgery.
Abstract #1060
METASTATIC PAPILLARY THYROID
CARCINOMA WITH MULTIPLE BRAIN CYSTS
AS THE INITIAL PRESENTATION
VOCAL CORDS EXAMINATION BY USE
OF REAL TIME, HIGH-RESOLUTION
ULTRASONOGRAPHY - A PROSPECTIVE PILOT
STUDY IN PATIENTS BEFORE AND AFTER
THYROIDECTOMY
Pornpoj Pramyothin, MD, Stephanie Lee, MD, PhD,
Sara Pietras, MD
Objective: The brain is an uncommon site of distant
metastasis from thyroid cancer. A case of papillary thyroid
carcinoma (PTC) with brain metastasis as the initial presentation is described.
Case presentation: A 41-year-old female presented
with 2-week history of headaches and dizziness. Cranial
CT and MRI revealed a 5.5 cm cyst in the right parietal
lobe, with 3 smaller cysts in the left frontal lobe and bilateral cerebellar hemispheres. The patient underwent extensive evaluation to rule out intracranial infection and locate
primary site of brain metastases. A 1.4 cm right thyroid
nodule was noted on chest CT. This nodule was not palpable during examination. Ultrasonography with fine-needle
aspiration biopsy was performed yielding results consistent with PTC. There was no evidence of cervical lymph
node metastasis. Craniotomy with biopsy of the dominant
brain lesion was performed, and pathology confirmed
the diagnosis of metastatic PTC. Management involved
whole brain radiation, total thyroidectomy and subsequent
radioiodine ablation in December of 2009. Post-therapy
radioiodine scan demonstrated that the brain metastases
were non-iodine avid. Plan was made to provide treatment
for residual brain lesions with stereotactic radiosurgery.
Discussion: The most common sites of distant metastasis from differentiated thyroid cancer are lungs (71%),
bone (20%) and mediastinum (10%), while the brain
constitutes only 3% of all metastases. Brain metastasis
is associated with poor prognosis, with median survival
of 12 months for differentiated thyroid cancer and 1-3
months for medullary and anaplastic cancers. Available
data suggests improved median survival in patients who
undergo surgical resection of metastases. Reports of treatment success of brain metastases with whole brain radiation, stereotactic radiosurgery, I-131 ablation or chemotherapy have been limited. There are reports of worsening
Marek Dedecjus, MD, PhD,
Zbigniew Adamczewski, MD, PhD,
Jan Brzeziński, MD, PhD,
Andrzej Lewinski, MD, PhD
Objective: Examination of the vocal cords is most
commonly performed by direct or indirect laryngoscopy,
but this may not be readily approached by some patients
and is difficult to register without advanced equipment.
Ultrasound examination is accessible, inexpensive and
may be easily registered, so it would be a perfect tool
for vocal cords examination. Therefore, this prospective
study was carried out to evaluate the morphology of the
vocal cords and the larynx by real-time, high-resolution
US and to correlate the ultrasonographical features with
the laryngological examination.
Patients/Methods: Fifty patients were included in the
study. All the patients had ultrasound examination (with
10 MHz linear probe) performed before and two days after
thyroidectomy. Simultaneously laryngological examination was performed.
Results: In an analyzed group, laryngological examination revealed unilateral vocal cord paralysis in two
cases. Moreover vocal cord dysfunction was diagnosed
in four cases. Examination performed after three months
follow-up confirmed transitory character of the above
mentioned pathologies. In simultaneously performed
US-examination of the vocal cords we observed changes
in vocal cords function in ten cases. In two cases the vocal
cords were not moving in US examination – this were the
patient with vocal cord paralysis. In further 8 cases we
observed changes in US image in relation to examination performed before operation. US-scan performed after
three months revealed that the image of the vocal cords
returned to the one registered before thyroidectomy.
– 175 –
Conclusion: after analysis of obtained results we
concluded that laryngeal ultrasound examination is a noninvasive, easily reproducible and inexpensive method of
examining the larynx. Moreover, thanks to many options
of registration it may be a perfect tool for early vocal cords
post operative dysfunction discovery and monitoring.
However, analysis on the bigger group of the patients is
necessary.
Abstract #1061
A CASE OF HODGKIN’S LYMPHOMA OF
THE THYMUS IMITATING RETROSTERNAL
GOITER – RETROSPECTIVE ANALYSIS OF THE
DIAGNOSTIC PROCESS.
Marek Dedecjus, MD, PhD, Anna Kedzierska, MD,
Jozef Kozak, Grzegorz Strozyk, MD, PhD,
Radzislaw Kordek, MD, PhD, Jan Brzezinski, MD, PhD
Objective: Hodgkin’s lymphoma is the most frequent
lymphoid proliferation in the mediastinum. Symptoms
and radiological findings are non-specific. These tumors
must be considered in case of thymus involvement in
order to avoid a surgical treatment which could lead to
many complications.
Case presentation: We report a case of primary
Hodgkin’s lymphoma of thymic origin in a 27-year-old
woman. She presented with a dyspnoe and chest pain.
Chest radiography showed an anterosuperior mediastinal
mass and echocardiography revealed a mass compressing right pulmonary artery and right ventricle. Ultrasound
examination revealed enlarged left lobe of the thyroid,
localized partially substernally Fine needle aspiration
(FNA) was not diagnostic. Thoracic computed tomography revealed heterogeneous tumor staying in connection
with thyroid and the diagnosis of substernal goiter was
suggested. The scintigraphy did not confirm substernal
goiter. Due to increasing compressive symptoms caused
by tumor the patient was referred to surgical treatment.
A cervicotomy was performed which did not revealed
goiter so consecutive sternotomy was performed revealing large intramediastinal cystic mass which was resected.
The definitive histologic study revealed a Hodgkin’s
lymphoma classified as a nodular sclerosing type, which
was confirmed by the immunohistochemistry. The patient
received postoperative treatment based on chemotherapy
and radiotherapy. The response was very good with a
complete remission without recurrences after a follow up
of 3 years.
Conclusion: Although the treatment was successful,
in present study we retrospectively and critically analyzed
the diagnostic process.
Abstract #1062
THE SPECTRUM OF THYROID DISORDERS IN
CHILDREN WITH TYPE 1 DIABETES MELLITUS
Noushin Khalili Boroujeni, MD,
Samaneh Khanpour, MD, Masoud Amini, MD,
Ammar Hassanzadeh Keshteli, MD,
Mahin Hashemipour, MD
Objective: Prevalence of thyroid disorders such as
goiter, nodules, thyroid autoimmunity, and thyroid dysfunction have rarely been investigated in children with
type 1 diabetes mellitus in contrast to those in adults. Our
aim was to investigate the spectrum of thyroid disorders
in type 1 diabetic children in comparison with results
obtained from nondiabetic ones.
Methods: The study population comprised 150 children with type 1 diabetes mellitus and 300 nondiabetic
subjects aged 7-12 years. Serum TSH, FT4, and antithyroperoxidase antibody (anti-TPO Ab) were measured.
Thyroid size and structure was estimated in each child by
inspection and palpation by an endocrinologist.
Results: Type 1 diabetic subjects had a higher risk
of known thyroid disorders [odds ratio (OR): 1.78, 95%
confidence interval (CI): 1.11–2.85, P<0.05], goiter (OR:
1.5, 95%-CI: 1.15–2.5, P<0.05) and anti-TPO Ab >200
IU/ml (OR: 1.94, 95%-CI: 1.28–2.95, P<0.05) compared
to the control group. The prevalence of thyroid nodules
was almost similar in diabetic and nondiabetic children.
Discussion: Type 1 diabetes mellitus is associated
with an increased risk of goiter and thyroid autoimmunity. Therefore, evaluation of thyroid function and thyroid
exam should be performed in children with type 1 diabetes
mellitus.
Conclusion: Children with type 1 diabetes mellitus
must be evaluated for thyroid function and thyroid exam.
Abstract #1063
FDG-PET INCIDENTALOMASHOW DO WE INTERPRET THEM?
Sunil Asnani, MD, FACE, Anupam Ohri, MD,
Nikhil Motiramani, MD
Objective: 18Fluorodeoxyglucose positron emission
tomography (FDG PET) is an essential tool of a modern
oncology practice and frequently demonstrates increased
activity in the thyroid gland. We present two cases of
FDG-PET ‘incidentalomas’ and discuss their implication.
Case Presentation: A 40-year-old woman with history of breast carcinoma diagnosed 6yrs ago, treated
with a lumpectomy, lymph node dissection and bilateral
– 176 –
oophorectomy was found to have an intense uptake in the
neck/thyroid area on a routine surveillance FDG -PET. The
uptake was bilateral and diffuse. The patient was asymptomatic except for fatigue. No goiter, nodules or cervical
lymphadenopathy was apparent on examination. TSH was
14.2µIU/ml (0.35-5.5); thyroid peroxidase antibody was
strongly positive at 192.5 IU/ml (0.0-3.9). She was diagnosed with Hashimoto’s thyroditis and primary hypothyroidism and started on levothyroxine replacement. Follow
up thyroid sonograms and neck CT scans remain negative
for any nodules or lymphadenopathy; she continues to
do well. A 64-year-old woman who underwent lumpectomy for breast cancer 1 year ago was found to have focal
increased uptake on the right side of the neck on a surveillance FDG-PET. The patient reported palpitations
and weight loss of 15 lbs in the last 12 months. Physical
examination revealed a goiter with multiple nodules, right
greater than left. There was no bruit and no lymph nodes
were palpable. A thyroid sonogram confirmed a multi
nodular goiter, the largest 3cm nodule being in the right
lobe. TSH was 0.59µIU/ml (0.35-5.5). Fine needle aspiration of the nodules was consistent with colloid goiter
and benign nodule. The patient elected not to have surgical excision. Serial sonograms at 6 months intervals show
neither growth nor the development of malignant features
and the TSH remains at the lower limit of normal.
Discussion: Thyroidal uptake of FDG on PET is worrisome given up to a 50% probability of malignancy, either
primary or secondary. The other 50% are ‘incidentalomas’
and common etiologies include thyroiditis, Graves’ disease, toxic nodule, recent FNA or surgical intervention.
Conclusion: Appropriate clinical, radiological and
pathological follow up after a positive FDG-PET may
avoid unnecessary extensive surgical procedures from
being undertaken for benign thyroid lesions.
dL (2.27-3.57), TSH 0.02 µIU/L (0.34-5.60) and free T4
5.38 ng/dL (0.50-1.26). EKG showed sinus tachycardia at
126 bpm. Therapy for thyroid storm was initiated including I.V. hydrocortisone, PTU followed by potassium
iodide, beta-adrenergic blockade, and IV normal saline at
125 cc/hr. Her sore throat and tachycardia improved over
2 days. On day 3 she developed a cough, dyspnea during normal speech and orthopnea; she was noted to have
hypoxia and ronchi. A chest x-ray revealed new bi-basilar
infiltrates consistent with pulmonary edema. Diuresis with
furosemide improved her exam and symptoms. An echocardiogram revealed a LVEF of 55-60%, with normal left
ventricular wall thickness. She had remarkable clinical
improvement and was discharged 2 days later.
Discussion: A case series of consecutive thyrotoxicosis patients found that heart failure affected 6%. Within
that subgroup the mean age was 66, half had an ejection
fraction <50% and 94% had atrial fibrillation [PMID
17005710]. Prolonged sinus tachycardia explained some
other cases. Thyrotoxicosis increases the blood volume
increasing preload, decreases the peripheral vascular
resistance, and increases contractility. These, combined
with sinus tachycardia, can predispose to high output failure in the setting of an otherwise normal heart. While this
case is unusual given her young age, it is likely that the
physiological effects of thyrotoxicosis, combined with 3
days of IV fluid combined to cause high-output heart failure. Her thyroid status was normalizing, so it is unlikely
this was a direct consequence of thyroid storm.
Conclusion: While pulmonary edema is an infrequent
occurrence, especially in such a young patient, physicians
should remain aware of the potential systemic effects of
thyrotoxicosis and take steps to minimize the risks.
Abstract #1064
CHALLENGES IN MANAGEMENT OF
CONSUMPTIVE HYPOTHYROIDISM IN
AN INFANT WITH DIFFUSE HEPATIC
HEMANGIOMATA
A STORM IS COMING: THYROTOXIC
CARDIOMYOPATHY
Sunil Asnani, MD, FACE, Swomya Bal, MD,
Nikhil Motiramani, MD, Michael Carson, MD
Objective: To present a case of thyrotoxic cardiomyopathy in a young patient.
Case Presentation: A woman in her 20’s with
Graves’ disease stopped her propylthiouracil (PTU) one
month ago. She presented to her endocrinologist’s office
complaining of fevers, chills, sore throat and palpitations,
and was directly admitted to the hospital to receive treatment for Thyroid Storm. EXAM: HR: 120 bpm; thyroid
enlarged and tender with a prominent bruit. LABS: normal electrolytes and complete blood count; Free T3 25 pg/
Abstract #1065
Jonathan Wasserman, MD, PHD, Kusiel Perlman, MD,
FRCPC, Alexandra Balma Mena, Sanjay Mahant, MD,
FRCPC, Manuel Carcao, MD, MSc, FRCPC,
Elena Pope, MD, MSc, FRCPC, Philip John, MD
Objective: To describe a young girl with severe hypothyroidism and diffuse hepatic hemangiomata, illustrating therapeutic challenges in managing her thyroid disease and underlying tumors, while minimizing iatrogenic
complications.
Case Presentation: This girl was admitted at 7 weeks
of age for evaluation of abdominal distension and jaundice.
She was the healthy product of a full-term pregnancy and
– 177 –
was previously well. Initial assessment she revealed significant hepatomegaly. Initial biochemistry revealed cholestasis with normal transaminases. TSH was 123 mIU/L
(0.5-5), FreeT4 9.3 pmol/L (10-23), TotalT3 0.8 (1.6-4.4)
and reverse T3 15.4 (0.12-0.54). Abdominal ultrasonography revealed diffuse hepatic hemangiomata. There were no
clinical or echocardiographic findings of high-output heart
failure. Review of the newborn screen revealed a TSH<17
at 48 hours of life. Thyroid function had been assessed at
28 days with TSH 11.4 and FreeT4 21.4. These findings
were felt to reflect an acquired consumptive hypothyroidism resulting from Type III deiodinase production within
the hemangiomata. Thyroid replacement was initiated
with liothyronine. Prednisone (2 mg/kg/d) was added to
promote tumor involution. An initial rise in TSH to 244
mIU/L three weeks after initiation of therapy prompted
addition of levothyroxine to her regimen. Additionally,
propanolol (2 mg/kg/d) was introduced at that time.
Within 3 weeks, TSH had declined to near-normal levels
(TSH=6.14) and a steroid taper was commenced. Repeat
abdominal ultrasound revealed a slight decrease in the
size of the hepatic hemagiomata. One month following
discontinuation of steroid therapy, TSH had again risen
to 71.2 mIU/L and prednisone was resumed with a concomitant increase in propanolol. Thyroid replacement was
adjusted biweekly to target biochemical euthyroidism.
Throughout the course of treatment, the patient remained
clinically euthyroid. Developmental milestones were met
age-appropriately. The initial cholestasis resolved within
4 weeks of initiation of thyroid replacement and did not
recur. At 15 months, the child remained on glucocorticoid
therapy with an inability to taper the dose. She was demonstrating significant growth restriction with length and
weight well below the 1st percentile, despite adequate
nutrition. Persistent steroid requirement, high doses of
thyroid replacement and concerns for iatrogenic growth
retardation prompted consideration of alternate therapies.
Treatment with weekly vincristine infusion was initiated.
Results: The results of this intervention and continued follow-up will be presented.
Abstract #1066
FOLLICULAR THYROID CARCINOMA
METASTATIC TO THE CHEST WALL 16 YEARS
AFTER TOTAL THYROIDECTOMY AND
I131 ABLATION THERAPY FOR PRIMARY
FOLLICULAR CARCINOMA OF THE THYROID.
after the primary diagnosis and discuss diagnostic
modalities.
Case Presentation: A 78-year-old woman with history of T2N0M0 stage II FTC and evidence of vascular
invasion who was diagnosed and treated with total thyroidectomy and ablative therapy16 years prior presented
with enlarging right posterior chest wall mass. Her initial
and one year post ablative therapy I131 whole body scan
(WBS) revealed no areas of abnormal uptake. Computed
tomography in 2009 demonstrated 5.3 x 12.5cm irregularly enhancing mass in the right posterior chest wall and
centered within fascia between the subcutaneous tissue
and intercostal muscles with partial destruction of the 10th
rib, prominent surrounding vasculature, and no evidence
of pleural invasion or extension into subcutaneous tissue.
Needle biopsy pathology revealed well formed thyroid
follicles with colloid and cells positive for thyroglobulin
and thyroid transcription factor-1. The I131 uptake and
WBS revealed abnormal tracer accumulation at the posterior right chest wall and 2% uptake in the neck with no
other areas of abnormal activity. The serum thyroglobulin
level was 159,000 ng/ml with TSH 71 mIU/L. The FDGPET scan confirmed abnormal activity in the right chest
wall but did not identify any other areas of abnormal FDG
uptake. Surgical resection of the mass with subsequent I131
therapy was recommended.
Discussion: The incidence of thyroid cancer is
increasing, with more than 37,000 new cases expected in
2009. However, FTC remains uncommon in the United
States. Follicular carcinoma represents approximately
5% of all thyroid cancers and exhibits rare hematogenous
spread to the lung, brain, liver and osseous structures. The
evidence of vascular invasion is not a part of TNM staging but important in predicting mortality. Use of PET in
addition to I131 WBS for identification of distant metastasis (DM) increases the sensitivity and provides important data, since multiple DM and advanced age are major
mortality predictors. Simultaneous use of PET and WBS
is important prognostically since presence of positive PET
and negative I131 scan implies more aggressive malignancy and worse prognosis.
Conclusion: This case emphasizes the importance of
past medical history and recognition of a rare propensity
of differentiated thyroid cancer to present as DM years
after the initial diagnosis.
Mikhail Signalov, DO, Christine Z. Dickinson, MD,
Michael M. Kaplan, MD, Douglas G. Paulk, DO
Objective: To present a rare case of follicular thyroid cancer (FTC) metastatic to the chest wall 16 years
– 178 –
Abstract #1067
acute hepatocellular toxicity as well as other potential
treatment options as demonstrated in this case.
PROPYLTHIOURACIL INDUCED ACUTE
HEPATOTOXICITY: CASE REPORT
Abstract #1068
Gaston Marcos Ponte, Jr., MD
Objective: Thionamide drugs have been used extensively in the treatment of certain hyperthyroid disorders.
Side effects common to these drugs include rash, muscle/
joint aches, headaches, rare complications have been
linked to kidney damage (nephritis), liver damage (hepatitis), and agranulocytosis. However hepatitis secondary to
these drugs usually develops 4-12 weeks after initiation.
To date few cases have been published with regards to
acute hepatotoxicity secondary to thionamide medication.
Here in, we report a case of hepatotoxicity immediately
after thionamide drug initiation in a female patient with
thyroid storm.
Case Presentation: A 22-year-old hispanic female
admitted to our center due to an acute abdomen secondary to an ectopic ruptured pregnancy (β-hcg=25541).
Upon presentation wide pulse pressure and uncontrollable
hypertension was noted. Two emergent surgical interventions within 48hrs after initial presentation were required.
During her post operative day in the ICU, patient was
found to have a TSH value of <0.01 with normal LFT and
an initial Burch-Wartofsky score of 60. Thyroid stimulating immunoglobulins were reported high at 145% and a
TSH receptor antibody was also elevated at 66 (nl <35).
Patient was immediately started on PTU as well as SSKI
and hydrocortisone therapy. 24 hrs after initiation with
PTU, LFT’s began to rise acutely. Patient was also found
to have high output cardiac failure with an EF= 35-40%,
subsequently propanolol was instituted. Extensive work
up yielded negative results for other causes for an acute
rise in LFT’s, concluding acute hypersensitivity hepatitis secondary to thionamide therapy. Due to an improvement in cardiac function as well as respiratory condition
surgical consultation was obtain. Patient underwent total
thyroidectomy with subsequent hormone replacement
therapy.
Conclusion: In 1997 Lock et al. reports a case of
severe hepatotoxicity soon after initiation of PTU treatment. Previous reports have demonstrated that older age
of the patient and higher dose of the drug are risk factors for cholestatic injury, frequently seen more often with
methimazole, however hepatocellular toxicity and vasculitis have been associated with high dose PTU, and acute
nephritis with either drug. Hepatotoxicity is one of the
possible side effects of thionamide drugs. It is usually seen
weeks to months after the initiation of treatment if occurs.
These complications are serious but rare. Physicians need
to be aware of the significance of thionamide induced
THE NATURAL HISTORY OF ENDOGENOUS
SUBCLINICAL HYPERTHYROIDISM:
A RETROSPECTIVE STUDY
Rama Divi, MD, Robert H. Caplan, MD, FACE,
Michelle A. Mathiason, MS
Objective: The treatment of subclinical hyperthyroidism is controversial because the natural history is
uncertain. We therefore undertook a retrospective study
to examine the natural history of endogenous subclinical
hyperthyroidism.
Methods: Between 2002 and 2006, we identified 122
patients with low TSH concentrations but normal FT4 and
T3 or FT3 levels. The medical records of these subclinical hyperthyroid patients were reviewed and demographic
data, clinical features, and thyroid function test results
were tabulated. Because the etiology of hyperthyroidism
could not be clearly identified in 58 (48%) patients, we
compared patients with normal sized or diffusely enlarged
thyroid glands (group A) to patients with nodular thyroid
glands (group B). Clinical outcomes and the presence
of atrial fibrillation were recorded. We also compared
the results of patients with TSH levels < 0.1 µIU/mL to
patients with TSH levels between 0.1 and 0.4 µIU/mL.
Results: Of 122 patients with subclinical hyperthyroidism, 91 (75%) were women and 31 (25%) were men.
They ranged in age from 19 to 98 years (mean, 55 years).
One hundred and four patients were in group A and 18
were in group B. The duration of follow-up was 1 month
to 6.5 years (mean, 3 ± 1.5 years). TSH reverted to normal in 64 (62%) of group A; only 4 (4%) of these patients
required treatment for hyperthyroidism. In contrast,
TSH levels in only 2 (11%) patients in group B reverted
to normal and 8 (44%) required anti-thyroid treatment.
Atrial fibrillation was present in 8 (8%) group A and 3
(17%) group B patients. TSH levels reverted to normal
in 16 of 31 (52%) patients with initial TSH levels < 0.1
µIU/mL; 6 (9%) patients required anti-thyroid treatment.
TSH reverted to normal in 50 of 91 (55%) patients with
TSH levels between 0.1 and 0.4 µIU/mL; 6 (7%) of these
patients required anti-thyroid drug treatment. Atrial fibrillation was present in 3 (10%) patients with TSH levels <
0.1 and 8 (9%) patients with TSH levels between 0.1 and
0.4 µIU/mL.
Discussion: Patients with subclinical hyperthyroidism and thyroid nodules may progress to overt hyperthyroidism to a greater degree than those with normal sized or
diffusely enlarged goiter.
– 179 –
Conclusion: We conclude that most patients with
subclinical hyperthyroidism without thyroid nodules do
not require immediate anti-thyroid therapy and can be followed safely. There were no statistically significant outcome differences in patients with TSH levels < 0.1 µIU/
mL and those with TSH levels between 0.1 and 0.4 µIU/
mL.
Abstract #1069
HCG SECRETING GERM CELL TUMOR
CAUSING HYPERTHYROIDISM
Hammad Hussain, MD, Mohamad Imam, MD,
Leigh M. Eck, MD, Robert N. Schimke, MD, FACE
Objective: We describe a patient with HCG secreting
germ cell tumor who presented with thyrotoxicosis.
Case Presentation: A 38-year-old male with no significant past medical history presented to the emergency
room with dyspnea on exertion, hemoptysis and night
sweats of two month duration. A chest x-ray showed diffuse pulmonary nodules confirmed on a subsequent chest
CT scan. He then underwent bronchoscopy with biopsy
of pulmonary nodules and initial pathology was negative
for malignancy. He was empirically treated for a fungal
infection. His dyspnea and hemoptysis however did not
improve. Repeat chest CT revealed an anterior mediastinal mass which on biopsy was found to be non-seminomatous germ cell tumor (NSGCT). Further staging revealed
metastasis to the brain, liver, spleen and kidney. The
patient subsequently developed symptoms of thyrotoxicosis. His thyroid profile revealed hyperthyroidism and
his serum β-hCG was significantly elevated at more than
200,000 U/L. He was started on propylthiouracil and propranolol with some symptomatic relief. This was followed
by chemotherapy for the tumor which resulted in dramatic
decline in β-hCG and improvement in his symptoms.
Discussion: Cross reaction with TSH receptors of
excessive levels of hCG in the first trimester of pregnancy or rarely in hCG secreting tumors may cause hyperthyroidism. Signs of hyperthyroidism in these patients
are obscured by features accompanying malignancy.
Tachycardia, tremor, gynecomastia, lid retraction and
proximal myopathy can be observed. Symptoms of hyperthyroidism in hCG secreting malignant disease represent a
paraneoplastic syndrome and therefore the definitive treatment is treatment of the cancer itself.
Conclusion: HCG induced hyperthyroidism in GCTs
is a rare event and can present with clinical signs of hyperthyroidism. Definitive treatment lies in treating the cancer.
Symptomatic therapy with β-receptor antagonists and/
or thyrostatic drugs may be of benefit until HCG levels
normalize.
– 180 –
ABSTRACTS – Subject & Author Index
Adrenal Disorders
Author
Agosto, Marielba
Agudelo, Nelson
Allende, Myriam
Ang, Nerissa Sia
Aoun, Paul
Aragon, Jimmy B.
Armellini, Denise
Aydin, Yusuf
Ayyagari, Aparna Madhav
Baciu, Ionela
Badiu, Corin
Bailey, Joy
Barnard, Karen
Berker, Dilek
Burshell, Alan
Cabral, Jose Maireni
Caner, Sedat
Chen, Louis C.
Cherqaoui, Rabia
Coculescu, Mihail
Concha, Ana Cecilia Apaza
Dailey, George
Doherty, Gerard M.
Elamin, Mohamed B.
Erden, Gonul
Fine, Kara Rysman
Gandikota, Praveena
Gauger, Paul G.
Ghany, Reyan
Gheorghiu, Monica Livia
Gossain, Ved V.
Guillén, Miguel
Guler, Serdar
Hammer, Gary D.
Hebdon, G. Matthew
Horenstein, Richard
Ibrahim, Ibrahim Mamoun
Isiavwe, Afokoghene Rita
Isik, Serhat
Jackson, Timothy Kevin
Kassar, Amer
Keenan, Daniel M.
Khan-ghany, Alina
Khare, Swapnil
Khayal, Saba
Kim, Paul
Kohli, Amitpal
Kumar, Pratima
– 181 –
Abstract #
Page #
108
103
108
122
105
122
118
100
116
106
106
105
125
100
104
120
100
125
113
106
115
111
114
102
100
109
109
114
118
106
112
119
100
114
112
121
126
127
100
128
104
105
118
124
104
101
111
107
5
2
5
13
3
13
10
1
9
4
4
3
14
1
3
12
1
14
8
4
9
7
8
2
1
5
5
8
10
4
7
11
1
8
7
12
15
15
1
16
3
3
10
14
3
1
7
4
Adrenal Disorders (Cont.)
Author
Lee, Wei-An
Levitt, NS
Lopez, Ricardo
Martinez, Meliza
Mason, M. Elizabeth
Melo, Andrea Marcela Sosa
Michael, Brian Ellis
Miguel, Jhosvani
Miles, John M.
Miller, Barbra Sue
Mirza, Lubna
Montori, Victor M.
Mundra, Vishal
Murad, Hassan M.
Muthusamy, Kalpana
Niculescu, Dan Alexandru
Nieves-Rodriguez, Mariela
Nunlee-Bland, Gail
Ortiz, Milagros
Ozcan, Hatice Nursun
Perez, Rolando
Pinto, Miguel E.
Poiana, Catalina
Radian, Serban
Ramirez-Vick, Margarita
Reddy, Archana
Reddy, Harigopal
Reich, David
Sachmechi, Issac
Sangsiraprapha, Wiroon
Sanyal, Debmalya
Scofield, Hal
Singh, Gurpreet
Siraj, Elias S.
Siraj, Elias S.
Sofka, Sarah
Solano, Maria del Pilar
Stefanescu, Ana Maria
Tekelek,Bekir
Thukuntla, Shwetha
Trifanescu, Raluca
Tutuncu, Yasemin Ates
Ullal, Jagdeesh
Veldhuis, Johannes D.
Vijayan, Soumia
Villena, Jaime E.
Wainwright, HC
Wigham, Jean
– 182 –
Abstract #
Page #
129
127
101
108
117
115
110
104
105
114
103
102
120
102
102
106
108
113
119
100
120
119
106
106
108
112
101
101
101
101
123
103
101
116
124
128
115
106
100
107
106
100
117
105
107
119
127
105
17
15
1
5
10
9
6
3
3
8
2
2
12
2
2
4
5
8
11
1
12
11
4
4
5
7
1
1
1
1
13
2
1
9
14
16
9
4
1
4
4
1
10
3
4
11
15
3
Adrenal Disorders (Cont.)
Author
Wolali, Odonkor
Yarlagadda, Madhavi
Young, William
Zarbalian, Kiarash
Diabetes Mellitus
Author
A., Ashwin
A., Ashwin
Abubakar, Aishatu A.
Adamu, Abdullah Ndaman
Adeleye, Jokotade
Adeleye, Jokotade O.
Adibi, Peyman
Adibi, Peyman
Adler, Suzanne
Agarwal, Niti
Ahmed, Asma
Ahmed, Asma
Ahmed, Saman
Aiyangar, Ashwin
Aken’ova, Yetunde A.
Akinlade, Kehinde
Alamir, Abdul-Razzak
Ale, Ayotunde O.
Ale, Ayotunde O.
Ale, Ayotunde O.
Ale, Ayotunde O.
Ale, Ayotunde Oladunni
Alkabbani, Abdulrahaman
Amass, Tim
Amin, Nikhil
Amini, Masoud
Amini, Masoud
Amini, Masoud
Aminorroaya, Ashraf
Aminorroaya, Ashraf
Anderson, James H.
Anumah, Felicia
Ar-urachai, Katcharin
Arnaud Viñas, Maria del Rosario
Aro, Pedro Alberto
Aro, Pedro Alberto
Artchararit, Napatorn
Asnani, Sunil
B., Vyas
B., Vyas
– 183 –
Abstract #
Page #
113
124
111
121
8
14
7
12
Abstract #
Page #
233
234
268
209
254
206
230
231
226
249
207
208
221
213
206
254
252
228
228
235
250
238
240
263
226
267
230
231
288
230
231
242
277
284
245
216
278
284
243
258
262
35
36
54
22
47
21
34
34
32
44
21
22
29
24
21
47
46
33
33
36
45
38
39
51
32
53
34
34
64
34
34
40
58
62
42
26
59
62
41
49
51
Diabetes Mellitus (Cont.)
Author
B., Vyas
Babaria, Bhavikaben
Bailey, Timothy S.
Bakari, Adamu Girei
Bakari, Mohammad
Bastyr, III, Edward James
Batcher, Elizabeth
Bawa, Tarunika
Belanger, Bruce
Bello-Sani, Fatima
Berman, Lance
Bhatia, Lovleen
Bhatt, K. N.
Blonde, Lawrence
Bode, Bruce
Bode, Bruce W.
Bohannon, Nancy
Bohinc, Brittany
Bohinc, Brittany
Boigon, Margot
Boonchaya-anant, Patachaya
Boroujeni, Noushin Khalili
Boss, Anders H.
Boss, Anders H.
Boss, Anders H.
Bota, Vasile Mihai
Botros, Fady T.
Brennan, Aoife M.
Brett, Jason
Brito, Juan Pablo
C., Vyas
C., Vyas
C., Vyas
C., Vyas
C., Vyas
C., Vyas
Cabral, Howard
Calle, Carlos
Camacho, Pauline
Carlson, Anders
Cevallos-Brennan, Janet
Chandrasekaran, Mercy
Chang, Ping-Chung
Chapp-Jumbo, Emmanuel
Charitou, Marina M.
Chehade, Joe
Chen, Xiaojing
Chernoff, Authur
Chinenye, Sonny
Chinenye, Sunday
– 184 –
Abstract #
Page #
264
243
212
224
205
242
239
249
225
224
222
233
233
255
244
212
244
273
274
200
282
288
267
269
270
275
242
225
255
291
257
258
259
260
262
264
220
216
280
227
275
232
283
289
272
252
212
236
218
285
52
41
24
31
20
40
38
44
31
31
30
35
35
47
41
24
41
56
57
18
61
64
53
54
55
57
40
31
47
66
48
49
49
50
51
52
29
26
60
32
57
35
61
65
56
46
24
37
27
62
Author
Christiansen, Mark
Clough, Lynn
Cornejo, Rubelio E.
Cornejo, Rubelio Enrique
Costelo, Evangeline P.
Dada, A.O
Dada, A.O.
Dagogo-Jack, Samuel
Danciu, Sorin C.
Desai, Piyush Harshadrai
Dhar, Gauranga Chandra
Dhillon, Sundeep
Dhingra, Vibha
Dombrowski, Nicole
Adeyemi-Doro, Kunle
Durazo, Ramon
During, Maria
Dy, Pearl
Edelman, Steve V.
Edeoga, Chimaroke
Effa, Emmanuel
Egbuonu, Nonso
Emanuele, Mary Ann
Eranki, Vijay Gopal
Escalante, Angel
F., Ekere
F., Iyayi
Faghihimani, Elham
Faghihimani, Elham
Faghihimani, Elham
Fasanmade, Adesoji
Fasanmade, Olufemi
Fasanmade, Olufemi
Fasanmade, Olufemi
Fasanmade, Olufemi
Fox, Kathleen M.
Frias, Juan P.
Garber, Alan J.
Georgieva, Rumyana
Glass, Leonard C.
Gliwa, Agnieszka
Gliwa, Agnieszka
Gomez, Maria Honolina S.
Grandy, Susan
Greer, Kenneth A.
Guerrero, Sol Virginia
– 185 –
Abstract #
Page #
225
256
216
278
292
250
238
289
232
213
233
234
217
276
249
279
290
280
255
282
212
289
204
289
280
232
278
228
228
230
231
288
285
211
218
285
290
241
212
255
287
242
215
253
281
241
275
223
31
48
26
59
66
45
38
65
35
24
35
36
26
58
44
59
65
60
47
61
24
65
19
65
60
35
59
33
33
34
34
64
62
23
27
62
65
39
24
47
63
40
25
46
60
39
57
30
Author
Gupta, Ankur
Gupta, Shuchita
H., Chandarana
H., Chandarana
H., Chandarana
Haghjoo, Shaghayegh
Hardy, Elise
Hasan, Sana
Hernandez, Edith
Hipszer,Brian
Hoskote, Sumedh
Howard, Campbell P.
Howard, Campbell P.
Howard, Campbell P.
Hsia, Daniel S.
Inayatullah, Saqib
Ipadeola, Arinola
Ipp, Eli
Irwig, Michael
Islam, Muhammad
Ismail-Beigi, Faramarz
Iyer, Bhanu
Jabbar, Abdul
Jabbar, Abdul
Jain, Akshay Bhanwarlal
Jain, Meenakshi
Jayanthi, Vimala
Jobanputra, Taral
Jones, Ronald
Jongjaroenprasert, Wallaya
Jorge, Efren Jason
Jose, Tessey
Joseph, Jeffrey
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Kalra, Sanjay
Kamenov, Zdravko Asenov
Kamran, Haroon
Kelman, Adam
Kennedy, John W.
Khan, Fazlarabbi
Khurana, Sheena
– 186 –
Abstract #
Page #
272
271
258
262
264
288
241
256
216
201
213
270
267
269
246
263
254
239
226
207
229
215
207
208
237
247
226
243
256
284
232
201
201
213
233
257
258
259
260
262
264
211
287
253
244
248
286
226
56
55
49
51
52
64
39
48
26
18
24
55
53
54
42
51
47
38
32
21
33
25
21
22
37
43
32
41
48
62
35
18
18
24
35
48
49
49
50
51
52
23
63
46
41
44
63
32
Author
Kim, Paul
Kipnes, Mark S.
Ko, Wilson
Kolawole, Babatope
Kos, Elizabeth
Lasser, Karen E.
Lee, Daniel
Leshabari, Kelvin M.
Licoco, Elizabeth
Liszek, Mary Jo
Lorber, Daniel Louis
Lorenzo, Zarina Guevarra
Lovertin, Paul
Luguang, Luo
Lyatuu, Goodluck Willey
M., Agrawal
M., Ladha
Madala, Hanumath Rao
Mahr, Claudius
Malhotra, Nidhi
Manankil, Marian
Mannah, Raaid Hassan Mannaa
Manrique, Helard Andres
Marina, Anna Leonidovna
Marre, Michel
Masood, Muhammad Qamar
Mathew, Leela Mary
McCauley, Robert Andrew
McCullen, Mary Kate
McGill, Janet
McKee, Charlotte
Meenattoor, Betty
Miles, John M.
Mintz, Shari
Mithal, Ambrish
MO, Orolu
Muazu, I. M.
Muhammed, Ahmad Bello
Multani, Satendra Kumar
Muthusamy, Kalpana
N., Shyamla
N., Sisodiya
N., Sisodiya
N., Sisodiya
Nadiminty, Syamala
– 187 –
Abstract #
Page #
221
212
253
251
280
220
253
202
203
203
280
270
281
267
275
205
259
259
214
232
249
232
248
216
278
210
255
219
237
276
201
222
225
221
265
244
249
228
277
224
247
265
213
258
262
264
233
29
24
46
45
60
29
46
19
19
19
60
55
60
53
57
20
49
49
25
35
44
35
44
26
59
23
47
28
37
58
18
30
31
29
52
41
44
33
58
31
43
52
24
49
51
52
35
Author
Nadiminty, Syamala
Nambi, Sridhar
Naseri, Hussain
Nathan, Muriel
Nauck, Michael
Niaki, Michael
Noriega, Julio
Nwagbara, Bridget Akudo
O., Dada
Ofoegbu, Esther
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Okpe, Innocent Onoja
Oladejo, Ayoola Olukunmi
Olubusola, Adeleye O.
Olubusola, Adeleye Olufunmilayo
Olugbodi, Tomi
Ongphiphadhanakul, Boonsong
Ortiz, Milagros
Oshungbohun, Itunuoluwa Yewande
Osi-Ogbu, Ogugua
P., Brahmkshatriya Priyanka
Padmanabhuni, Amitha
Panikar, Vijay
Panikar, Vijay
Parapunova, Rumyana
Paras, Christos
Parker, John
Parker, John
Pathan, Faruque
Payne, Hildegarde
Pedersen-White, Jennifer
Petrucci, Richard
Phillips, Martin
Pinto, Miguel
Pinto, Miguel E.
Pinto, Miguel E.
PO, Anaja
PP, Brahmkshatriya
– 188 –
Abstract #
Page #
234
244
275
227
255
232
242
204
235
285
211
218
228
235
238
240
250
285
277
206
238
250
228
235
251
284
266
290
285
257
258
261
200
213
233
287
215
273
274
286
221
223
267
283
278
216
266
224
259
36
41
57
32
47
35
40
19
36
62
23
27
33
36
38
39
45
62
58
21
38
45
33
36
45
62
53
65
62
48
49
50
18
24
35
63
25
56
57
63
29
30
53
61
59
26
53
31
49
Author
PP, Brahmkshatriya
PP, Brahmkshatriya
PP, Brahmkshatriya
Prabhu, Mukhyaprana M.
Puepet, Fabian H.
R., Balasubramanian
R., Phatak Sanjiv
Rabbani, Madiha
Rahman, Anisur
Rao, Nagashree Gundu
Raskin, Philip
Razak, Abdul
Reich, David
Ren, Hao
Ren, Hao
Resvanian, Hasan
Resvanian, Hasan
Reynolds, L. Raymond
Richardson, Peter C.
Rilling, Alexander
Rizzo, Vincent
RK, Goyal
Rodbard, Helena Wachslicht
Rosenberg, Daniel
Rosenfeld, Cheryl R.
Rosenzweig, James
Rossell, German
Rossiter, Alicia
Rossiter, Alicia
Russell-Jones, David
Ryan, Margaret
S., Vishwanathan
Saad, Marian Gaber
Saadatnia, Mohamad
Sabharwal, Anup
Saboo, Banshi Damodarlal
Sachmechi, Issac
Salak, Kathleen
Salem, James K.
Sandberg, Mark
Sangar, Madhusudhan
Savarese, Vincent
– 189 –
Abstract #
Page #
260
262
264
214
268
214
257
219
286
271
283
214
221
269
270
230
231
279
267
283
226
221
261
241
200
244
220
232
269
283
255
201
214
229
288
291
257
258
259
260
261
262
264
221
253
256
244
214
201
50
51
52
25
54
25
48
28
63
55
61
25
29
54
55
34
34
59
53
61
32
29
50
39
18
41
29
35
54
61
47
18
25
33
64
66
48
49
49
50
50
51
52
29
46
48
41
25
18
Author
Scaunasu, Adrian
Schorr, Alan
Sen, Sabyasachi
Severance, Randall
Shah, Bharat
Shah, Niti
Shah, Sanjiv J.
Shah, Sanjiv J.
Shah, Sanjiv J.
Shah, Sanjiv J.
Shah, Sanjiv J.
Shah, Sanjiv J.
Shamim, Khusro
Shi, Leon
Shu, Jianfen
Sialongo, Roselyn E.
Siu, Sarah
Smushkin, Galina
Soe, Kyaw K.
Solis, Jose
Solis, Jose
Sood, Poonam
SR, Phatak
Stote, Robert
Strange, Poul
Strange, Poul
Sweet, David
Tak, Vinay
Tan, Gerry H.
Taweewongsoontorn, Aruchalean
Terry, Peter
Threlkeld, Rebecca
Touza, Mariana Garcia
Trence, Dace Lilliana
Trivedi, Nitin
Uloko, Andrew Enemako
Uloko, Ayekame Tini
Unachukwu, Chioma N.
Uribe, Ana
Vaickus, Louis
Valentin, Maureen V.
Vargas, Estanislao Ramirez
Villena, Jaime E.
Vimalananda, Varsha
Wang, Xaingbing
Wang, Zhengke
Weinstein, Richard
Xiong, Fang
– 190 –
Abstract #
Page #
243
244
263
222
213
233
257
258
259
260
262
264
207
244
242
292
253
265
215
216
278
226
260
222
222
244
256
253
292
284
253
242
215
210
282
268
285
268
204
239
225
281
245
266
220
276
275
225
275
41
41
51
30
24
35
48
49
49
50
51
52
21
41
40
66
46
52
25
26
59
32
50
30
30
41
48
46
66
62
46
40
25
23
61
54
62
54
19
38
31
60
42
53
29
58
57
31
57
Author
Yalla, Naga M.
Yu, Wen
Zubairi, Lubna
Hypoglycemia
Author
Abstract #
Page #
279
267
207
59
53
21
Abstract #
Page #
Abstract #
Page #
403
405
407
409
410
409
402
410
400
400
406
403
403
405
403
405
404
409
403
410
408
403
403
405
402
401
403
401
403
410
404
409
401
410
409
403
408
407
69
70
71
72
73
72
69
73
68
68
71
69
69
70
69
70
70
72
69
73
72
69
69
70
69
68
69
68
69
73
70
72
68
73
72
69
72
71
No Entries
Lipid Disorders
Author
Abby, Stacey L.
Ahmed, Waqas
Akinlade, Akinyele Taofiq
Alba, Laura M.
Alcade, Rosalyn R.
Bhatti, Hammad
Bulchandani, Deepti
Ellrodt, Gray
Farahani, Pendar N.
Fasanmade, Olufemi
Fonseca, Vivian A.
Garvey, W. Timothy
Glueck, Charles J.
Goldberg, Ronald B.
Goldenberg, Naila
Haas, Michael J.
Haas, Michael J.
Handelsman, Yehuda
Herndon, Betty
IA, Abioye
Jin, Xiaoping
Jones, Michael R.
Khan, Naseer A.
Kim, Paul
Kourkoumpetis, T.
Lai, Yu-Ling
Livanis, G.
Misir, Soamnauth
Molteni, Agostino
Mooradian, Arshag D.
Mylonakis, E.
Nachnani, Jagdish S.
Naem, Emad
Nagendran, Sukumar
Ogbera, Anthonia O.
Ogbera, Anthonia Okeoghene
– 191 –
Lipid Disorders (Cont.)
Author
Ohwovoriole, Efedaye
Peleg, A.
Reich, David M.
Rosenstock, Julio
Sabir, Anas Ahmad
Sachmechi, Issac
Spanakis, Ilias
Sultan, Senan
Sultan, Senan
Whang, Ping
Wong, Norman C.W.
Metabolic Bone Disorders
Author
Agosto, Marielba
Allende, Myriam
Aloi, Joseph A.
Anabtawi, Abeer W.
Apaza-Concha, Ana Cecilia
Arnold, Andrew
Arora, Harkesh
Asnani, Sunil
Asnani, Sunil
Asnani, Sunil
Ayoub, Walaa A.
Baffoni, Claudia
Balestra, Ricardo
Barakat, Shadi
Barboza, Vanessa Escobar
Barengolts, Elena
Bejnariu, Cristina Iuliana
Bhadada, Sanjay
Bhan, Arti
Bhansali, Anil
Bindra, Sanjit S.
Bohinc, Brittany
Bohinc, Brittany
Borretta, Giorgio
Borretta, Valentina
Borst, Kevin L.
Borst, Kevin L.
Brietzke, Stephen
Brooks, Joel
Bruno, Christopher
Bucuras, Dana
Bucuras, Dana
Burshell, Allan
– 192 –
Abstract #
Page #
406
408
401
402
403
406
402
401
404
409
405
409
71
72
68
69
69
71
69
68
70
72
70
72
Abstract #
Page #
513
513
522
534
538
505
522
532
533
535
514
512
527
525
500
511
521
508
507
508
514
523
524
512
512
506
507
525
511
510
517
518
519
81
81
86
92
94
76
86
91
92
93
81
80
88
87
74
80
85
78
77
78
81
86
87
80
80
77
77
87
80
79
83
84
84
Metabolic Bone Disorders (Cont.) Author
Carlson, Harold E.
Cesario, Flora
Chaidarun, Sushela
Chaudhari, Shobhana
Chaychi, Leila
Cherepanova, Olga
Cohen-Lehman, Janna
Croce, Chiara Giulia
Dadu, Ramona
Daiana, Dragsineantu
Das, Sambit
Daw, Hamed
Ecaterina, Pavel
Ecaterina, Pavel
Elkins, Blake
Emmolo, Ignazio
Fackler, Sarah
Faichney, John David
Fernandez, Gina Gerardine Santos
Florea, Maria
Florez, Hermes
Gianotti, Laura
Golding, Allan
Grenfell, III, Raymond
Guddeti, Pallavi
Gulati, Shuchi
Gutierrez, Cristina
Huang, Jian
Ioan, Simedrea
Jiménez-Montero, Jose Guillemo
Juan, Zinnia San
Kamouh, Abdallah
Katz, Herman
Kaur, Harpreet
Kelly, Jennifer
Krikorian, Armand Ara
Kyaw, Tin Tin
Lagunas-Fitta, Myriam
Lann, Danielle Erin
Laufgraben, Marc J.
Lieb, David C.
Mahpara, Swaleha
Marginean, Otilia
Marginean, Otilia
Martinez, Meliza
Mathew, Leela Mary
Memoli, Vincent
Menoscal, Jean-Paul
– 193 –
Abstract #
Page #
530
512
503
504
503
511
531
512
520
518
508
516
517
518
515
512
515
537
504
517
538
512
503
519
505
516
500
529
518
536
519
528
530
510
510
528
529
500
535
501
522
533
517
518
513
534
538
503
500
90
80
75
76
75
80
91
80
85
84
78
83
83
84
82
80
82
94
76
83
94
80
75
84
76
83
74
90
84
93
84
89
90
79
79
89
90
74
93
74
86
92
83
84
81
92
94
75
74
Moses, Arnold
Naing, Soe
Neagu, Valeriu
Nwotite, Ezinne
Ohri, Anup
Onyeaso, Elizabeth
Onyeaso, Nduche
Paliou, Maria
Panunti, Brandy
Parker, John
Parker, John
Patel, Lipi Sekhadia
Patel, Romil
Patel, Ushir
Pathak, Neil
Pellegrino, Micaela
Penagaluru, Neena
Piech, Melissa Roether
Pinsker, Richard W.
Ramanathan, Ranjani
Ramirez, Maragarita
Rao, Sudhaker
Rao, Sudhaker
Riccardi, Timothy
Rohena, Jorge
Rosabal-Arce, Alexandra
Salat, Reema
Saleem, Tipu F.
Santhanam, Prasanna
Shah, Sapna S.
Sharma, Mohan
Shimshi, Mona
Siegel, Alan
Simedrea, Ioan
Suciu, Pavel
Sy, Alexander
Tassone, Francesco
Taylor, Harris
Titi, Mohammad
Towler, Dwight
Uzcategui, Nicolas
Valsamis, Ageliki
Vargas, Socorro
Venkatraman, Padma
Washington, Terri
Wasman, Jay K.
Weinerman, Stuart
– 194 –
Abstract #
Page #
510
529
511
533
535
533
533
504
519
523
524
511
532
532
526
512
532
501
526
509
513
527
506
507
510
513
536
532
502
502
528
526
520
503
517
521
504
512
516
534
509
510
531
505
502
511
528
531
79
90
80
92
93
92
92
76
84
86
87
80
91
91
88
80
91
74
88
79
81
88
77
77
79
81
93
91
75
75
89
88
85
75
83
85
76
80
83
92
79
79
91
76
75
80
89
91
Zahra, Tazneem
Zamfirescu, Isabelle
Obesity
Author
Alfonso, Bianca
Anhalt, Henry
Barbu, Carmen
Bhangoo, Amrit
Blum, Kenneth
Braverman, Eric
Case, Christopher
Damle, Uma
Dragan, Micic
Fica, Simona Vasilica
Florea, Suzana
Godbole, Chinmay
Godbole, Sanjay Ganesh
Gupta, Rishi
Heshmati, Hassan Massoud
Huang, Stanley
Ikem, Rosemary Temidayo
Kerner, Mallory
Kolawole, Babatope
Lenghen, Claudia
Mahadik, Sujata
Martin, Sorina
Matthews, Nicole A.V.
Mettayil, Jeevan
Narwal, Shivinder
Olorunfemi, Adebayo Joseph
Poiana, Catalina
Quon,Jennifer
Ron, Eyal
Sannino, Alessandro
Savarimuthu, Stella
Shah, Bhagyashri
Shah, Nirav R.
Sirbu, Anca
Soyoye, David
Stamenkovic-Pejkovic, Danica
Sumarac-Dumanovic, Mirjana
Tacchino, Roberto
– 195 –
Abstract #
Page #
500
530
74
90
Abstract #
Page #
601
601
604
610
603
610
609
609
600
609
607
603
603
602
602
610
605
609
608
606
609
606
603
602
603
610
608
610
601
606
603
609
605
605
609
602
609
603
606
607
607
605
96
96
98
101
97
101
100
100
96
100
99
97
97
97
97
101
98
100
100
99
100
99
97
97
97
101
100
101
96
99
97
100
98
98
100
97
100
97
99
99
99
98
Obesity (Cont.)
Author
Ten, Svetlana
Via, Michael
Wetzler, Gracilla
Zohar, Yishai
Other
Author
Abdel-Baky, Mohamad Salah Eldin
Abdel-Mohsen, Dalia
Afsana, Faria
Agosto, Marielba
Aguilar-Salinas, Carlos A
Aguilar-Salinas, Carlos A.
Al-Jumaili, Ali Hasan Dhari
Alappat, Rosemaria
Allende, Myriam
Almeda-Valdes, Paloma
Alsharif, Abdel
Anabtawi, Abeer W.
Anand, Rishi
Apostu, Luminita
Arellano-Campos, Olimpia
Asnani, Sunil
Avendaño Vazquez, Edgar
Aziz, Faiza
Bakir, Fatih
Balasubramanian, R.
Bantouna, Dimitra
Belbruno, Kathleen
Belzarena, Cristina
Berkelhammer, Charles
Berker, Dilek
Bickerton, Alex
Bohinc, Brittany
Busta, Augustin
Carsote, Mara
Cavaghan, Melissa K.
Cetin, Mustafa
Cetin, Zehra Guven
Chaudhuri, Ajay
Chaudhuri, Ajay
Chaychi, Leila
Chirita, Corina
Cicekcioglu, Hulya
– 196 –
Abstract #
Page #
610
604
610
605
101
98
101
98
Abstract #
Page #
721
721
707
717
715
706
710
701
724
715
706
710
713
735
720
724
709
706
710
735
713
732
722
711
734
727
733
730
722
703
736
708
726
705
722
722
731
728
727
726
722
113
113
106
111
110
105
107
102
114
110
105
107
109
120
112
114
106
105
107
120
109
119
113
108
120
116
119
118
113
103
121
106
116
104
113
113
118
117
116
116
113
Other (Cont.)
Author
Croitoru, Adina
Cruz-Bautista, Ivette
Cuevas-Ramos, Daniel
Dandona, Paresh
Dandona, Paresh
Dhindsa, Sandeep
Dhindsa, Sandeep
Doss, Umarshanker
Drincic, Andjela
Dunn, Barbara
El-Aziz, Noran Osama
Elhomsy, Georges Chehade
Enang, Ofem Egbe
Ene, Cristina
Fasanmade, Olufemi
Fasanmade, Olufemi
Galesanu, Corina H.
García Ramos, Freddy
Golding, Allan
Gomez-Perez, Francisco J.
Guler, Serdar
Haas, Michael J.
Hafez, Eman Ahmed
Hammad, Aziza Abdel Moez
Harshfield, Greg
Hurst, Margaret
Iovita, Petronela
Iranmanesh, Ali
Isik, Serhat
Iwuala, Sandra O.
Jayaraman, Muthukrishnan
Karanchi, Harsha
Khan, Khurshid Ahmad
Konduru, Chandana
Kothapally, Jaya Reddy
Kovesdy, Csava
Lawson, Donna
Lesi, Olufunmilayo
Lohano, Teekam
Lohano, Teekam
Lteif, Amale A.
Luque Cuba, Edith Jacqueline
Marrero Mcfaline,Yanira Ivelisse
Martinez, Meliza
– 197 –
Abstract #
Page #
726
706
710
706
710
713
728
731
728
731
720
723
725
721
704
702
726
702
714
709
738
727
706
710
713
722
712
721
721
700
720
709
725
722
714
737
716
718
724
723
725
725
714
728
731
705
738
715
715
116
105
107
105
107
109
117
118
117
118
112
114
115
113
104
103
116
103
109
106
122
116
105
107
109
113
108
113
113
102
112
106
115
113
109
121
110
111
114
114
115
115
109
117
118
104
122
110
110
Other (Cont.)
Author
Mehta, Roopa
Metha, Roopa
Meza-Arana, Clara Elena
Mueller, Eric J.
Murathanun, Rachanon
Navarrate-López, Mariana
Navarrete-Lopez, Mariana
Ohwovoriole, Augustine
Ozuguz, Ufuk
Pacak, Karel
Palacio, Carlos
Paparodis, Rodis
Parikh, Grishma
Parker, John Charles
Parsons, Dominic
Patel, Shashi
Penagaluru, Neena
Perez, Jr., Jose A.
Pineyro, Mercedes
Poiana, Catalina
Pramodh, Seshadrinathan
Rabbani, Madiha
Raheja, Prafull
Rajamani, Krishna Kumar
Ramirez, Margarita
Rawal, Deepti
Razak, Abdul
Reza-Albarran, Alfredo
Rull, Juan
S., Vishwanathan
Salat, Reema
Samoila, Ramona
Sangar, Masdhusdhan
Santiago, Alejandra
Schickler, Renee
Schwarcz, Monica
Sekhar, Prashanth Chandra
Serra, Maria del Pilar
Sheikh-Ali, Mae
Shiferaw, Zewge
Simmons, Debra
Singal, Pooja
Sosa, Gabriela
Stefan, Delia
– 198 –
Abstract #
Page #
719
713
710
706
704
712
716
730
706
710
702
722
704
720
734
708
736
703
720
700
735
716
733
726
711
703
719
712
720
715
728
711
713
713
711
735
726
711
715
734
724
700
733
712
732
729
705
733
729
112
109
107
105
104
108
110
118
105
107
103
113
104
112
120
106
121
103
112
102
120
110
119
116
108
103
112
108
112
110
117
108
109
109
108
120
116
108
110
120
114
102
119
108
119
117
104
119
117
Other (Cont.)
Author
Terzea, Dana
Trifanescu, Raluca-Alexandra
Ucar, Ozgul
Varanasi, Ajay
Vora, Mehul Ratilal
Whitesides, Jr., Paul Caldwell
Yasmeen, Tahira
Zamora, Haidee David
Zeballos, Maria
Pituitary Disorders
Author
Albu, Jeanine
Apaza Concha, Ana Cecilia
Azad, Nasrin
Baker, Mary Zoe
Bakhru, Nitasha
Batra, Manav
Bhatti, Hammad
Bickerton, Alex
Carsote, Mara
Cervellione, Kelly L.
Chhabra, Vaninder S.
Chirita, Corina
Christofides, Elena A.
Ciofoaia, Victor
Dandona, Paresh
Delashaw, Johnny B.
Demetri, Charalambos
Devabhaktuni, Madhuri
Dillard, Troy
Dillard, Troy
Doshi, Kaushik
Dumitrascu, Anda
Edenfield, Jeff
Escalaya, Glenda
Escalaya, María E.
Fleseriu, Maria
Fleseriu, Maria
Galloway, Allison
Gandikota, Praveena
Ghany, Reyan
Guillen, Danny
Hong, Lee
Hortopan, Dan
Houser, Dana Patrick
– 199 –
Abstract #
Page #
726
726
722
728
731
736
730
729
733
116
116
113
117
118
121
118
117
119
Abstract #
Page #
800
822
818
824
815
809
823
821
805
814
813
819
817
813
820
808
821
810
802
822
804
810
819
813
807
806
806
804
810
809
822
812
819
815
813
820
123
135
133
136
131
128
135
134
126
130
130
133
132
130
134
127
134
128
124
135
125
128
133
130
127
126
126
125
128
128
135
129
133
131
130
134
Pituitary Disorders (Cont.)
Author
Ioachimescu, Adriana G.
Ioja, Simona
Kannan, Subramanian
Kanth, Pooja
Khan-ghany, Alina
Kim, Paul
Kulaga, Mark
Kulkarni-Date, Mrinalini
Leonardo, Jody
Levine, Matthew
Licata, Angelo
Lohano, Teekam
Miranda-Palma, Bresta
Musat, Madalina
Neuwelt, Edward A.
Oyesiku, Nelson M
Oyesiku, Nelson M.
Padmanabhan, Sailatha
Parsons, Dominic
Pastorini, Vitor
Phil, D.
Pimentel, Diana M.
Pinsker, Richard W.
Pinto, Jose L.
Pinto, Miguel E.
Poiana, Catalina I.
Prieto Sanchez, Luz Marina
Puepet, Fabian H.
Rahi, Qasim
Rahnema, Fariba
Rawal, Deepti
Reich, David
Rennert, Nancy J
Rustagi, Tarun
Sachmechi, Issac
Sclair, Seth
Senatus, Patrick
Shah, Birju
Shah, Rakhi
Shah, Reshma
Shoukri, Kamal
Silva, Enrique
Sosa-Melo, Andrea Marcela
Taylor, Sherry
Terzea, Dana
– 200 –
Abstract #
Page #
811
817
808
801
819
812
805
808
803
821
823
811
821
812
813
810
811
817
809
814
812
814
817
819
806
806
813
814
818
816
800
803
821
805
808
801
805
812
801
819
803
811
802
802
824
818
824
802
813
129
132
127
123
133
129
126
127
125
134
135
129
134
129
130
128
129
132
128
130
129
130
132
133
126
126
130
130
133
132
123
125
134
126
127
123
126
129
123
133
125
129
124
124
136
133
136
124
130
Pituitary Disorders (Cont.)
Author
Uloko, Ayekame Tini
Varanasi, Ajay
Von Hofe, Stanley Edward
Wei, Kevin S.
Yedinak, Chris
Yedinak, Chris
Yusuf, Shehu M.
Reproductive Endocrinology
Author
Aflorei, Daniela
Ajayi, Godwin O
Akbaba, Gulhan
Albu, Jeanine
Alexandrou, Andreas
Alexandrou, Andreas
Aravantinos, Leon
Baculescu, Nicoleta
Berker, Dilek
Botelho, Julianne Cook
Brosnan, Patrick G.
Butler, Brittany E.
Caragheorgheopol, Andra
Cheng, Vicky
Christodoulakos, George
Coculescu, Mihail Gr.
Creatsa, Maria
Creatsa, Maria
Doshi, Krupa
Faiman, Charles
Falcone, Tommaso
Gandikota, Praveena
Goulis, Dimitrios G.
Grigorescu, Florin
Grogoriou, Odysseas
Gul Alimli, Ayse
Guler, Serdar
Gussi, Ilinca
Iliadou, Paschalia K.
Iranmanesh, Ali
Iranmanesh, Ali
Isik, Serhat
Jehaimi, Cayce
Kaparos, George
Kaparos, George
Karademir, Mehmet Alp
– 201 –
Abstract #
Page #
816
816
821
807
804
804
810
816
132
132
134
127
125
125
128
132
Abstract #
Page #
911
900
905
910
901
902
901
911
905
908
903
908
911
904
901
902
911
901
902
904
904
904
910
909
911
902
905
905
911
909
907
906
905
903
901
902
905
143
137
140
142
138
138
138
143
140
141
139
141
143
139
138
138
143
138
138
139
139
139
142
142
143
138
140
140
143
142
141
140
140
139
138
138
140
Reproductive Endocrinology (Cont.)
Author
Karaflou, Maria
Karaflou, Maria
Ketlz, Martin
Kouskouni, Evangelia
Lambrinoudaki, Irene
Logothetis, Emanuel
Logothetis, Emanuel
Omilabu, Sunday A.
Osinubi, Abraham Adewale
Ozuguz, Ufuk
Padmanabhan, Hema
Padmanabhan, Hema
Panoulis, Constantinos
Papadimas, Ioannis
Radian, Serban
Rizos, Demetrios
Rubio, Nunilo I.
Tangpricha, Vin
Tarlatzis, Basil C.
Toulis, Konstantinos A.
Tsametis, Christos
Vesper, Hubert W.
Wellington, J.O.
Thyroid Disease
Author
Abdelwahab, Suliman
Abdo, Toufic
Abele, John S.
Adamczewski, Zbigniew
Adeleye, Jokotade
Ahmed, Asma
Ahmed, Asma
Ahmed, Intekhab
Akande, Temilola
Akbaba, Gulhan
AlAama, Jumana
Allen, Lynn
Almeda, Paloma
Alon, Eran
Amini, Masoud
Amorosa, LF
Anastasilakis, Athanasios D.
– 202 –
Abstract #
Page #
901
902
910
902
901
902
901
902
900
900
905
905
906
907
902
909
911
901
903
908
909
909
909
905
908
900
138
138
142
138
138
138
138
138
137
137
140
140
140
141
138
142
143
138
139
141
142
142
142
140
141
137
Abstract #
Page #
1035
1046
1054
1060
1033
1006
1007
1055
1033
1005
1009
1041
1018
1016
1027
1062
1045
1042
162
168
172
175
161
147
148
173
161
146
149
165
154
153
158
176
167
166
Thyroid Disease (Cont.)
Author
Andukuri, Radha
Aniyan Poulose
Arduc, Ayse
Armas, Laura
Aro, Pedro Alberto
Asnani, Sunil
Asnani, Sunil
Asnani, Sunil
Aydin, Yusuf
Bahnampour, N.
Bal, Swomya
Balogun, Willliams
Baruah, Manash Pratim
Bazrafshan, Hamid Reza
Berker, Dilek
Berker, Dilek
Bernard, Nicola J.
Bhaghayath, Krishna
Bichala, Shalini
Bishara, Fayez
Biskobing, Diane
Bohinc, Brittany
Braverman, Lewis E.
Braverman, Lewis E.
Brito, Juan Pablo
Brzeziński, Jan
Brzeziński, Jan
Caplan Robert H.
Capuli-Isidro, Maria Jocelyn
Carcao, Manuel
Carpi, Angelo
Carson, Michael
Carsote, Mara
Chiniwala, Niyati
Chirita, Corina
Chow, Amy
Chudova, Darya
Ciric, Slavica
Cook, Gregory D.
Cornetero, Victor
Croitoru, Adina
Dagli, Muharrem
Davidov, Tomer
Dedecjus, Marek
Dedecjus, Marek
– 203 –
Abstract #
Page #
1047
1001
1005
1047
1048
1040
1063
1064
1003
1030
1064
1033
1051
1030
1003
1005
1045
1026
1047
1019
1037
1039
1062
1014
1031
1038
1060
1061
1068
1056
1065
1013
1064
1032
1055
1032
1011
1017
1028
1037
1048
1057
1032
1003
1045
1060
1061
168
144
146
168
169
165
176
177
145
160
177
161
170
ñ160
145
146
167
158
168
154
163
164
176
152
160
164
175
176
179
173
177
151
177
161
173
161
150
153
159
163
169
174
161
145
167
175
176
Author
DeMoranville, Beatrice M.
di Coscio, Giancarlo
Dickinson, Christine Z.
Divi, Rama
Doherty, Gerard M.
Drincic, Andjela
Eck, Leigh M.
Eledrisi, Mohsen
Enriquez, Bernardo Pérez
Erden, Gonul
Escalante, Angel
Faas, Fred
Faiz, Saba
Farghani, Saima O.
Farghani, Saima O.
Farwell, Alan
Fasanmade, Olufemi
Fica, Simona
Foo, Sandra
Friedlander, Camila
Friedman, Lyssa
Friedman, Lyssa
Furlong, Kevin
Fynn, Theresa
Fynn, Theresa Adadzewa
Gandikota, Praveena
Ganta, Vijaya
Gauger, Paul G.
Givens, Cheryl
Goldstein, Andrei
Guler, Serdar
Guler, Serdar
Guttler, Richard B.
H., Babul Reddy
Hamilton, Dale J.
Hasan, Farah
Hashemipour, Mahin
Haymart, Megan R.
He, Xuemei
Hislop-Chesnut, Tricia Diane
Hodge, Mary Beth
Horine, Lyndell Cheston
How, Jacques
Hughes, David T.
Hussain, Hammad
Imam, Mohamad
– 204 –
Abstract #
Page #
1031
1013
1066
1068
1012
1047
1069
1019
1016
1003
1048
1026
1034
1029
1045
1025
1043
1032
1018
1017
1004
1017
1055
1058
1035
1018
1035
1012
1052
1032
1042
1003
1005
1054
1050
1020
1002
1062
1012
1014
1021
1021
1026
1022
1012
1069
1069
160
151
178
179
151
168
180
154
153
145
169
158
162
159
167
157
166
161
154
153
146
153
173
174
162
154
162
151
171
161
166
145
146
172
170
155
145
176
151
152
155
155
158
156
151
180
180
Author
Ipadeola, Arinola
Isik, Serhat
Isik, Serhat
Islam, Najmul
Islam, Najmul
Iwuala, Sandra Omozehio
Jabbour, Serge
Jafari, Gh.
John, Mathew
John, Philip
Joya Péñate, Kenny Sofía
K, Neelaveni
Kamani, Dipti
Kaplan, Michael M.
Karabulut, Hayriye
Karanchi, Harsha
Karawagh, Abdulah
Kasinski, David
Kebebew, Electron
Kebebew, Electron
Kedzierska, Anna
Kennedy, Giulia C.
Kennedy, Giulia C.
Keshteli, Ammar Hassanzadeh
Khanpour, Samaneh
Kordek, Radzislaw
Kouvelas, Dimitrios
Kozak, Jozef
KV, Ragi
Lakshman, Kishore M.
Lanman, Richard Burnham
Lee, Stephanie
Lee, Stephanie
Lee, Sun
Leung, Angela M.
Leveque, Christopher
Lewinski, Andrzej
LiVolsi, Virginia
LiVolsi, Virginia
Lizarzaburu, Juan Carlos
Ma, Ly
Mahant, Sanjay
Makdissi, Antoine
Mathiason, Michelle A.
Mcdaniel, Fredysha
– 205 –
Abstract #
Page #
1033
1003
1005
1006
1007
1043
1055
1030
1001
1065
1016
1050
1024
1066
1003
1020
1009
1046
1004
1017
1061
1004
1017
1062
1062
1061
1042
1061
1001
1031
1004
1017
1025
1059
1014
1014
1020
1060
1004
1017
1057
1045
1065
1026
1048
1068
1058
161
145
146
147
148
166
173
160
144
177
153
170
157
178
145
155
149
168
146
153
176
146
153
176
176
176
166
176
144
160
146
153
157
175
152
152
155
175
146
153
174
167
177
158
169
179
174
Author
Mechanick, Jeffrey
Mena, Alexandra Balma
Miller, Barbra Sue
Miller, Jeffrey
Motiramani, Nikhil
Motiramani, Nikhil
Naem, Emad
Nasser, Tariq Abdulrahman
Neuffer, John
Newton, Kaye-Anne
Nicolini, Andrea
Nuñez, Valery
Nunlee-Bland, Gail
Nyenwe, Ebenezer A.
O’Brian, John T.
O’Donnell, Amy
Odonkor, Wolali
Ohri, Anupam
Ohri, Anupam
Ozuguz, Ufuk
Ozuguz, Ufuk
Pagan, Morita
Pakdaman, Michael
Pakdaman, Michael
Pakdaman, Michael
Parker, John
Paul, Bhakti
Paulk, Douglas G.
Payne, Richard J.
Payne, Richard J.
Pearce, Elizabeth N.
Pedersen-White, Jennifer R.
Peretianu, Dan
Perlman, Kusiel
Pietras, Sara
Pinto, Miguel
Poiana, Catalina
Poiana, Catalina I.
Ponte, Jr., Gaston Marcos
Pope, Elena
Pramyothin, Pornpoj
Qari, Faiza
Rabbee, Nusrat
Radian, Serban
Ramesh, Jayanthi
Randolph, Gregory W.
– 206 –
Abstract #
Page #
1013
1065
1012
1055
1063
1064
1002
1041
1009
1015
1058
1013
1057
1035
1052
1053
1046
1035
1040
1063
1003
1005
1000
1017
1022
1023
1024
1039
1010
1066
1022
1023
1014
1044
1032
1065
1059
1048
1036
1032
1067
1065
1059
1009
1017
1036
1050
1024
151
177
151
173
176
177
145
165
149
152
174
151
174
162
171
171
168
162
165
176
145
146
144
153
156
157
157
164
150
178
156
157
152
167
161
177
175
169
163
161
179
177
175
149
153
163
170
157
Author
Reynolds, Jessica
Rochon, Louise
Rosai, Juan
Rosai, Juan
Rossi, Giuseppe
Rubin, Daniel
Sahay, Rakesh Kumar
Saleem, Tipu
Sanalkumar, Nishanth
Santhanam. Parsana
Sanusi, Ibilola A.
Schimke, Robert N.
Sheikh-Ali, Mae
Sher, Jay A.
Shirodkar, Monika
Signalov, Mikhail
Solis, Jose
Sosa, Andrea
Spaulding, Stephen
Strozyk, Grzegorz
Taneja, Deepa
Terzea, Dana
Tom, Ed
Trabolsi, Mais
Trooskin, S.
Tutuncu, Yasemin
Tzellos, Thrasivoulos G.
Ullal, Jagdeesh
Urken, Mark
Vahedi, S.
Varanasi, Ajay
Vasilica, Madalina
Veloski, Colleen
Wang, Charles
Wang, Chung-Che Charles
Wang, Eric
Wang, Hui
Wang, Xiangbing
Wasserman, Jonathan
Weber, Sandra L.
Wei, Sun
Wilde, Jonathan
Woode, Dwain E.
Woody, Christopher
– 207 –
Abstract #
Page #
1017
1049
1023
1004
1017
1013
1025
1050
1034
1001
1034
1043
1069
1041
1029
1055
1066
1048
1038
1046
1061
1049
1032
1017
1042
1002
1036
1045
1003
1005
1042
1053
1027
1030
1046
1036
1008
1017
1004
1017
1017
1011
1065
1015
1011
1017
1052
1015
153
169
157
146
153
151
157
170
162
144
162
166
180
165
159
173
178
169
164
168
176
169
161
153
166
145
163
167
145
146
166
171
158
160
168
163
148
153
146
153
153
150
177
152
150
153
171
152
Author
Yalla, Naga M.
Yaqub, Abid
Yarlagadda, Madhavi
Yasmeen, Tahira
Ywakim, Rania
Zeiger, Martha
Zeiger, Martha
– 208 –
Abstract #
Page #
1049
1034
1008
1002
1022
1004
1017
169
162
148
145
156
146
153
ABSTRACTS – Author Index
Author (Cont.)
Author
A., Ashwin
A., Ashwin
Abby, Stacey L.
Abdel-Baky, Mohamad Salah Eldin
Abdel-Mohsen, Dalia
Abdelwahab, Suliman
Abdo, Toufic
Abele, John S.
Abubakar, Aishatu A.
Adamczewski, Zbigniew
Adeleye, Jokotade
Adeleye, Jokotade
Adeyemi-Doro, Kunle
Adibi, Peyman
Adibi, Peyman
Adler, Suzanne
Aflorei, Daniela
Afsana, Faria
Agarwal, Niti
Agosto, Marielba
Agosto, Marielba
Agosto, Marielba
Agudelo, Nelson
Aguilar-Salinas, Carlos A
Aguilar-Salinas, Carlos A.
Ahmed, Asma
Ahmed, Asma
Ahmed, Asma
Ahmed, Asma
Ahmed, Intekhab
Ahmed, Saman
Ahmed, Waqas
Aiyangar, Ashwin
Ajayi, Godwin O
Akande, Temilola
Akbaba, Gulhan
Akbaba, Gulhan
Akinlade, Akinyele Taofiq
Akinlade, Kehinde
– 209 –
Abstract ##
Abstract
Page ##
Page
233
234
403
721
721
1035
1046
1054
268
1060
209
707
254
1033
206
601
290
230
231
226
911
717
249
108
513
715
103
706
710
207
208
1006
1007
1055
221
405
213
900
1033
1005
905
206
601
407
254
701
800
35
36
69
113
113
162
168
172
54
175
22
106
47
161
21
96
65
34
34
32
143
111
44
5
81
110
2
105
107
21
22
147
148
173
29
70
24
137
161
146
140
21
96
71
47
102
123
Author (Cont.)
AlAama, Jumana
Alappat, Rosemaria
Alba, Laura M.
Albu, Jeanine
Albu, Jeanine
Alcade, Rosalyn R.
Ale, Ayotunde O.
Ale, Ayotunde O.
Ale, Ayotunde O.
Ale, Ayotunde O.
Alexandrou, Andreas
Alexandrou, Andreas
Alfonso, Bianca
Alkabbani, Abdulrahaman
Allen, Lynn
Allende, Myriam
Allende, Myriam
Allende, Myriam
Almeda, Paloma
Aloi, Joseph A.
Alon, Eran
Alsharif, Abdel
Amass, Tim
Amin, Nikhil
Amini, Masoud
Amini, Masoud
Amini, Masoud
Amini, Masoud
Aminorroaya, Ashraf
Aminorroaya, Ashraf
Amorosa, LF
Anabtawi, Abeer W.
Anabtawi, Abeer W.
Anand, Rishi
Anastasilakis, Athanasios D.
Anderson, James H.
Andukuri, Radha
Ang, Nerissa Sia
Anhalt, Henry
Aniyan Poulose
– 210 –
Abstract #
Page #
1009
252
409
1041
724
410
822
910
409
228
228
235
250
238
240
901
902
604
263
1018
108
513
715
706
710
713
1016
522
1027
735
226
267
230
231
288
1062
230
231
1045
534
720
724
1042
242
1047
122
610
1001
149
46
72
165
114
73
135
142
72
33
33
36
45
38
39
138
138
98
51
154
5
81
110
105
107
109
153
86
158
120
32
53
34
34
64
176
34
34
167
92
112
114
166
40
168
13
101
144
Author (Cont.)
Anumah, Felicia
Aoun, Paul
Apaza-Concha, Ana Cecilia
Apostu, Luminita
Ar-urachai, Katcharin
Aragon, Jimmy B.
Aravantinos, Leon
Arduc, Ayse
Armas, Laura
Armellini, Denise
Arnaud Viñas, Maria del Rosario
Arnold, Andrew
Aro, Pedro Alberto
Aro, Pedro Alberto
Aro, Pedro Alberto
Arora, Harkesh
Artchararit, Napatorn
Asnani, Sunil
Asnani, Sunil
Asnani, Sunil
Asnani, Sunil
Asnani, Sunil
Asnani, Sunil
Asnani, Sunil
Asnani, Sunil
Avendaño Vazquez, Edgar
Aydin, Yusuf
Aydin, Yusuf
Ayoub, Walaa A.
Ayyagari, Aparna Madhav
Azad, Nasrin
Aziz, Faiza
B., Vyas
B., Vyas
B., Vyas
Babaria, Bhavikaben
Baciu, Ionela
Baculescu, Nicoleta
Badiu, Corin
Baffoni, Claudia
Bahnampour, N.
Bailey, Joy
Bailey, Timothy S.
Bakari, Adamu Girei
– 211 –
Abstract #
Page #
277
105
818
824
538
709
284
122
901
1005
706
710
1047
118
245
505
216
278
1048
522
284
243
532
533
535
1040
1063
1064
735
713
100
1003
514
116
815
732
258
262
264
243
106
911
106
512
1030
105
212
224
58
3
133
136
94
106
62
13
138
146
105
107
168
10
42
76
26
59
169
86
62
41
91
92
93
165
176
177
120
109
1
145
81
9
131
119
49
51
52
41
4
143
4
80
160
3
24
31
Author (Cont.)
Bakari, Mohammad
Baker, Mary Zoe
Bakhru, Nitasha
Bakir, Fatih
Bal, Swomya
Balasubramanian, R.
Balestra, Ricardo
Balogun, Willliams
Bantouna, Dimitra
Barakat, Shadi
Barboza, Vanessa Escobar
Barbu, Carmen
Barengolts, Elena
Barnard, Karen
Baruah, Manash Pratim
Bastyr, III, Edward James
Batcher, Elizabeth
Batra, Manav
Bawa, Tarunika
Bazrafshan, Hamid Reza
Bejnariu, Cristina Iuliana
Belanger, Bruce
Belbruno, Kathleen
Bello-Sani, Fatima
Belzarena, Cristina
Berkelhammer, Charles
Berker, Dilek
Berker, Dilek
Berker, Dilek
Berker, Dilek
Berker, Dilek
Berman, Lance
Bernard, Nicola J.
Bhadada, Sanjay
Bhaghayath, Krishna
Bhan, Arti
Bhangoo, Amrit
Bhansali, Anil
Bhatia, Lovleen
Bhatt, K. N.
Bhatti, Hammad
Bhatti, Hammad
Bichala, Shalini
Bickerton, Alex
Bickerton, Alex
Bindra, Sanjit S.
Bishara, Fayez
Biskobing, Diane
– 212 –
Abstract #
Page #
205
809
823
722
1064
711
527
1033
734
525
500
603
511
125
1051
242
239
821
249
1030
521
225
727
224
733
730
100
1003
1005
722
905
222
1045
508
1026
507
610
508
233
233
402
805
1047
703
814
514
1019
1037
20
128
135
113
177
108
88
161
120
87
74
97
80
14
170
40
38
134
44
160
85
31
116
31
119
118
1
145
146
113
140
30
167
78
158
77
101
78
35
35
69
126
168
103
130
81
154
163
Author (Cont.)
Blonde, Lawrence
Blum, Kenneth
Bode, Bruce
Bode, Bruce W.
Bohannon, Nancy
Bohinc, Brittany
Bohinc, Brittany
Bohinc, Brittany
Bohinc, Brittany
Bohinc, Brittany
Bohinc, Brittany
Boigon, Margot
Boonchaya-anant, Patachaya
Borretta, Giorgio
Borretta, Valentina
Borst, Kevin L.
Borst, Kevin L.
Boss, Anders H.
Boss, Anders H.
Boss, Anders H.
Bota, Vasile Mihai
Botelho, Julianne Cook
Botros, Fady T.
Braverman, Eric
Braverman, Lewis E.
Braverman, Lewis E.
Brennan, Aoife M.
Brett, Jason
Brietzke, Stephen
Brito, Juan Pablo
Brito, Juan Pablo
Brooks, Joel
Brosnan, Patrick G.
Bruno, Christopher
Brzeziński, Jan
Brzeziński, Jan
Bucuras, Dana
Bucuras, Dana
Bulchandani, Deepti
Burshell, Alan
Burshell, Allan
Busta, Augustin
Butler, Brittany E.
C., Vyas
C., Vyas
C., Vyas
– 213 –
Abstract #
Page #
255
609
244
212
244
273
274
523
524
736
1039
200
282
288
1062
512
512
506
507
267
269
270
275
908
242
609
1014
1031
225
255
525
291
1038
511
903
510
1060
1061
517
518
410
104
519
708
908
257
258
259
47
100
41
24
41
56
57
86
87
121
164
18
61
64
176
80
80
77
77
53
54
55
57
141
40
100
152
160
31
47
87
66
164
80
139
79
175
176
83
84
73
3
84
106
141
48
49
49
Author (Cont.)
C., Vyas
C., Vyas
C., Vyas
Cabral, Howard
Cabral, Jose Maireni
Calle, Carlos
Camacho, Pauline
Caner, Sedat
Caplan Robert H.
Capuli-Isidro, Maria Jocelyn
Caragheorgheopol, Andra
Carcao, Manuel
Carlson, Anders
Carlson, Harold E.
Carpi, Angelo
Carson, Michael
Carsote, Mara
Carsote, Mara
Carsote, Mara
Case, Christopher
Cavaghan, Melissa K.
Cervellione, Kelly L.
Cesario, Flora
Cetin, Mustafa
Cetin, Zehra Guven
Cevallos-Brennan, Janet
Chaidarun, Sushela
Chandrasekaran, Mercy
Chang, Ping-Chung
Chapp-Jumbo, Emmanuel
Charitou, Marina M.
Chaudhari, Shobhana
Chaudhuri, Ajay
Chaudhuri, Ajay
Chaychi, Leila
Chaychi, Leila
Chehade, Joe
Chen, Louis C.
Chen, Xiaojing
Cheng, Vicky
Cherepanova, Olga
Chernoff, Arthur
Cherqaoui, Rabia
Chhabra, Vaninder S.
Chinenye, Sonny
Chinenye, Sunday
Chiniwala, Niyati
Chirita, Corina
Chirita, Corina
Chirita, Corina
– 214 –
Abstract #
Page #
260
262
264
220
120
216
280
100
1068
1056
911
1065
227
530
1013
1064
1032
726
813
600
705
819
512
722
722
275
503
232
283
289
272
504
731
728
503
727
252
125
212
904
511
236
113
817
218
285
1055
1032
726
813
50
51
52
29
12
26
60
1
179
173
143
177
32
90
151
177
161
116
130
96
104
133
80
113
113
57
75
35
61
65
56
76
118
117
75
116
46
14
24
139
80
37
8
132
27
62
173
161
116
130
Author (Cont.)
Chow, Amy
Christiansen, Mark
Christofides, Elena A.
Chudova, Darya
Cicekcioglu, Hulya
Ciofoaia, Victor
Ciric, Slavica
Clough, Lynn
Coculescu, Mihail
Coculescu, Mihail Gr.
Cohen-Lehman, Janna
Concha, Ana Cecilia Apaza
Cook, Gregory D.
Cornejo, Rubelio E.
Cornetero, Victor
Costelo, Evangeline P.
Creatsa, Maria
Creatsa, Maria
Croce, Chiara Giulia
Croitoru, Adina
Croitoru, Adina
Dada, A.O
Dada, A.O.
Dadu, Ramona
Dagli, Muharrem
Dagogo-Jack, Samuel
Daiana, Dragsineantu
Dailey, George
Damle, Uma
Danciu, Sorin C.
Dandona, Paresh
Dandona, Paresh
Dandona, Paresh
Das, Sambit
Davidov, Tomer
Daw, Hamed
Dedecjus, Marek
Dedecjus, Marek
Delashaw, Johnny B.
– 215 –
Abstract #
Page #
1011
225
901
902
820
1017
722
808
1028
256
106
911
531
115
1037
216
278
1048
1057
292
901
902
512
1032
726
706
710
706
710
713
250
238
520
1003
289
518
111
609
232
728
731
821
508
1045
516
1060
1061
810
150
31
138
138
134
153
113
127
159
48
4
143
91
9
163
26
59
169
174
66
138
138
80
161
116
105
107
105
107
109
45
38
85
145
65
84
7
100
35
117
118
134
78
167
83
175
176
128
Author (Cont.)
Demetri, Charalambos
DeMoranville, Beatrice M.
Devabhaktuni, Madhuri
Dhar, Gauranga Chandra
Dhillon, Sundeep
Dhindsa, Sandeep
Dhindsa, Sandeep
Dhingra, Vibha
di Coscio, Giancarlo
Dickinson, Christine Z.
Dillard, Troy
Dillard, Troy
Divi, Rama
Doherty, Gerard M.
Doherty, Gerard M.
Dombrowski, Nicole
Doshi, Kaushik
Doshi, Krupa
Doss, Umarshanker
Dragan, Micic
Drincic, Andjela
Drincic, Andjela
Dumitrascu, Anda
Dunn, Barbara
Durazo, Ramon
During, Maria
Dy, Pearl
Ecaterina, Pavel
Ecaterina, Pavel
Eck, Leigh M.
Edelman, Steve V.
Edenfield, Jeff
Edeoga, Chimaroke
Effa, Emmanuel
Egbuonu, Nonso
El-Aziz, Noran Osama
Elamin, Mohamed B.
Eledrisi, Mohsen
Elhomsy, Georges Chehade
Elkins, Blake
Ellrodt, Gray
Emanuele, Mary Ann
Emmolo, Ignazio
Enang, Ofem Egbe
Ene, Cristina
– 216 –
Abstract #
Page #
802
1031
213
233
234
822
217
276
728
731
249
1013
1066
804
810
1068
114
1012
279
819
904
720
607
1047
723
813
725
280
255
282
517
518
1069
212
807
289
204
289
721
102
1019
704
515
400
280
512
702
726
124
160
24
35
36
135
26
58
117
118
44
151
178
125
128
179
8
151
59
133
139
112
99
168
114
130
115
60
47
61
83
84
180
24
127
65
19
65
113
2
154
104
82
68
60
80
103
116
Author (Cont.)
Enriquez, Bernardo Pérez
Eranki, Vijay Gopal
Erden, Gonul
Erden, Gonul
Escalante, Angel
Escalante, Angel
Escalaya, Glenda
Escalaya, María E.
F., Ekere
F., Iyayi
Faas, Fred
Fackler, Sarah
Faghihimani, Elham
Faghihimani, Elham
Faghihimani, Elham
Faichney, John David
Faiman, Charles
Faiz, Saba
Falcone, Tommaso
Farahani, Pendar N.
Farghani, Saima O.
Farghani, Saima O.
Farwell, Alan
Fasanmade, Adesoji
Fasanmade, Olufemi
Fasanmade, Olufemi
Fasanmade, Olufemi
Fasanmade, Olufemi
Fasanmade, Olufemi
Fasanmade, Olufemi
Fasanmade, Olufemi
Fasanmade, Olufemi
Fernandez, Gina Gerardine Santos
Fica, Simona
Fica, Simona Vasilica
Fine, Kara Rysman
Fleseriu, Maria
Fleseriu, Maria
Florea, Maria
Florea, Suzana
Florez, Hermes
Fonseca, Vivian A.
Foo, Sandra
Fox, Kathleen M.
Frias, Juan P.
Friedlander, Camila
Friedman, Lyssa
Friedman, Lyssa
– 217 –
Abstract #
Page #
1016
232
100
1003
278
1048
806
806
228
228
1026
515
230
231
288
537
904
1034
904
400
1029
1045
1025
285
211
218
285
290
406
1043
702
714
504
1032
603
109
804
810
517
603
538
403
1018
241
212
1017
1004
1017
153
35
1
145
59
169
126
126
33
33
158
82
34
34
64
94
139
162
139
68
159
167
157
62
23
27
62
65
71
166
103
109
76
161
97
5
125
128
83
97
94
69
154
39
24
153
146
153
Author (Cont.)
Furlong, Kevin
Fynn, Theresa
Fynn, Theresa Adadzewa
Galesanu, Corina H.
Galloway, Allison
Gandikota, Praveena
Gandikota, Praveena
Gandikota, Praveena
Gandikota, Praveena
Ganta, Vijaya
Garber, Alan J.
García Ramos, Freddy
Garvey, W. Timothy
Gauger, Paul G.
Gauger, Paul G.
Georgieva, Rumyana
Ghany, Reyan
Ghany, Reyan
Gheorghiu, Monica Livia
Gianotti, Laura
Givens, Cheryl
Glass, Leonard C.
Gliwa, Agnieszka
Gliwa, Agnieszka
Glueck, Charles J.
Godbole, Chinmay
Godbole, Sanjay Ganesh
Goldberg, Ronald B.
Goldenberg, Naila
Golding, Allan
Golding, Allan
Goldstein, Andrei
Gomez, Maria Honolina S.
Gossain, Ved V.
Grandy, Susan
Greer, Kenneth A.
Grenfell, III, Raymond
Grigorescu, Florin
Grogoriou, Odysseas
Guddeti, Pallavi
Guerrero, Sol Virginia
Guillen, Danny
Guillén, Miguel
– 218 –
Abstract #
Page #
1055
1058
1035
709
809
109
1018
822
910
1035
255
738
403
114
1012
287
118
812
106
512
1052
242
215
253
405
602
602
403
405
503
727
1032
706
710
713
281
112
1042
909
241
275
519
911
902
505
223
819
119
173
174
162
106
128
5
154
135
142
162
47
122
69
8
151
63
10
129
4
80
171
40
25
46
70
97
97
69
70
75
116
161
105
107
109
60
7
166
142
39
57
84
143
138
76
30
133
11
Author (Cont.)
Gul Alimli, Ayse
Gulati, Shuchi
Guler, Serdar
Guler, Serdar
Guler, Serdar
Guler, Serdar
Guler, Serdar
Gupta, Ankur
Gupta, Rishi
Gupta, Shuchita
Gussi, Ilinca
Gutierrez, Cristina
Guttler, Richard B.
H., Babul Reddy
H., Chandarana
H., Chandarana
H., Chandarana
Haas, Michael J.
Haas, Michael J.
Haas, Michael J.
Hafez, Eman Ahmed
Haghjoo, Shaghayegh
Hamilton, Dale J.
Hammad, Aziza Abdel Moez
Hammer, Gary D.
Handelsman, Yehuda
Hardy, Elise
Harshfield, Greg
Hasan, Farah
Hasan, Sana
Hashemipour, Mahin
Haymart, Megan R.
He, Xuemei
Hebdon, G. Matthew
Hernandez, Edith
Herndon, Betty
Heshmati, Hassan Massoud
Hipszer,Brian
Hislop-Chesnut, Tricia Diane
Hodge, Mary Beth
Hong, Lee
Horenstein, Richard
Horine, Lyndell Cheston
Hortopan, Dan
Hoskote, Sumedh
Houser, Dana Patrick
How, Jacques
Howard, Campbell P.
– 219 –
Abstract #
Page #
905
516
100
1003
1005
722
905
272
610
271
911
500
1054
1050
258
262
264
404
409
712
721
288
1020
721
114
403
241
700
1002
256
1062
1012
1014
112
216
410
605
201
1021
1021
815
121
1026
813
213
820
1022
267
140
83
1
145
146
113
140
56
101
55
143
74
172
170
49
51
52
70
72
108
113
64
155
113
8
69
39
102
145
48
176
151
152
7
26
73
98
18
155
155
131
12
158
130
24
134
156
53
Author (Cont.)
Howard, Campbell P.
Howard, Campbell P.
Hsia, Daniel S.
Huang, Stanley
Huang, Jian
Hughes, David T.
Hurst, Margaret
Hussain, Hammad
IA, Abioye
Ikem, Rosemary Temidayo
Iliadou, Paschalia K.
Imam, Mohamad
Inayatullah, Saqib
Ioan, Simedrea
Ioja, Simona
Iovita, Petronela
Ipadeola, Arinola
Ipadeola, Arinola
Ipp, Eli
Iranmanesh, Ali
Iranmanesh, Ali
Iranmanesh, Ali
Irwig, Michael
Isiavwe, Afokoghene Rita
Isik, Serhat
Isik, Serhat
Isik, Serhat
Isik, Serhat
Isik, Serhat
Islam, Muhammad
Islam, Najmul
Islam, Najmul
Ismail-Beigi, Faramarz
Iwuala, Sandra O.
Iwuala, Sandra Omozehio
Iyer, Bhanu
Jabbar, Abdul
Jabbar, Abdul
Jabbour, Serge
Jackson, Timothy Kevin
Jafari, Gh.
Jain, Akshay Bhanwarlal
Jain, Meenakshi
Jayanthi, Vimala
– 220 –
Abstract #
Page #
269
270
246
609
529
1012
720
1069
408
126
608
606
909
1069
263
811
817
518
808
709
254
1033
239
725
907
906
226
127
100
1003
1005
722
905
207
1006
1007
229
714
1043
215
207
208
1055
128
1030
237
247
226
54
55
42
100
90
151
112
180
72
15
100
99
142
180
51
129
132
84
127
106
47
161
38
115
141
140
32
15
1
145
146
113
140
21
147
148
33
109
166
25
21
22
173
16
160
37
43
32
Author (Cont.)
Jayaraman, Muthukrishnan
Jehaimi, Cayce
Jiménez-Montero, Jose Guillemo
Jin, Xiaoping
Jobanputra, Taral
John, Mathew
John, Philip
Jones, Michael R.
Jones, Ronald
Jongjaroenprasert, Wallaya
Jorge, Efren Jason
Jose, Tessey
Joseph, Jeffrey
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joshi, Shashank
Joya Péñate, Kenny Sofía
Juan, Zinnia San
K, Neelaveni
Kalra, Sanjay
Kamani, Dipti
Kamenov, Zdravko Asenov
Kamouh, Abdallah
Kamran, Haroon
Kannan, Subramanian
Kanth, Pooja
Kaparos, George
Kaparos, George
Kaplan, Michael M.
Karabulut, Hayriye
Karademir, Mehmet Alp
Karaflou, Maria
Karaflou, Maria
Karanchi, Harsha
Karanchi, Harsha
Karawagh, Abdulah
Kasinski, David
Kassar, Amer
Katz, Herman
Kaur, Harpreet
Kebebew, Electron
Kebebew, Electron
Kedzierska, Anna
– 221 –
Abstract #
Page #
737
903
536
403
243
1001
1065
403
256
284
232
201
201
213
233
257
258
259
260
262
264
1016
519
1050
211
1024
287
528
253
801
819
901
902
1066
1003
905
901
902
1020
716
1009
1046
104
530
510
1004
1017
1061
121
139
93
69
41
144
177
69
48
62
35
18
18
24
35
48
49
49
50
51
52
153
84
170
23
157
63
89
46
123
133
138
138
178
145
140
138
138
155
110
149
168
3
90
79
146
153
176
Author (Cont.)
Keenan, Daniel M.
Kelly, Jennifer
Kelman, Adam
Kennedy, Giulia C.
Kennedy, Giulia C.
Kennedy, John W.
Kerner, Mallory
Keshteli, Ammar Hassanzadeh
Ketlz, Martin
Khan-ghany, Alina
Khan-ghany, Alina
Khan, Fazlarabbi
Khan, Khurshid Ahmad
Khan, Naseer A.
Khanpour, Samaneh
Khare, Swapnil
Khayal, Saba
Khurana, Sheena
Kim, Paul
Kim, Paul
Kim, Paul
Kim, Paul
Kipnes, Mark S.
Ko, Wilson
Kohli, Amitpal
Kolawole, Babatope
Kolawole, Babatope
Konduru, Chandana
Kordek, Radzislaw
Kos, Elizabeth
Kothapally, Jaya Reddy
Kourkoumpetis, T.
Kouskouni, Evangelia
Kouvelas, Dimitrios
Kovesdy, Csava
Kozak, Jozef
Krikorian, Armand Ara
Kulaga, Mark
Kulkarni-Date, Mrinalini
Kumar, Pratima
KV, Ragi
Kyaw, Tin Tin
Lagunas-Fitta, Myriam
Lai, Yu-Ling
Lakshman, Kishore M.
– 222 –
Abstract #
Page #
105
510
244
1004
1017
248
609
1062
910
118
812
286
718
405
1062
124
104
226
101
221
402
805
212
253
111
251
606
724
1061
280
723
401
902
1042
725
1061
528
808
803
107
1001
529
500
403
1031
901
902
1004
3
79
41
146
153
44
100
176
142
10
129
63
111
70
176
14
3
32
1
29
69
126
24
46
7
45
99
114
176
60
114
68
138
166
115
176
89
127
125
4
144
90
74
69
160
138
138
146
Author (Cont.)
Lann, Danielle Erin
Lasser, Karen E.
Laufgraben, Marc J.
Lawson, Donna
Lee, Daniel
Lee, Stephanie
Lee, Stephanie
Lee, Sun
Lee, Wei-An
Lenghen, Claudia
Leonardo, Jody
Lesi, Olufunmilayo
Leung, Angela M.
Leveque, Christopher
Levine, Matthew
Levitt, NS
Lewinski, Andrzej
Licata, Angelo
Licoco, Elizabeth
Lieb, David C.
Liszek, Mary Jo
Livanis, G.
LiVolsi, Virginia
LiVolsi, Virginia
Lizarzaburu, Juan Carlos
Logothetis, Emanuel
Logothetis, Emanuel
Lohano, Teekam
Lohano, Teekam
Lohano, Teekam
Lopez, Ricardo
Lorber, Daniel Louis
Lorenzo, Zarina Guevarra
Lovertin, Paul
Lteif, Amale A.
Luguang, Luo
Luque Cuba, Edith Jacqueline
Lyatuu, Goodluck Willey
M., Agrawal
M., Ladha
Ma, Ly
Madala, Hanumath Rao
Mahadik, Sujata
Mahant, Sanjay
Mahpara, Swaleha
– 223 –
Abstract #
Page #
1017
535
220
501
725
253
1025
1059
1014
129
603
821
202
203
714
1014
1020
823
127
1060
811
203
522
280
401
1004
1017
1057
901
902
821
728
731
101
270
281
267
705
275
738
205
259
259
1045
214
602
1065
533
153
93
29
74
115
46
157
175
152
17
97
134
19
19
109
152
155
135
15
175
129
19
86
60
68
146
153
174
138
138
134
117
118
1
55
60
53
104
57
122
20
49
49
167
25
97
177
92
Author (Cont.)
Mahr, Claudius
Makdissi, Antoine
Malhotra, Nidhi
Manankil, Marian
Mannah, Raaid Hassan Mannaa
Marginean, Otilia
Marginean, Otilia
Marina, Anna Leonidovna
Marre, Michel
Marrero Mcfaline,Yanira Ivelisse
Martin, Sorina
Martinez, Meliza
Martinez, Meliza
Martinez, Meliza
Mason, M. Elizabeth
Mathew, Leela Mary
Mathew, Leela Mary
Mathiason, Michelle A.
Matthews, Nicole A.V.
McCauley, Robert Andrew
McCullen, Mary Kate
Mcdaniel, Fredysha
McGill, Janet
McKee, Charlotte
Mechanick, Jeffrey
Meenattoor, Betty
Mehta, Roopa
Memoli, Vincent
Mena, Alexandra Balma
Menoscal, Jean-Paul
Metha, Roopa
Mettayil, Jeevan
Meza-Arana, Clara Elena
Miguel, Jhosvani
Miles, John M.
Miles, John M.
Miller, Barbra Sue
Miller, Barbra Sue
Miller, Jeffrey
– 224 –
Abstract #
Page #
232
1026
249
232
248
216
278
1048
517
518
210
255
715
603
108
513
715
117
219
719
237
534
1068
610
276
201
1058
222
225
1013
221
713
115
538
503
1065
500
710
608
706
110
704
104
105
265
114
1012
1055
35
158
44
35
44
26
59
169
83
84
23
47
110
97
5
81
110
10
28
112
37
92
179
101
58
18
174
30
31
151
29
109
9
94
75
177
74
107
100
105
6
104
3
3
52
8
151
173
Author (Cont.)
Mintz, Shari
Miranda-Palma, Bresta
Mirza, Lubna
Misir, Soamnauth
Mithal, Ambrish
MO, Orolu
Molteni, Agostino
Montori, Victor M.
Moses, Arnold
Motiramani, Nikhil
Motiramani, Nikhil
Muazu, I. M.
Mueller, Eric J.
Muhammed, Ahmad Bello
Multani, Satendra Kumar
Mundra, Vishal
Murad, Hassan M.
Musat, Madalina
Muthusamy, Kalpana
Muthusamy, Kalpana
Mylonakis, E.
N., Shyamla
N., Sisodiya
N., Sisodiya
N., Sisodiya
Nachnani, Jagdish S.
Nadiminty, Syamala
Nadiminty, Syamala
Naem, Emad
Naem, Emad
Nagendran, Sukumar
Naing, Soe
Nambi, Sridhar
Narwal, Shivinder
Naseri, Hussain
Nasser, Tariq Abdulrahman
Nathan, Muriel
Nauck, Michael
Navarrate-López, Mariana
Navarrete-Lopez, Mariana
Neagu, Valeriu
Neuffer, John
Neuwelt, Edward A.
Newton, Kaye-Anne
– 225 –
Abstract #
Page #
244
812
103
403
249
228
410
102
404
409
712
510
1063
1064
277
716
224
247
120
102
1002
730
813
102
265
401
213
258
262
264
410
233
234
409
1041
403
529
244
610
275
1009
227
255
706
710
511
1015
810
1058
41
129
2
69
44
33
73
2
70
72
108
79
176
177
58
110
31
43
12
2
145
118
130
2
52
68
24
49
51
52
73
35
36
72
165
69
90
41
101
57
149
32
47
105
107
80
152
128
174
Author (Cont.)
Niaki, Michael
Nicolini, Andrea
Niculescu, Dan Alexandru
Nieves-Rodriguez, Mariela
Noriega, Julio
Nuñez, Valery
Nunlee-Bland, Gail
Nunlee-Bland, Gail
Nwagbara, Bridget Akudo
Nwotite, Ezinne
Nyenwe, Ebenezer A.
O., Dada
O’Brian, John T.
O’Donnell, Amy
Odonkor, Wolali
Ofoegbu, Esther
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia O.
Ogbera, Anthonia Okeoghene
Ohri, Anup
Ohri, Anupam
Ohri, Anupam
Ohwovoriole, Augustine
Ohwovoriole, Efedaye
Okpe, Innocent Onoja
Olorunfemi, Adebayo Joseph
Olugbodi, Tomi
Omilabu, Sunday A.
Ongphiphadhanakul, Boonsong
Onyeaso, Elizabeth
Onyeaso, Nduche
Ortiz, Milagros
Ortiz, Milagros
Oshungbohun, Itunuoluwa Yewande
Osi-Ogbu, Ogugua
– 226 –
Abstract #
Page #
232
1013
106
108
242
1057
113
1035
204
533
1052
235
1053
1046
1035
285
211
218
228
235
238
240
250
285
408
407
535
1040
1063
702
406
277
206
601
606
238
250
228
235
408
251
900
284
533
533
119
266
290
285
35
151
4
5
40
174
8
162
19
92
171
36
171
168
162
62
23
27
33
36
38
39
45
62
72
71
93
165
176
103
71
58
21
96
99
38
45
33
36
72
45
137
62
92
92
11
53
65
62
Author (Cont.)
Osinubi, Abraham Adewale
Oyesiku, Nelson M
Oyesiku, Nelson M.
Ozuguz, Ufuk
Ozuguz, Ufuk
Ozuguz, Ufuk
Ozuguz, Ufuk
Pacak, Karel
Padmanabhan, Hema
Padmanabhan, Hema
Padmanabhan, Sailatha
Pagan, Morita
Pakdaman, Michael
Pakdaman, Michael
Pakdaman, Michael
Palacio, Carlos
Paliou, Maria
Panikar, Vijay
Panikar, Vijay
Panoulis, Constantinos
Panunti, Brandy
Papadimas, Ioannis
Paparodis, Rodis
Parapunova, Rumyana
Paras, Christos
Parikh, Grishma
Parker, John
Parker, John
Parker, John
Parker, John
Parker, John
Parker, John Charles
Parsons, Dominic
Parsons, Dominic
Pastorini, Vitor
Patel, Lipi Sekhadia
Patel, Romil
Patel, Shashi
Patel, Ushir
Pathak, Neil
Pathan, Faruque
Paul, Bhakti
– 227 –
Abstract #
Page #
900
811
817
100
905
722
1003
1005
905
257
258
261
704
906
907
809
200
1000
1017
1022
1023
1024
720
504
213
233
902
519
909
734
287
215
708
273
274
523
524
1039
736
703
814
812
511
532
720
532
526
286
1010
137
129
132
1
140
113
145
146
140
48
49
50
104
140
141
128
18
144
153
156
157
157
112
76
24
35
138
84
142
120
63
25
106
56
57
86
87
164
121
103
130
129
80
91
112
91
88
63
150
Author (Cont.)
Paulk, Douglas G.
Payne, Hildegarde
Payne, Richard J.
Payne, Richard J.
Pearce, Elizabeth N.
Pedersen-White, Jennifer R.
Peleg, A.
Pellegrino, Micaela
Penagaluru, Neena
Penagaluru, Neena
Peretianu, Dan
Perez, Jr., Jose A.
Perez, Rolando
Perlman, Kusiel
Petrucci, Richard
Phil, D.
Phillips, Martin
Piech, Melissa Roether
Pietras, Sara
Pimentel, Diana M.
Pineyro, Mercedes
Pinsker, Richard W.
Pinsker, Richard W.
Pinto, Jose L.
Pinto, Miguel
Pinto, Miguel
Pinto, Miguel E.
Pinto, Miguel E.
Pinto, Miguel E.
Pinto, Miguel E.
PO, Anaja
Poiana, Catalina
Poiana, Catalina
Poiana, Catalina
Poiana, Catalina
Poiana, Catalina I.
Poiana, Catalina I.
Ponte, Jr., Gaston Marcos
Pope, Elena
PP, Brahmkshatriya
PP, Brahmkshatriya
PP, Brahmkshatriya
PP, Brahmkshatriya
– 228 –
Abstract #
Page #
1066
221
1022
1023
1014
223
700
1044
401
512
532
735
1032
716
120
1065
267
814
283
501
1059
817
733
526
819
806
278
1048
119
216
266
806
224
106
1036
603
726
1032
813
1067
1065
259
260
262
264
214
711
814
703
178
29
156
157
152
30
102
167
68
80
91
120
161
110
12
177
53
130
61
74
175
132
119
88
133
126
59
169
11
26
53
126
31
4
163
97
116
161
130
179
177
49
50
51
52
25
108
130
103
Author (Cont.)
Pramyothin, Pornpoj
Prieto Sanchez, Luz Marina
Puepet, Fabian H.
Puepet, Fabian H.
Qari, Faiza
Quon,Jennifer
R., Balasubramanian
R., Phatak Sanjiv
Rabbani, Madiha
Rabbani, Madiha
Rabbee, Nusrat
Radian, Serban
Radian, Serban
Radian, Serban
Raheja, Prafull
Rahi, Qasim
Rahman, Anisur
Rahnema, Fariba
Rajamani, Krishna Kumar
Ramanathan, Ranjani
Ramesh, Jayanthi
Ramirez-Vick, Margarita
Ramirez, Maragarita
Ramirez, Margarita
Randolph, Gregory W.
Rao, Sudhaker
Rao, Sudhaker
Raskin, Philip
Rawal, Deepti
Rawal, Deepti
Razak, Abdul
Razak, Abdul
Reddy, Archana
Reddy, Harigopal
Reich, David
Reich, David
Reich, David
Reich, David M.
Ren, Hao
Ren, Hao
Rennert, Nancy J
Resvanian, Hasan
Resvanian, Hasan
Reynolds, Jessica
Reza-Albarran, Alfredo
– 229 –
Abstract #
Page #
1059
818
268
816
1009
609
214
257
219
719
1017
106
1036
911
712
800
286
803
720
509
1050
108
513
715
1024
271
527
506
507
283
821
728
214
711
112
101
101
221
805
402
269
270
808
230
231
1017
279
1049
713
175
133
54
132
149
100
25
48
28
112
153
4
163
143
108
123
63
125
112
79
170
5
81
110
157
55
88
77
77
61
134
117
25
108
7
1
1
29
126
69
54
55
127
34
34
153
59
169
109
Author (Cont.)
Abstract #
Riccardi, Timothy
Rilling, Alexander
Rizos, Demetrios
Rizzo, Vincent
RK, Goyal
Rochon, Louise
Rodbard, Helena Wachslicht
Rohena, Jorge
Ron, Eyal
Rosabal-Arce, Alexandra
Rosai, Juan
Rosai, Juan
Rosenberg, Daniel
Rosenfeld, Cheryl R.
Rosenstock, Julio
Rosenzweig, James
Rossell, German
Rossi, Giuseppe
Rossiter, Alicia
Rossiter, Alicia
Rubin, Daniel
Rubio, Nunilo I.
Rull, Juan
Russell-Jones, David
Rustagi, Tarun
Ryan, Margaret
S., Vishwanathan
S., Vishwanathan
Saad, Marian Gaber
Saadatnia, Mohamad
Sabharwal, Anup
Sabir, Anas Ahmad
Sachmechi, Issac
Sachmechi, Issac
Sachmechi, Issac
Sachmechi, Issac
Sahay, Rakesh Kumar
Salak, Kathleen
Salat, Reema
Salat, Reema
510
267
283
226
901
221
261
1023
241
513
605
536
1004
1017
200
244
403
220
232
1013
269
283
1025
903
713
255
801
201
214
711
229
288
291
406
257
258
259
260
261
262
264
101
221
402
805
1050
253
532
735
– 230 –
Page #
79
53
61
32
138
29
50
157
39
81
98
93
146
153
18
41
69
29
35
151
54
61
157
139
109
47
123
18
25
108
33
64
66
71
48
49
49
50
50
51
52
1
29
69
126
170
46
91
120
Author (Cont.)
Saleem, Tipu
Saleem, Tipu F.
Salem, James K.
Samoila, Ramona
Sanalkumar, Nishanth
Sandberg, Mark
Sangar, Madhusudhan
Sangar, Masdhusdhan
Sangsiraprapha, Wiroon
Sannino, Alessandro
Santhanam, Prasanna
Santhanam. Parsana
Santiago, Alejandra
Sanusi, Ibilola A.
Sanyal, Debmalya
Savarese, Vincent
Savarimuthu, Stella
Scaunasu, Adrian
Schickler, Renee
Schimke, Robert N.
Schorr, Alan
Schwarcz, Monica
Sclair, Seth
Scofield, Hal
Sekhar, Prashanth Chandra
Sen, Sabyasachi
Senatus, Patrick
Serra, Maria del Pilar
Severance, Randall
Shah, Bhagyashri
Shah, Bharat
Shah, Birju
Shah, Nirav R.
Shah, Niti
Shah, Rakhi
Shah, Reshma
Shah, Sanjiv J.
Shah, Sanjiv J.
Shah, Sanjiv J.
Shah, Sanjiv J.
Shah, Sanjiv J.
Shah, Sanjiv J.
Shah, Sapna S.
Shamim, Khusro
Sharma, Mohan
Sheikh-Ali, Mae
Sheikh-Ali, Mae
Sher, Jay A.
Shi, Leon
– 231 –
Abstract #
Page #
1034
502
256
726
1001
244
214
711
101
605
502
1034
715
1043
123
201
609
243
734
1069
244
724
812
103
700
263
801
733
222
602
213
819
609
233
803
811
257
258
259
260
262
264
528
207
526
1041
712
1029
244
162
75
48
116
144
41
25
108
1
98
75
162
110
166
13
18
100
41
120
180
41
114
129
2
102
51
123
119
30
97
24
133
100
35
125
129
48
49
49
50
51
52
89
21
88
165
108
159
41
Author (Cont.)
Shiferaw, Zewge
Shimshi, Mona
Shirodkar, Monika
Shoukri, Kamal
Shu, Jianfen
Sialongo, Roselyn E.
Siegel, Alan
Signalov, Mikhail
Silva, Enrique
Simedrea, Ioan
Simmons, Debra
Singal, Pooja
Singh, Gurpreet
Siraj, Elias S.
Siraj, Elias S.
Sirbu, Anca
Siu, Sarah
Smushkin, Galina
Soe, Kyaw K.
Sofka, Sarah
Solis, Jose
Solis, Jose
Solis, Jose
Sood, Poonam
Sosa, Andrea
Sosa, Gabriela
Soyoye, David
Spanakis, Ilias
Spaulding, Stephen
SR, Phatak
Stamenkovic-Pejkovic, Danica
Stefan, Delia
Stefanescu, Ana Maria
Stote, Robert
Strange, Poul
Strange, Poul
Strozyk, Grzegorz
Suciu, Pavel
Sultan, Senan
Sultan, Senan
Sumarac-Dumanovic, Mirjana
Sweet, David
Sy, Alexander
Tacchino, Roberto
Tak, Vinay
– 232 –
Abstract #
Page #
732
520
1055
802
242
292
503
1066
802
517
729
705
101
116
124
603
253
265
215
128
115
824
216
278
1048
226
818
824
1038
733
606
401
1046
260
607
729
106
222
222
244
1061
521
404
409
607
256
504
605
253
119
85
173
124
40
66
75
178
124
83
117
104
1
9
14
97
46
52
25
16
9
136
26
59
169
32
133
136
164
119
99
68
168
50
99
117
4
30
30
41
176
85
70
72
99
48
76
98
46
Author (Cont.)
Tan, Gerry H.
Taneja, Deepa
Tangpricha, Vin
Tarlatzis, Basil C.
Tassone, Francesco
Taweewongsoontorn, Aruchalean
Taylor, Harris
Taylor, Sherry
Tekelek,Bekir
Ten, Svetlana
Terry, Peter
Terzea, Dana
Terzea, Dana
Terzea, Dana
Threlkeld, Rebecca
Thukuntla, Shwetha
Titi, Mohammad
Tom, Ed
Touza, Mariana Garcia
Towler, Dwight
Trabolsi, Mais
Trence, Dace Lilliana
Trifanescu, Raluca
Trivedi, Nitin
Trooskin, S.
Tsametis, Christos
Tutuncu, Yasemin
Tzellos, Thrasivoulos G.
Ucar, Ozgul
Ullal, Jagdeesh
Ullal, Jagdeesh
Uloko, Ayekame Tini
Uloko, Ayekame Tini
Unachukwu, Chioma N.
Uribe, Ana
Urken, Mark
Uzcategui, Nicolas
Vahedi, S.
Vaickus, Louis
– 233 –
Abstract #
Page #
292
1049
908
909
512
284
516
802
100
610
253
726
1032
813
242
107
534
1017
1042
909
215
509
1002
210
106
1036
726
282
1045
909
1003
100
1005
905
1042
722
117
1053
268
285
816
268
816
204
239
1027
510
1030
225
66
169
141
142
80
62
83
124
1
101
46
116
161
130
40
4
92
153
166
142
25
79
145
23
4
163
116
61
167
142
145
1
146
140
166
113
10
171
54
62
132
54
132
19
38
158
79
160
31
Author (Cont.)
Abstract #
Valentin, Maureen V.
Valsamis, Ageliki
Varanasi, Ajay
Varanasi, Ajay
Varanasi, Ajay
Vargas, Estanislao Ramirez
Vargas, Socorro
Vasilica, Madalina
Veldhuis, Johannes D.
Veloski, Colleen
Venkatraman, Padma
Vesper, Hubert W.
Via, Michael
Vijayan, Soumia
Villena, Jaime E.
Villena, Jaime E.
Vimalananda, Varsha
Von Hofe, Stanley Edward
Vora, Mehul Ratilal
Wainwright, HC
Wang, Charles
Wang, Chung-Che Charles
Wang, Eric
Wang, Hui
Wang, Xaingbing
Wang, Xiangbing
Wang, Zhengke
Washington, Terri
Wasman, Jay K.
Wasserman, Jonathan
Weber, Sandra L.
Wei, Kevin S.
Wei, Sun
Weinerman, Stuart
Weinstein, Richard
Wellington, J.O.
Wetzler, Gracilla
Whang, Ping
Whitesides, Jr., Paul Caldwell
Wigham, Jean
Wilde, Jonathan
Wolali, Odonkor
Wong, Norman C.W.
Woode, Dwain E.
Woody, Christopher
Xiong, Fang
Yalla, Naga M.
Yalla, Naga M.
Yaqub, Abid
281
531
1046
728
821
245
505
1036
105
1008
502
908
604
107
119
266
220
807
731
127
1017
1004
1017
1017
276
1011
275
511
528
1065
1015
804
1011
531
225
900
610
405
736
105
1017
113
409
1052
1015
275
279
1049
1034
– 234 –
Page #
60
91
168
117
134
42
76
163
3
148
75
141
98
4
11
53
29
127
118
15
153
146
153
153
58
150
57
80
89
177
152
125
150
91
31
137
101
70
121
3
153
8
72
171
152
57
59
169
162
Author (Cont.)
Abstract #
Yarlagadda, Madhavi
Yarlagadda, Madhavi
Yasmeen, Tahira
Yasmeen, Tahira
Yedinak, Chris
Yedinak, Chris
Young, William
Yu, Wen
Yusuf, Shehu M.
Ywakim, Rania
Zahra, Tazneem
Zamfirescu, Isabelle
Zamora, Haidee David
Zarbalian, Kiarash
Zeballos, Maria
Zeiger, Martha
Zeiger, Martha
Zohar, Yishai
Zubairi, Lubna
124
1008
1002
730
804
810
111
267
816
1022
500
530
729
121
733
1004
1017
605
207
– 235 –
Page #
14
148
145
118
125
128
7
53
132
156
74
90
117
12
119
146
153
98
21

Table of Contents - American Association of Clinical Endocrinologists

Transcription

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