Table of Contents 2007 ABSTRACTS

Transcription

Table of Contents
2007 ABSTRACTS
1
Adrenal Disorders
9
Diabetes Mellitus
35 Hypoglycemia
40
Lipid Disorders
42
Metabolic Bone Disease
57
Obesity
59
Pituitary Disorders
70
Reproductive Endocrinology
72
Thyroid Disease
96
Other
109 Author Index
© 2007 AACE
ABSTRACTS
ADRENAL DISORDERS
Abstract #364
IMPROVEMENT OF ADDISON’S DISEASE
AFTER THERAPY OF ADRENAL METASTASES
(AM)
Anamaria Massier, MD, and
Harris C. Taylor, MD, FACP, FACE
Objective: To describe improvement of Addison’s
disease (AD) after therapy of AM in non-small cell lung
cancer (NSCLC).
Case Presentation: A 61 yo male with NSCLC had
bilateral adrenal masses on PET/CT. Fasting cortisol
(FaC) was 1.1 ug/dL, ACTH < 5 pg/mL, total testosterone
(TT) < 0.1 ng/mL, FSH/LH 1.9/1.0 mIU/mL, TSH 0.02
uU/mL, FT4 0.71 ng/dL. Cosyntropin (Cos) test (0.25 mg)
showed FaC/free cortisol (FC) (ug/dL)/DHEA (ng/dL) of
2.8/0.6 (nl. 0.2-1.8)/0.9 (nl. 82-338), then 4.4/-/1.2 at 30
min. and 4.6/0.8/0.9 at 60 min., indicating AD. ACTH was
7 pg/ml. Pituitary MRI was normal. The patient received
hydrocortisone and 4 cycles of chemotherapy. Repeat
PET/CT showed complete resolution of AM and primary
tumor. One month later, FaC/aldosterone (A) (ng/dL) was
7.4/7 and 60 min. after Cos, 11/13.1. Baseline ACTH was
22 pg/mL, TT 3.9 ng/mL, FSH/LH 22.5/10.1 mIU/mL.
Adrenal CT remained normal. Two months afterwards
ACTH was 33 pg/mL, FaC 10 ug/dL, renin 0.16 uU/mL
(nl. 5-47) and A 6.9 ng/dL. After Cos, C/A was 13.6/12.9
at 30 min. and 15.7/13.1 at 60 min. Repeat Cos test after 2
months showed FaC/FC/DHEA/A of 7.8/0.17/-/4.5, then
10.8/0.35/154/13.5 at 30 min. and 12.1/0.61/167/12.7 at
60 min. Baseline ACTH was 26 pg/mL.
Discussion: About one third of lung cancers develop
AM. AD occurs in only 1% of all AM since more than
90% of the adrenal cortex must be destroyed before there
is functional loss. Symptoms of AD are often attributed to
advanced malignancy or adverse reaction to medication,
and may be partially masked by intermittent use of corticosteroids included in chemotherapy. With one exception,
previous reports have not assessed adrenal function after
chemotherapy. Concurrent with resolution of AM, our
patient exhibited striking clinical improvement, partial
increase in glucocorticoid and DHEA secretion and either
maintenance or recovery of normal mineralocorticoid
secretion. Normalization of the pituitary–testicular axis
and low FT4 are consistent with transient hypogonadotropic hypogonadism and abnormal thyroid function
© 2007 AACE
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tests described in critical illness. The initial low ACTH
level may be due to improper collection or existence of
concomitant pituitary metastases which responded to
chemotherapy. However, pituitary MRI was normal and
several ACTH levels failed to show elevation. This is consistent with chronic as opposed to acute severe illness as
described by Vermes et al, JCEM 1995 80:1238-42.
Conclusions: Treatment of Addison’s disease in
patients with cancer can substantially improve their quality of life. Partial recovery from severe adrenal insufficiency after resolution of bilateral adrenal metastases may
occur. In this setting we recommend cosyntropin testing
every two to three months to determine whether adrenal
function improves.
Abstract #279
DIFFERENT PRESENTATIONS OF
CONGENITAL ADRENAL HYPERPLASIA
Naim Mitre Calderon, MD, and Siobhan Pittock, MD
Objective: Report two cases of congenital adrenal
hyperplasia (CAH) with different presentations in the
newborn period.
Case Presentation: Case 1 presented with ambiguous
genitalia at birth and was initially assigned a male gender.
Genital exam revealed a phallus, no visible urethral orifice
and pigmented bifid scrotum without palpable testes. Labs
revealed an XX karyotype, normal electrolytes and glucose, ACTH 848 pg/mL, 17-hydroxyprogesterone 14700
ng/dL, androstenedione 3210 ng/dL, DHEA 62 ng/dL and
renin activity 6.5ng/mL/hr. Ultrasound showed normal
appearing perinatal uterus and no gonads in the scrotal
folds. Hydrocortisone was started and clitoroplasty was
performed. She remained clinically stable until discharge.
Case 2 was a 6-day old male neonate with a positive newborn screen for CAH. He had normal external male genitalia. Hydrocortisone was started. Electrolytes were
monitored closely as an outpatient. 2 days later labs
showed potassium 7.4mmol/L, sodium 129mmol/L, bicarbonate 19mmol/L, glucose 64mg/dL, 17-hydroxyprogesterone 6300ng/dL, androstenedione 1200ng/dL and renin
activity 120ng/mL/hr. Stress doses of hydrocortisone were
given. He was discharged stable on hydrocortisone and
fludrocortisone.
Discussion: Congenital adrenal hyperplasia varies
depending on its severity. The enzyme deficiency of 21hydroxylase is most common accounting for 90-95% of
cases. Salt-wasting occurs in three-quarters of the classic
ABSTRACTS – Adrenal Disorders
form. The rest of classic cases present as simple virilizing
as in case 1. CAH is an autosomal recessive disorder;
however no family history is identified in many cases and
a good physical exam can lead to diagnosis in girls. The
baby in case 1 was asymptomatic but had severe prenatal
virilization which required surgery after birth. On the
other hand salt wasting CAH can present early in life with
salt-wasting crisis as in case 2. The diagnosis is more difficult in males in whom genital ambiguity is not present.
In case 2 family history of CAH was positive and the newborn screening was positive.
Conclusions: Our index of suspicion for CAH need to
be high since the severe forms can be life threatening.
Newborn screening is available in 48 states, allowing for
much earlier diagnosis of CAH, especially in boys where
genital exam is normal. Unfortunately, newborn screening
cannot yet help differentiate between simple virilizing and
salt-wasting forms of classic CAH, making close followup of electrolytes in post-natal period extremely important.
remember that there may be many other explanations,
besides organic etiologies of the puzzling clinical presentations. Such alternative reasons should be considered particularly in cases where protean and multifarious
subjective data are accompanied by only scarce or bizarre
objective findings. Most experts agree that early discovery
of somatization or factitious disorder is associated with the
best prognosis. Such approach is not only in the best interest of the particular patient, but it also serves society by
conserving limited medical resources.
Conclusions: Since physicians are traditionaly
trained to trust patients, even in cases characterized by
uncanny presentations, doctors tend to consider very
uncommon diagnoses rather than factitious disorders or
malingering. However, a proper diagnostic process calls
for proceeding from the most likely diagnoses to the least
likely ones and not to skip over factitious disorders.
Abstract #105
MEDICAL THERAPY OF CUSHING’S
SYNDROME
Abstract #101
FACTITIOUS HYPOADRENALISM
Teck-Kim Khoo, MD, Deepak Kumar, Pharm.D.,
Cheng Ean Chee, MD, and William F. Young, MD
Walter P. Borg, MD
Objective: Importance of the diagnostic paradigm
which incorporates somatization and factitious disorders
into diferential diagnosis.
Case Presentation: 50 year-old female with past
medical history of multiple medical problems including
“thyroid disorders”, and “hypoglycemia”, has been
referred for Endocrine consultation due to suspected
“autoimmune endocrine dysfunction”. In addition to the
convoluted past medical history patient gave a history of
present illness virtually consistent with a textbook description of primary hypoadrenalism. Although she had no
medical training, she has prepared herself a voluminous
quasi-medical chart. The results of past and current ancillary studies have been consistent with the diagnosis of primary hypoadrenalism. The appropriate treatment has been
instituted. However, a clinical course and patient's behavior became atypical. Ultimately, she has been hospitalized.
Testing performed in a controlled hospital environment
did not confirm presence of any significant adrenal abnormality.
Discussion: Physicians have an ethical duty to exert
due diligence in order to establish a true reason for which
a patient seeks medical care, rather than assume that all
patients must have an underlying serious organic disease.
Somatic disorders have to be vigorously sought out by all
available technical means at the disposal of medical science. At the same time, however, an astute clinician shall
Objective: To present the medical management of a
complicated case of Cushing's syndrome from ectopic
ACTH production.
Case Presentation: A 70-year old male presented
with Cushing’s syndrome from an ectopic ACTH source.
He had been treated with ketoconazole which resulted in
hepatitis. He was transferred for consideration of bilateral
adrenalectomy. Before he could undergo surgery, he
developed pneumocystic carinii and cytomegalovirus
pneumonitis requiring mechanical ventilation. His condition was felt to be too tenuous for surgery at that moment,
therefore his hypercortisolism was managed medically. He
had a 24-hour urine free cortisol (UFC) of 51728 ug, a.m.
cortisol 189.5 ug/dL, ACTH 529 pg/mL. The ACTH was
not suppressible. CT and octreotide scans did not reveal
the source of the ACTH. A pituitary MRI was normal. He
was started on mitotane with dexamethasone coverage.
Etomidate infusion was started on hospital day 7. This
decreased his a.m. cortisol to 54 ug/dL and 24-hour UFC
to 1092 ug. Aminoglutethimide was added on day 13 and
metyrapone 10 days later. This normalized his serum cortisol and 24-hour UFC. He underwent bilateral adrenalectomy a month later. The source of ACTH remains occult
at 1 year post-op.
Discussion: In patients with ectopic ACTH syndrome, the ideal treatment is surgical removal of the
source of ACTH. If this remains occult, bilateral adrenalectomy is usually recommended as the source can remain
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unknown for years. This demonstrates a complex situation
in which such a patient is unsuitable for surgery. In such
patients, medical adrenalectomy with mitotane can be
used. However, the onset is variable and therefore replacement corticosteroids is often started concomitantly.
Because of the slow onset, other agents were added in our
patient. Etomidate and metyrapone block the terminal step
of cortisol synthesis from 11-deoxycortisol while aminoglutethimide blocks the first step in cortisol synthesis.
Using this 4-drug regimen, we were able to normalize our
patient’s cortisol while he recovered his cardiopulmonary
function adequately to undergo surgery. Ketoconaloze is
usually the steroidogenesis inhibitor of choice, although
this was not utilized in our patient as it had previously
resulted in a drug-induced hepatitis. Use of the less toxic
fluconazole for treatment of Cushing’s syndrome has been
reported in the literature although evidence regarding its
efficacy is lacking.
Conclusions: Primary treatment of ectopic ACTH
syndrome is removal of the source. These are usually
found in the lung or abdomen. If the source remains
occult, adrenalectomy is indicated. If this is deemed
unsuitable, medical therapy aimed at destroying the adrenal cortex or blocking cortisol synthesis may be used successfully to decrease or normalize cortisol production.
These include mitotane, ketoconazole, aminoglutethimide,
etomidate and metyrapone.
Abstract #143
CYCLICAL CUSHING’S SYNDROME IN A
WOMAN DUE TO A BRONCHIAL CARCINOID
Zulekha Hamid, MD, Negah Rassouli, MD,
Palak Choksi, MD, and Fred H Faas, MD
Objective: To present a case of Cyclical Cushing’s
Syndrome (CS) due to bronchial carcinoid and to review
the literature
Case Presentation: A 43 year old female referred for
evaluation of CS. The diagnosis was made 2 months prior,
due to symptoms and elevated serum cortisol of 20µg/dl
and urine free cortisol (UFC) of 1022µg/d after dexamethasone suppression test (DST). Her symptoms improved
and results of lab studies on 2 occasions were normal. 2
months later symptoms developed again with elevated
UFC of 237 and 529µg/d and ACTH of 118pg/ml. There
was paradoxical response to low dose DST with baseline
UFC of 119 to 356 and 790µg/d at 24 and 48 hours.
Similar response noted with high dose DST with baseline
of 378 to 829 and 1183µg/d at 24 and 48h. CRH test suggested non-pituitary origin-basal ACTH 63 response
72pg/ml; basal cortisol 31 response 32mcg. MRI of pituitary was negative. CT and MRI of chest revealed nodule
in the right lung and octreotide scan showed increased
uptake. Calcitonin and 5HIAA were normal. She had right
lobectomy. Pathology revealed carcinoid tumor with
ACTH staining. Her cortisol levels were reduced; however steroid supplement was not required for 2 weeks, supporting cyclical nature of disease.
Discussion: Cyclical Cushing's Syndrome is a disorder of rhythmic secretion of ACTH resulting in cyclic
variation in adrenal steroid production. Pituitary function
may be normal between episodes and investigations are
only positive when performed during the period of excess
secretion. The timing of fluctuation can vary from few
days to several months. The mechanism of periodicity is
still poorly understood. One of the explanations is the
cyclical changes in central dopaminergic tone as a trigger
for periodic ACTH secretion. Clinical presentation is very
variable with episodes of biochemical and clinical remission alternating with episodes of frank symptoms. In the
majority of cases the etiology is an ACTH secreting pituitary adenoma; however few cases of ectopic ACTH secretion have been described. The diagnosis is challenging and
endocrine testing is often not conclusive in differentiating
pituitary from ectopic sources. Paradoxical response to
dexamethasone has been reported as one of the features of
cyclical CS. Our patient demonstrated paradoxical
increase in the cortisol levels on several occasions and did
not require steroid for two weeks postoperatively; both
supportive of cyclical CS.
Conclusions: This case is a rare occurrence of
Cyclical Cushing's Syndrome due to an ACTH secreting
bronchial carcinoid. Although uncommon, cyclical
Cushing's Syndrome can present as diagnostic challenge
and should be suspected in individuals with symptoms or
signs but with normal cortisol values, fluctuating cortisol
value or anomalous response to dexamethasone. Repeated
measurement of biochemical data is necessary to establish
the diagnosis.
Abstract #245
ABNORMAL 17-OHP RESPONSIVENESS IN A
PATIENT WITH ADRENOCORTICAL NEOPLASM
Colleen Veloski, MD, Mercedes Pinyero, MD, and
Elias Siraj, MD, FACE
Objective: To describe the unusual finding of 17-OHP
hyperresponsiveness to ACTH stimulation in a patient
with an adrenal neoplasm
Case Presentation: A 43 year old woman presented
with progressive hirsutism and hypertension of 3 years
duration. Her history is significant for oligodendroglioma
which was managed with radiation and a course of steroids
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years prior to presentation. Physical exam was notable for
severe hirsutism and central obesity. Laboratory evaluation showed findings consistent with ACTH independent
Cushing’s syndrome and hyperandrogenism. As part of
the workup for her androgen excess, the 17-OHP level was
measured after IV injection of 250 mcg of ACTH. The 17OHP level increased from a baseline of 2.0 ng/mL to a
level of 72.9 ng/mL at 60 minutes after the injection, indicating an exaggerated response. CT scan showed a 6.9 cm
right adrenal mass with some features suspicious for
malignancy. The patient underwent a right adrenalectomy.
Pathology revealed adrenal cortical neoplasm with no
definitive evidence for malignancy. After surgery, the
patient’s blood pressure normalized off blood pressure
medications and the hyperandrogenism significantly
improved. She did require a maintenance dose of corticosteroids.
Discussion: Cushing’s syndrome and hyperandrogenism are well known manifestations of some adrenocortical neoplasms. On the other hand, elevated 17-OHP at
baseline or following ACTH stimulation is typically found
in the most common type of late onset congenital adrenal
hyperplasia (CAH) secondary to 21-hydroxylase deficiency. In our patient, it is unlikely that late onset CAH is present since her hyperandrogenic presentation was of recent
onset, and it dramatically improved following removal of
the adrenal neoplasm. Therefore, we suspect that the elevated 17-OHP after ACTH stimulation in our patient may
be indicative of disturbance in steroidogenesis that is present in some adrenal neoplasms. At least one study has
shown that 25 % of patients with functional or nonfunctional adrenal adenomas demonstrated 17-OHP hyperresponsiveness to low dose ACTH stimulation. Another
study of adrenal incidentalomas also found 17-OHP
hyperresponsiveness to ACTH stimulation in some
patients.
Conclusions: Androgen excess may be the primary
manifestation of adrenal cortical neoplasms. The presence
of 17-OHP hyperresponsiveness to ACTH stimulation
may not always indicate presence of CAH, rather it may
be a result of disturbed steroidogenesis seen in some of
those neoplasms.
Case Presentation: A 65 year old man presented with
difficult-to-control systemic hypertension thirty years
after complete excision of a left sided pheochromocytoma.
He denied any paroxysmal symptoms and felt well otherwise. There was no family history of pheochromocytomas.
Physical examination revealed Grade II hypertensive
retinopathy. No vascular abnormalities were noted in the
ocular fundus. No abnormal skin lesions were noted. A
normal sized thyroid was palpable. Rest of the exam was
unremarkable. Laboratory studies were remarkable for
significantly elevated 24 hour urinary normetanephrines.
Magnetic resonance imaging of the abdomen revealed a
T2-hyperintense mass in the left para-aortic region consistent with an extra-adrenal pheochromocytoma (paraganglioma). Whole body MIBG (123-I-metaiodobenzylguanidine) scan showed an area of uptake in the posterior
mediastinum in addition to the lesion detected on MRI.
Surgical excision of the intra-abdominal lesion normalized
normetanephrine levels. Genetic tests for vHL, RET,
SDHB and SDHD were negative.
Discussion: Pheochromocytomas are rare catecholamine-secreting tumors that occur sporadically or as
part of familial syndromes, namely Von-Hippel Lindau
Syndrome, Multiple Endocrine Neoplasia Syndrome 2,
Neurofibromatosis-1. Familial extra-adrenal pheochromocytomas (paragangliomas) are associated with mutations
in succinate dehydrogenase subunit genes. The above
mutations are also detected with a variable frequency in
apparently sporadic, nonsyndromic pheochromocytomas.
In a series of 271 European patients, one of the above
mentioned mutations was detected in 24 percent of cases.
Genetic testing for vHL, RET, SDH subunit mutations is
recommended for apparently sporadic catecholamine
secreting tumors with one or more of the following features 1) Age less than 21 2) Bilateral adrenal pheochromocytomas 3) Extra-adrenal location (paragangliomas).
Conclusions: Germline mutations may be present in
12 to 24 percent of apparently sporadic pheochromocytomas. Genetic testing is recommended in individuals with
sporadic nonsyndromic catecholamine-secreting tumors
for all functional paragangliomas and pheochromocytomas with early onset, bilateralality or recurrence.
Abstract #390
Abstract #316
A CASE OF SPORADIC, NONSYNDROMIC,
RECURRENT PHEOCHROMOCYTOMA
UNUSUAL PRESENTATION OF A
CATECHOLAMINE SECRETING TUMOR
Sumit Bhagra, MBBS, Anjali Bhagra, MBBS, and
Vesna Garovic, MD
Rucha Jani, MD, Jan M Bruder, MD, Marion Jech, PhD,
Devjit Tripathy, MD, PhD, and
Patricia Dahia, MD, PhD
Objective: Pheochromocytomas are rare. Young age,
Sporadic onset, and recurrent multifocal extraadrenal
tumors warrant genetic testing.
Objective: Describe a striking presentation of a
metastatic catecholamine secreting tumor (CST) and the
utility of genetic testing.
–4–
Case Presentation: A 54 year old healthy man presented to the hospital with chest pain and diaphoresis. His
blood pressure was 230/180 mm of Hg. He arrested in
triage and was intubated. He suffered acute renal failure
requiring hemodialysis. A computed tomographic scan of
the abdomen showed a 3 cm (3 Hounsfield Units) left
adrenal lesion and multiple large hepatic lesions concerning for metastatic pheochromocytoma. Testing revealed
elevated plasma free normetanephrine, metanephrine and
catecholamines levels. On magnetic resonance imaging
the liver mass had a bright signal on T2 but not the left
adrenal mass. An I-131 metaiodobenzylguanidine (MIBG)
scan was positive in the liver and a region in the right
retroperitoneum suggestive of a primary focus . The
patient underwent resection of the hepatic mass en-bloc
with right adrenalectomy. A primary focus was not identified. The right adrenal (4.5 grams) and the liver lesions
stained positive for CD56, chromogranin and synaptophysin consistent with CST. Follow-up plasma free
normetanephrine, metanephrines and catecholamine levels
are normal with no evidence of tumor on imaging with I131 MIBG. Genetic testing revealed a germline mutation
of the succinate dehydrogenase (SDH ) B gene subunit at
a highly conserved domain, H242R.
Discussion: CSTs are rare and arise from neural crest
cells associated with autonomic ganglia. These tumors can
cause diagnostic dilemmas especially in the setting of
renal failure. Plasma free metanephrines and
normetanephrines levels are relatively independent of
renal function. Most CSTs are sporadic and benign.
However about 15-20 % are familial and are inherited in
an autosomal dominant fashion as part of at least 5 distinct
autosomal dominant hereditary syndromes: von HippelLindau syndrome, multiple endocrine neoplasia 2, neurofibromatosis type 1 and familial paraganglioma
syndromes types 1 (PGL1) or 4 (PGL4). The hereditary
paraganglioma syndrome has been associated with mutations in the D, B and C subunit of the SDH complex.
Mutations of SDHB are more likely to have extra adrenal
tumors with malignant potential as in our patient. These
mutations have also been associated with other neoplasms
such as renal cell cancer.
Conclusions: This case highlights that CST are rare
but life-threatening and should always be in the differential diagnosis when secondary hypertension is a consideration. Plasma free normetanephrines and metanephrines
testing is a sensitive and specific diagnostic tool. Although
the primary focus of CST remains unclear in this case, the
genetic mutation suggests an increased risk of recurrence
and warrants careful surveillance with genetic testing of
at-risk individuals in the family.
Abstract #416
CCAM AND ADDISON DISEASE
Nedim Cakan, MD, and Sermin A. Saadeh, MD
Objective: To present a case of Addison disease that
was initially missed because of an atypical type of pigmentation in a patient with cystic adenomatoid malformation (CCAM) of the lung.
Case Presentation: Three year old Yemeni male presented to emergency room with vomiting and fatigue. On
examination he was noted to have dusky lips and nails,
dehydration.laboratory showed hypoglycemia and metabolic acidosis. past medical history was positive for
repeated episodes of fatigue, dusky discoloration of lips
and nails and asthma.He was found to have CCAM of his
right lower lobe of his lung on CT scan which was part of
work up for "cyanosis" 2 weeks prior to his acute presentation. Family history was remarkable for the death of 4
brothers between the ages of 2 and 4 years of age in
Yemen and was reported as having the same discoloration
of lips and nails.There are 2 brothers and sisters from the
same parents who are alive an well with no
complaints.During his hospitalization diagnosis of addison disease was made while investigationg the etiology of
hypoglycemia with low cortisol and high ACTH levels.
ACTH stimulation test also failed to increase cortisol levels.Anti adrenal antibodies were negativeas well as investigation for Tuberculosis. Thyroid tests were normal. CT
scan of the abdomen did not show any abnormalities of the
adrenal glands. Two weeks after the glucocorticoid and
mineralo corticoid replacement therapy his CCAM was
resected with no complications.
Discussion: Addison disease is a potentially life
threatening disorderif not treated. The typical pigmentation is at the sun exposed areas and areas of friction such
as palmar creases. The diagnosis of Adrenal insufficiency
in his patient was delayed despite evaluations in different
countries and institutions mainly because of the lack of
hyperpigentation. The pigmentation of this patient was
thought as "cyanosis" or duskiness related to his asthma or
cardiac condition. To our knowledge there have been no
case reports with CCAM and Addison disease. Whethwer
his brothers who died from a familial adrenal insufficiency is undetermined becauseof the lack of information on
those siblings.It is our belief that they had a form of
Familial adrenal insufficiency with unknown mode of
inheritance.
Conclusions: The lack of typical pigmentation and
other diseases causing fatigue and color changes on lips
and nails can delay the diagnosis of Addison's disease.
Whether adrenal insufficieny plays any role in development of CCAM is unknown.
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Abstract #324
resection of the adrenal tumor, which was not the source
of excess androgens.
Conclusions: To the best of our knowledge, this is the
first described case of a virilizing ovarian Leydig cell
tumor in a patient with subclinical Cushing’s syndrome.
These tumors can be an ongoing source of both diagnostic
and therapeutic challenges.
AN OVARIAN LEYDIG CELL TUMOR IN A
WOMAN WITH SUBCLINICAL CUSHING’S
SYNDROME
Dima Diab, MD, Charles Faiman, MD,
Allan E. Siperstein, MD, William Grossman, MD, and
Amir H. Hamrahian, MD
Abstract #194
Objective: To report a patient with an ovarian Leydig
cell tumor and subclinical Cushing’s syndrome secondary
to an adrenal adenoma.
Case Presentation: A 49-year-old premenopausal
woman was referred for evaluation of a 2.5 cm left adrenal mass which was diagnosed 4 years ago during work up
for hirsutism. On exam, she had central obesity, facial hirsutism, and male-pattern hair loss. Work up was only significant for elevated total and free testosterone levels of
196 ng/dl (20-70) and 24 pg/ml (1-9), respectively. Other
results were as follows: DHEAS 7.5 mcg/dl (10-221),
ACTH 12 pg/ml (5-50), cortisol 1.4 mcg/dl during a 1-mg
dexamethasone suppression test (DST), and 24-hr UFC
48.8 mcg/24hr (20-100). The testosterone level decreased
by 14% during a 2-day low dose DST. Transvaginal ovarian ultrasonography and a CT scan of the pelvis were normal. A left laparoscopic adrenalectomy revealed an
adrenal adenoma. On the first day after surgery, the cortisol level was <1.0 mcg/dl; moreover, the testosterone level
remained high. At 6 months, a normal cortrosyn stimulation test indicated recovery of the HPA axis. Bilateral
oophorectomy revealed a 1.3 cm right ovarian Leydig cell
tumor. After surgery, the testosterone level dropped to <20
ng/dl.
Discussion: Leydig cell tumors are rare virilizing
tumors that constitute <0.5% of all ovarian tumors.
Diagnosis can be difficult since these are usually small and
can be missed on imaging studies. Subclinical Cushing’s
syndrome (CS) is a poorly defined disease reported in 520% of adrenal incidentalomas. Patients do not have the
typical manifestations of CS but develop adrenal insufficiency following resection of the adrenal tumor due to
chronic suppression of the contralateral adrenal gland. The
1-mg DST was endorsed by a 2002 NIH consensus panel
as the initial biochemical evaluation of choice. This case
shows the difficulty in diagnosing subclinical CS since all
the work up including the 1-mg DST was normal. It also
represents the challenge of identifying the correct source
of excess androgens in patients with normal ovarian imaging. The low DHEAS level and the lack of a significant
decrease in the testosterone level following a 2-day low
dose DST were suggestive of an ovarian source of androgens. However, the presence of an adrenal mass and the
lack of any abnormality on ovarian imaging prompted
ADRENAL GANGLIONEUROMA PRESENTING
AS ABDOMINAL PAIN
Lucy Dey, MD, Paula Butler, MD
Objective: To report a case of adrenal ganglioneuroma in a young patient who presented with abdominal pain.
Case Presentation: A 25- year old African American
female presented with right sided abdominal pain of one
month duration. The pain was constant, vague in nature
and radiated to the right flank. There were no other associated symptoms. Physical examination was unremarkable. Complete blood count, serum chemistry, and urine
analysis and human gonadotropic hormone results were
normal. Contrast-enhanced computed tomographic (CT)
scan of the abdomen revealed 4.6 x 5 x 7cm, homogeneous
right adrenal mass with no evidence of other intraabdominal pathology. Magnetic resonance imaging (MRI) findings revealed the mass was low signal intensity on the
T1-weighted sequence, and hyperintense to muscle on the
T2-weighted sequence. Hormonal work up including,
plasma aldosterone and renin 24 hour urine
metanephrines, catecholamines, and cortisol levels was
within normal limit. Laproscopic right adrenalectomy was
done. Histopathology finding revealed mature ganglion
cells surrounded by fascicles of Schwann-like cells, suggestive of ganglioneuroma. Post operatively, the abdominal pain disappeared.
Discussion: Ganglioneuromas (GNs) are benign neoplasms, arising from neural crest tissue and is composed of
mature ganglion cells and Schwann’s cells. 20% of these
tumors occur in adrenal medulla. GNs are usually asymptomatic regardless of their size. Non-enhanced CT reveals
a homogenous mass with less attenuation than muscle.
There is a delayed heterogeneous uptake of contrast in a
ganglioneuroma. This delay is directly proportional to the
amount of myxoid stroma in the tumor. Ganglioneuromas
appear homogeneous on MRI and have relatively low signal intensity on T1-weighted images. On T2-weighted
MRIs, the signal intensity is proportional to the ratio of
myxoid stroma cellularity and also the amount of collagen
present in the tumor. GNs may present with metabolic
activity such as increased secretion of catecholamines
and/or (123) I-metaiodobenzylguanidine (mIBG) uptake.
–6–
There are no specific diagnostic signs and symptoms differentiating GNs from neuroblastomas. Therefore, GNs
require tissue investigation for diagnosis. Prognosis after
surgical resection without further therapy is excellent.
Conclusions: We described a rare case of adrenal
ganglioneuroma, presenting as abdominal pain in a young
female. Clinical, laboratory, pathologic findings and characteristic patterns in imaging studies were discussed.
Abstract #225
TESTICULAR REST TUMOR IN 11-HYDROXY
CONGENITAL ADRENAL HYPERPLASIA
Jasleen Kaur Duggal, MD, Augusto Cigliano, Med Stu,
Daniel Ciltea, MD, Paula Butler, MD, and
Sant P Singh, MD
Objective: Report rare case of testicular tumor associated with 11-hydroxylase deficiency Congenital Adrenal
Hyperplasia( C A H).
Case Presentation: We present a case of a 14 year old
boy diagnosed with CAH due to 11-hydroxylase deficiency at the age of 3 yrs, when he developed precocious
puberty. At age 14 he was referred to our institution for
treatment of hypertension and found to have unilateral testicular mass on physical exam.Poor compliance of suppressive therapy was noted during the previous two years.
Hypertension was managed with spironolactone. On initial
physical exam for this visit, a painless, hard, motile testicular mass was found. Scrotal ultrasonography showed
approximately 2cm irregular and heterogeneous mass in
the left supra-testicular region.He was given hydrocortisone for replacement therapy. After 5 months surgical
intervention was considered due to the persistence of
tumor despite treatment.A unilateral,well encapsulated
polypoid portion of red gray soft tissue was removed.
Histopathologic exam. showed leydig cells separated by
fibrous tissue.Lipofuscin pigment identified,no reinke
crystals seen. Tumor was identified as adrenal rest tumor
on left testicle.11-deoxycortisol was elevated after
removal
Discussion: Unilateral and bilateral adrenal rest cell
tumors have been well described.CAH of 21, 11 and 17hydroxylase deficiency (8.2%) developed testicular masses. However, there are only seven reported cases of similar pathology in association with 11-hydroxylase
deficiency.Although testicles were normal to palpation in
one patient,affected testicles of the remaining seven
patients were irregular and hard. The tumors often
decrease in size with optimal steroid administration by
suppression of the elevated ACTH levels. Inadequacy of
treatment is often associated with poor therapeutic compliance.11- corticosteroids were elevated in our patient
after removal of tumor.This case was reviewed by intradepartmental consultation and also sent to Mayo clinic for
opinion.Histopathologically, testicular masses associated
with CAH resemble both adrenal cortical rest and leydig
tumors. Crystalloids of Reinke are present in 40% of leydig-cell tumors but are absent in testicular adrenal cortical
rests.The diagnosis may be suspected on the basis of history of CAH and ultrasonographic demonstration of the
testicular adrenal-like tissue.Steroid responsiveness is
determined and histopathology support it
Conclusions: This demonstrates our case of precocious puberty resulting from CAH deficiency complicated
by testicular rest tumor of adrenal origin and not Leydig
cell tumor (which can also present with precocious puberty and approximately 10% of cases are malignant).To the
best of our knowledge this is the eighth case presenting
with testicular enlargement in 11-hydroxylase-deficient
CAH, only one of which had unilateral presentation; this
case would be the second.
Abstract #275
A CASE OF MEN 2A DUE TO RARE RET
PROTO-ONCOGENE MUTATION
Mihaela Cosma, MD, Cacia V. Soares-Welch, MD,
Clive S. Grant, MD, William F. Young, MD
Objective: Describe a case of MEN 2A due to a rare
RET proto-oncogene mutation and review the reported
cases with the same RET mutation.
Case Presentation: A 67-yr-old woman presented
with uncontrolled HTN and spells. Past history included
primary hyperparathyroidism (HPT). Family history was
significant for HTN, hypercalcemia, Hirschprung disease
(HSCR) and early death from myocardial infarction and
strokes. 24-Hr urine collection showed marked elevation
of fractionated catecholamines and metanephrines.
Abdomen MRI showed a 6-cm RT adrenal mass. Thyroid
US showed a 2-cm nodule in the LT thyroid, two small
nodules in the LT thyroid and a 1.8-cm nodule posterior to
the inferior tip of the RT thyroid. FNA of the 2-cm LT thyroid nodule was suspicious, with cytologic features of
Hürthle cell neoplasm. After preoperative preparation with
alpha-adrenergic blockade, a 7.7-cm RT adrenal
pheochromocytoma was removed. Total thyroidectomy
was performed and pathology examination showed
medullary thyroid carcinoma (MTC) forming 0.5-cm nodule in the LT and 0.2-cm focus in the RT thyroid on a
background of C-cell hyperplasia. A 1.8-cm Hürthle cell
adenoma was found in the LT thyroid. A 470 mg hypercellular RT inferior parathyroid gland was removed.
Discussion: Genetic testing confirmed a mutation in
the RET proto-oncogene in codon 609, C609Y. Family
–7–
screening and genetic counseling were recommended. The
index case is part of a kindred with 43 living relatives; 24
were tested and 11 of them were positive for the same
RET mutation. MEN 2A is a rare hereditary cancer syndrome with autosomal dominant inheritance due to RET
proto-oncogene mutation and significant for the development of MTC (high penetrance), pheochromocytoma and
primary HPT as well as some cases of familial HSCR (low
penetrance). A phenotype-genotype correlation in MEN
2A led to recommendations of early genetic testing and
prophylactic thyroidectomy resulting in improved outcome of MTC. RET mutations at codon 609 are classified
as less than high risk in relationship with the development
of MTC. In some studies, patients with codon 609 mutations did not develop MTC until after 20 years of age; others report metastases from MTC as early as age of 4. There
is little consensus in the timing of thyroidectomy in these
patients. Reports of pheochromocytoma and HSCR in
these kindreds are variable.
Conclusions: The occurrence of HSCR, MTC, HPT
and pheochromocytoma in kindreds with exon 10 C609Y
mutations is probably very rare and insufficiently documented in the reviewed literature. More clinical data
regarding kindreds with this mutation are needed to guide
recommendations regarding prophylactic thyroidectomy
timing and prognosis.
–8–
ABSTRACTS – Diabetes Mellitus
DIABETES MELLITUS
Abstract #334
INSULIN RESISTANCE: AN INDEPENDENT RISK
FACTOR FOR CVD IN TYPE 2 DIABETES
Paresh Haribhai Zanzmera, MBBS
Objective: To study whether IR is an independent risk
factor of CVD in type 2 DM or not, & its relation with
other risk factors for CVD
Methods: 100 patients of type 2 DM,who were not on
insulin, were taken from SSGH, vadodara. Each patients
were asked history regarding complaints pertaining to DM
and its complications, had undergone clinical exam and
were subjected for biochemical investigations, S.insulin,
ECG, and ECHOCARDIOGRAPHY.
Results: Clinical feature of patient: men and women
were 50% each, average age was 55.5yr, mean duration of
DM was 6.36yr. Nearly half were overweight or obese and
had dyslipidemia and/or hypertension. The prevalence of
IR was high(88%). Average IR was 8.84.Among the
patient with IR, following information is noticed: 51.1%
were male. Mean age 56.0yrs, 29.6% patients were smoker, 68.2% were sedentary. 61.4% were obese, central obesity was seen in 86.7% males and 95.3% females. 90.9%
had systolic and 48.7% had diastolic hypertension. 61.4%
had microabuminuria. Among hypertensive patients,
66.3% were obese, 62.5% had microalbuminuria, and
73.8% had high LDL. 42 out of 88 patients had CVD,
which included 18 patients with RWMA, 9 with diastolic
& 2 systolic dysfunction, 7 LVH and 6 cardiomyopathy.
Discussion: IR is a hallmark of type 2 DM that precedes DM for years. In diabetics and nondiabetics, IR is
related to several CVD risk factors, like hyperglycemia,
dyslipemia, hypertension, and smoking. For such reasons,
IR might be regarded as an accomlice in pathogenesis of
CVD in type 2 DM. It is interesting to establish whether
IR does contribute to CVD through a shortcut direct or
indirect pathway. This information would be of great clinical value because it might strongly justify and encourage
use of theraputic options capable of improving insulin sensitivity and reducing morbidity. At baseline, HOMA-IR
was significantly correlated with age, BMI, DBP, FBS,
PP2BS, HDL, TG, Total cholesterol, & CVD, with
p<0.05. Obesity, hypertension, dyslipemia and IR were
independent predictor for CVD. It was found that IR was
a strong predictor of CVD in type 2 DM, independently of
classical risk factors and variables most strictly related to
IR. Therefore it seems that IR can strongly contribute to
more devasting chronic complication of type 2 DM
through a pathway that is distinct from those involving
many classic risk factors. This support idea that IR in type
2 DM deserves specific treatment.
Conclusions: IR, as assessed by HOMA-IR, is significantly associated with adverse cardiac outcome in type 2
DM and its an independent predictor of the CVD in type 2
DM. There is significant correlation of IR with other risk
factors for CVD in diabetic patients.It is evident from this
study that IR is not just coexistent but causal factor for
CVD in Type 2 DM. Hence, theraputic options capable of
ameliorating or reversing IR might be considered in treatment of these patients, most of whom will experience
CVD.
Abstract #346
TYPE 1 DIABETES VERSUS TYPE 2 DIABETES:
A CLASSIFICATION DILEMMA
Anjana Myneni, MD, Panchali Khanna, MD,
Nitesh Gadeela, MD, Saleh Aldasouqi, MD, andamal
Hammoud, MD
Objective: In some cases it is not easy to categorize
diabetic patients as type 1 versus type 2 based on the widely accepted criteria.
Case Presentation: A 41 year old man had Type 1
Diabetes for 20 years, when he underwent a successful
kidney and pancreatic transplant in 1992. Subsequently
his blood sugar levels normalized and he became insulin
independent. He was recently hospitalized for pneumonia
and his blood sugars were found to be elevated in the 300
range. He received high dose steroids during the course of
his hospitalization, and was prescribed glimepride which
he discontinued after discharge due to hypoglycemia.
Several weeks after discharge he continued to have hyperglycemia. Glycosylated hemoglobin (HbA1c) level was
increased from initial of 5.8% to 6.8% six weeks after his
illness. C-peptide level was found to be elevated at 7.5
ng/ml, pointing to endogenous insulin production, making
the possibility of complete pancreatic transplant failure
less likely. He was started on a diabetic diet and miglitol
as needed for heavy meals. Subsequently his blood sugar
levels improved and HbA1c decreased to 6.2%.
Discussion: The prevalence of diabetes, its specific
complications and presence of other diseases that often
accompany diabetes, make it one of today’s prominent
social and public health problems. Increasing information
available on the etiology and pathophysiology of diabetes
has led to several revisions of diagnostic criteria and
reclassification of the disease. In most cases, it easy to categorize diabetic patients as type 1 versus type 2 based on
the widely accepted criteria. However in some cases it
may be difficult to classify a case of new onset hyper-
–9–
glycemia. Given that our patient had a previous diagnosis
of type 1 diabetes, the clinical dilemma now is whether to
classify him as type 1 diabetes or as new onset type 2 diabetes, with relative insulin deficiency. Measuring islet cell
antibodies or GAD antibodies may not be helpful given his
prior history of type 1 diabetes. Not only is this an intellectually stimulating question, but it is also relevant in further management of this patient’s diabetes.
Conclusions: This case illustrates the challenges in
classification of diabetes that clinicians may encounter in
some patients with new-onset or even pre-existing diabetes. We highlight the significance of early accurate classification of the type of diabetes mellitus, as this has
implications on management for individual patients.
complicances. The achievement of a GCSM-evaluated
good glucose control in almost 60% of the sample is a confirmation of the result obtained and attest a contextual
reduction of glycemic variability. On the other hand the
decreased number of complications in the 6 months follow
up is a good confirmation of the reliability of insulin pump
therapy. Unlike other studies we did not find any significant increase of the body weight or of the BMI during
insulin pump therapy.
Conclusions: In our experience insulin pump therapy
can lead to a very significant reduction of HbA1c values
and to achieve a good glucose control, with a reduction of
insulin requirement without any significant body weight
increase.
Abstract #338
Abstract #409
IMPROVED GLUCOSE CONTROL WITH
INSULIN PUMP THERAPY IN 129 T1 DM
SUBJECTS
COLESEVELAM HCL ADDED TO
SULFONYLUREA (SU)-BASED THERAPY IN
PATIENTS WITH INADEQUATELY
CONTROLLED TYPE 2 DIABETES MELLITUS
(T2DM) IMPROVES GLYCEMIC CONTROL
Giovanni D'Agostino, MD, Vincenzo Provenzano, MD,
Gabriella Saura, MD, Vito Aiello, MD, and
Mattia Fleres, MD
Objective: To evaluate glucose control in terms of
HbA1c and percent of patients achieving a good glucose
control with pump therapy
Methods: 129 type 1 DM patients treated with multi
injective insulin therapy, with poor glycemic control, have
been switched to pump therapy and studied for 6 months.
We evaluated HbA1c, glucose control with a continuos
monitoring system (GCSM), insulin requirement, body
weigh and BMI (Body Mass Index).
Results: 6 pregnant women and 18 teen agers were
included. At study onset the mean age was 26,01 +/- 10,34
years; the body weight (Kg) 56,8 +/- 25,6; HbA1c (%)
9,22 +/- 2,05 and only 15,6 % of the patients showed good
glucose control (>60% of GCSM essays in the 70-140
mg/dl range). 4 subject stopped pump therapy and were
excluded. The BMI of all subjects except pregnant women
did not show any variation during the sudy. Insulin
requirement was significantly reduced from the original
value of 0,78 (+/- 0,26) per Kilogram of body weight to
the value of 0,65 (+/- 0,30) at the end of our study
(p=0.02). As shown in the figure HbA1c significantly
decreased after 3 and 6 months. The percent of patients
with good glucose control significantlyincreased from the
initial 15,6% to 58,2% (p=0,002).
Discussion: The dramatic reduction of the HbA1c
value after 3 months of pump therapy (confirmed with a
further decrease at the 6 months control) is considerably
important in terms of reduction of the risk of diabete’s
Vivian Andrew Fonseca, MD, FACE,
Julio Rosenstock, MD, Kenneth Truitt, MD,
Carl Dmuchowski, MPH, and Michael Jones, PhD
Objective: The bile acid sequestrant colesevelam
hydrochloride (COL) is indicated for lowering low-density lipoprotein cholesterol (LDL-C). However, the addition
of COL to existing oral antidiabetic agent(OAD) therapy
in a pilot study improved glycemic control in patients (pts)
with type 2 diabetes mellitus (T2DM), significantly reducing A1C by 0.5% in the total patient population and by
1.0% in subjects with a baseline A1C >/=8%. The current
study evaluated in a larger population the efficacy and
safety of adding COL to sulfonylurea (SU)-based therapy
in patients with inadequately controlled T2DM.
Methods: A randomized, double-blind, parallelgroup, multicenter study was conducted in pts with T2DM
(A1C 7.5%-9.5%) receiving a stable dose of an SU alone
or in combination with other OADs for 3 months. Pts
entered a 2-week (wk), single-blind placebo (PLA) run-in,
after which pts were randomized to COL 3.8 g/d (n=230)
or PLA (n=231), added to their pre-study SU-based regimen. The primary endpoint was change from baseline in
plasma A1C at wk 26 (last observation carried forward
[LOCF]; intent-to-treat [ITT] population).
Results: COL therapy resulted in significantly greater
reductions in A1C and fasting plasma glucose (FPG) levels vs PLA at wk 26 (Table). A significant treatment difference in A1C was seen as early as wk 6 (–0.44%;
P<0.001). COL also produced a significantly greater
– 10 –
reduction in fructosamine level vs PLA at wk 26 (–21.5
µmol/L; p<0.001). The proportion of patients with
glycemic control response (decrease from baseline of
>/=30 mg/dL in FPG or >/=0.7% in A1C) was significantly higher with COL vs PLA (47.5% vs 32.1%; P=0.001).
Drug-related treatment-emergent adverse events (TEAEs)
were generally mild to moderate, occurring in 63.3% of
COL recipients and 54.5% of PLA recipients. Drug-related TEAEs occurred in 20.5% of COL recipients (most
commonly gastrointestinal) vs 9.1% of PLA recipients.
There were no drug-related serious AEs. The incidence of
hypoglycemia in the COL group was similar to that with
PLA and mean body weight change was not different
between COL and PLA.
Discussion: no discussion
Conclusions: In patients with T2DM inadequately
controlled on SU-based regimen, the addition of COL led
to significantly improved glycemic control and was well
tolerated over a 26-wk period.
R and HOMA-β, but the difference was not statistically y different.
Discussion: In T2DMpatients acanthosis nigricans is
associated with obesity and not only high insulin resistance and but also compensatory insulin hyper-secretion.
Absence of hyertriglyceridemia could be because of action
of high insulin levels on adipose tissue. Though, skin tags
are also associated with obesity and hypertriglyceridemia,
but only marginally high, but statistically insignificant
insulin resistance and secretion. It is possible that these
two cutaneous signs reflect two different patho-physiologies associate with obesity in diabetics.
Conclusions: Presence of acanthosis nigricans and
skin tags in diabetics are associated with obesity.
Nevertheless, the acanthosis nigricans is associated with
not only insulin resistance but also insulin hyper secretion.
Skin tags on the other hand reflects predominantly insulin
secretion defect in presence of obesity. It is possible that
these two cutaneous signs reflect two different pathophysiologies consequent to obesity in T2DM patients
Abstract #418
Abstract #137
CUTANEOUS SIGN SUGGESTING INSULIN
RESISTANCE AND SECRETION IN T2DM
PATIENTS
HYPERGLYCEMIC UNAWARENESS: AN
INSULIN (MAL)PRACTICES SURVEY
Sandeep Kumar Mathur, MBBS, MD, DM,
Piyush Chandra, MB, BS, and Lokender Sharma, MD
Objective: Although, questions have been raised on
existence of metabolic syndrome, but it is clinically
importance to predict insulin resistance and secretion in
T2DM patients. Acanthosis nigricans and skin tags are
cutaneous signs, which suggest underlying insulin resistance and obesity. Their relative importance in predicting
insulin resistance and secretion is not clear. Therefore, we
assessed association of these cutaneous signs with insulin
resistance and secretion in T2DM patients.
Methods: One hundred and thirty nine T2DM patients
(age 42 to 74 years, male to female ratio 78:61) participated in the study. Acanthosis nigricans and skin tags were
diagnosed based on clinical criteria. Other physical parameters studied were BMI and waist circumference.
Laboratory investigations included apart from routine
tests, homeostasis model assessment of insulin resistance
(HOMA-R) and secretion (HOMA-β)
Results: Presence of acanthosis nigricans was associated with high BMI (p = 1.08E-06), HOMA-R (p =
0.036592) and HOMA-β (p = 0.000308). Presence
of skin tags was associated with higher BMI (0.045033),
triglyceride level (0.049392). Though it was also associate
with higher waist circumference (p = 0.055479), but the
difference was not statistically significant. Similarly, skin
tags were also associated with marginally higher HOMA-
Shehzad Topiwala, MD, MBBS, DD,
Vikram Sodhi, MHA, MBBS, Radha Lachhiramani, MSc,
Dip Clin Dermat, MBBS,
Rakesh Parikh, FCPS, DD, MBBS, and
Mitali Vaidya, DD, MBBS
Objective: To determine knowledge, attitude and
practices, amongst health care professionals, pertaining to
in-patient insulin therapy
Methods: We administered a 26-point questionnaire
to 52 subjects, comprising nursing and medical students,
staff nurses, interns and resident doctors (medical, surgical
and allied specialties). Topics particularly related to care
of inpatients, insulin(I) practices, hypoglycaemia management and SMBG (Self Monitoring of Blood Glucose)
Results: Overall 57% followed incorrect I practices.70% knew the correct Sick Day Schedule.49% were
aware that Capillary Glucose sticks need to be stored away
from sunlight.39% correctly preferred oral over intravenous glucose,for managing minor hypoglycemia in an
inpatient.40% knew the correct storage techniques for
vials/syringes.19% appreciated that insulin can be given in
odd number doses.50% roll the vial between their palms
and 44% push air into it,before drawing I.70% are correct
in drawing regular insulin first.71% & 48% agreed that I
can be given in abdomen and buttocks respectively.23%
correctly gave regular I 30 minutes prior to meal.31% verified the correct syringe capping method.57% were famil-
– 11 –
iar with I sliding scale.44% had heard of I analogues.67%
had heard of I pen devices.
Discussion: “A little knowledge is a dangerous
thing”—this adage could well apply to the care of diabetes
patients. In particular, we are concerned about the lack of
awareness amongst health professionals with regard to
insulin therapy. A wide range of health care providers are
responsible for the care of hospitalised diabetes patients.
These include interns, nursing students and staff, resident
house physicians and surgeons. These individuals are
actively involved in several processes pertaining to the
management of diabetic patients in the hospital. They are
also required to teach the same to patients and hence it is
imperative that they follow the right practices. We therefore set out to assess the knowledge and practices of representative members of the diabetes care team.The
startling results from this multi speciality private hospital
were corroborated by similar findings in a premier national academic institute of excellence. The latter studies'
results were not published out of concern that the university's reputation might get tarnished. Its easy to imagine
the situation across the country, if one India's best hospitals lacks competence in this basic yet crucial arena.
Conclusions: There remains substantial unawareness
amongst health care providers with regard to care of inpatient diabetics.Health care professionals are not adept at
managing such patients.We plan to hold workshops for
educating them on an ongoing basis.We will assess it’s
impact by re administering the questionnaire several
months later as well as periodically over regular intervals
of time.Standardised surveys should be validated for testing worldwide to accredit an institution's Insulin-ability.
Abstract #232
THE PARADOX OF HYPOGLYCEMIA WITH
ELEVATED HBA1C-A RARE CAUSE
Sudip Nanda, MBBS, Mohammad Arastu, MD
Objective: To discuss causes of discrepancy between
HbA1c and blood glucose and when to consider hemoglobin variants.
Case Presentation: A 45 year old male was admitted
with a two week history of polyuria, polydipsia and
fatigue. He denied personal or family history of diabetes
mellitus. On physical examination, he was obese with a
body mass index of 30. Systemic examination was normal.
Random blood glucose was found to be 547 mg/dl. Serum
acetone was negative. Glycosylated hemoglobin (HbA1c)
was found to be beyond the estimable level of 18.9% by
high performance liquid chromatography (HPLC).His
blood glucose was controlled with insulin and he was discharged on insulin. At follow up visits patient reported
hypoglycemia by accucheck though his HbA1c was
repeatedly greater than 18.9. Glycated serum protein was
determined by fructosamine assay which was normal. Hb
electrophoresis revealed a fast moving Hb J variant comprising 54% of total Hb causing spuriously high HbA1c.
His blood glucose is currently controlled with minimal
doses of insulin. His diabetes is managed based on total
glycohemoglobin.
Discussion: Normal Hb consists of HbA1 97%,
HbA2 2.5% and HbF<0.5 %.HbA yields HbA1a, HbA1b
and HbA1c. HbA1c is formed by glycation of N-terminal
valines of beta chains. Conditions affecting HbA1c
include hemolytic anemias-decreased HbA1c, post
splenectomy- increased HbA1c and HbSS/HbCC where
there is no HbA. HbA1c is estimated by Boronate affinity
chromatography (BAC), Ion exchange high performance
liquid chromatography (HPLC), Immunoassays,
Electrophoresis and Electrospray mass spectroscopy
(ESMS). HPLC separates Hb by charge and then spectrophotometer measures concentration of various fractions. It gives errors with Hb variants. BAC has least
interference from Hb variants. ESMS is a reference
method where HbA1c is unaffected by any modification.
Common Hb variants affecting HbA1c by HPLC method
are Carbamyl Hb in uremia causing spurious increase at
2% carbamyl Hb, HbAS (7.8 % African American)- spurious increase at low level HbA1c and HbSS, HbCC,
HbSC and HbF where falsely low values occur.
Uncommon Hb variants with spuriously high HbA1c
include Raleigh, South Florida amongst others.
Uncommon Hb variants with spuriously low HbA1c
include D, North Manchester and Riyadh.
Conclusions: 700 Hb variants exist. 200,000 of 20
million diabetics carry at least one variant. HbS and HbC
are most common. Hb J is rare and causes both spuriously
low and high HbA1c.Consider Hb variants when HbA1c >
15%, HbA1c below lower limit of normal and significant
change in HbA1c occur with change in method of estimation. Differentials for spurious HbA1c levels are hemoglobinopathies, altered red cell turnover and chemically
modified Hb. For correct HbA1c reassay with boronate
chromatography or ESMS
– 12 –
Abstract #302
school. This problems are frequently reported at this age
group.
Conclusions: Twenty nine juvenile Type-1 DM subjects replaced lunch-time dose of regular insulin for split
doses of Oral-lyn™ for 6 months. GC was observed in 21
of them and PC in 8 subjects. As expected in Type-1DM
and especially in adolescent subjects, metabolic control
corresponded to compliance in each subset.
ORAL INSULIN (ORAL-LYN™) 6-MONTH
LUNCHTIME REPLACEMENT IN JUVENILE
TYPE-1DM
Jaime Guevara-Aguirre, MD,
Marco Guevara-Aguirre, MD, and
Jeannette Saavedra, M.D.
Abstract #377
Objective: Lunch-time Oral-lyn™ replacement in
juvenile Type-1 DM on basal insulin analogue and prebreakfast/pre-dinner regular insulin
Methods: Stabilization Phase (SP): 21 days (d) with
sc injected basal BID insulin analogue and 3 pre-prandial
sc injections of regular insulin (RI) + 7 additional d for
comparison. Oral-lyn™ Replacement Phase (OR): After
SP, split doses of Oral-lyn™ replaced the lunch-time sc
injection of RI for 6 months
Results: Baseline(B) (n=27):Fructosamine (F) 476.9
(130.2) mmol/L; % HbA1c(A1c) 9.9 (2.4). End of Regular
Phase(RP) (n=29) F 371.3 (90.6) p<0.001 / A1c 8.8 (1.8)
p<0.001; End of 6-Month OR (n=27) F 392.8 (110.3)
p<0.002 / A1c 8.5 (2.0) p<0.004; GOOD COMPLIANCE(GC) (72.41%):B-GC (n=19): F 443.4 (102.1) /
A1c 9.1 (1.9) End of RP GC (n=21) F340.9 (54.5) p<0.001
/ A1c 8.1 (1.2) p<0.002 End of 6-Month OR-GC (n=21) F
349.7 (54.4) p<0.001 / A1c 7.7 (1.1) p<0.002 POOR
COMPLIANCE (PC):(27.58%):B-PC (n=8) F 556.5
(160.9) / A1c 11.9 (2.4) End of RP PC (n=8) F 451.3
(119.5) p<0.002 / A1c 10.5 (2.1) p<0.011 End of 6-Month
OR-PC (n=6) F 543.7 (127.9) p<0.863 / A1c 11.3 (1.9)
p<0.508 GC SCORE: 51.86 (14.97) vs. PC score 14
(10.87) p<0.001
Discussion: 29 Juvenile Type-1 DM subjects underwent a SP followed by a OR phase (24 adolescents (12M;
12F) and 5 young adults (2M; 3F) were included.
Demographics (Adolescents): Age 14.7y (2.1); Height
153.8cm (9.4); Weight 51.0kg (10.2); BMI 21.7 (3.2); DM
since onset 6.7 (2.8). Demographics (Adults): Age 20.6y
(2.2); Height 161.1cm (12.8); Weight 62.5kg (9.3); BMI
23.0 (1.8); DM since onset 7.0 (1.7). Age (All): 15.7y
(3.0); DM since onset is 6.8 (2.6)). Two groups of GC and
PC were identified at study end by 6 independent evaluators blinded to biochemical results. They assessed compliance using a 9-parameter method. 21 subjects had good
compliance (GC) and 8 subjects had very poor compliance
(PC). Important reasons for PC compliance in this subset
of adolescent Type-1 DM subjects included: 1. Frequent
missing of doses (of either basal, pre-prandial or prandial
insulin); 2. Absence of exercise; 3. Obvious psychological
problems; 4. Alcohol abuse; 5. Drug abuse; 6. Severe family problems; 7. Severe problems with girl/boyfriend; 8.
Severe eating problems; and 9. Serious problems at
EFFECTIVENESS OF EXENATIDE THERAPY IN
THE TREATMENT OF TYPE 2 DIABETES
Krithi Bangalore Ramesh, MD,
Rajika Munasinghe, MD, FACP,
Opada Alzohaili, MD, FACE, and Gary Edelson, MD
Objective: This study was conducted to evaluate the
effectiveness of exenatide in type 2 diabetes at 2 private
endocrinology practices.
Methods: Medical records of 30 poorly controlled
type 2 diabetic patients between Oct05-Aug06 were
reviewed. Exenatide was initiated at 5mcg twice daily and
increased to 10mcg twice daily in 4 weeks. The change in
HbA1c, lipid profile and body weight before and after initiation of exenatide were evaluated.
Results: The mean age of the study subjects was 54.7
years, 53.3% were female and 93% were white. Treatment
prior to initiation of exenatide included oral hypoglycemic
drugs [Metformin (22) +/- Sulfonylurea (18) +/Thiazolidinedione (13)] with or without insulin (9). The
mean duration of follow up was 15 weeks (range 8-28
weeks). The mean HbA1c of the study subjects declined
from 7.80% to 7.32% (p<.0008) and the mean body
weight decreased from 244.3 to 238.6 lbs (p <0.0004), a
loss of 5.7 lbs. There was no statistically significant
change in lipid profile. The majority (90%) of patients
continued exenatide after the first follow up visit.
Hypoglycemia was noted in 10% of patients while nausea
and vomiting was reported by 31% of patients. Other gastrointestinal side effects were reported in 23%.
Discussion: Exenatide, an incretin mimetic and GLP1 agonist improves glucose homeostasis and promotes
weight loss by glucose dependent insulin release, regulation of glucogan secretion, delaying gastric emptying, and
decreasing appetite. It is approved as adjunctive therapy
for type 2 diabetes in conjunction with Metformin and/or
sulfonylurea to improve glycemic control. Principal side
effects are gastrointestinal manifestations such as nausea,
vomiting and diarrhea. In our study we found statistically
significant reductions in HbA1c levels and body weight.
No statistically significant change was observed in lipid
profile. Gastrointestinal side effects were most come in
our patients.
– 13 –
Conclusions: In typical ambulatory practice, exenatide is effective in improving glycemic control and promoting weight loss in poorly controlled type 2 diabetic
patients on oral hypoglycemic with or without insulin
therapy. Although a substantial number of patients reported gastrointestinal side effects, the majority of patients
managed to remain on exenatide therapy.
Conclusions: Mercy Health center was in compliance
with HEDIS-CDC benchmarks. A follow up study will
need to determine if residents were compliant with both
fundoscopic eye exams and diabetic foot exams. Also,
adherence with the American Diabetic Association regarding HA1c and LDL-c should be the goal for all providers
taking care of patients with diabetes.
Abstract #341
Abstract #412
COMPLIANCE WITH HEDIS-CDC MARKERS AT
MERCY HEALTH CENTER
SAFETY, TOLERABILITY AND
FUNCTIONALITY WITH BASAL/BOLUS
INSULIN DELIVERY SYSTEM H-PATCH(TM)
Rahul Warrier, DO, Michael Koren, MD, and
Jann Johnston, MD
Poul Strange, MD, and Seymour Fein, MD
Objective: The purpose of this study was to determine
the compliance with HEDIS CDC markers at Mercy
Health Center.
Methods: The sample was comprised of those who
filled oral hypoglycemic and/or insulin prescriptions at
Mercy Health center pharmacy. Using the computerized
medical record system at Mercy Hospital, each patient was
evaluated from January 1st 2005 to January 1st 2006 to
determine adequate monitoring.
Results: 138 diabetic patients were identified. Of
these, 91% patients had their HA1c checked within the
specified time and 12% had poor diabetes control (HA1c
>9.5) placing them in top percentile for both markers. 71
% patients had their LDL-c checked and this placed them
in bottom percentile for appropriate LDL-c monitoring.
Additionally 70 % had LDL-c levels below 130mg/d placing them in top percentile for achieving LDL-c goal.
Regarding urine micro-albunuria, 64% of the sample had
this checked placing the MHC in the top percentile for
monitoring for diabetic nephropathy. Descriptive analysis
showed that the mean HA1c was 8.1 mg/dl and the mean
LDL-c was 114mg/dl at the health center
Discussion: HEDIS (Health Plan Employer Data and
Information Set)-CDC (Comprehensive Diabetes Care)
measures includes six indicators for effective, multiphasic
management of diabetes and its complications. Indicators
include yearly HA1c and LDL-c monitoring, poor diabetes
control (HA1c >9.5), LDL-c (<130mg/dl), yearly urine
micro-albminuria and fundoscopic eye exams. Internal
medicine trainees were compliant with monitoring five of
the six HEDIS-CDC indicators. Our study will help elucidate where providers at MHC can improve their diabetes
management. Based on this study, we have done various
interventions to further improve the practice standards and
provide better diabetes care. These studies can also serve
as an important tool to assess, monitor and improve the
practice standards in other training programs and office
settings.
Objective: Current approaches to achieving appropriate insulin delivery in Type 2 Diabetes Mellitus (T2DM)
typically require multiple daily injections of insulin or
injections of fixed ratio premix or basal insulin in combination with OADs. The h-Patch is a discrete, simple-to use
once-daily disposable device allowing for the titration of
basal/bolus insulin delivery. The device adheres to the
patient’s skin delivering insulin through a 30 gauge needle. Here we evaluate the pharmacodynamics, safety and
tolerability of delivering insulin aspart using h-Patch in
patients with T2DM.
Methods: 6 patients with T2DM receiving glargine
(≥15 U/day)±OADs were transitioned off glargine
to receive basal and bolus insulin administration using the
h-Patch while maintaining OADs. Each h-Patch was
applied once-daily for 7 days (3-day inpatient followed by
4-day outpatient). The h-Patch gave a continuous basal
infusion of insulin aspart (0.6 U/hour) subcutaneously and
up to three individualized bolus doses in increments of
2U) of insulin aspart each day. Patients’ ability to use the
device was assessed.
Results: The Six patients had a baseline A1c of
7.7±1.2% (mean±SD), a duration of T2DM of 10.5±7.9
years, an age of 59.5±5.2 years and had been on insulin
glargine therapy for 2.4±0.9 years. The h-Patch demonstrated excellent adhesion to the skin and all 42 devices
remained firmly attached for 24 hours. Patients did not
report pain or discomfort wearing the h-Patch. Mild irritation was reported in 3 patients and these reactions resolved
spontaneously. All 42 devices functioned as expected for
both basal and bolus modes. The devices were found to be
discrete, convenient to wear and use during normal daytime activities and while sleeping. Insulin aspart administered using h-Patch was safe and well tolerated. Glycemic
control was maintained. One episode of mild hypoglycemia was noted and was not associated with clinical
symptoms. Lab values assessed during this study showed
no clinically meaningful changes. No SAEs . There were
no early discontinuations from the study.
– 14 –
Discussion: While the number of patients in this early
study of the h-Patch is limited the repetitive successful use
of the device, the study offers a good basis for future
investigations.
Conclusions: Insulin administration with the h-Patch
device was safe and well tolerated. Both basal and bolus
modalities with h-Patch functioned as anticipated. No
SAEs or early discontinuations were reported.
Abstract #342
MORTALITY AMONG DIABETIC IN- PATIENTS
IN NIGER DELTA REGION OF NIGERIA
ters and ward electrolyte analysers would have enabled
frequent monitoring of metabolic changes, with a resultant
reduction in mortality.
Conclusions: This study shows that many diabetic
patients died from preventable and treatable causes. The
reasons for this pattern of mortality which peaked in middle age are probably inadequate diabetes care services,
poverty and lack of diabetes education. The acquisition of
basic medical facilities/ services should constitute a priority in diabetic care in developing countries.
Abstract #304
HOW TO IMPROVE PATIENTS ADHERENCE TO
DM TREATMENT GUIDELINES?
Chioma Nwaonu Unachukwu, MBBS, FWACP
Objective: To determine the causes of death among
diabetic in-patients at a tertiary hospital in the Niger Delta
region of Nigeria.
Methods: The medical records of patients admitted
with diabetes mellitus into the medical wards of the
University of Port Harcourt Teaching hospital from 19952004 were reviewed. The sources of data were the ward
admissions and death registers, death certificates and medical records.
Results: During the period under review, 6,574
patients were admitted into the medical wards. Out of
these, 686 (10.4%) were due to diabetes and its complications . The patients comprised of 428 (62.4%) males and
258 (37.6% ) females giving a M:F ratio of 1.7:1 . One
hundred and eighteen of the diabetic patients died giving a
case fatality of 17.2%. The main causes of death were diabetic ketoacidosis( DKA)(21.2%), diabetic mellitus foot
syndrome (DMFS) (19.5%) and renal failure (12.7%).
Diabetic emergencies i.e. diabetic ketoacidosis, hyperosmolar nonketotic state and hypoglycaemia accounted for
39.8% of all deaths.
Discussion: The case fatality among the diabetic
patients was unacceptability high. Whereas diabetes
accounted for 10.4% of medical admissions; it contributed
to 11.1% of total medical deaths. The majority of the
deaths were in the middle- aged and mainly due to preventable causes. Diabetic ketoacidosis, hyperosmolar nonketotic state and hypoglycaemia accounted for almost
40% of the diabetic deaths. The high diabetic deaths from
these acute and rather preventable causes are a true reflection of the poor state of our diabetic care services. A previous study in the same centre revealed that 35.5% of the
diabetic deaths occurred within 24 hours of admission and
were mainly due to acute metabolic and preventable causes. Late presentation to hospital, misdiagnosis, a lack of
insulin, infections and overall lack of adequate healthcare
delivery system are main causes of acute diabetic deaths.
Good laboratory support, provision of bedside glucome-
Saad Sakal, MD, FACE, and
Anthony Michael Albisser, PhD
Objective: Patients adherence to therapy is a major
challenge.Improving adherenc will improve diabetic control .How do we help adherence
Methods: We tested Humalink software systm for
better diabets control in 87 insulin using poorly controlled
diabetics on DCCT protocol.Patients called via toutchphone telephone4-6 BGSM values twice/week for 1year.
Monthly calls records and hypoglyc. were documented to
derive adherence rate.
Results: Active users were 60 (69% compliance)
Monthly calls between the first month (48+/-3) and last
month (43+/-3) were relatively stable(adherence90% total
calls 22257. Hypoglyceia was3% in the first month and
0.7% at the end (average 0.8%) Hyperglyc. (Gl>250)
decreased from 5% to 2%. Hga1c decr. from9.7% to 7.9%.
Average FBS decr. from 167 to 140,2 HPP Gluc. from 194
to 152, Trig. from 330 to 196, chlesterol from 261 to 200,
fructosamine from 348 to 294, insulin dose decreased
22%, and weight was stable 81 Kg.Costs of care were
$1640/patient (DCCT average cost $6400-$9760/ patient)
All comarative numbers were signi-ficant at P value of
0.001 or less
Discussion: it is by now well established that the
DCCT/EDIC has proven the value good glycemic control
for intermed. and long term outcome. But keeping most
patient adhering to a therapy is still a major challenge,
mostly in the range of 53-65% for oral Rx, 60% for diet,
19% for exercise, daily BGSM in 39% of patients on
insulin, and just5% on oral agent/diet/exer. in general
TypeI has better adher. a recent article journal in "clinical
Diabetes" described factors effecting adherence,and as
result control,complications and life. Humalink software
system has been also proven byond a doubt its efficacy,validity,cost effectivness,and safety in a number of
studies now in more than 8oo patients.We tested in this
– 15 –
study effect on adherence, for near a year. We were very
happy to see adherence rate in excellent range (90%)
whish is rare in any chronic disease. This adherence led to
a better glycemic control aswell as full metabolic control
as seen in FBS,PPGluc, HgA1c, Fructosamine, Triglyc,
Cholesterol.And excellent drp in Hypog/Hyerglycemic
episodes ,while maintainig stable weight at lower insulin
dose. The reason is the collaboration therapy mode whish
only Humalink has today.
Conclusions: Humalink offers a 90% adherence
rate,with instant feedback, better than any other system or
protocol exists today, at a greater savings, less resources
(one MD, RN, clerck), better value index, safety, and cost
effectivness. This is a result of its advanced collaboration
mode whish makes the patient an active participant in care
enjoiying the shared interaction twice weekly whish is
within the range most patients will tolerate(40-50%) as
most adherence studies shows. Humalink is best well
proven system.
Abstract #318
ONCE-DAILY SITAGLIPTIN, A DPP-4
INHIBITOR, IMPROVES GLYCEMIC CONTROL
AND IS WELL TOLERATED AS MONOTHERAPY
OR ADD-ON THERAPY IN PATIENTS WITH
TYPE 2 DIABETES
Peter Paris Stein, MD, Debora Williams-Herman, MD,
Matilde Sanchez, PhD, Jared Lunceford, PhD, and
John Amatruda, MD
Objective: To examine the efficacy and safety of
once-daily sitagliptin (SITA) in patients with type 2 diabetes using data from 4 placebo (PBO)-controlled, Phase
III studies (2 monotherapy [18 wks or 24 wks in duration]
and two 24-wk add-on [to metformin or pioglitazone]
studies).
Methods: Patients were randomized to the following
once-daily treatments (PBO, SITA 100-mg, or SITA 200mg in monotherapy studies only) if A1C was >=7% and
<=10% after run-in and washout periods. For efficacy
analyses, SITA 100-mg data were pooled from the common 18-wk time point for the monotherapy studies and
presented separately for the add-on studies. A meal tolerance test (MTT) was performed in the 24-wk monotherapy and add-on to metformin studies. Safety and
tolerability were assessed in all treatment groups.
Results: The patients in these 4 Phase III studies
(N=2316) had generally mild to moderate hyperglycemia
(mean baseline A1C ~8.0%). With SITA 100-mg, PBOsubtracted A1C reductions were 0.7% in the pooled
monotherapy and the add-on studies. In the monotherapy
studies, PBO-subtracted A1C reduction was 1.4% in
patients with a baseline A1C of >=9%. The proportion of
patients achieving an A1C<7% with SITA 100-mg ranged
from 36-47% across studies. PBO-subtracted reductions in
FPG ranged from 17-25 mg/dL with SITA 100-mg. In
patients receiving a MTT, PBO-subtracted reductions in 2hour postprandial glucose were ~50 mg/dL with SITA
100-mg. For safety assessments, 1538 patients were treated with SITA (n=1082 on 100-mg, n=456 on 200-mg) and
778 with PBO. The overall incidence of AEs was similar
across groups, as was the incidence of hypoglycemia
(1.2% [100-mg], 0.9% [200-mg], and 0.9% [PBO]). No
clinically meaningful changes in weight from baseline or
PBO were observed with SITA.
Discussion: Sitagliptin is first in a new class of
agents, DPP-4 inhibitors, for the treatment of patients with
type 2 diabetes. Prior studies have shown that sitagliptin
acts by increasing the concentrations of the active incretin
peptides GLP-1 and GIP which, in turn, leads to glucosedependent enhancement of insulin release and suppression
of glucagon. These hormonal changes lead to improved
post-meal and fasting glucose levels. Results from 4 Phase
III studies (2 in monotherapy and 2 in add-on combination
use) were analyzed to assess efficacy and safety/tolerability, and demonstrated that once-daily sitagliptin 100-mg
effectively and consistently improved fasting and postprandial glycemic control in patients with type 2 diabetes.
The safety profile of once-daily sitagliptin at the approved
therapeutic dose of 100-mg, and at a dose twice (200-mg)
the approved therapeutic dose, was generally similar to
placebo including absence of weight gain and a very low
incidence of hypoglycemia.
Conclusions: In patients with type 2 diabetes,
sitagliptin improves glycemic control, was well tolerated
without weight gain and with an incidence of hypoglycemia similar to placebo.
Abstract #296
1,5-ANHYDROGLUCITOL, A PPG EXCURSION
MARKER IN PRAMLINTIDE-TREATED
SUBJECTS
Juan P Frias, MD, FACE, Eric Button,
Cameron Lush, PhD, Rocco Brunelle, MS, and
Toshikazu Yamanouchi, MD
Objective: To assess 1,5-anhydroglucitol (1,5-AG) as
a marker of PPG control in pramlintide-treated subjects
with type 1 diabetes (T1DM)
Methods: Post-hoc analysis of a randomized, doubleblind, placebo-controlled study of a subset of subjects with
T1DM on intensive insulin therapy with a baseline
A1C</=8% (N=37, age 40±12 y; A1C 7.5±0.3%; weight
85.9±20.8 kg; mean±SD) treated with pramlintide (30/60
µg) or placebo with major meals.
– 16 –
Results: A repeated measures analysis across all visits was performed comparing pramlintide and placebo
groups. Subjects in both groups targeted similar glycemic
goals. At Wk 29, pramlintide (n=18) improved 2-hr PPG
excursions (-43.9±10.9 vs +6.5±7.6 mg/dL, P<0.001;
mean±SE), reduced body weight (-2.0±1.2 vs +1.3±0.7
kg, P<0.01), and resulted in similar reductions in A1C (0.18±0.31 vs. -0.22±0.21%) compared with placebo
(n=19). Consistent with the improvement in PPG, fasting
plasma 1,5-AG levels increased significantly from baseline to Wk 29, relative to placebo (+0.96±0.91 vs 0.65±0.41 µg/mL, P<0.05; +30±16% vs -9±8%, P<0.01).
The most common adverse event associated with pramlintide use was mild-to-moderate nausea.
Discussion: Postprandial hyperglycemia contributes
significantly to overall glycemic control (A1C) and has
been shown to be an independent risk factor for long-term
morbidity and mortality. Pramlintide, an analog of the
beta-cell hormone amylin, when administered as an
adjunct to mealtime insulin, lowers PPG more effectively
than insulin alone. 1,5-AG (GlycoMark assay) is a monosaccharide found in various food sources. Due to structural similarities with glucose, 1,5-AG renal reabsorption is
competitively inhibited when plasma glucose rises above
the renal threshold for glucosuria. Therefore, during
hyperglycemia, 1,5-AG urinary excretion increases, so
plasma concentrations decline. Clinically, 1,5-AG can be
used as a marker of postprandial glycemia in patients with
A1C levels below approximately 8%. In this post-hoc
analysis in moderately well controlled subjects with
T1DM, the change in 1,5-AG levels was consistent with
the improvement in PPG control in pramlintide-treated
subjects as measured by SMBG.
Conclusions: 1,5-AG, as a complement to the A1C,
may be a useful marker of PPG control.
Abstract #203
IMPACT OF A HIGH FIBRE DIET ON TYPE 2
DIABETES CONTROL IN NIGERIA
Babatope Kolawole, MD, Rosemary Ikem, FMCP(Nig),
and Ebenezer Ojofeitimi, PhD
Objective: We studied the effect of high caloric fibre
diet on the glycaemic and lipid profile of tablet treated
Nigerian T2DM patients.
Methods: 52 T2DM were assigned to either an intervention(35)or control group (17. The intervention group
consumed a diet providing at least 40g of fibre per day
while the control group were fed a regular diet. The effect
of both diets on glucose and and lipid profile were then
tested at 4 and 8 weeks.
Results: One way repeated measures analysis of variance for the follow up period showed a significant lowering of waist circumference p = 0.002, Fasting Blood
Glucose, 2hr post prandial glucose, Total Cholesterol,
Triglyceride, and LDL-C (p = 0.000 in all cases) by the
third visit in the intervention group. At the end of the third
visit, the mean FBG decreased by 4.9 ± 2.7mmol/l 95% CI
-5.8 to -3.9 in the intervention group and by 3 ± 2.8mmol/l
95% CI -4.5 to -1.5 in the control group p = 0.02. 23
(65.7%) intervention group subjects had attained FBG levels ≤ 7.0 mmol/l by the third visit. None of the control subjects had their FBG lowered below 7.0 mmol/l by
the third visit.By the third visit,control subjects required
higher doses of sulphonylureas than subjects in the intervention group.
Discussion: The ideal diabetic diet should maintain a
satisfactory body weight with euglycaemia and normolipidaemia and provide adequate energy and essential nutrients for normal body homeostasis. Our study showed that
consumption of a high fiber diet for 8 weeks resulted in a
greater change (lowering) in blood glucose than a control
(conventional) diet without concomitant hypoglycaemia.
In addition, more subjects in the intervention group
attained normoglycaemia even though both groups
demonstrated significant plasma glucose lowering by the
end of the study. Expectedly, the high fibre diet significantly reduced plasma total cholesterol concentrations and
other lipid parameters except HDL-C. The diet also
induced a greater change in mean lipid parameters compared with the control group. The cholesterol reducing
effects of soluble fibre is well established. The hypolipidemic effects of dietary fibre are mediated by the actions
of soluble fibre in binding bile acids, thereby increasing
their faecal excretion and interrupting the enterohepatic
circulation of bile salts. The fermentative end products of
fibre- acetate, propionate, and butyrate also play a role in
this process.
Conclusions: Consumption of a high fibre diet provided mainly through soup thickeners and vegetables by
Type 2 diabetic patients being treated with oral hypoglycaemic agents resulted in early attainment of normoglycaemia and improved glycaemic and lipid profile
compared with a conventional diet. These findings underscore the need for our dietary guidelines to include specific recommendations on increased utilization of dietary
fibre, while also providing a cheaper means of achieving
normoglycaemia.
– 17 –
Abstract #282
THE USE OF U-500 INSULIN PUMP THERAPY IN
PATIENTS WITH INSULIN RESISTANCE
Deepti Bulchandani, MD, Tara Konrady, RN, CDE,
Mitchell S. Hamburg, MD
Objective: To determine the safety and efficacy of U500 insulin pump therapy vs conventional insulin in
severe insulin resistance.
Methods: We performed a retrospective review of
medical records of patients with type 2 diabetes and
insulin resistance who were using U-500 in a CSII regimen for at least 3 months .The study group consisted of 6
patients The pumps used were Medtronic 715 and 712.The
data was analyzed using paired t test.
Results: There were 6 patients in our study. The mean
age of the patients was 57 +/- 5 years.Of the 6 patients,
67% were Caucasians and 50% were females. The mean
HbA1C prior to CSII with U-500 regular insulin was 9.05
+/- 1.08 and the mean U-100 insulin dose required was
391 +/- 91 units. The mean U -500 insulin at 6 months
required was 59.2 +/- 13.6 which was equivalent to 296
+/- 68 units of conventional insulin and was lower than the
initial insulin requirement(p value < 0.04). The mean
HbA1C at 6 months after treatment with CSII using U500
regular insulin was 6.9 +/- 0.9. This was statistically significant (Two tailed p value < 0.03). Though better
glycemic control has been associated with weight gain,
there was a mean decrease in weight of 6.1 lbs(95 % CI
1.53-10.69.p value < 0.02).
Discussion: Severe insulin resistance is defined as a
situation in which a patient requires > 200 units of insulin
for > 2 days. There have been very few studies which have
looked at the glycemic control and the efficacy of using U500 regular insulin delivered in a pump (CSII) in patients
with severe insulin resistance. All 6 patients had poorly
controlled diabetes and were using more than 200 units of
insulin before initiating CSII(Continuous Subcutaneous
Insulin Infusion) with U500. There was a substantial
decrease in the insulin requirement after being started on
CSII with U500 regular insulin. The CSII therapy may
eliminate issues of compliance and provide a better delivery of insulin and improved bio availability. There was a
rapid and considerable improvement in the glycemic control as reflected by a decrease in the HbA1C.The U-500
which 5 times more concentrated than the U-100 insulin
reduced the volume of insulin used per day which made
the pump therapy feasible. There were no clinically significant episodes of hypoglycemia during the treatment
with U-500.
Conclusions: CSII therapy with U-500 regular insulin
is a novel alternative for patients with insulin resistance
who have not met glycemic control goals with standard
intensive regimens. CSII pump therapy was not only associated with decreased insulin requirements, but also
showed better glycemic control.This is the first reported
series which includes 2 patients who have been on CSII
using U500 regular insulin for a period of more than one
year and supports continued efficacy on a long term basis.
Abstract #204
ADDITION OF COLESEVELAM HCL TO
METFORMIN (MET)-BASED THERAPY IN
PATIENTS WITH INADEQUATELY
CONTROLLED TYPE 2 DIABETES MELLITUS
IMPROVES GLYCEMIC CONTROL
Harold Bays, MD, Ronald B. Goldberg, MD,
Kenneth Truitt, MD, Carl Dmuchowski, MPH, and
Michael Jones, PhD
Objective: Colesevelam hydrochloride (COL) is a
specifically engineered bile acid sequestrant indicated for
lowering low-density lipoprotein cholesterol levels. In a
previous pilot study of 65 patients (pts) with type 2 diabetes mellitus (T2DM), COL added onto an existing oral
antidiabetic (OAD) regimen improved glycemic control,
significantly reducing A1C by –0.5%. The current study
of a larger population of 316 pts, evaluated the efficacy
and safety of adding COL to MET-based therapy in pts
with inadequately controlled T2DM.
Methods: A randomized, double-blind, parallelgroup, multicenter study was conducted in pts with T2DM
(A1C 7.5%-9.5%) receiving a stable dose of MET or MET
plus other OAD for 3 months. Pts entered a 2-week (wk),
single-blind placebo (PLA) run-in, after which pts were
randomized to 26 wks of COL 3.8 g/d (n=159) or PLA
(n=157) added to their prestudy MET-based T2DM regimen. The primary efficacy endpoint was change from
baseline in A1C at wk 26 (last observation carried forward
[LOCF]; intent-to-treat population).
Results: COL therapy resulted in significant least
squares mean (LSM) placebo-corrected reductions in A1C
(–0.54%; Table) at wk 26 LOCF, with a significant treatment difference observed as early as wk 6 (–0.46%;
P<0.001). LSM levels of fasting plasma glucose (FPG)
(–13.9 mg/dL) and fructosamine (–23.2 µmol/L; P<0.001)
were reduced in the COL group by wk 26 relative to PLA.
The proportion of glycemic control responders (pts with a
decrease in FPG of >/=30 mg/dL from baseline or
decrease in A1C of >/=0.7% from baseline) was also significantly higher (47.7% vs 35.5%; P=.033) in the COL
group than the PLA group at wk 26 LOCF. Drug-related
treatment-emergent adverse events occurred in 18.2% of
pts receiving COL (most were gastrointestinal related)
– 18 –
versus 8.9% of those receiving PLA. There were no treatment-related serious adverse events. Incidence of hypoglycemia was similar to PLA and mean body weight
change was not different between the COL and PLA
groups.
Discussion: no discussion
Conclusions: In pts with T2DM inadequately controlled on a MET-based regimen, the addition of COL led
to significantly improved glycemic control without weight
gain and with good tolerance over a 26-wk period.
Abstract #170
PULMONARY RHIZOPUS IN A DIABETIC MALE
WITH NONKETOTIC HYPEROSMOLAR STATE
Daniela Ciltea, MD, and Paula Butler, MD
Objective: To report the case pulmonary mucormycosis in a diabetic patient found to be in a nonketotic hyperosmolar state.
Case Presentation: An 83 year old diabetic Latino
male presented with one week history of abdominal pain,
nausea and vomiting. He reported poor appetite and
unquantified weight loss but no fever, chills, cough or
haemoptysis. Upon evaluation blood glucose was 1013
mg/dl with nonketotic hyperosmolar state (NKHS). The
NKHS was corrected with hydration and intravenous (IV)
insulin drip. Chest X-ray and chest computed tomography
(CT) scan showed bilateral perihilar infiltrates with cavitary lesions and the patient was started on IV antibiotics
(cefixime, metronidazole and vancomycin). Bronchoalveolar lavage was negative for acid-fast bacilli but grew
Rizopus species. Transbronchial biopsy showed fungal
hyphae consistent with mucormycosis. Antibiotic therapy
was switched to IV Amphotericin B. Despite aggressive
medical treatment and glycemic control the patient’s respiratory status deteriorated. Repeated chest x-rays and
chest CT scans over the course of the next 3 weeks of hospitalization showed worsening infiltrates and cavitary
lesions. Patient succumbed due to respiratory failure.
Discussion: Mucormycosis is an opportunistic infection caused by fungi from the order Mucorales, which can
cause an angioinvasive infection with infarction, necrosis
and hematogenous disseminated disease. Mucormycosis
presents with rhino-orbito-cerebral, pulmonary, disseminated, cutaneous, gastrointestinal or renal involvement.
Pulmonary mucormycosis is difficult to diagnose since its
presentation is similar to diffuse pneumonia. Chest X-ray
shows focal consolidation masses, pleural effusion or multiple nodules however evidence of infarction with cavitary
lesions and air crescent sign are unusual. Most patients
present with multilobular involvement and early pulmonary infections may be cured with lobectomy. Due to
advanced disease and diffuse pulmonary involvement,
surgery for was not an option for our patient. Diabetic
patients have increased serum iron resulting from
impaired transferin binding, as well as impaired neutrophil
function both of which facilitate growth of Rhizopus
organism. Additionally, the presence of a ketone reductase
allows Rhizopus to thrive in high glucose, acidotic conditions making early diagnosis and control of hyperglycemia
and metabolic acidosis essential.
Conclusions: Our case of Mucor infection in a diabetic patient with nonketotic hyperosmolar state demonstrates the rare manifestation of a complication usually
associated with diabetic ketoacidosis. Predisposition to
infection necessitates early diagnosis of infection, treatment of underlying medical conditions, surgery, and an
Amphotericin B product to increase the likelihood of a
successful outcome. Pulmonary involvement is the second
most common presentation of mucormycosis and has a
high mortality rate.
Abstract #383
MULTIPLE DAILY INJECTIONS [MDI] V/S
INSULIN PUMPS[IP] IN TYPE 1 DIABETES
Krithi Bangalore Ramesh, MD, and
Surendra Marur, MD, MPH
Objective: An evidence based research on the various
studies comparing Insulin Pumps and MDI for glycemic
control in Type 1 Diabetes.
Methods: Articles were searched in Ovid, PubMed
and Cochrane. The search criteria were IP and MDI. The
search yielded 38, 89 and 5 articles in Ovid, PubMed and
Cochrane respectively. Articles in English, comparing IP
and MDI in terms of glycemic control, in adults with Type
1 diabetes were considered.
Results: Many articles were common in the search
results.Articles dealing with non comparison on glycemic
control, those dealing with children, pregnancy or Type 2
Diabetes were considered as irrelevant. This filtering
yielded 7, 12 and 0 relevant articles in Ovid, PubMed and
Cochrane.Many articles were common in the search
results. The relevant studies were randomized controlled
trials, meta-analysis, prospective studies or literature
reviews. The studies by investigators like Hissa, Hanaire
–Broutin, Retnakaran , Lepore, Colquitt, Weissberg and
Home PD, all had a P <0.05 indicating a statistically significant improvement in glycemic control with IP.
Discussion: 1 out of 800 people in the United States
have Type 1 Diabetes. The Diabetes Complications and
Control Trial (DCCT) was a randomized controlled clinical trial that studied the relation between glycemic control
and microvascular complications in Type 1 Diabetes.
– 19 –
DCCT concluded that intensive therapy of diabetes
decreased the complications significantly. Intensive therapy is possible with either Multiple Daily Injections (MDI)
of Insulin or Continuous Subcutaneous Insulin Infusion/
Insulin Pumps [IP]. Most of the studies indicated a statistically significant improvement in glycemic control with
IP. However, two studies showed no difference between
IP and MDI. Many of these studies noticed a reduction in
insulin dose, a reduction or no difference with hypoglycemic episodes between the two. No consistent observation was made regarding incidence of DKA or weight
changes. Overall the quality of life was better with IP.
Conclusions: Thus, it appears that a better glycemic
control can be achieved with IP compared to MDI.
However, not all these studies considered the other aspects
of diabetes management like patient education, cost effectiveness and patient participation together with the above
discussed variables. For best results with IP, patient participation is pivotal. Hence, though IP appears to offer better glycemic control, this treatment modality needs to be
individualized to each patient.
patients in Group 1. Overall, only 4.3 % of all patients
attained the glycemic target.
Discussion: In this Saudi Arabian population with
type 2 diabetes on insulin, there was a frequent use of
intensive insulin management along with higher doses of
insulin. This deserves further evaluation and may be related to late diagnosis of diabetes. The majority of the population had glucose control that is far from acceptable,
emphasizing the increased need for higher insulin doses
and intensive management in a large proportion of these
patients. Possible contributing factors to the low rates of
acceptable glycemic control include decreased compliance
with therapy with more frequent insulin injections and
physician knowledge and experience in managing diabetes.
Conclusions: There is an increased need for the use
of intensive insulin therapy with high doses in Saudi
patients with type 2 diabetes. These findings can help in
directing health care providers when managing such
patients and provide guidance to education and quality
improvement programs.
Abstract #353
Abstract #108
HIGH NEED FOR INTENSIVE INSULIN
THERAPY IN SAUDI PATIENTS WITH TYPE 2
DM
CLINICAL IMPLICATIONS OF
HYPOMAGNESEMIA IN DIABETES MELLITUS:
A CASE STUDY
Mohsen Eledrisi, MD, FACE, Buthina Alhaj, RN, CDE,
Rifat Rehmani, MD, BSc, Munera Otaibi, MBBS, and
Mahmoud Mustafa, MD
Seth Charatz, DO, and Samir Malkani, MD
Objective: To evaluate the patterns of insulin use and
associated rates of glucose control in Saudi patients with
type 2 diabetes
Methods: This cross sectional multicenter study conducted in the eastern and western provinces of Saudi
Arabia consisted of adult patients with type 2 diabetes
attending internal medicine, family medicine, primary
care and endocrine clinics and receiving insulin therapy
with a minimum follow up of 6 months
Results: A total of 458 patients were evaluated (age
63 ± 9.3 years; duration of diabetes since diagnosis 13 ±
4.4 years; HbA1c 9.4 ± 2.4 %). Insulin was used once
daily in 2 % of patients (Group 1); twice daily in 82.5 %
(Group 2); and 3 or more times daily in 15.1 % (Group 3).
Premixed insulin was used in 59.4 % of subjects while
split-mix (Regular/NPH) insulin was used in 40.6 %.
Insulin dose was found to be > 1.5 units/kg/day in 18.3 %
and a total daily insulin dose of > 100 units in 28.5 % of
patients. There was no difference in glucose control
among patients on premixed and split-mix insulin regimens (P = 0.5). The AACE target of HbA1c < 6.5 % was
achieved in 4.1 % of Group 2, 0.2 % of Group 3 and no
Objective: To discuss the implications of magnesium
deficiency in diabetes, and review the literature to explore
the proposed mechanism.
Case Presentation: A 64 year old male with type 2
diabetes and diabetic polyneuropathy presented to the
Emergency Department with a one week history of severe
numbness and tingling in his extremities along with general malaise and nausea. His diabetes was sub-optimally
controlled for many years. Physical exam showed no
Chvostek sign, absent ankle reflexes, and loss of perception of vibratory sense in the toes. Laboratory studies were
as follows (normals in parenthesis): calcium 6.4 mg/dL
(8.7-10.1) 6 months ago calcium 8.7 mg/dL, magnesium
(Mg) 0.9 mg/dL (1.6-2.4), phosphorus 3.7 mg/dL (2.54.5), intact PTH 171 pg/mL (7-53), vitamin D 25-OH 13
ng/mL (40), and vitamin D 1-25 OH 38 pg/mL (15-75).
The most likely cause of hypocalcemia was thought to be
hypomagnesemia. Symptoms resolved after Mg and calcium replacement and 24 hour urine for Mg excretion was
appropriately low. Fractional Mg excretion was 1.4%
(<2%). Despite continuous repletion with Mg oxide and
calcium carbonate for over 5 months, the patient’s Mg levels remained low and calcium low/normal, however he
continued to be asymptomatic.
– 20 –
Discussion: Diabetes is one of the most common disorders associated with magnesium (Mg) deficiency. The
incidence of hypomagnesemia in diabetes has been reported to be 25-39%. It has been observed that serum Mg concentration correlates inversely with serum glucose. The
mechanisms still have not been clarified, but it is proposed
that in diabetes Mg is lost via osmotic renal losses from
glycosuria, decreased intestinal Mg absorption, and
insulin increasing free Mg into cells. Hypomagnesemia
can have many manifestations, but the most classical sign
of severe hypomagnesemia is hypocalcemia. A major factor is the influence of Mg on the parathyroid. Low Mg can
both impair release of PTH in response to hypocalcemia
and cause skeletal resistance of end organs to PTH. Mg
has also been shown to play a role in vitamin D metabolism. Patients with hypomagnesemia frequently have low
vitamin D 25-OH levels probably due to a co-existing
nutritional vitamin D deficiency. Interestingly, vitamin D
supplements have been shown to correct these levels, but
do not increase calcium. This suggests that hypocalcemia
is not a result of low vitamin D, but due to impaired PTH
release and action due to hypomagnesemia.
Conclusions: This case illustrates hypomagnesemia
as a result of diabetes causing symptomatic hypocalcemia.
As illustrated in this patient, Mg deficiency in diabetes can
be a complex disorder and the mechanisms of hypomagnesemia in diabetes are still not well understood.
Physicians should keep in mind the possibility that in
poorly controlled diabetes early intervention of hypomagnesemia could avert potentially fatal electrolyte abnormalities.
Abstract #171
TYPE 2 DIABETES PRESENTING WITH A
CEREBRAL VEIN THROMBOSIS AND
KETOACIDOSIS
Lisa S. Usdan, MD, Karen Choong, MD, and
Marie E. McDonnell, MD
Objective: To report an unusual presentation of type 2
diabetes in an adult with an extensive cerebral vein thrombosis and ketoacidosis
Case Presentation: A 30 year old man presented to
the ER with a severe headache. His review of symptoms
was positive for polyuria, polydipsia, and malaise. He had
no past medical or surgical history. His family history was
notable for maternal type 2 diabetes mellitus (T2DM). The
patient was afebrile on admission with stable vital signs.
Physical exam revealed an ill appearing, man of his stated
age with provokable diplopia, acanthosis nigricans, and
abdominal obesity. Admission labs were significant for
hyperglycemia, leukocytosis, and acidemia. Magnetic res-
onance imaging and angiography revealed an extensive
cerebral vein thrombosis (CVT). The CVT was treated
with a heparin infusion. His ketoacidosis was corrected
with intravenous fluids and insulin. Further lab studies
included a hemoglobin A1C of 10.3%. Islet cell and glutamic acid de-carboxylase-65 autoantibodies were negative. Physical exam findings, lab results, and family
history were most consistent with a diagnosis of T2DM.
Discussion: DKA is frequently the presenting pathological process in patients with Type 1 Diabetes (T1DM).
It is now increasingly more common in patients with
T2DM. Acidosis is generally less severe in patients with
T2DM as compared to those with T1DM. Patients with the
metabolic syndrome and T2DM who develop DKA are
more likely to have greater beta cell functional reserve and
less exogenous insulin requirements than patients without
metabolic syndrome. CVT are relatively uncommon. Most
patients with CVT are young adults and children with an
established risk factor. With rapid diagnosis and appropriate therapy, patients with CVT generally have very good
clinical outcomes. Diabetes is now understood as an ongoing inflammatory state with an imbalance of prothrombotic and fibrinolytic factors. Hyperglycemia leads to
increased hypercoagulability via increasing activation of
the coagulation cascade and abnormal platelet responsiveness. Concomitant development of CVT and DKA is very
unusual with only three cases currently in the literature.
The previously described cases all involved patients with
T1DM and all had an established risk factor.
Conclusions: This case is a rare presentation of
T2DM with DKA and a CVT. This is the first case in the
literature of a patient presenting with a CVT and a new
diagnosis of T2DM. From a pathophysiological perspective, it is likely that hyperglycemia promotes a prothrombotic state both chronically and acutely, which may
increase the risk of certain types of arterial and venous
thromboses. With an increasing prevalence of diabetes,
physicians can expect to see greater variability in presentation.
Abstract #208
YOUTH ONSET TYPE 2 DIABETES IN JAMAICA
Marshall Tulloch-Reid, MBBS, DSc, FACE,
Michael S. Boyne, MBBS,
Rosemarie A. Wright-Pascoe, MBBS, DM,
Robert Parkes, MBBS, DM, and
Rainford A Wilks, MBBS, DM
Objective: To determine whether youth onset diabetes
is present in Jamaica, a country where 19% of adolescents
are overweight or obese
– 21 –
Methods: Patients from 2 major referral hospitals
diagnosed with diabetes before age 25 years and < 6 years
prior to evaluation were eligible for the study. Diabetes
classification was based on medical history, physical
examination, diabetes autoantbodies (GAD65 and IA2)
and serum C-peptide measurement.
Results: Subjects were classified as follows: Type 1A
diabetes – antibody (AB) +; Type 1B diabetes – AB- and
fasting C-peptide(FCP) < 0.7ng/dl or stimulated c-peptide(SCP) < 2.0ng/dl; Type 2 diabetes – AB- and FCP >
1.5ng/dl or SCP > 3.5ng/dl; Untypeable diabetes – ABand FCP 0.7-1.5ng/dl and SCP 2.0 - < 3.5 ng/dl;
Lipoatrophic diabetes – clinical phenotype. Fifty-eight
participants (21M 37F, age 20±8years, duration of diabetes 2.6±2years) were enrolled. Using the classification
criteria 22% had type 2 diabetes. These subjects were
more likely to be female (OR=9.6[95%CI=1.15,80.2]
p=0.04) and overweight/obese (OR=24.1[95%CI=
4.4,130.5] p<0.01). Type 1 diabetes was present in 62% of
participants (18 type 1A diabetes, 18 type 1B diabetes).
Three had lipoatrophic diabetes and 10%(6/58)remained
untyped.
Discussion: Youth onset type 2 diabetes was first
described in Pima Indians over 30 years ago. Since then
youth onset type 2 diabetes has been recognised in other
United States Minority populations - Native Americans,
Hispanic Americans and African Americans resulting
from the obesity epidemic.Jamaica has a high prevalence
of obesity in adults (30% men and 60% women) and it is
therefore not surprising that youth onset type 2 diabetes
was present in this population. There are no standard criteria for the diagnosis of type 2 diabetes in youth. The
female predominance, the presence of obesity and no
ketoacidosis in the absence of insulin are consistent with
other case reports of patients with type 2 diabetes and help
to validate the criteria we have used for diabetes classification. Six subjects remained unclassified. These subjects
were antibody negative and had some residual pancreatic
function. There have been several reports Afro-Caribbean
youth in Brooklyn with similar clinical features. This was
however not the predominant form of diabetes in our population. The high proportion of participants with lipoatrophic diabetes, a rare form of diabetes, will need further
evaluation.
Conclusions: While type 1 diabetes was the predominant form of diabetes in this study a significant number of
Jamaicans with recently diagnosed youth onset diabetes
may have type 2 diabetes.
Abstract #110
ESCALATED INSULIN PROTOCOL IMPROVES
GLYCEMIA IN DIABETIC FOOT INFECTIONS
Alicia Leung, MD, Rasa Kazlauskaite, MD, FACE,
Ikna Espinosa, DO, Sylvia Velinova, MD, and
Gustavo A Jurado, MD
Objective: Investigate if protocol-directed management is superior to individualized management of
glycemia on medical/surgical wards.
Methods: 23 patients with type 2 DM and blood glucose >200 mg/dl, admitted for debridement of diabetic
foot ulcer, were randomized to receive individualized
glycemic management by medical consult team (n=11) or
protocol-driven subcutaneous insulin therapy with NPH &
R insulin twice a day (n=12). Blood glucose (bedside
check 4 times daily)targeted to 70-120 mg/dl per Rush
University insulin escalation protocol (see table).
Results: Glucose and A1c on admission were similar
in both groups. Average daily glucose in protocol-driven
management group (144±19 mg/dl) was significantly
lower (p<0.001) than the individualized group (200±29
mg/dl). Patients went to surgery on average by day 3 of
hospitalization in each group (p=0.86), with average glucose on the day of surgery 133±42 mg/dl in protocol treated, and 214±41 mg/dl in individualized group (p<0.01).
There was no difference (p=0.30) in number of hypoglycemic events (glucose below 50 mg/dl) between protocol and individualized groups (4 vs. 1 episode), and there
was no severe hypoglycemia in either group. The mean
hospital stay was 8.7 days in individualized group and 6.3
days in protocol group (p=0.09).
Discussion: Glycemic control using insulin infusion
in intensive care unit patients can decrease morbidity and
mortality by 30-50%. However, the hyperglycemia management on medical/surgical wards has not been studied
extensively. AACE/ACE guidelines target preprandial
blood glucose levels below 110 mg/dl and peak postprandial below 180 mg/dl. Our study targeted glucose below
180 mg/dl on day of surgery. Capillary blood glucose was
measured four times daily aiming to glucose levels below
120 at all times. Achieving a significantly lower average
daily glucose, the protocol-treated patients had average
glucose on day of surgery well below 180 mg/dl. Compare
to admission, the glucose was safely lowered by the day of
surgery on average by 125+/-50 mg/dl more in protocol
– 22 –
group than in individualized management (p=0.02). As
metabolic derangements of hyperglycemia result in
greater susceptibility to bacterial infections, decreased tissue anabolism and poor healing, it may be intuitive that
better glycemic control reflects in faster recovery time as
it was observed in our study were protocol patients had a
shorter length of stay by 2.5 days.
Conclusions: Protocol-driven insulin management in
patients with type 2 diabetes admitted to medical/surgical
wards results in superior glycemic outcomes compared to
individualized management. In patients admitted for diabetic ulcer debridement better glycemic control may result
in shorter hospital stay; however, our cohort was not large
enough to prove statistical significance.
Inpatient Diabetes and Metabolic Control recommend a
target pre-prandial BG <110mg/dl and maximal BG
<180mg/dl in non-critical care units and BG <110mg/dl in
intensive care units.
Conclusions: We observed that stress HG was commonly seen in patients with AMI, regardless of a prior history of diabetes and was associated with greater lengths of
stay and increased incidence of adverse outcomes. Despite
substantial evidence in support of tight BG control, in-hospital management of hyperglycemic patients with AMI
remained sub-optimal. System reform and development of
novel protocols will be required to improve future performance.
Abstract #354
Abstract #173
QUALITY OF OUTPATIENT DIABETES CARE IN
SAUDI ARABIA
BLOOD GLUCOSE CONTROL IN PATIENTS
WITH ACUTE MYOCARDIAL INFARCTION
Ashwini P Gore, MBBS, Doron Schneider, MD, and
Daniel Rosenberg, MD
Mohsen Eledrisi, MD, FACE, Buthina Alhaj, RN, CDE,
Rifat Rehmani, MD, BSc, Daad Akbar, FRCP, FACP,
and Shadia Matboli, MBBS
Objective: We examined the adequacy of blood glucose (BG) control in patients admitted with acute myocardial infarction (AMI).
Methods: A retrospective chart review was conducted. BG data was collected. The effect of hyperglycemia
(HG) on length of stay (LOS), in-hospital mortality as well
as other adverse outcomes such as acute congestive heart
failure, renal failure, infection, sepsis and readmission
within 1 year was determined.
Results: Out of 110 charts that were studied, 86
patients (78.18%) were noted to have HG as defined by
the American College of Endocrinology (ACE) guidelines
(26 known diabetics, 60 without diabetes history). Only 28
out of these 86 people (32.56%) had accuchecks ordered
to further monitor their BG levels. Out of the 26 diabetics
with HG, 23 received some form of treatment. Five diabetics received sliding scale alone. Elevated BG was
addressed in only 2 out of the 60 nondiabetics with HG.
Both received sliding scale insulin. The HG group experienced a greater percentage of adverse outcomes as compared to the non-HG group (composite of LOS >5days,
acute CHF, ARF and in hospital death or readmission
within 1 yr) (p=0.035). Endocrinology consult was
ordered in only 5 out of 86 people with HG (5.81%).
Discussion: The relationship of HG to clinical outcomes in patients with AMI has been a topic of research
for many years. A recent meta-analysis of 15 studies by
Capes et al. reported that stress hyperglycemia (BG >110
mg/dL) was associated with an increase in in-hospital
mortality and CHF in patients with AMI irrespective of a
prior diagnosis of diabetes. The ACE guidelines on
Objective: To evaluate the quality of diabetes care
among patients with type 2 diabetes in Saudi Arabia
Methods: This national cross sectional study evaluated adult patients with type 2 diabetes attending outpatient
clinics with a minimum follow up of 6 months.
Measurements of urine albumin:creatinine ratio, annual
foot, dental and dilated eye examination, and pneumococcal vaccination were assessed.
Results: A total of 1,107 patients were evaluated with
a mean age of 52.6 ± 11 years, mean duration of diabetes
since diagnosis 8.5 ± 7 years. Urine albumin: creatinine
ratio was measured in 29 % (95% CI, 26.1 – 33.5 %); foot
examination in 15.4% (95% CI, 12.1 – 18.5 %); dental
examination in 32.2 % (95% CI, 28.8 – 35.8 %); dilated
eye examination in 55.8 % (95% CI, 52.1- 58.8 %); and
pneumococcal vaccination in 17.8 % (95% CI, 14.4 – 21.3
%). Patients who received their care from endocrinologists
had better achievement in all quality measures compared
to non-endocrinologists (P < 0.001) except foot examination, which was not significant (P = 0.06).
Discussion: In this Saudi Arabian population with
type 2 diabetes, overall rates of measurements of quality
of diabetes care were low. Less than one-third of patients
had screening for kidney disease; only about one-third had
annual dental examination; about half had dilated eye
examination as a screening for retinopathy; about 1 in 7
had annual foot examination; and only about fifth received
pneumococcal vaccination. Endocrinologists compared
with non-endocrinologists better achieved these quality
measures, which is in agreement with published data from
other countries.
– 23 –
Conclusions: A wide gap exists between diabetes
care guidelines and the actual care patients with diabetes
receive in Saudi Arabia. Physician education and focused
quality improvement programs are needed to improve the
care of patients with diabetes.
INSULIN DELIVERY AND IMPROVED POSTMEAL GLYCEMIC CONTROL WITH THE
BASAL/BOLUS INSULIN DELIVERY SYSTEM HPATCH(TM) IN TYPE 2 DIABETES MELLITUS
Discussion: While the total insulin dose using the hPatch was smaller than the previous Lantus dose, the post
meal glucose was lower with no apparent changes in fasting glucose. It is possible that a distribution of part of the
total insulin dose from basal to bolus with meals will
improve glycemic control. Larger prospective randomized
trials are necessary to test this hypothesis.
Conclusions: The once-daily h-Patch may offer the
ability to individually titrate insulin in patients with
T2DM. Improved glycemic control may be achieved without substantial increases in insulin dose. Further studies
are needed aimed at optimizing insulin dose titration.
Poul Strange, MD, and Seymour Fein, MD
Abstract #355
Objective: The basal bolus insulin concept aims to
control blood glucose (BG) through the appropriate delivery of insulin mimicking physiologic insulin secretion.
The h-Patch is a discrete, simple to use disposable oncedaily insulin delivery device designed to deliver basal and
bolus insulin. The h-Patch device adheres to patients much
like a patch and delivers regular or rapid acting insulin
subcutaneously through a 30 gauge needle. The purpose of
this proof of concept study was to evaluate the pharmacodynamic effects of insulin administration with the h-Patch
system in patients with T2DM.
Methods: In 6 patients with T2DM receiving insulin
glargine (≥15 U/day) ± OADs, glargine was discontinued, but OADs maintained, and an h-Patch administered to each patient once-daily for 7 days (3 days
inpatient, 4 days outpatient) using insulin aspart. The hPatch provided patients a continuous basal infusion of
insulin aspart (0.6 U/hour) subcutaneously and up to three
individualized bolus infusions in increments of 2 U each
day. BG was measured at 11 and 4 points in the inpatient
and outpatient phases, respectively.
Results: The mean±SD baseline A1c was 7.7±1.2 %
and duration of T2DM was 10.5±7.9 years. Patients had a
BMI of 28±2.5 kg/m2, were 59.5±5.2 years old and had
been on insulin glargine therapy for 2.4±0.9 years. Mean
baseline daily dose of glargine was 35.6 U. The mean
daily total insulin dose with the h-Patch was 32.7 U, highlighting the fact that this study was not designed as a dose
titration/glucose optimization trial. Mean daily glucose
levels decreased with the h-Patch. FBG with the h-Patch in
the inpatient (148±35 mg/dL) and outpatient (150±40)
phases remained similar to pre-study glargine+OAD levels (146±32 mg/dL). Post-meal BG levels improved at 1
and 2 hour measures after breakfast (-19.4 and -36.3
mg/dL), lunch (-55 and -68 mg/dL), and dinner (-22.6 and
-50.8 mg/dL) compared to pre-study glargine±OADs.
Bedtime BG improved as well (-32.1 mg/dL). Bolus doses
of insulin blunted the post meal glucose excursions more
effectively than glargine±OADs had pre-study.
DECREASED GLUCOSE CLEARANCE
CONTRIBUTES TO THE RISE IN FPG IN THE
NON-DIABETIC RANGE
Abstract #410
Rucha Jani, MD, Muhammad Abdul-Ghani, MD, PhD,
Marjarie Molina, MD, and Ralph A. DeFronzo, MD
Objective: To assess the contribution of decreased
glucose clearance to the rise in fasting plasma glucose in
the non-diabetic range.
Methods: 165 subjects free of type 2 diabetes, each
received an OGTT and insulin clamp with 3-[3H] glucose.
Rate of glucose appearance, glucose clearance, hepatic
insulin resistance index, total glucose disposal, and
insulin-stimulated glucose clearance were calculated.
Simple Pearson correlation was used to assess the relationship between variables.
Results: The increase in FPG (range= 75 to 120
mg/dl) correlated (r=0.30, p<0.0001) with the increase in
BMI (range 20-50 kg/m2). The fasting plasma insulin
(FPI) also increased progressively with the increase in
BMI (r=0.41, p<0.0001); however despite increasing FPI,
glucose clearance rate markedly decreased and correlated
with the increase in BMI (r =-0.54, p<0.0001). Notably,
basal hepatic glucose production decreased with increasing BMI (r = -0.49, p<0.0001) and inversely correlated
with the increase in FPI(r= -0.32, p< 0.0001). Hepatic
insulin resistance increased with increasing BMI (r=0.48,
p<0.0001). Insulin-stimulated glucose disposal declined
with increasing BMI (r= -0.64, p<0.0001) and strongly
correlated with the basal glucose clearance (r=0.41,
p<0.0001).
Discussion: Our results demonstrate that in non-diabetic subjects, rising FPG is associated with a decrease in
basal hepatic glucose production and a reduction in glucose clearance. We postulate that the decrease in basal
glucose clearance leads to an increase in fasting plasma
glucose which stimulates basal insulin secretion. The
resultant fasting hyperinsulinemia inhibits hepatic glucose
– 24 –
production, thereby ameliorating the rise in fasting plasma
glucose.
Conclusions: Impaired insulin independent glucose
uptake by skeletal muscle is a strong predictor of the rise
in fasting plasma glucose (FPG) in the non-diabetic range.
recommendations may result in significantly different
clinical outcomes. A better understanding of the unique
approaches of each pump will benefit patients with diabetes and those caring for them.
Abstract #420
Abstract #392
EYE COMPLICATIONS OF DIABETES MELLITUS IN LAGOS STATE,NIGERIA
DISPARATE REAL-WORLD USE OF BOLUS ON
BOARD FEATURE IN INSULIN PUMP THERAPY
Banji Abiodun Olaitan, MBBS
Timothy Silleck Bailey, MD, FACE, and
John Thomas Walsh, PA, CDE
Objective: To determine use and consequences of
bolus-on-board feature with carb intake coverage in actual insulin pump datasets.
Methods: Data from more than 300 insulin pumps
with associated glucose data was electronically uploaded
and analyzed. 30 consecutive days from each data set were
analyzed regarding patterns of insulin bolus use.
Results: Data was uploaded from each pump for 30
consecutive days of use. Bolus frequency included carb
boluses that were given with a mean of 3.4 per day and a
range of 0 to 17. The maximum number of boluses in one
day averaged 6.9 with a range of 0 to 40. Over one third of
pumpers averaged 5 or more carb boluses per day.
Correction boluses were given less often with a mean of
2.0 and a range of 0 to 8.1. The maximum number of
boluses in one day averaged 6.9 with a range of 0 to 40.
Additional data is being prepared on the frequency distribution for time between boluses, the amount of bolus on
board (BOB) present when combined carb and correction
boluses are given, and how the amount of BOB varies by
time of day.
Discussion: Current insulin pumps recommend bolus
doses that are automatically calculated to cover both carb
intake and the current glucose level. This dose is then
adjusted for any residual bolus insulin on board (BOB)
that remains from previous boluses to provide the user a
recommended bolus. All pumps subtract BOB from correction boluses. However, insulin pumps differ in whether
or not they subtract BOB from carb boluses. Some pumps
subtract BOB from all carb boluses, some subtract only
when the glucose is below the target glucose, and some
never subtract BOB from carb boluses. Given the frequency of boluses and the marked increase in the the frequency of boluses on some days, significant variations in
recommended boluses are likely from different insulin
pumps. In many situations, these differences will be
greater than 3% of the person's total daily insulin dose.
Conclusions: This data shows that significant differences occur in the bolus recommendations by different
pumps despite identical clinical circumstances. These dose
Objective: This study therefore sets out to document
the pattern and prevalence of eye diseases in Nigerians
with Diabetes mellitus(DM).
Methods: This is a retrospective study in which
records of DM patients seen at the Lagos Eye Institute
were reviewed. Data obtained included, biodata, results of
visual acuity (VA) and intraocular pressure (IOP), blood
pressure, blood glucose level, duration of DM and eye
complications.
Results: 108 patients were seen. Mean age was
64.5years (range 30-82years). 44% were males while 56%
were females. All study subjects had impairment of their
visual acuity. 22% of the subjects had elevated intra ocular pressure and 15% were diagnosed as having glaucoma.
Refractive error was noted in 19% patients. The mean
duration of DM was 7 years. Poor glycaemic control was
noted in 26% of patients. 40 patients had elevated blood
pressure with even distribution in both sexes. The commonest ocular complication was cataract and this was seen
in 70% of patients of which the Male: Female ratio was
1.1:1. Retinopathy was detected in 19% of patients. There
was a prominence of proliferative retinopathy as this was
documented in 20% of patients. Subconjuctival hemorrhage and uveitis were noted in 2% and 6% of patients
respectively.
Discussion: Diabetes mellitus (DM) is a metabolic
disorder with multisystemic involvement.It is one of the
commonest causes of medical deaths reported in Nigeria.
DM also accounts for reduced quality of life because of
associated chronic complications. The eye complications
of DM is a cause of disability that often leads to reduced
productivity, reduced quality of life and adverse psychosocial sequelae. There is gross under reporting of this
all important complication of DM in sub-Saharan Africa.
In the Western world the prevalence of the major ocular
complications of DM is time dependent viz twenty five
percent at fifteen years, fifty percent at twenty years of
diabetes. This recent study is best explained and discussed
using the Figure and table below
Conclusions: The eye complications in people with
DM are varied with possible contributions from poor glycaemic control, hypertension and long duration of DM.
– 25 –
Therefore, management of eye complications of diabetes
must be early, prompt and adequate in order to prevent
irreversible blindness. Maintenance of tight control of diabetes mellitus in line with the world accepted Control and
Complication Treatment Trial guideline and treating any
coexisting ocular and systemic diseases such as hypertension is impo.
Abstract #118
RARE PRESENTATION;RARER DISEASE —
FIBRO CALCULOUS PANCREATIC
DIABETES(FCPD)
Radha Lachhiramani, MSc, Dip Clin Dermat, MBBS,
Vikram Sodhi, MBBS, MHA,
Rakesh Parikh, FCPS, DD, MBBS, and
Nalini Shah, MD,DM
Objective: To describe 2 cases of secondary diabetes
caused by a pancreatopathy due to a rare condition called
FCPD, and to enhance it's diagnosis.
Case Presentation: 1) A 27 year old male,non alcoholic,was diagnosed diabetic 3 yrs ago with osmotic
symptoms.Initial blood glucose was not known.There was
no evidence of a DKA then.He was started on oral anti diabetics.Insulin was started 6 months later for uncontrolled
sugars.He was asymptomatic for the next 1 yr with moderate glycemic control on insulin alone.2 weeks before
presentation to us early this year for anasarca,he had
stopped insulin.He was lean and poorly built(BMI 16)
with periorbital puffiness and bilateral pitting pedal
edema.A clinical impression of type 1 diabetes with
nephropathy was strongly considered,with the edema
attributable to nephrotic syndrome. Labs: S. Albumin 2.5
g/l. S. Creatinine 0.7 mg/dl. However Urine albumin was
repeatedly negative.USG abdomen:atrophic pancreas with
large calculi.Stool for fat globules was positive. CT
abdomen confirmed FCPD.2) 26 yr old male,k/c/o
urolithiasis; urinary diversion procedures for urethral
strictures at age 15. Now,his incidental perioperative
blood glucose was 400 mg/dl.No ketosis.BMI 14.5 kg/m2.
CT abdomen: atrophic pancreas(Abortive FCPD)
Discussion: It is important to image the pancreas in
young patient with non ketotic (severe) hyperglycaemia.
The first was an unusual case of FCPD because it presented with anasarca thereby mimicking a T1D with
nephropathy/nephrotic syndrome.It is important to diagnose FCPD (and distinguish it from type 1 diabetes
{T1D}) for several reasons:1) A trial of oral anti diabetics
may be worthwhile (10-20% may respond for at least 5 –
10 years.2) There is no need to screen for other autoimmune diseases (as recommended for T1D).3) We must
look for exocrine pancreatic deficiency,which has unique
diagnostic and therapeutic issues.4) Complications of
chronic pancreatitis may occur-pseudocyst, abscess,
ascites and obstructive jaundice. Treatment modalities are
both medical and surgical.5) FCPD is a premalignant condition with enhanced risk for the development of carcinoma of the pancreas.6) Malnutrition is another important
cause of mortality in this condition.Imaging the pancreas
(X ray, US, CT) is diagnostic. This is particularly relevant
in our limited resource settings where insulin auto antibodies are seldom done. The second patient has MRDM
(Malnutrtion Related DM), but the term has been done
away with.
Conclusions: MRDM identified by WHO study
group on DM in 1985 has been eliminated from the new
classification of diabetes by the American Diabetes
Association (ADA). FCPD which was described as one of
the types of MRDM is now reclassified under diseases of
exocrine pancreas. The disease is reported only occasionally from developed countries and even in countries where
it is more common it accounts for only 1% of the total
number of patients. According to Indian data it accounts
for 4% of young diabetics.
Abstract #181
GLYCEMIC CONTROL IN NIGERIANS WITH
TYPE 2 DIABETES MELLITUS
Ifedayo Adeola Odeniyi, MBBS,
Olufemi Adetola Fasanmade, MBBS, FWACP,
Anthonia O. Ogbera, FMCP, and
Efe Ohwovoriole, FMCP, FWACP
Objective: To survey Nigerian Diabetic clinics
Records for level of glycemic control in type 2 diabetes
mellitus patients.
Methods: Data from Diabetes Registers of participating institutions were collated and analyzed. The parameters analyzed include gender, age, fasting blood sugar
(FBS), Glycated Haemoglobin (HbA1c), and treatment.
Good glycaemic control was set at FBS of <110mg/dl and
HbA1c <7%.
Results: A large proportion of the patients are
females. Majority of the patients are between 35-55 years.
A third of the patients have good glycaemic control while
the remaining two thirds have poor control using the FBS.
A third of those with good glycaemic control with FBS
have good control using the glycated haemoglobin
(HbA1c <7%) while the rest have HbA1c above 7%. Most
of the patients are on two drugs, (Sulphonyurea and
Biguanide), for their glycaemic control. A higher number
of the female have good glycemic control compared with
the males.
– 26 –
Discussion: Most patients with type 2 diabetes mellitus were noted to have poor glycemic control.Drug compliance may have contributed significantly to the poor
control.In a resource poor country like Nigeria the drugs
are not affordable to the poor who forms the bulk of those
with diabetes mellitus. Assessmnet of glycemic control
using HbA1c is not readily affordable.Most of the patients
apparently were not taking their drugs as appropriate and
only start taking them when their clinic appointment is due
hence the good glycemic control with FBS and not
HbA1c.
Conclusions: Most patients with type 2 diabetes mellitus have poor glycaemic control. There is need to ensure
that good glycaemic control is achieved in diabetes patient
to delay the development and progression of chronic complications
Abstract #394
individual needs let alone community needs, particularly
in populations at high risk for diabetes. Addressing diabetes treatment and prevention, particularly in a culturally
diverse society requires a departure from the traditional
one-on-one care that endocrinologists are familiar with.
We have been able to develop a community-based program through partnership with community leaders and
resources. This has allowed us to proceed in with a relevance that is appropriate to the culture and driven by the
needs of the community.
Conclusions: We have found that an individual may
have diabetes, but it may take a community to treat it
effectively. A multidisciplinary partnership between a tertiary care hospital and a community service organization
has provided the scientific and cultural expertise to develop a roadmap for achieving diabetes care and prevention
at a community level for the Korean Americans residing in
the Philadelphia metropolitan area.
DIABETES IN A KOREAN COMMUNITY
Abstract #191
Arthur Chernoff, MD, FACE,
Nadine Uplinger, MS, MHA, RD, CDE, LDN,
Young Nam Kim, MD, FACE, and Chee Y. Lee, MSW
PREVALENCE AND PREDICTORS OF DIABETES
IN CHRONIC HEPATITIS C INFECTION
Objective: To develop and deploy a community-based
diabetes program in an urban Korean American community.
Case Presentation: The Philadelphia Korean community (20 - 60 K) is at high risk for DM. In FY 2004 DM
occurred in 30% of hospital discharges in those over 40.
Blood sugar measured by finger stick (AccuChek™) at
community events in FY 2004 showed 16 % had glucose
> 180, 30% had glucose > 125 < 180 and only 54% had
glucose < 125. A partnership between a multidisciplinaty
team from a tertiary care medical center, and the staff of
the principal community service support organization
within the Korean community was established. Meetings
with community leaders were held leading to the deployment of a program to enhance community awareness of
DM, its consequences and its prevention. Modalities
employed have included: a support group (Diabetes Club),
producing patient and physician educational materials in
Korean which assess DM awareness and educate patients
about DM. We have written and published a Diabetes
Handbook in Korean. CME for MDs in the community
was provided. Further development of culturally appropriate programs for the community is proceeding based on
input from community leaders.
Discussion: The rising tide of diabetes is a major
challenge facing 21st century endocrinologists. It is clear
that there are many more patients with diabetes than there
are endocrinologists to take care of them. The traditional
model of one-on-one care may not be sufficient to meet
Deepti Bulchandani, MD, Jagdish S. Nachnani, MD, and
Lamont G. Weide, MD
Objective: i) The prevalence of Type II DM in
patients with chronic HCV infection. ii)Host and viral factors associated with Type II DM.
Methods: From January 2001 to November 2005, we
retrospectively reviewed a cohort of 148 consecutive
patients with chronic Hepatitis C who underwent liver
biopsy. Factors collected included age, race, gender, BMI,
presence of diabetes, family history, lipids, Viral genotype & liver biopsy results.
Results: Out of 148 patients in our cohort, there were
20 patients who had Type II diabetes. (13.51%). The mean
age of our patients was 48 years +/- 10 years. The mean
BMI was 27 +/- 5. Out of the 20 patients who had Type II
DM, 7 were females. Also out of the 20 patients, 9 were
African Americans, 11 Caucasians and 2 Hispanic. In univariate analysis, Nonwhite race, age > 45 and a higher
BMI was associated with Type II DM. In multivariate
analysis, BMI was the only factor associated with Type II
DM. In 75% of the patients with Type II DM, the viral
genotype was 1.
Discussion: Type II DM is highly associated with
chronic HCV infection. However not all patients with
chronic HCV develop DM. Our study has identified the
risk factors in patients with chronic HCV associated with
DM, namely increasing age, NonWhite race and obesity.
Also, DM was more common in patients with genotype 1.
By including patients having a liver biopsy, we have
– 27 –
excluded cirrhosis as the cause of DM in our study. Our
study has shown an increased prevalence of diabetes mellitus in patients with chronic HCV and has identified a
high risk population of chronic HCV who may have a
increased chances of DM. Further studies would be needed to strengthen this association as well as to explore the
pathogenesis behind this phenomenon.
Conclusions: Type II DM occurs more commonly in
patients with chronic HCV infection and was present in
almost 14% of our patient population. In our study, Type
II DM was more commonly seen in patients with a higher
BMI, age > 45 and Non White race, though only BMI was
significant in multivariate analysis. The high prevalence of
diabetes found in HCV-infected patients observed in our
study suggests that early screening for glucose abnormalities should be a guideline in care of patients with chronic
HCV.
allocate to the Control Group (CG) and 14 subjects to the
Treated Group (TG). Subjects in the CG continued receiving BID-NPH and TID-RI. Subjects in the TG received
BID-NPH and TID prandial split doses of Generex Orallyn™ (OI). Comparison Phase lasted 99 days.
Fructosamine (F) and Glycated Hemoglobin (HbA1c)
were determined on average every 14 days. Results
demonstrated that both forms of insulin administered at
meal time appropriately maintain the good control attained
at SP.
Conclusions: Near normalization of parameters of
DM metabolic control was achieved in each and all subjects as reflected by continuous improvement in F and
HbA1c concentrations documented every 2 weeks.
Straightforward comparison of HbA1c during CP showed
a superior effect for Generex Oral-lyn™ over subcutaneously injected regular insulin.
Abstract #360
Abstract #326
REGULAR INSULIN REPLACEMENT BY ORAL
INSULIN AT MEALTIME IN TYPE-1 DM
DOES VITAMIN D STATUS CORRELATE WITH
GLYCEMIC STATUS IN DIABETIC SUBJECTS?
Jaime Guevara-Aguirre, MD,
Marco Guevara-Aguirre, MD, and
Jeannette Saavedra, MD
Jayalakshmi Udayasankar, MBBS, Jenny Tong, MD, and
Dace L. Trence, MD, FACE
Objective: Comparison of effects of 2 insulin forms
administered at mealtime in Type-1 DM subjects maintained on basal isophane insulin
Methods: Stabilization Phase with basal s.c. twice
daily (BID) isophane insulin (BID-NPH) and 3 pre-prandial s.c. injections of regular insulin (TID-RI) followed by
a 2-cohort 99-day Comparison Phase (CP). Control group
(CG): BID-NPH + TID-RI versus Treated Group (TG):
BID-NPH + TID-Oral insulin
Results: Participating subjects were 25 Type-1 DM
(17M; 8F). Demographics: Age 28.6y (9.0); Height
164.8cm (8.53); Baseline weight 62.4kg (8.68); End of the
study weight 64.5kg (8.66); Baseline BMI 22.9 (1.97);
End BMI 23.8 (2.0). Duration of DM 9.7y (5.1). COMPARISON PHASE (CP) (99 days) between two cohorts of
adult Type-1 DM Baseline CG (Day 0) (n=11)
Fructosamine (F) 355.7 (48.6) / Glycated Hemoglobin
(HbA1c) 7.3 (0.9) // End of Study CG (+99d) (n=11) F
354.6 (57.5) N.S. / HbA1c 6.8 (0.8) p<0.049 // Baseline
TG (Day 0) (n=14) F 313.2 (51.5) / HbA1c 6.8 (0.6) // End
of Study TG (+99d) (n=13) F 319.2 (49.7) N.S. / HbA1c
6.1 (0.7) p<0.001 // HbA1c (CP): Control group: 7.3 (0.9)
to 6.8 (0.8) versus Treated Group 6.8 (0.6) to 6.1 (0.7)
p<0.035 // Fructosamine (CP): CG versus TG N.S.
Discussion: After a stabilization phase (SP), twenty
five adult Type-1 DM subjects entered a 99-day
Comparison Phase (CP) of 2 cohorts, 11 subjects were
Objective: To examine the relationship between
Vitamin D status and glycemic control in subjects with
diabetes mellitus (DM).
Methods: From May to October 2006, 53 subjects
with DM (T1DM: n=24; T2DM: n=29) had serum 25(OH)D and plasma A1C levels measured at the initial
visit. Subjects with 25-(OH)D insufficiency (<30 ng/mL)
were asked to initiate 1200 IU of Vitamin D per day.
Repeat 25-(OH)D and A1C levels were drawn at followup.
Results: 86% (46/53) had 25-(OH)D insufficiency
upon the initial visit. A negative correlation was observed
between age and 25-(OH)D levels (p=0.04) and no correlation between 25-(OH)D and A1C levels (p=0.55). A
sub-analysis separating T1DM from T2DM did not show
any correlation (p=0.83 and p=0.28, respectively). We did
not observe any correlations between 25-(OH)D and A1C
levels in the low, middle or high tertiles of the initial 25(OH)D levels (p=0.46, p=0.06 and p=0.22 respectively).
Only 19% (9/46) of subjects who had received Vitamin D
replacement therapy had follow-up measures of both 25(OH)D and A1C within the study period. All (9/9) of these
patients had 25-(OH)D levels >30 ng/mL. No significant
correlation was found between change in 25-(OH)D and
A1C post Vitamin D replacement (p=0.
Discussion: There is increasingly documented evidence of contribution of hypovitaminosis D to reduction
of insulin secretion, increasing insulin resistance, hyper-
– 28 –
glycemia and increased risk of T2DM. The very few studies that have looked into the effect of Vitamin D replacement on glycemic control in T2DM have shown
conflicting results. A key finding in our study is that we
did not find any significant correlation between Vitamin D
status and glycemic control even after separating data for
T2DM from T1DM. Notably, replacement with Vitamin D
did not show a trend towards improved glycemic control.
The small number of subjects with follow-up data and not
accounting for the influence of subject characteristics and
other treatments known to affect glycemic control, may
limit our finding. However, our finding is in line with an
intervention study, in which another preparation of
Vitamin D was used for replacement therapy. In this double-blinded, placebo-controlled, crossover trial of 1,25dihydroxyvitamin D[1,25](OH)2D] therapy in 20 subjects
with T2DM and Vitamin D insufficiency, Vitamin D
replacement, had no major effect on glucose homeostasis,
similar to the finding in our study.
Conclusions: Vitamin D status does not seem to be
directly associated with glycemic control in subjects with
DM. Replacing Vitamin D to sufficient levels did not
show a trend to improved glycemic control, although the
small number of subjects with follow-up data limits this
finding. Further analysis regarding glycemic excursion, as
well as separating T2DM from T1DM might allow for
more specific insights as to the impact of Vitamin D
replacement on insulin resistance and glycemic control in
T2DM.
DELAYED PROGRESSION OF DIABETIC
NEPHROPATHY BY TZD, METFORMIN, AND
RAMIPRIL
Hyperkalemia so Ramipril (2.5mg) was continued. After
Rezulin was unavailable the patient was switched to
Avandia. The Gemfibrizol was changed to a statin. With
this triple therapy his renal situation improved steadily. In
2005, the Creatinine was 1.1, and 24-hr Proteinuria was
915 mg. In 2006 the 24-hr Protein is 788 mg, with
Creatinine of 1.1; Potassium, 4.9; and HgA1C of 6.3, nine
years since it was first detected at 516 mg.
Discussion: After a short time on Rezulin, without
apparent significant lab improvements, the patient was
then able to tolerate at first Glucophage and then Ramipril.
He was then continued on small doses of TZD, Metformin
and Ramipril for several years. The HOPE trial showed
that Ramipril is known to reduce the rates of death from
cardiovascular causes: MI, revascularization procedures,
cardiac arrest, heart failure, and complications related to
diabetes (1). The EMPIRE trial also showed combination
therapy of TZD and Metformin was at least as effective in
improving HbA1C as Metformin monotherapy. It showed
greater reductions in FPG levels, and had a better tolerability profile compared with the maximal effective doses
of Meformin therapy (2). Metformin is known to decrease
endogenous glucose production. TZDs are known to
increase peripheral glucose disposal and decrease glucose
production. They reduce insulin resistance through the
peroxisome proliferator-activated receptor (PPAR)(3).
Together TZD and Metformin are synergistic in lowering
both fasting and post prandial glucose by 18%.
Conclusions: The progression of diabetic nephropathy and the need for dialysis were postponed if not eliminated in this patient with the combination of TZD,
Metformin and Ramipril. The effect has remained for nine
years. Also, the patient had coronary bypass in 1995 and
remains symptom free for eleven years. This triple therapy may also be beneficial in reversing CAD.
Lee Pletts Goscin, MD, PhD, Kathryn Rooth, BS,
Gabriel Valle, MD, and Paul DiMarco, MD
Abstract #327
Abstract #264
Objective: Demonstrate judicious use of small doses
of TZD, Metformin and Ramipril delays progression of
Diabetic Nephropathy.
Case Presentation: A 62-year-old male with NIDDM
for 10 years with coronary artery disease treated by triple
bypass was in reasonable diabetic control with diet, exercise and sulfonylurea. His labs measured: HgbA1C, 6.5;
Cr, 1.4; K, 5.5; 24-hr Protein, 516 mg; and CrCl, 88
ml/min. Renal insufficiency precluded use of Metformin.
Ace Inhibitors or an ARB with or without a diuretic were
not tolerated due to Hyperkalemia. In 1998, a TZD,
Resulin, became available and the patient was placed on it.
Gradually, Creatinine was reduced and Potassium stayed
about 5.2. Metformin was added when Creatinine was 1.3.
A two-week trial of Ramipril did not worsen the
AMZYLITE F 1.2 AS AN IN-VITRO AND IN-VIVO
GLUCOSE REDUCING AGENT
Tarig Sayed Mustafa Arbab, MD, MSc, DIC, and
Zeinab Abdulla Elias, MB, BS
Objective: To determine the efficacy of Amzylite as
in-vitro / in-vivo hypoglycaemic agent. Amzylite is registered medicine in UAE
Methods: In-vitro testing to determine glucose units
in a glucose solution before and after mixing with
Amzylite. In-vivo 48 patient with type I and type II D.M
underwent testing for two weeks to determine any changes
in postprandial blood glucose values without and with
Amzylite
– 29 –
Results: In vitro results showed glucose readings
were significantly reduced immediately after mixing with
Amzylite. Glucose values of 60 mg/dl and lower were
obtained immediately. Lower values were also obtained
after 15, minutes and more (hours). In vivo tests, results
showed that Amzylite, has reduced blood sugar values
within 3 hours in 46 patients by 60 to 100 mg/dl or more.
In some patients blood glucose reduction rate was up to 60
mg/dl or more per hour, others had reduction rate of 20 to
30 mg/dl per hour. 2 patients showed no significant
changes on values 3 hours from ingestion of Amzylite. 29
0ut of 46 patients had reduced values to range (70 to 110
and 120 mg/dl), 11 patients had values ranging from 135
to 165 mg/dl and 6 had values ranging 170 to 200 mg/dl.
None of the patients had hypoglaycaemia.
Discussion: In-vitro: 10 mls of 10% concentrated glucose solution tested for glucose values using glucose oxidase and or hexokinase (glucometers can also be used).
Glucose values were more than 600 mg/dl (Glucometer
readings were Hi, 600 mg/dl or more ;). One capsule of
Amzylite added to the glucose solution and immediately
after good mixing, glucose values were found to be significantly reduced. Glucose values of 60 mg/dl and lower
were obtained immediately.Amzylite worked as
Hydrolizing agent for glucose. For In-vivo test, 48 patients
Type 1 and Type 2 D.M underwent testing for two weeks;
Tests for week one and week two were designed to determine and compare any changes in glucose values with and
without Amzylite. Both tests were carried out initially by
recording blood glucose values 2 hours postprandial, then
hourly for 3 hours. In test two, 2 Amzylite were given 2
hours postprandialy. Initial postprandial blood glucose
values were 200 to 300 mg/dl for test 1 and 2. All 48
patients were known diabetics, diet control only. All 48
patients were on no known hypoglaycaemic agents.
Amzylite absorbed reduced blood glucose by hydrolisis,
and catalization of glucose oxidation into water and CO2.
Conclusions: Amzylite is a trade mark for a private
formulation of mainly enzymes. Amzylite is registered in
United Arab Emirates by Ministry of Health, and used as
dietary supplement. This study demonstrated that
Amzylite F1.2 is effective as glucose lowering agent for
both in-vivo and in-vitro testing. Amzylite capsule should
be considered for treatment of diabetic patients. Due to its
in-vitro immediate glucose lowering action Amzylite
could become a potential life saving hypoglycaemic agent.
Abstract #375
CHARACTERISTICS OF DIABETIC
KETOACIDOSIS IN PERUVIAN PATIENTS WITH
TYPE 2 DIABETES
Miguel E. Pinto, MD, Jaime E. Villena, MD, and
Arturo Villena, MD
Objective: To describe the clinical and laboratorial
characteristics of Diabetic Ketoacidosis (DKA) in patients
with Type 2 Diabetes (T2D).
Methods: The clinical charts at Cayetano Heredia
Hospital (Lima, Peru) of all patients with DKA and T2D
diagnosis between 2001-2005 were reviewed. Patients
older than 18 years old and confirmed DKA diagnosis
(according ADA criteria) were included. Patients with
Type 1 Diabetes (T1D) diagnosis were excluded.
Results: We reviewed 53 episodes of DKA between
2001-2005. 68% patients were male, the mean age was 44
years old, 60% of the patients had previous history of diabetes, 25% had insulin therapy, 34% had therapies either
with sulfonilureas or metformin, and 41% without any
treatment. The mean blood pressure measurement was
120/76 mmHg, the mean heart rate was 96 beats/minute,
and the mean BMI was 21.6. At the time of DKA diagnosis the mean results of the laboratory blood tests were:
glycemia 458 mg/dl, pH 7.16, bicarbonate 7.64 mEq/l, and
potassium 4.41 mEq/l. In 23 patients the HbA1c were
available with a mean value of 12.21%. Infection was
associated in 45% of the episodes and lack of T2D therapy in 72%. During the time of the study, only two episodes
of DKA in T1D patients were observed.
Discussion: Peru has the lowest incidence of T1D in
the world, with less than 0.4 cases per 100 000 children
under 15 years old. However, the prevalence of T2D is
approximately 9% in the general population (approximately 2 million people with T2D). This phenomenon
could explain why more than 95% of the DKA episodes
were observed in patients with T2D. Recently, the medical
literature had described the "ketosis-prone type 2 diabetes"
(KP-T2D), and the "latent autoimmune diabetes of the
adult" (LADA). The pathogenic process of these diseases
could involve autoimmune factors. We did not perform
immunological studies in order to correlate with LADA or
KP-T2D. Most of these DKA episodes are considered
severe because the great levels of glycemia, and the very
– 30 –
low levels of pH and bicarbonate. These could be in relation to glucotoxicity and poor metabolic control due to
factors like infection (i.e. urinary tract, pneumonia, and
soft tissues) or lack of treatment.
Conclusions: In conclusion, in countries were the
incidence of T1D is low, DKA could be reported frequently in patients with T2D. In this study, 40% of the
patients had the diagnosis of diabetes during the acute
complication and most of these episodes are severe, and
related with infection and lack of treatment.
us, and to report the effect of the pilot program on clinical
outcomes in deaf patients with diabetes.
Conclusions: Developing culturally sensitive educational techniques, methods and materials can help to
reduce the gap in diabetes knowledge and glycemic control between the deaf and the hearing populations.
Abstract #330
DIABETIC KETOACIDOSIS AND ADULT
RESPIRATORY DISTRESS SYNDROME
Abstract #272
Ahmad Ali, MD, Gail Nunlee-Bland, MD,
Maria Nowkike, MD, Wolali Odonkor, MD, and
Mariam Semega-Janneh, MD
DIABETES EDUCATION FOR THE DEAF:
UNEXPLORED TERRITORY
Ramon E. Martinez, MD, Leonid Poretsky, MD,
Amy Lam, RN, Marina Krimskaya, ANP, CDE , and
Gordon Burke
Objective: To describe the initiative for the development of a diabetes education curriculum for the deaf.
Methods: Twenty deaf patients with diabetes are
being enrolled in a Diabetes Self-Management Education
Program (DSME) designed for the deaf by Certified
Diabetes Educators (CDE) and sign language interpreters.
Clinical outcomes will be measured before and after intervention.
Results: 1. Diabetes education materials for the deaf
have been developed. These include glucose self-monitoring logbook and hyperglycemia and hypoglycemia symptoms guides. Additional materials are in development. 2.
An initial workshop with 9 deaf patients was held. 3.
Outcomes report (HbA1c, lipid profile, BMI, and BP) to
be presented at the meeting.
Discussion: Nine percent of the US population have a
hearing impairment (the most common disability in the
US) and approximately 5 million individuals are considered deaf. Twenty five percent of the deaf population have
a second disability. The deaf community shares a common
language (American Sign Language). The level of education differs from the rest of the US population: average
education level for an 18 y/o deaf person is 3rd grade.
Level of English literacy is low as well. There is no data
regarding the prevalence or incidence of diabetes mellitus
in this population. Available educational materials are not
appropriate for deaf patients’ level of education and perception. Our search, including medical literature, printed
and web-based material provided by national organizations (e.g. American Association of Diabetes Educators
and American Diabetes Association) and internet at large,
failed to identify diabetes education materials or programs
for deaf individuals. At the meeting, we plan to describe
the program, present educational materials developed by
Objective: Adult respiratory distress syndrome
(ARDS) is a rare but potentially fatal complication of diabetic ketoacidosis (DKA).
Case Presentation: A 37-year- old African American
woman with Type I diabetes mellitus, presented with
polyuria, weakness, hypotension, dehydration and severe
metabolic acidosis. She was admitted with diabetic
ketoacidosis (DKA), possible sepsis and treated with
aggressive fluid management, insulin drip and other therapeutics using the DKA protocol. Her initial arterial blood
gas (ABG) analysis showed pH of 6.87, PaCO2 10.7 mm
Hg and PaO2 204 mm Hg on FiO2 1.0. Her blood pressure
was 88/51 mm Hg, pulse 110 beat per minute. She
required intubation for severe hypoxia, Labs on admissions were corrected Na 146 meq/L, K 6.0 meq/L, HCO3
4 meq/L, creatinine 3.3 meq/L, glucose > 800 mg/dL, and
acetone 154. Within 24 hrs serum electrolytes were corrected. Initial chest radiographic image was clear, then few
days later patient developed diffuse bilateral parenchymal
infiltration consists with ARDS and PO2/FIO2 ratio of
139. Sepsis was ruled out. Echocardiography showed
LVEF 55-60%, BNP was normal and central venous pressure (CVP) was 11 cm. One week later patient was extubated and recovered completely.
Discussion: Diabetic ketoacidosis remains a significant cause of death in Type I diabetes mellitus. DKA can
lead to rare complication such as ARDS (with no other
obvious risk factor for ARDS), which is a life-threatening
condition that increases mortality and lengthens hospital
stays. During rehydration with fluid and electrolytes,
reduced colloid osmotic pressure and increasing left atrial
pressure, excessive crystalloid infusion favors edema formation in the lungs (even in the presence of normal cardiac function).
Conclusions: Early rapid hydration in a patient with
DKA, and severe dehydration and acidosis may lead to
ARDS and non-cardiogenic pulmonary edema. Caution is
required during fluid administration.
– 31 –
Abstract #356
Abstract #402
LIRAGLUTIDE IMPROVES FIRST-PHASE AND
MAXIMAL SECRETION CAPACITY IN T2DM
STOP DM: STUDENTS TAKE ON THE
PREVENTION OF DIABETES
Tina Vilsbøll, MD, DMSC, Sten Madsbad, MD, DMSc,
Birgitte Brock, MD, PhD, Hans Perrild, MD, and
Hans-Henrik Lervang, MD, PhD
Arthur Chernoff, MD, FACE, and
Nadine Uplinger, MS, MHA, RD, CDE, LDN
Objective: Assessment of beta-cell parameters during
liraglutide treatment in subjects with type 2 diabetes.
Methods: At baseline and 14 weeks subjects randomized to placebo, 0.65, 1.25 and 1.90 mg/d liraglutide and
12 matched healthy subjects (BMI, gender, age) underwent insulin modified frequently sampled i.v. glucose tolerance test (FSIGTT) and hyperglycemic clamp (20 mM)
combined with i.v. arginine stimulation.
Results: 28/39 subjects with diabetes completed the
study. The 1.25 mg and 1.90 mg liraglutide dosages significantly increased maximal beta-cell secretory capacity,
by 6.27 pM (95% CI [2.92; 9.63]); ~114% and 7.17 pM
(95% CI [3.32; 11.01]); ~97%, respectively (p<0.05). The
same dosages increased first phase insulin secretion significantly by 11.0 pM*h (95% CI [6.6; 15.4]); ~124%
(1.25 mg), and 9.5 pM*h (95% CI [3.5; 15.5]); ~107%
(1.90 mg) (p<0.05). Second phase insulin secretion
increased significantly at the 1.25 mg dose level. No treatment related effect was seen on glucose effectiveness or
insulin sensitivity; for all parameters, except second phase
secretion, response in healthy subjects remained greater
than subjects with diabetes treated with liraglutide.
Discussion: Liraglutide is a once-daily s.c. GLP-1
analogue under development for the treatment of type 2
diabetes. We showed that after 14 weeks' treatment oncedaily liraglutide (1.25 and 1.9 mg/d) markedly improved
beta-cell function, significantly increased first-phase
insulin secretion and maximal beta-cell secretory capacity.
The data presented here are from a sub-study to a main
study including 165 subjects with type 2 diabetes. Data
presented elsewhere from this study have shown that
liraglutide can improve glycemic control in type 2 diabetes without risk of either major or minor hypoglycemic
episodes, lower body weight and improve blood pressure
and biomarkers of cardiovascular risk. These further findings, of improved beta-cell function following liraglutide
treatment, are highly encouraging.
Conclusions: Once-daily treatment with liraglutide
markedly improves beta-cell function in subjects with type
2 diabetes.
Objective: To develop a peer to peer education program for diabetes prevention in an urban high school.
Case Presentation: A multidisciplinary team from a
tertiary care medical center developed a partnership with a
nationally recognized regional public high school to
develop a community-based diabetes prevention program.
A faculty sponsor was identified and in turn recruited a
cohort of students possessing diverse skills, talents and
interests. These ranged from leadership, communication,
science, community action, etc. An endocrinologist and
diabetes educator met periodically with the students to
educate them about the problem of diabetes and then challenged them to develop a program for diabetes prevention
that could be rolled out to their peers and local communities. The students developed the idea of using drama to
communicate with their peers. A script based on a talk
show format was developed. It focused on life style modification in a way that was accessible to teens and preteens. As a result of these activities a radio program was
produced which aired in January 2004.
Discussion: The rising tide of diabetes particularly in
youth and young adults has prompted efforts to prevent
diabetes particularly among youth. It is not easy to talk to
teenagers about healthy choices let alone to effect change.
The concept of peer to peer education is not new; however, the use of drama and media directed at teens is more
novel. Programs such as AACE's POP reach into schools
but at times a message delivered by adults falls on a deaf
teen ear. STOP DM provided the opportunity to circumvent this effect by reaching a select group of students without being the barrier to the message. Meanwhile the
students through their drama became both the message
and the messenger. The cooperation of school officials, a
savvy faculty sponsor and dedicated students are critical
elements for success. Unfortunately, as successful as this
approach can be there are limitations and barriers. First
and foremost is the students' primary job is to be students.
Time and scheduling is a significant issue. It was often difficult to meet with the entire group because of different
schedules and outside commitments such as athletics, jobs
and college interviews.
– 32 –
Conclusions: The use of drama as a means of delivering a serious message to a difficult audience was the
masterstroke of the students of this regional high school.
However, diabetes prevention education is a serious issue
that needs a professional hand. An outgrowth of the STOP
Diabetes project could be the development of a professionally produced drama that could be brought into
schools nationwide.
Abstract #239
IMPACT OF INHALED INSULIN ON
TREATMENT CHOICES IN UNCONTROLLED
T2DM
initiation or intensification when given the option of
inhaled insulin, regardless of subject demographics, duration of diabetes, number of OAs, baseline HbA1c, geographic location, type of insurance, or method of
prescription payment.
Conclusions: The results from this randomized, parallel-group, multicenter, questionnaire-based study suggest that the availability of inhaled insulin may increase
the number of uncontrolled type 2 diabetes patients who
are willing to initiate or intensify insulin therapy in order
to attain improved glycemic control.
Abstract #196
CINNAMON SUPPLEMENTATION IN TYPE 2
DIABETES MELLITUS: A META-ANALYSIS
Richard M. Bergenstal, MD
Objective: To assess if the availability of inhaled
insulin permits greater acceptance of starting or intensifying prandial insulin.
Methods: Subjects and their physicians were asked to
select their next treatment choice based on previously provided educational materials (importance of glycemic control, value of a good meal/activity plan, standard therapies
for diabetes). Some subjects also received material on
inhaled insulin therapy.
Results: Subjects with uncontrolled T2DM (HbA1c
>7.0%) were stratified into 2 groups (>/= 2 OAs [n = 393]
or >/= 1 OA + insulin glargine [n = 216]) and then randomized to standard therapies or standard therapies +
inhaled insulin. Joint decisions of subjects and their physicians were significantly more likely to include insulin in
their future treatment regimen or choose a more intensive
insulin regimen for future treatment when inhaled insulin
was an option (>/= 2-OAs group: 47.1% vs 27.5%, P =
0.0002; >/= 1 OA + insulin-glargine group: 66.0% vs
40.0%, P = 0.0005). Nearly all subjects who chose insulin
chose inhaled insulin when given the option. The decision
by subjects to start insulin or intensify the insulin regimen
was more frequent when inhaled insulin was an option.
Discussion: Although insulin is highly effective for
achieving glycemic control, physicians and patients often
delay insulin initiation or intensification. There is a need
for an approach to insulin delivery that is well tolerated
and that improves patient acceptance. Exubera is a novel
inhaled insulin formulation for prandial use in patients
with type 2 (or type 1) diabetes with demonstrated efficacy in reducing hemoglobin HbA1c. The availability of
inhaled insulin as a treatment option had a dramatic effect
on subjects’ and physicians’ therapeutic choices. While
physicians were likely to choose insulin or insulin intensification regardless of whether inhaled insulin was included as a treatment option, most subjects, alone or jointly
with their physicians, were more likely to choose insulin
Domingo Pait Solimen, MD
Objective: To determine the effect of cinnamon supplementation in the glycemic and lipid profiles of patients
with type 2 diabetes.
Methods: All randomized controlled trials (RCTs)
involving non-insulin requiring type 2 diabetics given cinnamon supplementation compared against placebo will be
searched in MEDLINE. Change in the glycemic and lipid
profiles are primary outcomes. RevMan 4.2.8 will be utilized for meta-analytic calculations.
Results: Three RCTs were identified and retrieved
using the MEDLINE search, all fulfilling the selection criteria. All determined similar outcomes. Using the Quality
Scale for Meta-Analytic Reviews, the study by Khan et al
was graded B due to the presence of subtle performance
bias. The 2 other studies by Mang et al and
Vanschoonbeek et al received grade A in all fields.
Combining the 3 studies, the overall reduction of fasting
blood glucose from baseline is 1.26 mmol/L (95% CI 2.08, -0.44; p<0.003). There is a statistically significant
reduction of triglycerides and total cholesterol from the
baseline, 0.52 mmol/L (95% CI – 0.82, -0.22, p=0.0006)
and 0.40mmol/L (95% CI -0.68, -0.13, p=0.004). There is
a minimal LDL reduction from the baseline [0.05 mmol/L
(95% CI -.024, 0.14, p=0.60).
Discussion: The epidemic of diabetes mellitus and its
recognized complications deserves a closer look not only
on its impact on the patient and patient’s family but on the
state of the nation’s health and economic capabilities. The
combinations of medical nutrition therapy (diet and exercise) with anti-diabetic agents entail an expensive investment. In light of the tremendous cost of diabetes, both in
terms of monetary resources and human suffering, it
would be highly desirable to have practical nutraceuticals
and pharmaceuticals which such individuals could use to
control diabetes and prevent development of major organ
– 33 –
complications. For most patients worldwide, the ideal
drug treatment for diabetes is not feasible. In this era of
evidence-based medicine (EBM), the physician is challenged by the massive use of herbal supplements claiming
exaggerated health benefits despite lack of clinical study,
or if present, there is misapplication of data. This review
confirmed the role of cinnamon in increasing insulindependent utilization of glucose and its ability to modulate
lipids. Cinnamon is readily accessible, cheap and safe.
Cinnamon may be a safe add-on both for dysglycemia and
dyslipidemia.
Conclusions: This systematic review was able to
show a modest but significant reduction in the FBS, serum
triglycerides and total cholesterol level of type 2 diabetics
given cinnamon supplementation. No ill-effects were likewise noted. The benefits need to be further strengthened
and established in clinical trials with longer follow-up.
The emergence of various herbal treatments as primary or
as adjuncts in medical management of diseases should be
taken as an opportunity for medical research.
Abstract #299
INTENSIVE INSULIN THERAPY POST CARDIAC
SURGERY REDUCED DIABETIC MORTALITY
Laurence A. Gavin, MD, FRCP, FACP, FACE,
Vincent Guadiani, MD, and Donald Keating, MD
Objective: Determine impact of improved diabetes
BG control on mortality rate morbidity outcomes in diabetics undergoing cardiac surgery
Methods: A prospective nonrandomized interventional study was performed over 7 yrs. Insulin therapy was
implemented using a continuous intravenous infusion protocol. Data from ea study group & a pre study retrospective group (non infused: 2 yrs) was statistically analyzed
(ANOVA). (Stat Pack Soc Sci SPSS)
Results: The retrospective review showed noninfused
baseline diabetics (n=256) had significantly higher mortality rate (P<0.05) compared to nondiabetics(n=806).
Analysis showed mean BG (mg/dl) (+/- S.E.M.)achieved
at postop Day 2 significantly lower (P<0.001) in ea study
group [Transition 149 +/- 2.3, (2 yrs); Proactive 132 +/1.2, (3 yrs); Titrate to target 116 +/- 4.8, (2 yrs)] compared
to the baseline group (290 +/- 6.3). There was significant
reduction (P <0.05) in mean (%) mortality rate in the
proactive (3.8) (n=382) & titrated (3.4)(n=206) groups
compared to the noninfused group (7.0)(n=256). There
was no significant difference in mean length of stay, sternal wound infection or stroke rate.There was a significant
reduct.in mean hypoglycemia rate(BG <60mg/dl)in
insulin infused vs noninfused grps
Discussion: This prospective 7 yr study demonstrated
that it is feasible to safely achieve current recommended
ICU BG goal(s)at a community hosp thru implementation
of cont.intravenous insulin infusion protocol. The hypoglycemia rate was decreased 3 fold in the infused study
groups. The reduced mean blood glucose levels achieved
in the insulin infused groups was assoc.with a significant
reduction (P< 0.05)in diabetes mortality rate post cardiac
surgery. This outcome was equivalent to a 50% reduction
in mortality compared to baseline non infused group.
Although there was a downward trend in the mean BG
there was no difference in the mortality rate between the
infused groups. Compared to baseline (n=806) there was
not a significant reduction in non-diabetic (n = 2583) mortality over the equivalent study yrs. The improved BG
control was also associated with significant reduction (P<
0.05) in the mean stroke rate in the proactive and titrate to
target insulin infused groups however this response was
matched by an equivalent mean stroke rate reduction in
non diabetic group. Thus we could not exclusively
attribute reduction in the diabetic stroke rate to intensive
insulin &/or improved BG control
Conclusions: These data demonstrate the positive
impact of glucose control and/or intensive insulin infusion
on ICU mortality rate reduction post cardio-thoracic
surgery in diabetic subjects. Mean BG reduction was
achieved safely with a significant reduction in the hypoglycemia rate. We were unable to demonstrate a significant correlation between the reduced stroke rate and
improved BG control. These data support current recommendations and guidelines for intensive glucose control
within the hospital setting.
– 34 –
ABSTRACTS – Hypoglycemia
HYPOGLYCEMIA
Abstract #164
HYPOGLYCEMIA DUE TO IV TRIMETHOPRIMSULFAMETHOXAZOLE IN AN HIV PATIENT
Sonia Soni, MD, Arati Wagh, MD, and
Marc del Rosario, MD
Objective: To describe a case of sustained hypoglycemia after trimethoprim sulfamethoxazole in an HIV
patient with normal renal function
Case Presentation: A 58 y/o woman with a history of
HIV and substance substance abuse presented to the ER
with a one-week history of cough and diarrhea. Initial laboratory data demonstrated a creatinine of 1.6 mg/dL which
returned to 1.1 mg/dL after IV hydration and random cortisol of 29 mg/dL. Her CXR showed a right middle lung
infiltrate and she was empirically started on
trimethophrim-sulfamethoxazole (TMP-SMX) for PCP
pneumonia. The next day, she became more lethargic,and
her BG was <40 mg/dL. She was given an ampule of 50%
dextrose, with subsequent improvement in her mental status. Less than two hours later, she was again noted to be
hypoglycemic with capillary BG (<21 mg/dL). She continued to have multiple episodes of hypoglycemia, and
eventually required a D50 drip. During a hypoglycemic
episode (BG<21 mg/dL) serum insulin was 3.9 uU/mL
(1.4-14), C-peptide 726 pmol/L (29pmol/L (297-1419),
Pro-insulin 20pmol/L (3-20) and sulfonylurea screen
(negative). CT of her abdomen showed a normal pancreas.
Trimethophrim-sulfamethoxazole was discontinued and
she was started on diazoxide for refractory hypoglycemia.
Discussion: Hypoglycemia in non-diabetic patients is
a rare phenomenon. The usual diagnostic approach is to
categorize insulin mediated versus non-insulin mediated
causes by measuring insulin, pro-insulin and c-peptide at
the time of hypoglycemia. Non-diabetics generally have a
pancreatogenous etiology for their hypoglycemia, including insulinoma. It is also important to exclude other causes of such as adrenal insufficiency and severe
hypothyroidism both of which where excluded in our
patient. In HIV-infected patients, the most important
cause of pancreatic dysfunction is reported to be drug
effect. The risk factors for hypoglycemia associated with
these drugs are dose, duration of therapy, and renal insufficiency. The typical side-effects of TMP-SMX (rash/
hepatotoxicity/cytopenias) occur more frequently in HIV
patients. However, hypoglycemia has been reported infrequently in these patients, despite the use of this drug to
treat PCP. In patients without HIV, hypoglycemia associated with TMP-SMX has been reported in the setting of
renal insufficiency.To our knowledge this is the first case
of TMP-SMX associated with hypoglycemia in the setting
of normal renal function in an HIV patient.
Conclusions: Trimethoprim-sulfamethoxazole is an
important cause of prolonged hypoglycemia even in patiets with normal renal function. It has been suggested that
TMP-SMX alters glucose homeostasis in a similar fashion
to sulfonylureas by stimulating the pancreas to secrete
endogenous insulin. Diazoxide decreases the secretion of
insulin and is an effecive treatment for hypoglycemia
caused by hyperinsulinimia. The clinician should be aware
of this cause in the setting of otherwise unexplained hypoglycemia
Abstract #103
RATHKE POUCH REMNANT PRESENTING AS
HYPOGLYCEMIA AND GH DEFICIENCY IN A
BOY
Sigfrido Miracle-Lopez, MD, FACE,
Fernando Elizundia, MD, FAAP,
Gerardo Zambito, MD, Lyzbeth Vega, MD, and
Ilan Shapiro, MD
Objective: To describe the association of severe
recurring hypothermia, hypoglycemia and growth hormone deficiency in a 4-year-old boy
Case Presentation: 4-year-old boy, presented to the
Emergency Room with rhinorrea and flu like symptoms.His temperature was taken in the ER and showed
33.8 °C.Physical examination only showed cervical and
axillary lymph node. During the periods of hypothermia
the patient presented with signs of adrenergic surges,
which included diaphoresis, cold and clammy skin, shakes
and tachycardia. Hypoglycemia was suspected and a glucometer showed 50 mg/dL. A 72-hour fasting protocol
was started and stopped during the 21st hour with
Whipple’s triad and a central glucose of 52 mg/dL. The
insulin, glucagon, epinephrine and cortisol response were
adequate for the hypoglycemia, but the peak Growing
Hormone (GH) response was 0.61 ng/Ml , an IGF-1 and
IGF-2 were performed with a result of 53.3 and 468
respectively. Clonidine stimulation test was done with a
peak GH of 5.43 ng/ml at 120 minutes. An MRI of
theSella Turcica showed a Rathke Cleft Cyst that was
compressing the pituitary gland. GH replacement was
started at a dose of 0.3 mg/Kg/Week divided in daily
doses. No further hypoglycemia or hypothermia were
reported.
Discussion: Healthy neonates and young children are
unable to maintain normal plasma glucose concentrations
after even a short fast, and exhibit a progressive decline in
plasma glucose concentration to hypoglycemic values. For
hypoglycemia to occur, the rate of appearance of glucose
into the plasma space must be less than its rate of utiliza-
– 35 –
tion. Hypoglycemia may occur in association with various
hormone deficiencies. It is common among children with
primary or secondary GH deficiency. When patients who
have GH deficiency are hypoglycemic, they become ketotic, have a blunted glycemic response to exogenous
glucagon and also typically have low plasma concentrations of alanine and glutamine (potential gluconeogenic
substrates in the liver and kidney). Most patients with GH
deficiency have decreased insulin concentrations.
Hypothalamic-pituitary dysfunction should be considered
in patients who have hypoglycemia and midline defects,
septo-optic dysplasia, short stature or decelerating height
velocity, or a history of cranial irradiation. The management and prevention of hypoglycemic episodes in these
children center on diagnosis of the deficiency and appropriate hormone replacement therapy.
Conclusions: We concluded that the patient suffered
from hypothermia due to hypoglycemia due to GH deficiency due to a Rathke Cleft Cyst. Although transsphenoidal surgery is an appropriate approach for the radical
excision of intrasellar-suprasellar lesions, even in children,this child had only hormonal deficit, with no visual or
neurological symptoms. As the reports of hormonal deficit
recovery after surgery are not encouraging, we decided on
a non-surgical course of treatment.
Abstract #350
RESIDENT MD TREATMENT OF IN HOSPITAL
HYPOGLYCEMIA PRE AND POST PROTOCOL
event documentation increased from 26% (n=31) to 97%
(n=30) and follow up blood glucose was noted 97% of the
time after the protocol vs. 45% prior to the protocol.
Further results will be discussed.
Discussion: As the first step in the development of an
inpatient diabetes management program we developed and
implemented a hospital wide hypoglycemia treatment protocol (will be described in detail). Using a survey tool and
chart review, we tracked various measures of resident
physicians' treatment of in hospital hypoglycemia.
Notable differences pre and post protocol including documentation of treatment plan and time to recheck glucose
and other results will be detailed. In addition, resident
physicians evaluated the protocol with 68% stating the
protocol was clear and 73% that it improved patients care.
69% thought the protocol was a good tool for documentation of hypoglycemia episodes and most (85%) always or
frequently ordered it for appropriate patients. There is a
nationwide trend towards developing protocols to improve
inpatient glucose management. Our Hypoglycemia
Protocol provides a standard of care for treatment of in
hospital hypoglycemic episodes and serves to document
the events in a consistent way.
Conclusions: The development and implementation
of a Hypoglycemia Protocol in our community teaching
hospital resulted in improvement in evaluation, documentation and proper treatment of hypoglycemic episodes by
resident physicians. The protocol is associated with a positive impact on clinical practice and provides standardized
inpatient hypoglycemia management.
Anna Boron, MD, Nicoleta Ionica, MD,
Adina Turcu, MD, Linda Ferro, APRN,
Mark Kulaga, MD, FACP, and
Nancy J. Rennert, MD, FACE, FACP
Abstract #291
Objective: To assess resident physician treatment of
inpatient hypoglycemia (pre and post protocol) in a community teaching hospital.
Methods: Resident physicians' knowledge and attitudes concerning hypoglycemia (before and after the protocol) were assessed with a survey tool. Chart review data
on hypoglycemic events were collected and evaluated.
Results: Before the protocol, treatment was inconsistent. For example, 59% of resident physicians surveyed
(n=37) reported they would treat hypoglycemia in an alert
and stable patient with IV D50 as initial therapy (pre-protocol, our hospital's use of IV D50 was the highest of
regional hospitals surveyed). Additionally, the time to
recheck glucose after the initial low reading was variable,
ranging from 15 minutes to over 12 hours. Chart review
revealed that documentation of the hypoglycemic events
was poor. Three months after protocol implementation,
many of these parameters improved, i.e. hypoglycemic
Afshan Afzal Chaudhry, MD,
Siham D. Accacha, MD, CDE,
Mariano Castro-Magana, MD, Moris Angulo, MD, and
Monika Zak-Aptekar, MS
NOVEL ABCC8 GENE (c.2659a>c) MUTATION
CAUSING CONGENITAL HYPERINSULINISM.
Objective: To present a novel compound mutations in
the ABCC8 gene leading to congenital hyperinsulinism
(CHI).
Case Presentation: We report a 2 day old female
infant with severe hypoglycemia in the range of 11 to 23
mg/dl. She was started on intravenous fluids with dextrose
(GIR 10mg/kg/min). Laboratory evaluation revealed a
serum insulin of 5.9 µIU/ml, blood sugar of 45mg/dl,
growth hormone of 7.39ng/ml, serum cortisol of
38.9mcg/dl, no ketonuria and a positive glucagon test with
delta glucose >30 mg/dl confirming the diagnosis of CHI.
Medical treatment with diazoxide, 5 mg/kg/day and
octreotide, 15 mcg/kg /day was unsuccessful. PET scan
– 36 –
was performed before considering surgery and suggested
diffuse involvement of pancreas. Patient underwent near
total (98%) pancreatectomy. Her blood sugars became
normal the first day after surgery. Genetic testing revealed
a genetic compound, including the well recognized mutation c.4120-19C>T, responsible for diffuse CHI and a de
novo missense mutation, c.2659A>C, inducing an amino
acid change, p.Thr.887Pro and impairing K ATP channel
activation. Genetic testing on parents revealed that both
parents are carrier for the classic c.4120-19C>T mutation.
Discussion: Congenital hyperinsulinism (CHI) is an
autosomal recessive disorder most commonly due to
mutation of the ATP-sensitive potassium channel gene,
ABCC8 also known as SUR1, which is responsible for
most cases of severe, persistent hypoglycemia during
neonatal period.Many reports have shown the importance
of identifying an ABCC8 mutation in a patient with CHI,
by providing a firm diagnosis and helping to predict the
likely course of the disease and clinical management of the
patient. Because the clinical picture presented by our
patient is similar in severity to the homozygous autosomal
recessive form of CHI, it’s likely that this new mutation
may be responsible for the diffuse form rather than the
focal form of CHI.
Conclusions: Larger number of patient with this de
novo mutation will be necessary for better genotype-phenotype correlation.
ketones negative, anti-insulin antibodies negative, prolactin 37.9 and TSH 5.71. The electrolytes, liver function
tests, free T4, anti-TPO, cortisol, and ACTH were normal.
Quinine was discontinued and a 72 hour fast was initiated.
Results in Figure 1. A dose of 1 mg glucagon was given at
the end of the fast which raised the glucose from 32 to 40
mg/dL.
Discussion: The workup of fasting hypoglycemia in
patients with ESRD is difficult because normal laboratory
values for a 72-hour fast are not established and hypoglycemia in renal failure may be multifactorial. The workup was consistent with non-insulin mediated
hypoglycemia. Although the quinine level was within
therapeutic range when checked (1.5 mcg/mL), it was
drawn 5 days after the drug was stopped reflecting a probable supratherapeutic level on admission. The patient followed-up in the clinic after a month and denied any
hypoglycemia off quinine. He was not re-challenged with
the drug because it would require taking him off dialysis
for the fasting protocol and that he had arrhythmia previously.
Conclusions: The 72-hour fast is useful in the diagnosis of non-insulin mediated hypoglycemia even in renal
failure. Quinine should be considered as a cause of hypoglycemia in dialysis patients.
Abstract #217
INSULIN AUTOIMMUNE SYNDROME (IAS); A
RARE BUT REAL CAUSE OF HYPOGLYCEMIA
HYPOGLYCEMIA COMPLICATED BY RENAL
FAILURE, PERITONEAL DIALYSIS AND
QUININE
Abstract #122
Shazia Faiz, MD, C. Elisa Perez, MD, and
Olga Kaliebe, MD
Kenneth Patrick Lazaro Ligaray, MD, and
Alan Bernard Silverberg, MD
Objective: Demonstrate that the 72-hour fast is indispensable in renal failure and that quinine can cause hypoglycemia in ESRD patients.
Case Presentation: A 67 year old man was admitted
for loss of consiousness. He had syncope hours after a
meal that was preceded by mental status changes,
diaphoresis, and shakiness. Blood sugar by EMS was 29
mg/dL. He has a history of anemia, COPD, PVD and
ESRD on PD. He was on multiple medications including
quinine 325 mg prescribed by his nephrologist as a daily
medication for leg cramps. However, the patient reported
taking 4-6 tablets if the leg cramps were severe. Vital
signs were stable on admission. He was hemodialyzed, but
remained hypoglycemic requiring a glucose infusion.
ECG revealed irregular rhythm with widened QRS complexes. Initial laboratory data were remarkable for BUN
64, creatinine 10.7, hemoglobin 10.9, glucose 52, urine
Objective: We are presenting a case of IAS in 80 yr
old white male who presented with symptoms of sever
hypoglycemia.
Case Presentation: Our patient presented with
episode of hypoglycemia with serum blood glucose
17mg/dl. Patient had previous episodes of hypoglycemia
with neuroglycopenic symptoms. Patient experienced
occasional symptomatic episode of hypoglycemia in hospital. Lab results are shown in table. His blood work was
consistent with hyperinsulinemic hypoglycemia. Serum
sulfonylurea screen was negative. All imaging studies
were negative. Insulin auto antibodies came back positive
81% bound. After discovery of insulin auto antibodies in
association with hyperinsulinemia and no previous history
of exogenous insulin exposure,it was proposed that our
patient had IAS. A pattern of postprandial hypoglycemia
was observed in association with high carbohydrate diet.
He was discharged on a low carbohydrate diet and was
instructed to check CBG four times a day. He recovered
completely in three months which was proved by continu-
– 37 –
ous glucose monitoring system (CGMS) that was placed
for 72 hours and there were no documented low blood glucose readings. This information led us to believe that IAS
had resolved.
Discussion: IAS is defined by recurrent, spontaneous
hypoglycemia in individuals with high serum insulin and
insulin autoantibodies (IAA) without prior history of
exposure to exogenous insulin. There have been 31 cases
of IAS reported in white populations in European literature. Average age of onset is between 40 - 70 years old. It
has been found in pregnant women and children. IAS has
been associated with medications and autoimmune diseases, involving the thyroid gland, rheumatoid arthritis,
SLE and ulcerative colitis. Some cases report a link to
medications that contain sulfhydryl groups, like captopril,
methimazole, procainamide etc. It is believed that the
sulfhydryl group (S-H) interacts with the disulfide bond of
insulin to form haptene and cause an autoimmune reaction, resulting in the formation of IAA. The observation of
frequent postprandial hypoglycemia in IAS has led to
believe that perhaps the insulin that is released early during the glucose load binds to antibodies, this bound insulin
is released from the antibodies out of synchrony with the
ambient glucose levels and able to exert its action at the
insulin receptor at an inappropriate time, resulting in
hypoglycemia.
Conclusions: Insulinoma is the most prevalent cause
of hyperinsulinemic hypoglycemia. Therefore, its localization should be the initial focus of treatment. However,
when its search leads nowhere, IAS thought to be in the
differential. It is a cause of hypoglycemia that can be treated without surgery, thus preventing an unnecessary surgical procedure. It has been associated with an 80%
spontaneous remission and about 30% recover in less than
one month, and few last for about a year.
Abstract #271
THE CASE OF THE MISSING INSULINOMA
Michael Benjamin Davidson, DO, Thottathil Gopan, MD,
Sylvia L. Asa, MD, PhD, S. Sethu K. Reddy, MD, and
Eren Berber, MD
repeat 72 hour fast, admission blood glucose was 46
mg/dL, insulin 4.6 uU/mL, C-peptide 1.4 ng/mL, proinsulin 86.0 pmol/L, negative sulfonylurea screen, with mild
confusion present. After 1 hour, glucose was 41 mg/dL,
insulin 5.9 uU/mL, C-peptide 1.5 ng/mL, proinsulin 103.7
pmol/L, with severe neuroglycopenic symptoms. The fast
was terminated and the patient taken to the operating
room. On laparotomy, ultrasound revealed a 9 mm isoechoic mass in the pancreatic head. It was removed and
pathology demonstrated a well-differentiated neuroendocrine tumor with diffuse staining for chromogranin and
insulin. Following surgery, he has done well without any
further hypoglycemia.
Discussion: In this case, a proinsulinoma resulted in
severe hypoglycemia in an otherwise healthy, young
patient. Despite much difficulty in pre-operative localization of his tumor, he was cured by surgery without further
clinical hypoglycemic episodes or biochemical evidence
of hyperproinsulinemia. Insulinomas are often difficult to
confirm and localize. More than 50% of patients with
insulinoma have symptoms present for >5 years prior to
their diagnosis and treatment. This was true with our
patient, in whom recognition was delayed at least in part,
because proinsulin rather than insulin was the main secretory product. Isolated proinsulin secreting insulinomas
have been very infrequently reported in the literature.
However, proinsulin/insulin ratios tend to be higher in
those with insulinomas. Proinsulin typically has a modest
hypoglycemic effect, with approximately 20% bioactivity
of insulin. Insulinomas, such as the one described here,
present with symptoms of hypoglycemia in contrast to
familial hyperproinsulinemia, which is usually associated
with euglycemia or hyperglycemia.
Conclusions: This patient’s presentation was typical
of most patients with insulinoma, although he had a proinsulin-secreting
pancreatic
endocrine
tumor.
Hypoglycemia caused by an isolated proinsulin-secreting
neuroendocrine tumor of the pancreas is extremely rare.
Measurement of proinsulin concentration at the time of
provocative testing for hypoglycemia should always be
performed so as not to miss this diagnosis. Surgical resection is usually curative.
Abstract #135
Objective: To present a case of a proinsulin secreting
pancreatic endocrine tumor causing severe hypoglycemia.
Case Presentation: A 32 year old white male had
episodic confusion and blackouts progressing over 2
years. Lab tests demonstrated true hypoglycemia at time
of episodes. Two admissions at a local hospital for 72 hour
fast showed hypoglycemia without definite hyperinsulinemia. CT scan of the pancreas was normal. Arterial calcium
stimulation did not localize an insulin secreting mass. A
trial of diazoxide did not improve his symptoms. On a
PLASMAPHERESIS IN TREATMENT OF
INSULIN AUTOIMMUNE SYNDROME
Thottathil Gopan, MD, Michael B Davidson, DO,
Elias Siraj, MD, FACE, Manjula Gupta, PhD, and
Robert Zimmerman, MD
Objective: To describe the clinical presentation, laboratory evaluation and treatment of a patient with Insulin
Autoimmune Syndrome(IAS)
– 38 –
Case Presentation: An 89 yr old man presented with
a history of multiple falls, loss of consciousness and
seizures for 1 month. BG of 30 mg/dl was noted during
one episode and he improved with dextrose. His medications included aspirin and simvastatin. On admission for
72-hour fast protocol, the BG was 70 mg/dl, which
decreased to 21 mg/dl after 4 hours, at which time he
developed altered mental status. The insulin level was
49261 µU/ml, C-peptide level, 10.6 ng/ml and proinsulin
level, 40450 pmol/l at that time. CT of the pancreas was
normal. Insulin antibodies in the serum were significantly
elevated at 90% (nl< 5%). After polyethyleneglycol (PEG)
precipitation, the free and total insulin levels were 1007
µU/ml and 7360 µU/ml respectively. Serum protein electrophoresis showed IgG Kappa type of monoclonal gammopathy. He had recurrent hypoglycemia in spite of
treatment with high doses of prednisone and plasmapheresis was initiated. After the initiation of plasmapheresis, the
blood glucose levels stabilized and the insulin antibody
levels decreased to 52%. He was doing well at follow-up
after 6 months.
Discussion: IAS is characterized by spontaneous
hypoglycemia, extremely high insulin levels (usually>100
µU/ml) and the presence of circulating insulin antibodies
in patients who have never been exposed to exogenous
insulin. Although IAS is considered to be the third greatest cause of hypoglycemia in Japan, it is extremely rare
elsewhere. Patients present with severe neuroglycopenic
symptoms like confusion, loss of consciousness, and even
coma. The hypoglycemia is mostly postprandial, although
fasting hypoglycemia can occur. This probably results
from the dissociation of insulin from its antibodies several hours after meals, when no further glucose absorption is
occurring. IAS is associated with medications (methimazole, captopril etc.), autoimmune disorders and plasma
cell dyscrasias. Extremely high insulin levels are common
due to interference of the insulin antibodies with the
insulin assay. C-peptide and pro-insulin levels are also elevated. Treatment with steroids and other immunosuppressive agents might be beneficial. There is little published
data on the use of plasmapheresis. Our patient was unresponsive to steroids, but improved after initiation of
plasmapheresis.
Conclusions: IAS should be suspected in patients
with hyperinsulinemic hypoglycemia associated with post
prandial neuroglucopenic symptoms and extremely high
insulin levels. Associated autoimmune disorders and plasma cell dyscrasias should be looked for and offending
medications should be stopped. Treatment options include
corticosteroids, other immunosuppressants and frequent
low-carbohydrate meals. Use of plasmapheresis should be
considered in patients who do not respond to conservative
treatment.
– 39 –
ABSTRACTS – Lipid Disorders
LIPID DISORDERS
HYPERCHOLESTEROLEMIA SECONDARY TO
LIPOPROTEIN X
Conclusions: Lipoprotein X is an uncommon cause
of hypercholesterolemia. In patients with cholestasis,
however, it should always be considered; the risk of cardiovascular death does not appear to be increased in this
population despite significantly elevated cholesterol
levels.
Brian Alan Swiglo, MD, and Diana S. Dean, MD
Abstract #314
Objective: To present a case of lipoprotein X, review
its pathogenesis, and discuss its lack of association with
cardiovascular disease.
Case Presentation: A 56-year-old woman presented
to our clinic with significant hypercholesterolemia. She
had hypertension, but no previous history of cardiovascular disease. Other cardiac risk factors including diabetes,
smoking, and a significant family history were absent. On
examination, she had multiple small yellowish papules
over her abdomen and the extensor tendons of her hands.
These were proven to be xanthomas on biopsy. Her total
cholesterol was 741 mg/dL, triglycerides were 82 mg/dL,
HDL was 79 mg/dL, and LDL was 646 mg/dL. Her past
medical history also included vitiligo, breast cancer (s/p
mastectomy and chemotherapy, with no evidence of recurrence), and primary biliary cirrhosis (PBC). She was taking cholestyramine 4 grams three times a day for pruritus,
and prior to starting this, her total cholesterol was 1164
mg/dL. Given the history of a cholestatic disorder, a
lipoprotein metabolism profile was obtained and lipoprotein X was detected as a major portion of the LDL cholesterol. She was continued on the cholestyramine but no
additional cholesterol lowering medications.
Discussion: Lipoprotein X (Lp-X) is an abnormal low
density lipoprotein consisting primarily of phospholipids
and unesterified cholesterol. It is found commonly in
patients with cholestasis, often PBC, and familial
lecithin:cholesterol acyltransferase (LCAT) deficiency.
Lp-X is thought to develop as a result of cholestasis, as
bile (which contains lipoproteins with similar phospholipid and unesterified cholesterol concentrations) refluxes
into plasma where it is exposed to albumin and other proteins. Reduced LCAT activity, due to impaired hepatocellular function or overwhelmed LCAT capacity, may also
play a role as the cholesterol cannot be esterified. The
presence of Lp-X increases hepatic cholesterol synthesis
and inhibits hepatic remnant lipoprotein uptake, thus causing its own accumulation. For the above reasons, Lp-X is
commonly present with cholestasis and significant hypercholesterolemia can occur. Patients with hypercholesterolemia and PBC do not seem to have an increased risk
for cardiovascular death, even with elevated total cholesterol and LDL levels. This appears to be because Lp-X is
resistant to oxidation and prevents oxidation of normal
LDL as well.
EFFECTS OF ANABOLIC ANDROGENIC
STEROIDS (AAS) ON SERUM LIPOPROTEIN
PROFILE
Abstract #306
Negah Rassouli, MD, Palak Choksi, MD,
Zulekha Hamid, MD, and Fred Faas, MD
Objective: To report a case of lipid profile alteration
and cholestatic jaundice due to AAS abuse.
Case Presentation: A 28 year-old previously healthy
white male presented with 2-week complaints of nausea,
jaundice, pruritis and dark urine. Two months before the
onset of his symptoms, he had started using OTC bodybuilding supplements Orastan-E 50 mg and Superdrol 40
mg a day. Physical examination was remarkable for icteric
sclera with several scratch marks throughout the skin.
Laboratory studies showed high AST and ALT of 92 ( 1537 U/L), and 121 (11-63 U/L), respectively. His direct
bilirubin level was also elevated at 5 (0-0.3 g/dl). While
the serum lipoprotein level prior to the supplements use
was normal, on this admission, HDL was 4 mg/dl, LDL
355 mg/dl, triglycerides 288 mg/dl and total cholesterol
423 mg/dl. Extensive work up to determine the etiology of
hepatitis was essentially negative. Liver biopsy was performed which showed canalicular cholestasis, consistent
with adverse drug reaction. HDL level increased to 39 mg
/dl and LDL decreased to 160 mg/dl six months after discontinuation of the anabolic products. Liver function tests
normalized in 3 months.
Discussion: Superdrol (Methasterone) and Orastan- E
(prostanozol) belong to AAS family. AAS products have
been advertised to enhance physical fitness and are available OTC as well as over the Internet. Side effects of AAS
abuse include but not limited to hepatic dysfunction,
remodeling of myocardium and atherogenic changes in
lipoprotein profiles. Of particular concern are alterations
in lipoprotein profiles, resulting in premature coronary
events. Poly drug regimen of AAS causes an increase in
serum Apo B and a decrease in serum HDL and Apo A1.
The effects on serum lipids seem to be exerted by oral
rather than parenteral administration of AAS drugs. Oral
AAS containing 17 alpha alkyl steroids, stimulate hepatic
lipase, whereas parenteral ones have less effect on this
enzyme. This is due to the lack of first-pass circulation
through liver. Our patient consumed the combination of
– 40 –
ABSTRACTS – Lipid Disorders
superdrol, with active ingredient of methasterone (a 17alpha alkyl steroid), plus Orastan E (prostanozol) to augment the androgenic effect. The available data shows that
the effect of AAS on lipid profile is dose dependent and
the recovery after stopping AAS depends on the lengths of
AAS use.
Conclusions: The reported case is a unique presentation of the alterations in lipoprotein profile and cholestasis
due to AAS .The degrees of changes in serum HDL (90%)
and LDL (55%) level was striking in our case. Because of
increased risk of cardiac events with AAS, the abuse of
such substance should be considered a public health problem. The information regarding the side effects of AAS
must be made available to the consumer when the product
is being advertised.
Abstract #352
SEVERE INSULIN RESISTANCE IN
CONGENITAL LIPODYSTROPHY
Brian William Hanrahan, MD
Objective: To describe a case of severe insulin resistance in a patient with congenital lipodystrophy.
Case Presentation: A 41-year-old female with a medical history of congenital lipodystrophy presented to the
emergency department of a university hospital for severely elevated blood glucose, documented persistently greater
than 600 mg/dL, despite being previously controlled on an
acceptable regimen of regular insulin sliding scale and
glargine. An endocrinology consult was obtained and an
intensive intravenous insulin infusion protocol was started. The insulin infusion was titrated rapidly to 92 units/hr,
which produced glucose readings in the range of 120-150
mg/dL. Using the large daily insulin requirement from the
insulin infusion, the endocrinology consult team estimated
her 24-hour insulin need. They felt the best way to have
the patient safely and effectively administer that much
insulin was using a unique type of insulin, U-500, which
has 500 units of insulin per mL. She was started on this
regimen, getting 500 units of insulin every eight hours.
She tolerated this well, with no significant hypoglycemic
or hyperglycemic events, and was able to be discharged
home on the new insulin regimen.
Discussion: The lipodystrophies are disorders of
selective loss of adipose tissue. They can be acquired or
inherited. Patients often become insulin resistant, sometimes severely so, making hyperglycemia and its complications difficult to manage. This case illustrates one of the
more common management issues that arise with severe
lipodystrophy. Many patients with both congenital and
acquired lipodystrophies develop diabetes. They often
become severely insulin resistant and require larger and
larger doses of insulin for glycemic control. Patients with
lipodystrophies who develop diabetes also experience the
same complications that other poorly controlled diabetics
experience. And because they are often so significantly
resistant to insulin, these complications are often severe in
these patients.
Conclusions: Tight glycemic control, although often
challenging to achieve, is absolutely necessary to help
avoid severe complications in patients with lipodystrophy.
– 41 –
ABSTRACTS – Metabolic Bone Disease
METABOLIC BONE DISEASE
Abstract #422
Abstract #303
THIRTEEN YEAR DATA ON THE EARLY
TREATMENT OF PAGET’S DISEASE: LONGER
REMISSIONS WITH REDUCED RISK?
COST-EFFECTIVENESS OF RISEDRONATE AND
IBANDRONATE: IMPACT OF PERSISTENCE
Brian Craig Jameson, DO, and Arnold M. Moses, MD
Andreas Grauer, MD, PhD, D. Grima, PhD,
Margaret Pasquale, PhD, Jeffery Lange, PhD, and
M. Thompson, PhD
Objective: To use a Markov model of post
menopausal osteoporosis to compare the cost effectiveness of risedronate and ibandronate.
Methods: This study uses a Markov model of postmenopausal osteoporosis (PMO) to compare the therapeutic- and cost-effectiveness of risedronate and ibandronate
at a wide range of persistency levels, measured by the percentage of patients on therapy at the end of this three-year
period.
Results: The Markov model simulated a cohort of
women aged 65+, with previous vertebral fracture and
BMD T-score <-2.5, under a three-year time horizon.
Fracture rates were derived from US epidemiological
studies. Vertebral and nonvertebral risk reduction measures are 52% and 0% for ibandronate respectively
(Chesnut, Skag, Christiansen, et. al., 2004), and 41% and
40% for risedronate respectively (Harris, Watts, Genant,
et. al., 1999). Annual drug costs were $876.46 for risedronate and $809.04 for ibandronate. For simplicity, the
model assumes all patients who discontinue do so early
(within the first 3 months), and that patients who discontinue in this time frame incur 3 months of drug costs but
without any efficacy benefit.
Discussion: At equal levels of persistence, treatment
with risedronate results in fewer total fractures (nonvertebral and vertebral combined), lower fracture costs and
lower total costs of treating fractures. The difference in
fractures, fracture costs and total costs rises with increasing persistence. Fracture costs are always lower for risedronate, even at 10% risedronate persistence and 100%
ibandronate persistence, due to the lack of proven efficacy
of ibandronate on nonvertebral fractures (Fig. A)
Conclusions: The cost-effectiveness (CE) ratios (cost
of avoiding one fracture) versus no therapy are also lower
for risedronate. Persistence at 20% or above for risedronate results in a lower CE ratio than ibandronate at a
perfect 100% (Fig B). The lower (improved) CE ratio for
risedronate is expected given its better efficacy. In this
analysis, overall cost-effectiveness is more dependent on
efficacy than persistency.
Objective: To report our 13 year follow up experience
in patients initially treated for mild to moderately severe
Paget’s disease of bone with intravenous pamidronate
from 1994-1996.
Case Presentation: Our index case is a man diagnosed with Paget’s disease of the left hip after presenting
with severe hip and left leg pain when active and at rest.
He had an elevated urinary deoxypyridinoline (d-Pyr)
level of 15.3 nmol/mmol Cr (ULN 10.7), but his serum
alkaline phosphatase (SAP) level was 88 IU/Liter (normal
21-126). Tc scanning showed expansion and increased
activity of the left ischial bone. He was infused with 180
mg of pamidronate in divided doses over 3 weeks. Soon
after his pain resolved, his d-Pyr and bone scan normalized, and his SAP reached a nadir of 53 IU/liter. He
remains asymptomatic with normal bone turnover markers
and bone scans for more than 13 years. A review of treated patients (pts)from 1994-1996 found those with a pretreatment SAP < 2 X ULN (mild) had longer remissions
(time of normal SAP) than those with a pre-treatment SAP
2-5 X ULN (moderate). Eleven pts with mild disease had
a median initial SAP of 165 IU/L and a median duration
of remission of 48 months. Two women had remissions of
96 months. Six pts with moderate disease had a median
initial SAP of 369 IU/L and a median duration of remission of 19.5 months. One woman had a remission of 48
months. Five of 11 pts with mild disease had longer remissions than any with moderate disease (P = 0.06)
Discussion: A 2006 review by Whyte, M.P. (N Engl
J Med 355;6)suggests delaying treatment of patients with
asymptomatic Paget’s disease unless the location of disease activity was in a weight bearing bone likely to fracture. Our data, as well as a previous report in 2003 by Ang
et al. (Endocr Prac 9;4), suggest that patients with SAP
levels < 2 X the ULN benefit from early treatment in terms
of longer remission. As recent data suggests a total dose
and time dependent relationship between bisphosphonate
therapy and the development of osteonecrosis of the jaw,
early treatment may lessen total exposure to these compounds.
Conclusions: We found an inverse relationship
between pre-treatment level of SAP and duration of remission for Paget’s disease following treatment with
– 42 –
pamidronate. We therefore suggest that patients with evidence of clinically active Paget’s disease be considered for
antiresorptive therapy to prevent progression of the disease and promote longer remissions. These patients may
also benefit from a decreased risk of osteonecrosis of the
jaw by less total exposure to antiresorptive medication.
Abstract #317
SECONDARY HYPOGONADISM PRESENTING
WITH RIBS FRACTURE
Mirna Maldonado, MD, Myriam Z Allende, MD, FACE,
Vilma M. Rabell, MD, FACE, and Marielsa Rabelo, MD
(IHH), Kallmann's syndrome, tumor in pituitary or hypothalamus, infections, and infiltrative disorders among others. Because of no abnormalities on brain MRI and no
other pituitary deficiencies, IHH was diagnosed once infiltrative diseases such as sarcoidosis and hemochromatosis
were excluded. He was started on alendronate with calcium supplements. He was referred for infertility treatment,
for which no testosterone replacement was prescribed.
Conclusions: This case reported a young man whose
first presentation for IHH was ribs fracture. Although it is
well known that osteoporosis and osteoporotic fractures
occur in hypogonadism, rib fracture is not a common
reported presentation of this condition.
Abstract #169
Objective: To present a case of a 33-year-old man
who presented non-traumatic ribs fracture as the first manifestation of hypogonadism.
Case Presentation: A healthy 33-year-old man, taking no medications, no toxic habits, and no previous fracture suffered two ribs fracture after a hug by his wife (BMI
of 25). A bone DXA showed Z scores of -2.2 at lumbar
spine, -2.6 at total femur and -1.9 at upper distal radius. He
was presenting some loss of libido, fatigue and infrequent
headaches in past months. He had no anosmia and
nephrolithiasis. There was no history of head trauma and
radiation. At age 13, he suffered left testicle torsion with
rapid correction by surgery. His puberty was at 12-13year-old, similar to his brothers. He never suffered mumps
and he had no offspring. There was family history of
nephrolithiasis, but no fractures or osteoporosis. On physical exam he was with normal vital signs and BMI-28, it
was unremarkable including genitalia except for left testicle being higher than the right one. The serum total testosterone was 184 ng/dl (normal: 241-827). The serum free
testosterone levels was 0.80 ng/dl (normal: 0.80-3.50)
with LH 1.98 uIU/mL and FSH 1.90 mIU/mL. Both serum
LH and FSH were inappropriately low for the corresponding testosterone levels. The other pituitary hormones,
CBC and electrolytes were in the normal range. A brain
MRI showed no abnormalities.
Discussion: The presence of a fragility fracture is
considered osteoporosis. In men, secondary causes for this
condition needs to be ruled out and hypogonadism is the
best characterized risk factor. On this young man with
osteoporosis, normal electrolytes and CBC, with no toxic
habits and no use of medications including glucocorticoids, hypogonadism was considered first. The history of
testicle torsion was remarkable because it has been reported autoimmune damage of the non-torsion testicle. The
inappropriate low normal gonadotropin levels pointed
toward secondary hypogonadism. The major causes of
secondary hypogonadism include congenital anomalies,
isolated idiopathic hypogonadotropic hypogonadism
PRIMARY HYPERPARATHYROIDISM (PHP)
MASKED BY PROFOUND VITAMIN D
DEFICIENCY
Susan Wang, DO, John B. Schenck, MD,
Jeffrey A. Guy, MD, Juraj Osterman, MD, PhD
Objective: To describe a case of severe PHP and low
vitamin D level and effects of treatment on restoration of
metabolic abnormalities.
Case Presentation: A 31-year-old morbidly obese
African-American male sustained a non-traumatic hip
fracture. Because of severe demineralization of his entire
skeleton and poor healing of his surgically repaired fracture, comprehensive metabolic evaluation was initiated. It
showed normal total and ionized serum calcium, low
phosphorous, markedly elevated iPTH, total and bonespecific alkaline phosphatase, osteocalcin, and an undetectable 25-hydroxyvitamin D level. Sestamibi
parathyroid scan was positive and at surgical exploration,
an 8.8 gram adenoma was resected. Following surgery,
severe hypocalcemia ensued and was treated with intravenous calcium. During the next 14 months of treatment
with oral calcium (3grams/day) and ergocalciferol
(50,000-100,000 units/week), we monitored and documented gradual and persistent decline of markers of bone
formation to near normal levels. In addition, there was definite radiologic evidence of improved mineralization of
both cortical and trabecular bone. The most likely cause of
this patient’s vitamin D deficiency is his marked skin pigmentation.
Discussion: PHP is usually diagnosed in the setting of
mild or moderate hypercalcemia. Patients with normocalcemic hyperparathyroidism probably represent an early
stage of the disease. Coexisting mild hyperparathyroidism
and mild vitamin D deficiency are common and most
patients present with mild to moderate hypercalcemia.
Several conditions have been reported that can mask PHP
– 43 –
in the setting of normocalcemia, one of them being coexisting vitamin D deficiency, particularly when severe. Our
patient represents such a rare situation in which correct
diagnosis was made only after a fragility fracture
occurred. Some studies suggest that patients with coexisting vitamin D deficiency and PHP have higher skeletal
fracture rates, larger adenomas, higher iPTH and markers
of bone turnover. Our patient exhibited all these features.
In addition, we document progressive resolution and nearnormalization of markers of bone turnover and skeletal
healing following removal of the parathyroid adenoma
and treatment with large doses of ergocalciferol required
to maintain the level of 25-hydroxyvitamin D in the normal range. Such treatment apparently requires in excess of
one year.
Conclusions: Coexisting severe PHP and profound
vitamin D deficiency presenting with normocalcemia is
apparently a rare disorder. Severe demineralization affecting both cortical and trabecular bone should prompt
detailed metabolic evaluation including vitamin D, iPTH
and markers of bone turnover as shown by this case report.
Long-term treatment with calcium and adequate oral vitamin D doses after parathyroid adenoma removal leads to
improved skeletal mineralization and restores metabolic
abnormalities.
Abstract #332
VALUE OF SESTAMIBI SCANS FOR ECTOPIC
GLANDS IN TERTIARY
HYPERPARATHYROIDISM
Tc sestamibi scintigraphy. In comparing the patients with
and without ectopic glands, the scans were true positive in
78% and 75% and false negative in 22% and 25%, respectively. There were no false positive scans in either group.
Discussion: Ectopic parathyroid glands present both
diagnostic and operative challenges in patients with tertiary hyperparathyroidism. These glands are believed to
occur as a result of abnormal migration during embryogenesis. Failure to identify an ectopic gland is an important
cause of operative failure and often leads to lengthy reoperation with concurrent increased morbidity and cost.
Although there is ample data in the literature regarding the
incidence of ectopic parathyroid glands in primary hyperparathyroidism, there is little data in patients with secondary and tertiary hyperparathyroidism. The reported
rates of ectopic glands in this patient population vary from
8% to 32%. Our series revealed a higher incidence of
ectopic glands (43%). The value of preoperative sestamibi
scans in patients with tertiary hyperparathyroidism has
been long debated. In our series, however, the high sensitivity and positive predictive value supported their routine
use.
Conclusions: The incidence of ectopic parathyroid
glands in patients with tertiary hyperparathyroidism may
be higher than previously reported. Fortunately, 99m-Tc
sestamibi scintigraphy had both high positive predictive
value and sensitivity, making them a valuable tool in preoperative localization.
Abstract #349
ONCE MONTHLY RISEDRONATE IS AS
EFFECTIVE AS ONCE DAILY IN PMO
Kelly Ann Loftus, MD, David J. Terris, MD,
Susan Anderson, MD, and Anthony Mulloy, DO
Objective: To determine the incidence of ectopic
parathyroid glands and the value of sestamibi scans in tertiary hyperparathyroidism.
Case Presentation: Between March 2004 and
September 2006, 21 patients with tertiary hyperparathyroidism underwent parathyroidectomy at our institution. A
retrospective chart review was performed to collect epidemiologic data, laboratory results for pre and postoperative calcium and PTH, location of diseased glands and
results of preoperative 99mTc-sestamibi scintigraphy. Of
the 21 patients, 3 were re-operative cases for persistent
hypercalcemia and were each found to have a single diseased gland. Of the 18 patients undergoing first time
surgery, 15 were found to have four gland hyperplasia, 2
patients had single adenomas and 1 patient had a double
adenoma. Nine of the 21 patients had ectopic glands (2 of
these patients had 2 ectopic glands each). Seven of the
ectopic glands were inferior in location and four were
superior. All of the patients underwent preoperative 99m-
Andrea Beth Klemes, DO, FACE,
Louis-Georges Ste-Marie, MD, Jacques P. Brown, MD,
John F. Beary, MD, and Lynn Darbie, MS
Objective: Determine whether oral risedronate once
monthly is as effective as daily resedronate in
Postmenopausal Osteoporosis
Methods: A randomized, multi-center, active-control,
double-blind, sequential escalating dose study in postmenopausal women with low bone mineral density. 370
women were randomized to receive 1 of 4 treatments for 6
months: risedronate once monthly 100mg (n=91), 150mg
(n=88)or 200mg n=88)or 5mg daily(n=103)
Results: The primary efficacy endpoint was the percent change in lumbar spine BMD at 6-months. Both the
150 mg (Least squares [LS] mean 2.99) and 200 mg (LS
mean 3.38) monthly dose groups had a similar increase in
lumbar spine BMD when compared to the 5 mg (LS Mean
3.05) daily group at Month 6, Day 30. The 150 mg dose
was shown to be most similar to 5 mg daily with respect
– 44 –
to percent change in lumbar spine BMD with a LS mean
difference of 0.06%. The lumbar spine BMD changes
between the 150 mg and 200 mg were not statistically different (p=0.520). Within each treatment group, significant
decreases from Baseline in the bone resorption markers,
urine NTX and serum CTX, were seen at the earliest timepoint measured (Month 1 Day 14).
Discussion: In general, decreases in bone turnover
markers (BTMs) for the 150 mg and 200mg monthly treatment groups were similar to those seen in the 5 mg daily
treatment group. In addition, the overall area under the
effect curves (AUECs) at Month 6 for the 150 and 200 mg
monthly groups were comparable to those for the 5 mg
daily group. The 150 mg dose was shown to be most similar to 5 mg daily with respect to percent change in BTMs.
Overall, risedronate was shown to be well tolerated across
all doses, and assessment of clinical laboratory results
showed no clinically relevant differences among the treatment groups.
Conclusions: Dosing risedronate 150 mg once-amonth significantly increased lumbar spine BMD after 6
months of treatment, and was shown to be as efficacious
as the 5mg daily regimen. Unlike some other bisphosphonates, risedronate when dosed at a monthly interval, does
not require the dose to be greater than 30 times the daily
equivalent to provide comparable efficacy.
Abstract #243
CALCIFIED MYOCARDIUM: A REPORT OF
TERTIARY HYPERPARATHYROIDISM
Salma Haque, MD
Objective: To report a case of tertiary hyperparathyroidism with multiple cardiac calcified masses and findings of bone demineralization
Case Presentation: A 51 yo patient with end stage
renal disease (ESRD) and hypertension on routine labs
was found to have a PTH-intact of 3335 pg/ml, calcium of
11mg/dl with ionized calcium of 1.05 mmol/L, and PO4
6.9 mg/dl. Despite multiple combinations of phosphate
binders, her levels remained unresponsive to medical therapy. Physical exam was significant for a blowing 2/6 systolic murmer greatest at the apex with radiation to the
axilla. Radiographic bone survey revealed cortical erosion
of the radial aspect of the 2nd and 3rd phalanges, salt and
pepper skull, and rugger jersey changes of the spine.
Sestamibi scan had prominent uptake in all four poles of
the thyroid lobes. A TEE identified a mobile echo dense
mass consistent with a large accumulation of calcium
attached to the left atrial appendage. The left atrial wall
was calcified with extension to the mitral leaflets and multiple large mobile masses involving the left ventricle and
aorta. The patient underwent total parathyroidectomy, followed by urgent cardiac surgery with resection of the left
atrial masses and mitral valve repair.
Discussion: Persistent hypocalcemia, hyperphosphatemia, and reduced calcitriol lead to deregulated
parathyroid hyperplasia. Tertiary hyperparathyroidism
develops when there is autonomous PTH secretion despite
hypercalcemia. As PTH is inappropriately expressed, calcium and phosphate reabsorption from bone leads to demineralization
and
calciphylaxis
of
arteries.
Pathopneumonic radiographic features include the rugger
jersey sign, alternating sclerotic and lucent bands along
the vertebral bodies (11). Subperiosteal resorption along
the radial aspects of the phalanges and diffuse punctate
osteopenic lesions of the cranial vault described as “salt
and pepper” are also patterns specific for hyperparathyroidism (10). Previous reports of myocardial calcifications
have presented with embolic infarcts, coronary artery disease, and arrythmias with diagnosis often delayed until
autopsy (1,3,4,8). The frequency of cardiac calcification
has been underestimated in the setting of chronic hyperparathyroidism. A previous report of autopsies from 56
patients with renal disease found cardiac calcification in
majority, with 7 cases of fatal atrioventricular block from
calcified conduction pathways (7).
Conclusions: Cardiac calcification from inadequate
control of hyperparathyroidism is more frequent than
assumed and remains underdiagnosed. As patients are
often asymptomatic even in late stages of disease, hyperparathyroidism screening should be initiated prior to
ESRD or nephrologist referral in those with renal insufficiency. A low threshold for suspecting valvular, myocardial, and arterial calcification is necessary in these
patients, as urgent surgery is often required to prevent fatal
complications.
Abstract #307
MONTHLY IBANDRONATE REDUCES BONE
TURNOVER IN BISPHOSPHONATE-NAÏVE
WOMEN
Peter N. Weissman, MD, FACE, Neil Binkley, MD,
Anthony Sebba, MD, Robert Recker, MD, and
Keith Friend, MD
Objective: Assess bone turnover markers (BTMs) in
bisphosphonate-naïve women with postmenopausal osteoporosis given monthly ibandronate.
Methods: 308 patients received monthly oral ibandronate 150 mg. BTM levels were measured immediately
prior to ibandronate doses at baseline and at months 1, 2,
3 and 6. BTM levels were also measured 7 days after ibandronate doses at baseline and month 4. Adverse events
were monitored throughout the study.
– 45 –
Results: Maximum suppression (approx -70%) of the
bone resorption marker sCTX was seen at 7 days after
ibandronate. A cycle of offset and onset in sCTX levels
was seen between the maximum suppression (squares in
figure) and the levels seen before an ibandronate dose,
which decreased over time (diamonds in figure). Bone formation markers P1NP, osteocalcin, and BSAP did not
vary concordantly with the levels of sCTX and declined
gradually over time to -58%, -42%, and -35% of baseline,
respectively, by 6 months. Most AEs (428/578) were considered unrelated or remotely related to study medication.
90 (29.2%) patients had 150 AEs that were possibly or
probably related to study medication. 17 (5.5%) patients
had a total of 23 serious AEs, and 24 (7.8%) patients were
withdrawn from the study due to AEs.
Discussion: The NAÏVE trial was a 6-month study of
150 mg monthly oral ibandronate that examined changes
in levels of the bone turnover markers (BTMs) serum Cterminal cross-linking telopeptide of type I collagen
(sCTX), serum procollagen type 1 N-terminal propeptide
(P1NP), serum osteocalcin, and serum bone-specific alkaline phosphatase (BSAP) in bisphosphonate-naïve women
with postmenopausal osteoporosis. To determine maximum suppression of BTMs, levels were measured at 7
days after the doses of ibandronate at baseline and at
month 4. To determine the progressive suppression of
BTMs, BTM levels were measured immediately prior to
the monthly doses (at trough levels of ibandronate) at
months 1, 2, 3 and 6. The maximum suppression in sCTX
levels seen in this study was at the timepoints 7 days after
ibandronate dosing. The maximum suppression of P1NP,
serum osteocalcin, and BSAP was at the 6-month timepoint.
Conclusions: Bisphosphonate-naïve postmenopausal
women with osteoporosis treated with oral 150 mg oncemonthly ibandronate for 6 months achieved a rapid reduction in bone turnover markers within 7 days which was
sustained over the 6-month study period. Once-monthly
oral ibandronate was generally well tolerated.
Abstract #322
TREATMENT OPTIONS FOR A MAN WITH
PROGRESSIVE DIAPHYSEAL DYSPLASIA (PDD)
Airani Sathananthan, MD, and Bart L. Clarke, MD
Objective: Discuss the clinical manifestations and
treatment options for Progressive Diaphyseal Dysplasia, a
rare genetic bone disease.
Case Presentation: A 34 year old man was referred
for significant pain in his lower extremities and back. He
has a family history of PDD in his grandmother, father,
and four uncles. As a child, a diagnosis of PDD was made
on clinical and radiographic findings. Subsequently, the
R128C TGF-B1 gene mutation was identified. The patient
was tall and slender, with mild spinal scoliosis and a waddling gait. He had a prominent forehead and mild proptosis. He had long extremities with bilateral elbow
contractures. Skeletal x-rays of his knees, hips, femurs,
spine and chest showed marked cortical thickening and
patchy sclerosis. His BMD test revealed a lumbar spine Tscore of +2.7, left total hip T-score of +5.9, and left
femoral neck T-score of +5.4. The patient complained of
variably extreme bone pain, at times requiring narcotics
for pain relief. The patient was treated with prednisone
beginning at 10mg every other day with initial improvement in his symptoms. However, within 3 months, the
patient noted that his symptoms had worsened despite
prednisone and resumed taking an increased dose of
NSAIDs.
Discussion: PDD, an autosomal dominant disorder, is
characterized by limb bone pain, unusual gait, muscle
weakness, and fatigue. Treatment of PDD has been difficult because all approved antiresorptive therapies target
suppression of osteoclast activity. The one available anabolic therapy stimulates osteoblast function.
Glucocorticoids are normally thought harmful to bone due
to their osteoblast suppressive effects, but these have been
used in PDD to suppress inappropriately overactive
osteoblasts in order to decrease new bone formation. No
other agents are available that target osteoblast suppression. Patients in one study remained pain-free while
receiving continuous low-dose steroid therapy on alternate
days. In some patients, cessation of therapy or lower doses
was associated with exacerbation of bone pain and fatigue.
Glucocorticoids adversely affect bone metabolism in multiple ways, primarily by decreasing bone formation during
chronic use, and stimulating bone resorption transiently
with initiation of therapy. PDD is one example of bone
disease that may benefit from glucocorticoid therapy
because of the osteoblast-activating effect of the constitutively active TGF- B1 in skeletal matrix.
Conclusions: Although a rare disease, clinicians
should be aware of PDD because of its unusual clinical
manifestations and treatment options. Although glucocorticoids are not typically recommended for treatment of any
metabolic bone disease, alternate day prednisone may help
control pain symptoms in some patients with PDD.
– 46 –
Abstract #218
osteosclerosis and increased bone density. Although
unique, it is well described in the literature and stresses the
importance of considering osteopetrosis as a differential
diagnosis in the patient with sclerotic bone disease.
OSTEOPETROSIS (OP): A RARE HEREDITARY
BONE DISORDER
Bhavin Rajendrabhai Shastri, MD, and
Joseph Shaker, MD
Abstract #288
Objective: To educate the physicians about the presentation and management of autosomal dominant
osteopetrosis and review of literature.
Case Presentation: A 18 y/o white male presented
with a h/o left hip pain. Initially the pain occurred only
during exercise. Eventually however, the pain worsened
and was noticed even at rest. The patient’s PMH was significant for few dental caries. The only medication he was
taking was an NSAID. His examination was unremarkable
except for some limitation in the movement of left hip.
The x-ray of left hip showed diffuse increased bone density with joint space narrowing. A limited bone survey
showed generalized dense osteosclerosis of the axial
skeleton and bone-within-bone formation in the tibia. A
DXA scan revealed Z-scores of 9.3-12.6. On laboratory
evaluation, the fluoride level was normal. The CPK-BB
level, a marker of osteoclast activity was severely elevated. These findings were suggestive of autosomal dominant, adult onset OP. The patient was treated with a high
dose calcitriol regimen and dietary calcium restriction.
The therapeutic goal was spot urine Ca++ to Cr ratio of
0.2-0.3. At the time of his last visit, he was on calcitriol 3mcg tid with a Ca++/Cr ratio of 0.21.
Discussion: OP represents a spectrum of clinical variants with heterogeneous genetic defects resulting in osteoclast dysfunction. It was first recognized in 1904 by
German radiologist Heinrich Ernst Albers-schonberg.
Three main types of OP have been identified based on
inheritance, age of onset, severity and secondary clinical
features: AR (Autosomal recessive) infantile malignant
OP, AR intermediate mild osteopetrosis, and AD adult
onset benign osteopetrosis (ADO). Unlike the other two
types, ADO has delayed phenotype (adult onset) and presents mainly with mild symptoms and benign prognosis.
Due to its rarity, there is limited data to assist us in the
management but trials showed that high dose calcitriol has
been associated with improved outcomes. Long-term
administrations of human interferon gamma, steroid and
parathyroid hormone also have been used with varying
degree of response. Bone marrow transplant is considered
to be an effective, somewhat curative treatment for severe
forms of OP. Proper hydration, fall precaution, dental
care, management of hematologic sequelae and low calcium intake are the other common supportive measures.
Conclusions: OP is an extraordinarily rare hereditary
bone disorder characterized by diffuse, symmetric
IBANDRONATE QUARTERLY INJECTION OR
MONTHLY TABLETS IMPROVED GI
TOLERABILITY
Keith E. Friend, MD, Mark Martens, MD, and
William Koltun, MD
Objective: Evaluate GI tolerability of monthly oral
and quarterly IV ibandronate in women with GI intolerance to weekly bisphosphonates.
Methods: Postmenopausal women with osteoporosis
or osteopenia received oral or IV ibandronate and could
switch therapies once because of adverse events. At
months 1, 4, 7, and 10; patients completed a GI
Experience Survey to assess changes from baseline in
severity or frequency of GI symptoms.
Results: Of the 542 women in the intent-to-treat population, 73% (396) chose IV ibandronate and 27% (146)
chose the oral regimen. An interim analysis (as of April
2006) showed that GI tolerance scores improved from
baseline levels at 1 month and 4 months after beginning
either oral or IV ibandronate therapy (Figure). By 6
months, 87.7% (128) of oral patients and 94.9% (376) of
IV patients were compliant with their chosen therapy.
During the same timeframe, 9.2% (50) patients withdrew
because of any adverse event (oral, 12.3% [18 of 146]; IV,
8.1% [32 of 396]). There were 26 patients who switched
administration route, 11 switched to IV ibandronate due to
GI intolerance, while 15 switched to oral therapy for various reasons, including influenza-like symptoms (n=2) and
injection-site reactions (n=3).
Discussion: PRIOR was 1-year, open-label, multicenter study in women with postmenopausal osteoporosis
or osteopenia. Eligible women had discontinued daily or
weekly alendronate or risedronate therapy because of perceived or actual GI intolerance at least 3 months before
enrolling in the study. Women with GI intolerance to daily
or weekly bisphosphonates were more likely to select
ibandronate therapy administered as a quarterly IV injection than as a monthly tablet. Regardless of the original
choice of administration route, few patients chose to
switch administration route and few women withdrew
from the study because of adverse events.
Conclusions: IV ibandronate was the preferred treatment option in women who had stopped weekly oral bisphosphonate treatment due to GI intolerance. Ibandronate
therapy was associated with improved GI tolerability in
– 47 –
patients with GI intolerance to weekly bisphosphonates.
The majority of patients receiving once-monthly oral ibandronate were adherent to therapy at 6 months.
Abstract #237
EVALUATION OF SECONDARY CAUSES OF
OSTEOPOROSIS IN A PRIMARY CARE SETTING
Abstract #315
Abid Yaqub, MBBS, Eyad Hamoudeh, MD, and
Bruce Chertow, MD, FACE, FACP
PHARMACOKINETICS OF RISEDRONATE
FOLLOWING DAILY AND MONTHLY DOSING
REGIMENS
Andreas Grauer, MD, PhD, Gary A Thompson, PhD,
Darrell A Russell, BS, Dan J. Schnell, PhD, and
Lu Amy Sun, MD, PhD
Objective: The objective of this study was to assess
the pharmacokinetics of risedronate following daily and
monthly dosing regimens
Methods: This was a randomized, multiple oral dose,
parallel group study conducted in 58 healthy postmenopausal women to assess risedronate pharmacokinetics. Subjects were orally administered 150 mg/month (75
mg on 2 consecutive days per month) or 5 mg/day risedronate for four months.
Results: Blood and urine samples were collected for
96 hours and 28 days, respectively following the first dose
of Month 1 and 4, with additional urine samples collected
at the end of Month 2 and 3. Serum was analyzed via
LC/MS/MS and urine was analyzed using an ELISA
assay. Serum concentration and urinary excretion
rate–time data were simultaneously analyzed using nonlinear regression. Of the 58 subjects enrolled, 51 completed the study. Overall, risedronate was shown to be well
tolerated in both dose groups. Risedronate pharmacokinetics are summarized in Table 1.
Discussion: Results from this study indicate that
steady-state was achieved during the first month for both
daily and monthly dosing. At steady-state (Month 4),
Cavg was the same for both daily and monthly dosing regimens. As expected, Cmax was higher (approximately 11fold) while Cmin was lower (approximately 65%) for
monthly dosing. Due to the longer dosing interval, accumulation upon multiple dosing was significantly lower for
monthly (1.07) versus daily dosing (1.53). No dose-related differences for renal (CLr) and oral (Clo) clearance or
for the percentage of dose recovered in urine (AEτ)
were observed.
Conclusions: Overall, these results indicate that the
pharmacokinetics of risedronate are linear from 5 mg/day
to 75 mg administered two consecutive days per month.
Objective: To evaluate the clinical and laboratory
work-up for secondary causes of bone loss in a primary
care setting.
Methods: This was a retrospective chart review study.
We reviewed the medical records of 100 patients with
either osteoporosis (T<2.5) or advanced osteopenia (T<2.0) presenting to a university based primary care clinic.
Patients with chronic kidney disease or a history of organ
transplant were excluded.
Results: Age at menopause was ascertained in 44% of
female patients. Only 2% were asked specifically about
symptoms of malabsorption, whereas a history of malignancy or chemo/radiotherapy was obtained from 24%
patients. 50% patients were asked about a history of thyroid disease and 18% about a history of liver disease.
Serum calcium and thyroid function tests were evaluated
in 100% of patients. Vitamin D status was assessed in only
1 patient while none of the patients studied had their 24hour urine tested for calcium excretion. Serum PTH was
tested in 7% and serum phosphorus in 10% of patients.
50% of male patients had their testosterone levels
assessed. Although serum creatinine was checked in virtually all of the patients, only 1% had a formal estimation of
their creatinine clearance or GFR.
Discussion: Osteoporosis is the most common bone
disease in US and a major risk factor for fractures, which
can lead to considerable morbidity and mortality. While
the majority of cases of bone loss are a result of idiopathic/postmenopausal/senile changes, several secondary
causes such as Vit D deficiency, hypogonadism, primary
and secondary hyperparathyroidism, hyperthyroidism,
malabsorption, and idiopathic hypercalciuria also exist.
These can be effectively distinguished and managed by
appropriate clinical and laboratory evaluation. In the light
of prevalence of these secondary causes and benefits of
their correction, prompt recognition and treatment is
essential. Since a vast majority of patients with osteoporosis and osteopenia are managed by their primary care
providers, we designed this study to determine whether
appropriate clinical and laboratory evaluation was performed to look for possible secondary causes of bone loss.
– 48 –
The results of our study show remarkably inadequate evaluation of secondary causes of bone loss in a primary care
setting. We found that appropriate clinical and laboratory
workup was not carried out in an overwhelming majority
of patients in the patients studied.
Conclusions: The evaluation of secondary causes of
bone loss was markedly inadequate in our study population. Since most of the patients with osteoporosis and
osteopenia are managed in the primary care setting, there
is a strong need for consensus guidelines and recommendations from the endocrine organizations to advise the primary care physicians on appropriate workup for secondary
causes of bone loss in these patients.
Abstract #249
ANALYSIS OF SURGICAL CRITERIA IN
ASYMPTOMATIC PRIMARY
HYPERPARATHYROIDISM
Giorgio Borretta, MD, Francesco Tassone, MD,
Laura Gianotti, MD, Flora Cesario, MD, and
Anna Pia, MD
Objective: to evaluate in a series of consecutive
patients with aPHPT older than 50 yrs, those who meet or
fail to meet the NIH criteria
Case Presentation: 93 out of 110 patients with
aPHPT were older than 50 years and represented the study
group (age, mean ± SD= 66.5 ± 8.4 yrs; Female/male=
71/22; PTH=212.7±296.0 pg/ml; serum calcium = 11.1 ±
0.90 mg/dl). RESULTS: 30,1% of these patients (28/93)
did not meet the criteria for surgery. The whole group of
patients was divided according to age in group A
(50<age<60 yrs), group B (60<age<70 yrs) and group C
(>70 yrs). Patients that did not meet the criteria for surgery
were 11/26 (43.3 %) , 11/37 (29.7%), 6/30 (20.0 %) in
group A, B and C, respectively. The serum calcium criterion was met by 38.5 % in group A, 30.8 % in B and 33.3
% in C; hypercalciuria was found in 25 % in group A, 12.5
% in B and C; reduced Ccr was present in 16.7% in group
A, 21.2 % in B and 56.0% in C (p= 0.022 A vs C); T-score
lower than -2.5 DS was found in 50.0% in group A, 68.4
% in B and 68.8 % in C.
Discussion: the number of patients with aPHPT that
meet the NIH criteria for surgery increases with advancing
age and thus surgery should be performed in most patients
older than 70 yrs. This is due to the increasing number of
patients with reduced BMD and impaired renal function.
Conclusions: In conclusion, on the basis of our experience, we believe that in aPHPT, the age criterion might
be reconsidered in order to extend surgical indications in
aging.
Abstract #210
UNDIAGNOSED LOW BONE MASS IN AN
ELDERLY PODIATRIC POPULATION: A PILOT
STUDY
Marisha Newton, MD, Juanita A. Archer, MD,
Michangelo Scruggs, DPM, Hiba Al-Dabagh, MD, and
Errol Lloyd, MD
Objective: To determine if evidence of osteopenia
and/or fractures (frxs)on foot x-rays are suggestive of
undiagnosed osteoporosis.
Methods: Ninety subjects, ages 50 and older with foot
x-rays done at Howard University Hospital between 2003
and 2005 were randomly selected. X-rays were reviewed
for evidence of osteopenia and/or frxs. Risk factors for
osteoporosis and DXA scan data were obtained.
Results: Eighty-five subjects (94.4%) were African
American; 50% were women; mean (mn) age 65.0 yrs. Xray reports revealed 53 (58.9%) subjects with osteopenia
and/or frxs. Twenty were excluded. Of the remaining 33
subjects, 22 (66.7 %) had osteopenia on x-ray (mn age
68.2 +11.8); 3 (9.1%) had frxs (mn age 61.7 +15.1), and 8
(24.2%) had both osteopenia and frxs (mn age 64.13+
12.0). There were a total of 11 subjects (33.3%) with frxs
(mn age 63.5 + 12.2). Nine subjects (27.3 %) had DXA
scans; four (44.4%) of the nine had fragility frxs. Two
(22.2%) had scan evidence of osteoporosis, 6 (66.7%) had
osteopenia, 1 was normal. Eight subjects (88.9%) had at
least one major risk factor.
Discussion: Osteoporosis is a major cause of frxs and
disability. In the USA, DXA is usually used to diagnose
osteoporosis. Although risk factors such as older age or
postmenopausal status, prior frx, small size, frx in a first
degree relative, current smoking and prolonged glucocorticoid use may suggest the diagnosis, frequently they are
not obtained. Many elderly people have podiatric problems that require foot x-rays however, suggestions of low
bone mass may be ignored on those x-rays. X-ray indices
for the proximal femur, calcaneum and hand are used by
radiologists to evaluate low bone mass. These indices are
complex and have poor inter-observer reliability. This
pilot study suggests that evidence of osteopenia and/or
frxs on foot x-rays in subjects age 50 and older without
active malignancy, infiltrative or genetic bone disease,
renal or hepatic disease or high impact trauma is predictive
of osteopenia in the spine or hips. Further, in this study,
33.3% and 11.1% of the subjects had unsuspected and
undiagnosed osteopenia and osteoporosis, respectively.
Limitations of the study include the small number of subjects and possible bias of the radiologists.
– 49 –
Conclusions: This pilot study strongly suggests that
in an elderly podiatric population evidence of osteopenia
or frxs on foot x-rays are highly suggestive of spine or hip
low bone mass. Since osteopenia is associated with more
than 50% of the fragility fractures in the USA, and African
Americans have the highest post fracture morbidity and
mortality, osteopenia or frxs on foot x-rays should not be
overlooked. Evidence of thin bones at any site demands
further evaluation and therapy.
persistence with their osteoporosis therapy. Improving
persistence with osteoporosis medications can lead to
increased bone mineral density and reduced risk of fractures.
Conclusions: The early postlaunch results of this
study suggest that, at 9 months, women in the monthly
ibandronate cohort are more persistent with their osteoporosis therapy compared to women in the weekly BP
cohort. Long-term follow-up is ongoing.
Abstract #286
Abstract #187
PERSISTENCE IS BETTER WITH MONTHLY
IBANDRONATE VS WEEKLY
BISPHOSPHONATES
HYPERCALCEMIA CAUSED BY ACTIVE
CROHN’S DISEASE
Adriana Gabriela Ioachimescu, MD, PhD, and
Angelo Licata, MD, PhD
E. Michael Lewiecki, MD, Richard Derman, MD,
Carolyn Harley, PhD, Charles Barr, MD, and
Sara Poston, PharmD
Objective: We examined 9-month persistence in a
cohort of women newly prescribed either monthly or
weekly bisphosphonate (BP) therapy.
Methods: Female patients 45 years and older were
identified using a retrospective claims database accessed
through i3 Innovus. Eligible patients filled a new prescription for a weekly BP or monthly ibandronate beginning
April 2005. Persistence was defined as no refill gaps
exceeding specified grace periods.
Results: Longitudinal data were obtained in this 9month analysis of 967 women prescribed monthly ibandronate and 8662 women prescribed weekly BPs. Of
patients receiving monthly ibandronate, 40.7% were
osteoporosis medication-naïve, 13.1% were BP-naïve, and
46.1% had switched from another BP dosing regimen. The
unadjusted 9-month persistence rates for monthly and
weekly BP users were 47.7% and 35.4%, respectively
(P<0.0001). Cox proportional hazard analysis was used to
control for the effects of potential confounding factors
such as age, copay, and comorbidities. Monthly users were
38% more likely to persist with therapy versus weekly
users after adjusting for confounding factors (hazard
ratio=0.620, 95% CI: 0.563-0.683, P<0.0001).
Discussion: Managed care claim databases are useful
for evaluating patient persistence with osteoporosis treatments because they provide access to real-world information, enable noninvasive determination of persistence, and
allow data collection from large patient populations over
long periods of time. It has been suggested that a oncemonthly BP may lead to improved persistence compared
to a weekly BP. This analysis of persistence at 9 months
finds that more patients receiving monthly ibandronate are
persistent compared to weekly BP users. Monthly ibandronate users also demonstrate an increased likelihood of
Objective: We present a rare case of Crohn’s disease(CD) with 1,25-(OH)2 vitamin D-mediated hypercalcemia and a review of the literature
Case Presentation: A 50 year old man with longstanding CD was found hypercalcemic on admission for
takedown ileostomy. He reported fatigue and constipation.
On exam: surgical abdominal scars. Ionized calcium was
1.53 mmol/l (1.08-1.30), total calcium 11.5 mg/dl (8.510.5), phosphate 2.1 mg/dl, magnesium 2.1 mg/dl and creatinine 1.1 mg/dl. The iPTH and PTHrP were
undetectable. Perioperatively he received parenteral
hydrocortisone for 3 days. Upon discharge calcium was
9.3 mg/dl and 1,25-(OH)2-D 10.5 pg/ml (25.1-55.1). No
glucocorticoids were prescribed. A month later, calcium
rose again (11.6 mg/dl). Other labs at the time: albumin
4.2 mg/dl, phosphate 4.3 mg/dl, iPTH<4 pg/ml, 1,25(OH)2-D 42.6 pg/ml, 25-hydroxyvitamin D 37.4 ng/ml
(10-60), urinary calcium 580 mg/day, and ACE level 106
U/l (3-48). A chest CT ruled out sarcoidosis. After operative histopathology report reviewed, infliximab was prescribed. Serum and urinary calcium normalized,
1,25-(OH)2-D decreased to 14.1 pg/ml and ACE level to
71 U/l. Over the past year he required multiple immunossupressants for arthritis and calcium has been normal.
Discussion: Although increased 1-alpha-hydroxylase
expression in the colonic mucosa of patients with CD has
been demonstrated, hypercalcemia was rarely reported.
Our case of hypercalcemia caused by active CD is supported by the histopathology exam of the small bowel
mucosa and the resolution of hypercalcemia with
immunosuppressants on two different occasions. At the
time of the hypercalcemia, iPTH and PTHrP were suppressed and 25-hydroxyvitamin D level was normal. This
is the 4th reported case of hypercalcemia mediated by
excess of 1,25-(OH)2-D in CD. Similarly to our case,
1,25-(OH)2-D level correlated with serum and urinary cal-
– 50 –
cium, and immunosuppressive therapy caused normalization of calcium levels within few days. In one of the previously published cases the ACE level was measured and
found high, similarly to our case. Although small studies
reported low or normal ACE levels in CD, there is no data
regarding ACE level in patients with CD and hypercalcemia. Our case’s particularity is the normal level of 1,25(OH)2-D at the time of the hypercalcemia. However, this
was inappropriate for the high calcium level indicating the
increased production of 1,25-(OH)2-D within the granulomas.
Conclusions: Active Crohn’s disease should be considered among the causes of 1,25-dihydroxyvitamin Dmediated hypercalcemia. The calcium response to
immunossupressive therapy occurs within few days.
Abstract #114
IMPLICATIONS OF HRPT2 MUTATIONS IN
FAMILIAL ISOLATED
HYPERPARATHYROIDISM
John T. Chow, MD, Lori A. Erickson, MD,
Clive S. Grant, MD, and Robert A. Wermers, MD
(FHH), or hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Mutations typical of each of these conditions have
been reported in patients with FIH. The identification of
mutations in HRPT2 is particularly important in the genetic counseling of FIH kindreds. Special consideration must
be given to screening for components of HPT-JT syndrome, including parathyroid carcinoma, fibro-osseous
jaw tumors, renal tumors, and uterine tumors. The recent
link between HRPT2 and sporadic parathyroid carcinoma
further highlights the importance of heightened cancer
surveillance. Proliferative activity, as evaluated with Ki67
immunostaining, has been shown to be useful in differentiating parathyroid adenomas from carcinomas; such testing can be a useful tool in FIH.
Conclusions: FIH can rarely be associated with mutations in HRPT2, the gene responsible for HPT-JT syndrome. Due to the association of HRPT2 mutations and
parathyroid carcinoma, detailed analysis of families carrying germline mutations should be performed to elucidate
the resultant phenotype. Histopathologic evaluation of
parathyroid tissue is important for the classification of
parathyroid pathology and to rule out parathyroid
carcinoma.
Abstract #246
Objective: To review the clinical implications of
HRPT2 mutations in familial isolated hyperparathyroidism.
Case Presentation: A 32-year-old man with history
of primary hyperparathyroidism (PHPT) requiring 2 previous neck explorations was evaluated for recurrent
asymptomatic hypercalcemia. His family history was significant for PHPT in at least 3 generations. Laboratory
evaluation was consistent with PHPT, with localization to
an abnormal left superior parathyroid gland on imaging.
Genetic testing for CASR and MEN1 gene mutations was
unremarkable. Testing for HRPT2 revealed a nonsense
mutation at codon 53, with designation E53X. Surgical
excision of the left superior parathyroid gland was performed, with pathology revealing hyperplasia. Ki67
immunostaining using the MIB-1 monoclonal antibody
did not show increased proliferative activity. Pathologic
review was also performed in 3 family members (parathyroid adenomas in 2, asymmetric hyperplasia in 1), with
immunostaining showing no significant proliferative
activity. On further testing, 3 family members, in addition
to our patient, had normal panoramic jaw radiographs;
none had any history of renal lesions.
Discussion: Familial isolated hyperparathyroidism
(FIH) encompasses a heterogenous group of disorders,
affecting an estimated 1% of patients with primary hyperparathyroidism. In many instances, FIH can be found as
the incomplete expression of multiple endocrine neoplasia
type 1 (MEN-1), familial hypocalciuric hypercalcemia
OSTEOPOROSIS AWARENESS PROTOCOL FOR
PATIENTS WITH FRAGILITY FRACTURES
Hiba Al-Dabagh, MBBS, Juanita Archer, MD,
Marisha Newton, MD, John Kwagyan, PhD, and
Gail Nunlee-Bland, MD
Objective: Develop and implement a protocol that
improves recognition of osteoporosis in patients with
fragility fractures (frag. frxs).
Methods: Our awareness protocol included: six meetings with Emergency Department (ED) staff, the orthopedic chairman and residents; a reminder poster was placed
in ED triage and orthopedic residents’ rooms; distributions
of pocket sized posters to residents; and verbal reminders
to orthopedics residents.
Results: From June 2005 to December 2005, a total of
291 patients with fractures were admitted to Howard
University Hospital. Fragility fractures were evident in 32
of the 291 patients (11%). All of these patients were
admitted to the hospital from the ED. Of the patients with
frag. frxs, 81% were African American; 62.5% were
female with the mean age of 73.3 years (SD± 15.8). The
orthopedists requested an endocrine consult for eight
patients whose characteristics did not differ from those of
their cohorts. Osteoporosis was diagnosed in 7 of these
patients (22% of the total patients with frag. fxs). This is a
significant increase (13%, p= 0.02) of the diagnostic rate
– 51 –
at this institution. Bisphosphonates were prescribed for
three of the 32 patients (9%) prior to hospital discharge.
Discussion: Osteoporosis is under-diagnosed and
under-treated in African American patients who have the
highest morbidity and mortality after a fracture. In the
USA, there is often a failure to diagnose osteoporosis even
after patients have a frag. frxs. Use of this practical awareness protocol helped to significantly increase the frequency of diagnosing osteoporosis in patients with frag fxs.
Several studies present other more complex protocols
however review of the literature does not reveal other
intervention strategies developed to improve the diagnosis
of osteoporosis in a majority African American population. Since most patients with frag. frxs are initially evaluated by the ED staff and the orthopedists, this study
successfully targeted these two groups of clinicians. It is
of concern that although therapy was recommended by the
endocrinologists at the time of diagnosis, this protocol
failed to show an increase in the pre-discharge treatment
rate. If combined with an institutional pre-discharge protocol for education and therapy, this study may establish
the basis for improved rates of diagnosis and therapy in a
larger hospital population with osteoporosis.
Conclusions: In this pilot study, we were able to
develop and implement a practical, easy to execute awareness protocol that significantly improved the detection of
osteoporosis in African American patients with frag fxs.
Also this study suggests that when patients with frag. frxs.
present to the ED, cooperation between the ED, orthopedic and endocrine clinicians may result in a significant
improvement of the osteoporosis diagnostic rate.
P=.003) (Figure). An additional increase in total hip BMD
(0.3%) was seen in the 150mg cohort; total hip BMD values decreased by 0.1% in the 100mg cohort. Both monthly regimens were well tolerated, with no meaningful
differences in the overall incidence of adverse events or
treatment-related adverse events. The overall frequency of
clinical osteoporotic fractures in the LTE was low (3.6%
and 2.2% in the 100mg and 150mg cohorts, respectively).
Rates of withdrawal due to AEs were also low (1.7% and
1.9% in the 100mg and 150mg cohorts, respectively). No
cases of osteonecrosis of the jaw were reported.
Discussion: Results from the 2-year MOBILE study
demonstrated that patients who completed the study
achieved significant improvements in BMD. A 3-year
extension study was initiated to further explore the efficacy and safety of continued 100mg and 150mg monthly
ibandronate therapy. Data from the first year of the
MOBILE LTE provides evidence that long term monthly
ibandronate treatment provides continuous improvements
in efficacy. The adverse event profile during the LTE confirms the good tolerability of monthly ibandronate seen in
the core MOBILE study.
Conclusions: Further improvements in the lumbar
spine BMD gains achieved during the 2-year MOBILE
study treatment period were observed during the first year
of the extension study. BMD gains at the total hip were
essentially maintained after an additional year of treatment.
Abstract #319
GI TOLERABILITY IN WOMEN WHO CHANGED
BISPHOSPHONATES TO MONTHLY
IBANDRONATE
Abstract #289
MONTHLY IBANDRONATE: EFFICACY DURING
THE FIRST YEAR OF THE MOBILE LTE STUDY
Michael A. Bolognese, MD, FACE,
Ronald D. Emkey, MD, Farhad Sederati, PhD, and
Paul D. Miller, MD, FACP
Objective: Assess efficacy of continued 100mg and
150mg monthly ibandronate therapy during the first year
of the MOBILE extension study.
Methods: Patients from the 2-year MOBILE study on
100mg or 150mg monthly ibandronate received the same
dose in the long-term extension [LTE]; those on 2.5mg
daily or 50+50mg monthly were re-randomized to 100mg
or 150mg. BMD changes during the core MOBILE trial
were compared to those after 1 year of the LTE.
Results: Mean lumbar spine BMD values observed
during the 2-year MOBILE study were further increased
during the first year of the LTE by 1.1% (100mg cohort,
n=347, P<.0001) and 1.5% (150mg cohort, n=346,
Keith E. Friend, MD, Neil Binkley, MD,
Sydney Lou Bonnick, MD, Felicia Cosman, MD, and
Stuart Silverman, MD
Objective: Assess changes in GI tolerability with
monthly oral ibandronate in patients who switched from
once-weekly bisphosphonates.
Methods: Postmenopausal women taking weekly bisphosphonates for 3 months or more switched from their
current weekly bisphosphonate to monthly ibandronate.
Patients’ GI tolerability was assessed based on their
response to the Osteoporosis Patient Satisfaction
Questionnaire (OPSAT-Q) at baseline and Month 6.
Results: Improvement in the bother or frequency of
heartburn or acid reflux and of other stomach upset at 6
months was reported by more than 60% and 70%, respectively, of the 669 patients who reported GI symptoms at
baseline (Table). Patients who reported stomach upset
within 48 hours of taking their previous weekly bisphos-
– 52 –
phonate were 2.98 times more likely to be more satisfied
with once-monthly ibandronate than with their previous
bisphosphonate compared with participants who reported
no stomach upset. The proportion of patients with at least
one adverse event (AE) was 41%. 40 patients (2.4%) had
a fracture-related AE. 11.3% percent of patients had possible or probable drug-related AEs. The overall incidence
of serious AEs was 3.2%. None of the serious AEs were
judged to be study drug-related.
Discussion: The CURRENT trial was a prospective,
open-label, multicenter (144 study centers), 6-month study
of once-monthly oral ibandronate in patients currently taking weekly bisphosphonates. The analysis reported here
assessed GI tolerability through analysis of patients who
reported GI symptoms at baseline in the side effects
domain of OPSAT-Q. The OPSAT-Q is a validated instrument composed of the side effects domain and 3 additional domains: convenience, satisfaction, and quality of life.
At baseline, 26.1% (438/1678) of patients reported heartburn or acid reflux symptoms and 13.8% (231/1678) of
patients reported other stomach upset symptoms. Most of
these patients experienced improvement in GI symptoms
after 6 months of monthly ibandronate.
Conclusions: A majority of patients who experienced
GI tolerability issues with weekly bisphosphonates reported improvements in GI symptoms after receiving oncemonthly ibandronate in an open-label fashion for 6
months. Once-monthly ibandronate 150 mg was generally
well tolerated in this study.
Abstract #393
CAN PAMIDRONATE PREVENT HUNGRY BONE
SYNDROME AFTER PARATHYROIDECTOMY?
to undergo parathyroidectomy. Parathyroid scan revealed
an adenoma in the posterior left lower pole of the thyroid
gland. An adenoma weighing 419 mg was excised. Intraoperative iPTH values decreased from 2332 pg/ml to 31
pg/ml (reference range 10-69 pg/ml). Laboratory values
are shown in table 1.
Discussion: Hungry bone syndrome is a consequence
of parathyroidectomy. It can present with severe hypocalcemia caused by a sudden fall in PTH release. Features
predictive of development of the hungry bone syndrome
are high serum alkaline phosphatase and PTH concentrations as well as elevated BUN, large size of adenoma and
advanced age. Bisphosphanates inhibit osteoclast-mediated bone resorption. Bone formation may be also inhibited
by products from the resorbed matrix and from osteoclasts
themselves. Thus, theoretically, administration of bisphosphonates can lead to reduced bone formation and prevention of hungry bone syndrome. First report describing the
use of bisphosphonates to prevent hungry bone syndrome
involved a 62-year-old woman with severe hyperparathyroidism who received 60 mg of pamidronate prior to
parathyroidectomy. Post-operative calcium level normalized, there was no acute hypocalcemia. Another study retrospectively reviewed medical records to determine the
effect of pre-operatively administered bisphosphonates on
serum calcium levels following parathyroidectomy. Out of
14 patients who did not have hungry bone syndrome 6 had
received bisphosphonates prior to surgery.
Conclusions: Our patient had several risk factors for
the development of hungry bone syndrome. However, she
was able to avoid this complication. As suggested by our
case and several other cases in the literature, bisphosphonates may be beneficial in preventing hungry bone syndrome. Prospective randomized studies are needed to
resolve this issue definitively.
Yuriy Gurevich, DO, and Leonid Poretsky, MD
Abstract #284
Objective: To describe a case of a possible prevention
of hungry bone syndrome with preoperative administration of pamidronate.
Case Presentation: A 73-year-old female was hospitalized with a serum calcium of 14.5 mg/dl. Diagnosis of
primary hyperparathyroidism had been made six years
prior to presentation. Throughout this time her calcium
and iPTH ranged 10.2 – 15 mg/dl and 56.2 – 2000 pg/ml,
respectively. She repeatedly refused parathyroidectomy.
Physical examination was unremarkable, except for a
heart rate of 57 beats per minute. Treatment with 0.9%
NaCl and diuresis were initiated. 90 mg of intravenous
pamidronate was administered during hospitalization.
Patient was discharged with serum calcium concentration
of 11.2 mg/dl. Two weeks later she was readmitted with
serum calcium of 14.6 mg/dl. 90 mg of pamidronate was
again administered intravenously. At this point she agreed
ACINAR CELL CARCINOMA AND HYPERPARATHYROIDISM
Ahmad Ali, MD, Gail Nunlee-Bland, MD,
Maria Nwokike, MD, Wolali Odonkor, MD, and
Mariama Semega-Janneh, MD
Objective: To report on a women with acinar cell carcinoma who developed hyperparathyroidism and hypercalcemia.
Case Presentation: A 46-year-old African American
woman presented with a 2 month history of intermittent
6/10 epigastric pain radiating to the back, with no aggravating or relieving factors. She admitted weakness, weight
loss, dark urine, pruritis and jaundice for 4 weeks.
Physical exam revealed normal vital signs, icteric sclera,
– 53 –
mild epigastric tenderness and hepatomegaly. Admission
labs were significant for total bilirubin 16.8 (0.2-1.2
mg/dL), alkaline phosphatase 612 (30-165 mU/mL), PTH
106 (10-69 pg/mL), corrected calcium 12.4 (8.5-10.6
mg/dL),phosphorus 2.9 (2.5-4.5 mg/dL), 25-hydroxy vitamin D 8 (20-100 ng/mL) and 1, 25-dihydroxy vitamin D
75 (6-62 pg/mL). Thyroid function tests and cortisol level
were normal. Abdominal CT showed significant dilatation
of the pancreatic and common bile ducts. Exploratory
laparotomy with excision of a periampullary mass was
done. Histology report showed moderately differentiated
to undifferentiated (1.2 x 1 cm) acinar cell carcinoma with
tumor invasion of the duodenal muscular wall. A few days
following surgery PTH levels decreased from 106 to 94
then to 67.
Discussion: There is no case report or any paper published under such topic. The available data suggests that
the hypercalcemia in our patient may have been caused by
PTH secretion by the acinar cell tumor, since PTH and calcium decreased a few days after removing acinar cancer
without any other treatment for hypercalcemia. To our
knowledge, this is the first case report of hyperparathyroidism from acinar cell carcinoma.
Conclusions: Acinar cell carcinoma may cause
hyperparathyroidism and hypercalcemia.
Discussion: We treated him with 2,000 International
Units of vitamin D3 and 1200-1500 mg of calcium daily.
He has seen a gastroenterologist for recommendations of a
gluten free diet. The plan is to normalize calcium and vitamin D levels and then repeat a DXA scan. We expect a
marked improvement in bone mass as the bone mineralizes. Celiac disease or gluten-sensitive enteropathy is an
autoimmune disorder that primarily occurs in whites of
Northern European ancestry. Epidemiological studies
have shown a prevalence of 1:300. In response to the
gliadin component of gluten, genetically predisposed people produce autoantibodies to the enzyme tissue transglutaminase. This in turn stimulates inflammatory cells. The
malabsorption resulting from celiac disease can cause iron
deficiency anemia, vitamin D deficiency and metabolic
bone diseases including osteoporosis, secondary hyperparathyroidism and osteomalacia. It is frequently associated with other autoimmune disorders such as type 1
diabetes mellitus, thyroid disease and liver disease.
Conclusions: This patient presented with classic
signs of celiac disease, but many patients do not have any
gastrointestinal complaints. Clinicians need to have a high
index of suspicion for celiac disease in patients with low
bone mass and/or vitamin D deficiency.
Abstract #297
Abstract #222
IV IBANDRONATE INJECTIONS
DEMONSTRATE FAVORABLE RENAL
TOLERABILITY
A WEAK STOMACH EQUALS WEAK BONES?
Laura Anne Graeff Armas, MD, and
Andjela Drincic, MD
E. Michael Lewiecki, MD, Paul Miller, MD,
Mone Zaidi, MD, and Keith Friend, MD
Objective: To raise awareness of celiac disease as a
risk factor for vitamin D deficiency and low bone mass.
Case Presentation: A 59 year old male was referred
to endocrine with a high alkaline phosphatase of 380 U/L
and low calcium of 7.6 mg/dL. His history revealed several years of diarrhea and anemia of unknown cause. He had
lost about 40 pounds in the past 8 months. Physical exam
revealed a slim male with some wasting of his facial muscles. He had no tenderness over his tibia or sternum. His
workup included a bone specific alkaline phosphatase of
80.1 g/L, parathyroid hormone of 136 pg/mL, hemoglobin
of 13.2 g/dL, calcium of 8.8 mg/dL, 25-hydroxyvitamin D
of 16 ng/mL, and 1,25-dihydroxyvitamin D of 71 pg/mL.
Tissue transglutaminase antibody was elevated at 26.7 AU
and stool fatty acids were increased. DXA scan revealed a
hip T-score of -2.41 standard deviations below the mean.
The spine T-score was -4.41 standard deviations below the
mean. A small bowel biopsy had villous blunting and focal
areas of completely flat epithelium. The crypts were elongated with hyperplastic changes suggestive of celiac disease.
Objective: Evaluate the renal safety profile of intermittent IV ibandronate in women with postmenopausal
osteoporosis (PMO).
Methods: Renal safety data from 4 IV ibandronate trials (0.25-3mg every 2-3 months) were pooled and compared to oral ibandronate or placebo. Patients were
followed for 3 or fewer years. Patients with severe renal
impairment were excluded. Cr clearance changes were
calculated using the Cockroft-Gault formula.
Results: 3295 patients received IV ibandronate, 1442
patients received daily oral ibandronate, and 2078 patients
received placebo. A low incidence of renal adverse events
was observed in patients who received ibandronate injections; this was comparable with placebo. The change in
estimated Cr clearance (mean [SD], range ml/min) seen in
patients treated with IV ibandronate (-0.9 [9.01], -90.8 to
127.3 mL/min) was similar to that of patients receiving
oral ibandronate (-0.28 [13.14], -96.9 to 127.5ml/min) or
placebo (-0.91 [14.27], -121.3 to 119.1ml/min). Very few
patients (0.2–0.7%) experienced a clinically relevant
– 54 –
change in estimated Cr clearance (Table). No cases of
acute renal failure were reported and no renal safety concerns were identified in any patient.
Discussion: Ibandronate is a potent BP that has
demonstrated efficacy orally and as a 15- to 30-second
intravenous (IV) injection. IV delivery of BPs can be clinically useful for patients who are intolerant to oral BPs or
for those in whom oral BPs are contraindicated. Renal
adverse events have been reported with some IV BPs. This
pooled analysis suggests that the effect of IV ibandronate
on renal function is comparable to placebo or oral ibandronate in patients with PMO and GFR >30ml/min. Cr
clearance remained stable with IV ibandronate injection in
patients with PMO, including those patients with mild or
moderate renal impairment. Similar trends were observed
with oral ibandronate or placebo.
Conclusions: This pooled analysis of IV ibandronate
studies suggests that the effect of intermittent IV ibandronate on renal function is comparable with placebo and
daily oral ibandronate (2.5 mg) in women with PMO who
do not have severe renal impairment.
Abstract #240
MUSCULOSKELETAL MANIFESTATIONS IN
SECONDARY
HYPERPARATHYROIDISM-DIALYSIS
Maria Fleseriu, MD, Liana Chicea, MD,
Ioana Basaraba, MD, Cristina Teodoru, MD, and
Ioan Boca, MD
Objective: To assess the prevalence of muscular,
skeletal and articular disorders associated with hyperparathyroidism in dialysis pts
Case Presentation: We studied 70 consecutive
patients from the Dialysis Unit, University Hospital Sibiu,
Romania (IRB approved protocol). Median age was 51.1
(range 25-76), 60% male and median duration of dialysis
was 7.6 (2-10)years. Patients were extensively interviewed and history of present illness, associated diseases,
muscular and articular symptoms scored. All patients had
also a scored physical examination, lab tests (serum calcium, phosphate and PTH) and Rx hands and pelvis. All
patients were treated with Calcium and Calcitriol. Median
PTH was 700.2pg/ml(12-2500), while median calcium
and phosphate were 4.03 mg/dl (2.4-5.8), respectively 6.8
mg/dl (3.8-12.8). Serum concentration of PTH as well as
calcium concentrations increased along with prolonged
duration of hemodialysis, mostly after 10 years. We found
musculoskeletal manifestations in 75% of the patients,
more frequent in women with muscular weakness and
arthralgias in the top of the list. Fractures,carpal tunnel
syndrome and tendon ruptures were rare. The most fre-
quent sites for arthralgias were wrist (men), knee (women)
and shoulder.
Discussion: Radiological findings were: bone demineralization (42, 8%), bone erosions (35, 7%), and calcifications of periarticular tissues (12, 8%). These were
significantly more frequent in patients dialyzed for more
than 5 years (p=0,001) and the incidence rises along with
duration of dialysis as treatment for renal insufficiency.
Interestingly enough, the prevalence of musculoskeletal
disorders did not significantly correlate with PTH or phosphate serum concentration, but was slightly correlated
with calcium serum levels (p=0, 04). Unfortunately, serum
concentrations of Vitamin D were not available (affordability), nor the biologic markers of bone resorbtion. It is
known that people treated with prolonged hemodialysis
survive longer but develop musculoskeletal problems,
more frequent renal osteodystrophy. Hyperparathyroid
disease is the most frequent form of osteodystrophy in
these patients. It is usually asymptomatic, but may be the
source of musculoskeletal problems such as bone pain,
polyarthralgia or enthesopathy. Our results are concordant
with data from the literature.
Conclusions: Musculoskeletal disorders are extremely frequent in dialysis patients due in part to hyperparathyroid osteodystrophy.These debilitating symptomps
have a profound effect on their quality of life.It is unclear
how to properly adress the treatment of these corolary of
symptomps, as just calcium and vitamin D seemed not to
be enough in our patients.As we advance our understanding of mechanisms that lead to rheumatic disorders in
endocrine disease, we will improve our ability to treat
them.
Abstract #300
PREDICTING 12 MONTH BMD RESPONSE
FROM 3 MONTH SCTX CHANGES: MOBILE
DATA
Veronica Kelly Piziak, MD, Marc Hochberg, MD, MPH,
Stuart L. Silverman, MD, FACP, FACR,
Charles E. Barr, MD, and Paul D. Miller, MD, FACP
Objective: Assess if changes in sCTX at 3 months can
predict BMD response at 12 months in postmenopausal
women from the MOBILE study.
Methods: This post-hoc analysis included women
who received 150 mg monthly ibandronate (n=401) in the
MOBILE study. Classification and regression tree
(CART) analysis was used to examine the non-linear relationship between changes in sCTX levels at 3 months and
BMD response at 12 months.
Results: The regression tree for lumbar spine BMD
responders is shown in the Figure. Based on BMD values,
– 55 –
the overall probability of being a BMD responder at 12
months (percent changes from baseline ≥3.0%) was 62%.
In patients grouped by decreases in sCTX at 3 months
≥67%, 73% were BMD responders (11% better than in the
overall population). Using an increase in sCTX of ≥5%,
91% were nonresponders after 12 months (53% more than
the overall population). Similar results were observed at
the trochanter. Based on BMD values, 59% of patients
were BMD responders. Using a ≥67% decrease in sCTX at
3 months as a cut-off, 72% of patients were responders
(13% better than in the overall population); with an
increase in sCTX of ≥5%, 87% were nonresponders after
12 months (46% more than the overall population).
Discussion: In this study, CART was used to classify
patients as BMD responders or non-responders, based on
combinations of predictor variables. Percent changes in
sCTX values from baseline to 3 months were used as predictor variables in the final CART models. Changes in
sCTX levels at 3 months were not good predictors for total
hip or femoral neck BMD response at 12 months using the
CART methodology. This may be because fewer patients
were BMD responders at the total hip (41.6%) and femoral
neck (30.7%).
Conclusions: Changes in sCTX at 3 months is a
potentially useful predictor of ≥3% increases in LS and TR
BMD at 12 months among postmenopausal women taking
150 mg monthly ibandronate. Measurement of sCTX levels at baseline and after 3 months of therapy may be a useful tool for physicians to monitor and reinforce patient
compliance with ibandronate therapy.
Results: Patients, identified within 2 pooled data sets
of health services utilization, were new users of once-aweek dosing of risedronate (n = 12,215) or of alendronate
(n = 21,615). Two fracture outcomes were identified:
patients with nonvertebral fractures (hip, wrist, humerus,
clavicle, pelvis, leg) and those with vertebral fractures (n
= 376 and 507 through 6 and 12 months, respectively) (n
= 73 and 109 through 6 and 12 months, respectively). Cox
proportional hazard modeling was used to compare the
incidence of fractures between cohorts.
Discussion: A greater percentage of the risedronate
cohort had baseline risk factors for fracture than the alendronate cohort. After statistical adjustment for these differences, the risedronate cohort had a lower incidence of
nonvertebral fractures [19% (p-value=0.05) at 6 months
and 18% (p-value=0.03)at 12 months] and of hip fractures
[46% (p-value=0.02) at 6 months and 43% (p-value=0.01)
at 12 months] than did the alendronate cohort. Both risedronate and alendronate therapies have been shown to
reduce the incidence of nonvertebral fractures in randomized, placebo-controlled clinical trials. Further analyses of
these data suggested that risedronate may protect more
patients from fracture fractures.
Conclusions: As with all cohort studies, the interpretation of results may be limited by the non-randomized
nature of the study design. However, these results do not
appear to be from baseline differences in fracture risk
between cohorts and are consistent with the results of
analyses of clinical trials. Hence, these results suggest that
during the period studied, more patients on risedronate are
protected from fracture than patients on alendronate.
Abstract #408
RETROSPECTIVE STUDY OF RISEDRONATE &
ALENDRONATE: REDUCTION OF FRACTURES
Nelson B. Watts, MD, MACE, P. D. Delmas, MD,
S. L. Silverman, MD, J. L. Lange, PhD, R. Lindsay, MD
Objective: To compare the fracture reduction between
risedronate and alendronate therapies.
Methods: we conducted a retrospective cohort study
to assess the 6- and 12-month incidence of nonvertebral
fractures & hip fractures in cohorts of female patients (>
65 years) newly treated with risedronate & alendronate.
Sensitivity analyses were conducted.
– 56 –
ABSTRACTS – Obesity
OBESITY
Abstract #339
Abstract #370
UNDERSTANDING CHILDHOOD OBESITY:
INFLUENCES ON MILK AND SOFT DRINK
INTAKE
HIRSUTISM IN PATIENTS WITH POLYCYSTIC
OVARY SYNDROME
Armand Ara Krikorian, MD,
Arax Ara Balian, BSN, MPH, PhD, and
Elizabeth A. Madigan, PhD, RN
Morva Tahmasbi Rad, MD, and Parvin Pasalar, PhD
Objective: Polycystic Ovary Syndrome (PCOs) is one
of the most common endocrinopathies in women of reproductive age.
Methods: This study was performed in PCOs patients
that were registered in Dr.Maleknia Endocrinology
Laboratory (Tehran-Iran) (patients were referred from all
over Iran). BMI, Age,and fasting glucose and insulin were
recorded for all patients.
Results: These patients were randomly selected from
the patients' group that had fasting Glucose to Insulin ratio
(G/I) less than 4.5. These patients were divided into two
groups, the group with BMI<25 (group 1) and the group
with BMI>25 (group 2). These two groups were compared in G/I ratio, positive objective evidence of hirsutism
and also hirsutism in their 1st degree family.We had 48
patients in group1 with age 28.27±6.0 years and 46
patients in group 2 with age 28.22±5.0 years.
Discussion: Fasting G/I ratio in group1 was
4.00±0.34 and in group 2 was 3.85±0.36, which there was
a significant difference between these two groups(
p=0.04). Positive objective of hirsutism in group1 was
18.8% (n=9) and in group 2 was 39.1% (n=18), hirsutism
in group 2 with p=0.02 was significantly higher. Positive
family history of hirsutism in group1 was 29.2% and in
group2 was 26.1%.Although the prevalence of hirsutism
in family of group 1 and 2 had no significant difference,
the group with higher BMI had lower G/I ratio and higher
prevalence of hirsutism.
Conclusions: It may indicate that weight increase
will affect the genetic features of this syndrome. In
patients with PCOs, weight decrease or prevention of
weight increase may improve some features oh this disease.
Objective: To study personal and social influences on
school-age children's milk and soft drink intake in relation
to obesity
Methods: Due to the lack of available instruments,
the Milk & Soda Pop Intake questionnaires were constructed following the Theory of Planned Behavior guidelines. A cross-sectional descriptive pilot study was
conducted to investigate applicability and usefulness of
the measures with 10 to11-year-old children
Results: A convenience sample (n=10, 5 males, 5
females) of 10 to 11-year-olds completed the measures.
There was acceptable level of variation in the items with
no skip patterns. Average completion time was 15 minutes. All children stated that being healthy is important
and 90% believed that gaining weight is bad. 100% of
children felt that drinking milk is a healthy choice and
drinking soda is unhealthy. Both soda and milk intake
were deemed to be contributing to weight gain (80% vs
60% respectively). While only 30% reported drinking
soda, 44% stated they would prefer soda over milk if provided with a choice. 60% of children reported that availability of soda at home is an important determinant of
consumption. None of the children reportedly drank soda
at school.
Discussion: This pilot study established the feasibility and applicability of the Milk and Soda Pop Intake questionnaires in 10 to 11-year-old school-age children. Pilot
data show that maintenance of good health and avoidance
of weight gain appear to be important concerns of children. Although all surveyed children agreed that drinking
milk contributes to health while soda does not, confusion
seems to exist regarding the impact of soda and milk
intake on weight as both were thought to promote weight
– 57 –
ABSTRACTS – Obesity
gain. Availability of milk and soda both at school and
home settings appears to be a major determinant of consumption, as all of the soda intake was reported to occur at
home while none occurred at school, since the schools surveyed did not dispense any. Moreover, 30% of children
reported that their parents offer them soda during meals.
This finding underscores the need for an inclusive
approach to influence children's behaviors, as banning
soda from schools tackles only one aspect of the problem.
The alarming finding that nearly half of the children
(44%), if given the choice, would prefer to drink soda over
milk indicates the need for further targeted interventions
Conclusions: This pilot study uncovers various personal, social and environmental influences on children's
milk and soft drink intake. Children's beliefs and attitudes,
availability of soda and milk as well as parental influences
appear to be determining factors. A larger study is needed
to confirm these findings and guide further interventions
aimed at providing a comprehensive approach to preventing childhood overweight and obesity and its sequelae
such as Type 2 Diabetes.
Abstract #395
LIFESTYLE AND BIOCHEMICAL
CHARACTERISTICS OF OKLAHOMA NATIVE
AMERICANS
Andrew Darien Lancaster, MD, Rhett Jackson, MD,
Chris Aston, PhD, and Lancer Stephens, BA
Objective: Our goal was to characterize a Central
Oklahoma Native American group by examining their
excercise, diet, and biomarkers.
Methods: Using the support of the Citizen
Potawatomi Nation Health Center (CPNHC), we recruited
Native Americans to complete a survery on general health,
a modifiable activity questionnaire, and a four day food
journal. Participants also had a fasting lab draw as well as
measurement of physical attributes.
Results: 87.9% of the study participants were overweight or obese (19.9% [n=30] overweight, 48.1% [n=76]
obese/WHO class I&II, and19.9% [n=30] severely
obese/WHO Class III). Of our 157 subjects, 56% had CRP
levels higher than the highest reference value for normal
(3 mg/L). 39.5% (n= 62) of the participants had CRP’s
between 3 and 10 mg/L, indicating a high risk for future
vascular events. 27 participants had CRP’s greater than 10
mg/L. The data on exercise and diet appears to have been
unreliable. This may have been due to recall bias in regard
to exercise and variably recorded food intake.
Discussion: Both the incidence and prevalence of diabetes, coronary artery disease (CAD), and obesity have
been increasing in the United states and Oklahoma at
alarming rates. While our study does not address the incidence of these diseases within the central Oklahoma
Native American population, it strongly suggests that both
obesity and cardiovascular risk factors are greater in this
population than the general population of Oklahoma. Now
that we have a starting point, having defined the magnitude of these health risks, we must turn towards finding
successful interventions. Obesity and CAD are intertwined
diseases and so are their treatments. We propose that one
of the more efficient routes for future study would be
designing an intervention aimed at lowering the CRP in
this population. Other studies have suggested that statins,
diet, and even periodontal care may help reduce CRP levels. With further evaluation of our data (e.g. activity at
work, food journals, blood pressure analysis), we hope to
design an intervention to decrease the cardiovascular risk
factors in Oklahoma Native Americans by decreasing their
BMI and/or other risk factors such as CRP.
Conclusions: It is evident from our study that there is
an alarming prevalence of obesity in this Central
Oklahoma Native American population, and that this
might be reflected by the increased CRP’s. Future studies
should be aimed at reducing both the obesity and the CRP,
in turn reducing the cardiovascular risk for this population.
– 58 –
ABSTRACTS – Pituitary Disorders
PITUITARY DISORDERS
PNEUMOCOCCAL MENINGITIS AS A CAUSE OF
CENTRAL DIABETES INSIPIDUS
Conclusions: This case illustrates the adverse consequences of bacterial meningitis and bring awareness to
infection-induced central diabetes insipidus. The recognition of CDI in bacterial meningitis is important as electrolyte abnormalities from CDI can further increase
morbidity and even mortality in these patients.
Karen Choong, MD
Abstract #174
Objective: Emphasize the rare complication of pneumococcal meningitis : central diabetes insipidus
Case Presentation: A 45-year-old HIV+ African
American male was admitted to the ICU for altered mental status. His vital signs upon admission included a temperature of 106°F rectally, blood pressure of 140/80
mmHg and heart rate of 95. Intravenous antibiotics were
initiated for presumed meningitis. A lumbar puncture was
performed and confirmed the diagnosis of pneumococcal
meningitis. CSF cultures were negative for acid-fast bacilli, cytomegalovirus, cryptococcus, fungal culture, herpes
simplex virus and varicella. Approximately 36 hours after
initial presentation, his urine output increased to as high at
300 to 400cc/hr. During this time, his sodium level
increased from 132mmol/L at admission to 160mmol/L
with an increase in serum osmolality from 293mmol/kg
H20 to 312mmol/kg H20. A diagnosis of diabetes
insipidus was made after initiation of desmopressin resulted in complete resolution of polyuria and improvement in
his plasma sodium. The patient had a protracted course in
the MICU but eventually improved. At follow up 3
months later, his sodium level was 140 with complete resolution of polyuria.
Discussion: Central diabetes insipidus (CDI) is
caused by the inability of the hypothalamus-pituitary unit
to release arginine vasopressin in response to the rise in
plasma tonicity.Intracranial infections with mycobacterium, cryptococcus and treponema have been known to
induce CDI. On the other hand, CDI from pneumococcal
meningitis is a less common occurrence. CDI caused by
bacterial meningitis is known to more commonly affect
infants and young children but is rarely reported in the
adult population.A study by Greger et al found that 7 (9%)
of the 73 children studied had CDI from bacterial meningitis. Group B streptococcus, Haemophilus influenza and
Strep.pneumoniae accounted for majority of these bacterial infections. Currently, there are only two case reports in
the medical literature reporting the occurrence of diabetes
insipidus in two adult patients with Pneumoccocal meningitis. The exact pathophysiology is not well known.
Suggested mechanisms include increased intracranial
pressure and cerebral edema with resultant damage to the
hypothalamic-pituitary axis. Another possibility is the
development of basal arachnoiditis leading to irritation
and resultant tension on the pituitary stalk.
UNUSUAL PRESENTATION OF PITUITARY
APOPOLEXY FOLLOWING CABG SURGERY
Abstract #198
Robert Andrew McCauley, MD, Nicholas Rider, DO, and
Andrea Manni, MD
Objective: To present an atypical case of pituitary
apoplexy and pan-hypopituitarism following coronary
artery by-pass surgery
Case Presentation: A 66 year male presented with
chest pain and was found to have an ST elevation myocardial infarction. He emergently underwent stent placement
to the right coronary artery however, was hemodynamically unstable after the procedure requiring intra-aortic
balloon pump and pressor support. He subsequently
underwent four vessel coronary artery by-pass graft
surgery successfully. On post-operative day two, patient
developed mental status changes described as an inability
to recognize wife and surroundings and to follow simple
commands. Electrolyte evaluation showed mild hyponatremia and normokalemia. A CT scan and MRI showed a
large pituitary mass demonstrating infarction without evidence of hemorrhage. The patient was started on dexamethasone and within two days mental status returned to
baseline. Laboratory studies confirmed pan-hypopituitarism with low ACTH, TSH, LH, and GH. He was managed conservatively without surgery receiving hormone
replacement and is currently doing well.
Discussion: Pituitary apoplexy is a rare complication
following cardiac surgery with only 15 cases reported.
The classic symptoms of apoplexy, headache and visual
field deficit, were not present in this patient unlike the
reported cases where 13 cases had these symptoms.
Pituitary apoplexy occurs most often in the setting of an
undiagnosed pituitary macroadenoma. Of the 15 cases following cardiac surgery 13 had a macroadenoma but only
3 were diagnosed prior to presentation of apoplexy. Risk
factors for apoplexy include anticoagulation therapy,
thromboembolic event, hypoxic ischemia, hypertension,
and diabetes mellitus. The patient was hypotensive which
may have lead to ischemic infarction. It is difficult to say
if the initial insult was the myocardial infarction, resultant
hypotension, or cardiac surgery. Cardiac surgery poses
unique stresses that can lead to apoplexy including loss of
pulsatile blood flow, risk of embolus and anticoagulation
– 59 –
therapy. Management for apoplexy is either transphenoid
surgery or conservative medical therapy. Patients who
have minimal or improving symptoms, such as this
patient, may be managed medically while those with progressive symptoms will undergo surgery.
Conclusions: The importance of this case is the atypical presentation of pituitary apoplexy following coronary
surgery. The classic symptoms of headache and visual disturbance many not be present making the diagnosis more
difficult. A high index of suspicion is needed to recognize
the potential for apoplexy when the only presenting symptom is mental status changes and minimal hyponateremia
Abstract #167
THYROTROPINOMA WITH NEGATIVE
IMMUNOSTAINING FOR THYROTROPIN
Carmen Vanessa Villabona, MD, Alicia Leung, MD,
Manuel Utset, MD, and Rasa Kazlauskaite, MD
Objective: To report a thyrotropin-immunostainingnegative pituitary thyrotropinoma.
Case Presentation: A 40 y/o male who presented to
the Emergency Department with a 50 pounds unintentional weight loss and disabling fatigue. Upon workup for a
head and neck cancer, incidentally a 3.9 cm multilobulated invasive pituitary mass was discovered. The endocrine
evaluation revealed panhypopituitarism and prolactin of
27.91 (4 –15.2 ng/mL). However TSH was elevated at
7.45 (0.27-4.2) mU/L, and free T4= 2.05 (0.93-1.70) ng/dl
with free T3=7.37 (2.00-4.40) ng/dl, with glycoprotein
alpha-subunit=7mcg/L, and markedly elevated molar
alpha-subunit/TSH ratio of 9.3. The thyrotropin and thyroid hormones normalized in response to preoperative
somatostatin/cabergoline therapy, differentiating diagnosis of thyrotropinoma form thyroid hormone resistance.
70% of the tumor mass was resected transsphenoidally,
and serum TSH and FT4 levels dropped approximately a
70% of his pre-surgical values. Surgical specimen analysis confirmed pituitary adenoma, which abundantly
stained for prolactin, yet immunostaining was negative for
TSH (confirmed in two laboratories).
Discussion: Despite this pituitary adenoma exhibited
negative immunostaining for TSH, the diagnosis of thyrotropinoma was confirmed by the fact that after 70 % of
tumor mass was resected concomitantly a similar drop of
the FT4 and TSH levels occurred.
Conclusions: This is a sixth reported case of nonTSH staining thyrotropinoma, indicating that thyrotropinoma diagnosis may relay on biochemical work OR
pathology report OR combination of both. Diagnosis of
thyrotropinoma allows utilizing pituitary-thyroid hormonal axis as a valuable marker for pituitary tumor follow up
and response to therapy, as our case has illustrated.
Abstract #389
MAJOR TUMOR SHRINKAGE IN NON-FUNCTIONING MACROADENOMAS TREATED WITH
DOPAMINE AGONISTS
Daniel Cuevas-Ramos, MD,
Alejandra Ramos-Guifarro, MD,
Francisco J Gómez-Pérez, MD, FACE,
Bernardo Pérez-Enríquez, MD, and Juan Rull, MD
Objective: The aim of the study was to evaluate safety and efficacy of pharmacological therapy in non-functioning pituitary tumors.
Case Presentation: We studied three patients with
non-functioning pituitary macroadenomas and visual
impairment, treated with dopamine agonists. All of them
declined neurosurgery for personal reasons. We determined the treatment outcome by visual perimetry, and
tumor size decrement with magnetic resonance imaging
(MRI). Two women patients, 21 and 27 years-old, were
put on cabergoline treatment with 1 mg and 2 mg per
week, respectively, and their tumor shrank 30% of its initial volume. After twelve weeks, in the patient with the
higher dose of cabergoline the visual compromise was
completely solved. In the other patient, the visual perimetry progressively improved in eight months until normalization. The other patient was treated with bromocriptine,
20 mg per day, and after eight years of treatment, the
tumor became extinct. The three patients are being evaluated every 3 to 6 months, and no significant side effects of
the therapeutic regimens have been observed. The basal
characteristics and changes in tumor size with treatment
are described in Table 1.
Discussion: Studies upon the treatment of non-functioning adenomas with dopamine agonists have been performed with bromocriptine and tumor shrinkage has been
observed with high doses of up to 60 mg daily, a dose
often badly tolerated. Recently, cabergoline, another
dopamine agonist, was introduced showing fewer side
effects and being more effective. While doing our study,
we knew of two reports on the effectiveness of cabergoline
treatment in patients with NPA, and we have treated, with
dopamine agonists too, three patients with non-functioning pituitary macroadenomas and visual compromise. The
three patients showed tumor shrinkage in MRI, with progressive improvement in chiasm decompression, confirmed by imaging and visual field perimetry.
Contrastingly, the response was considerably delayed in
the patient under bromocriptine therapy. Nevertheless, in
our study is not possible to differentiate between tumor
shrinkage and shrinkage of residual normal pituitary tissue. Despite these factors, through pharmacological therapy, the distance between tumor and optic chiasm was
– 60 –
increased, which is an important therapeutic goal in
patients with this disease.
Conclusions: Medical therapy with potent dopamine
agonists, such as cabergoline, may evolve as a novel therapeutic option in patients with clinically and biochemically non-functioning pituitary macroadenomas, declining
operation. Although treatment was both safe and effective,
a well-designed randomized control trial is necessary to
better clarify the role of these agents for treatment of this
large tumors.
of second malignancy in patients with pituitary tumors
(although the registry did not report any patient with
Cushing’s disease).
Conclusions: Corticotropin-secreting Pituitary adenoma presenting with a concomitant sarcomatoid renal
cell carcinoma is rare. Our report may provide insight in
future investigations of neuroendocrine tumorigenesis.
Abstract #205
Abstract #236
PITUITARY METASTASIS FROM RENAL CELL
CARCINOMA
CONCOMITANT ACTH PITUITARY ADENOMA
IN A WOMAN WITH RENAL CELL CARCINOMA
Palak U Choksi, MD, Zulekha Hamid, MD,
Negah Rassouli, MD, and Fred Faas, MD
Silviya Velinova, MD, Saima Iqbal, MD,
Carmen Vanessa Villabona, MD, and
Rasa Kazlauskaite, MD
Objective: To describe the presentation, evaluation
and management of a patient with pituitary metastasis
from renal cell carcinoma.
Case Presentation: A 63 year old white male presented with diplopia, blurred vision and headaches. He
had a history of renal cell carcinoma (RCC) diagnosed 4
years previously, and was treated with a left nephrectomy
and adrenelectomy for locally advanced disease. No further metastases were found and he had been disease free
since then. He complained of heat intolerance and absent
sexual desire for 2 years. He had been on long standing
prednisone for COPD exacerbations. CT of brain showed
a pituitary mass with cavernous sinus extension.
Laboratory studies revealed: TSH 0.17uIU/ml, free T4
0.85ng/dl (0.58-1.64ng/dl), prolactin 23.8ng/ml (2.6413.13ng/dl), total testosterone l59ng/dl, FSH 6.73mIU/ml
(1.27-19.26mIU/ml) and LH 2.96mIU/ml (1.248.62mIU/ml). MRI revealed "macroadenoma" measuring
5cm x 3cm x 3.5cm; extending into the right cavernous
sinus. A transsphenoidal biopsy showed metastatic clear
cell carcinoma. Further imaging showed multiple lung
nodules. He was treated with radiotherapy and chemotherapy was considered.
Discussion: Metastasis of renal cell carcinoma to the
pituitary is a rare occurrence. Neoplastic cells can reach
the sella via hematogenous route, hypothalamo-hypophyseal portal system, direct extension or via meningeal
spread. Metastatic deposits may occur in the anterior as
well as the posterior lobe. Diabetes insipidus is usually
reported, reflecting a predominance of metastasis to the
posterior pituitary. Early diagnosis of pituitary metastasis
is usually difficult as these lesions may be small and clinically silent. With a large pituitary mass, as noted in our
patient, mild elevation of prolactin may be found due to
stalk compression. Pituitary metastasis should be suspected in an elderly patient with a rapidly growing tumor or
sudden onset of symptoms of DI, ophthalmoplegia or
headache. It is imperative to differentiate a metastatic
Objective: To present the first reported case of concomitant Cushing’s disease and a renal cell carcinoma.
Case Presentation: A 27-year-old previously healthy
female came to the Emergency room complaining of dyspnea on exertion. The clinical and laboratory workup
revealed hypercorticotrophic hypercortisolemia (urine free
cortisol of 3,435.4 mcg/24h; ACTH of 132 pg/ml), including insulin-resistant diabetes. A pulmonary CT angiogram
investigating for pulmonary embolism incidentally
revealed a 5 x 6 x 4.8 cm mass in the left kidney. Serum
cortisol post 8 mg dexamethasone was 29.8 mcg/ dl. Yet
the patient had hypogonadotropic hypogonadism and
hypothyrotropinemic hypothyroidism. The patient was
discovered to have 16 x 11 x 7 mm pituitary tumor which
was proven to be ACTH-secreting pituitary adenoma after
a trans-sphenoidal biopsy. The left kidney tumor was
removed via laparoscopic nephrectomy and was diagnosed as sarcomatoid renal cell carcinoma.
Discussion: The coexistence of renal cell carcinoma
and corticotrophin-secreting pituitary macroadenoma is
puzzling in this 27-year-old patient. There have been several case reports of renal cell carcinoma, producing
ACTH, as well as renal cell carcinoma with metastases to
the pituitary gland. Yet in our case, this young patient had
two co-existent tumors. Genetic mutations in tumor suppressor genes have been described in familial multiple
tumor syndromes, including either renal cell cancer (e.g.
VHL gene), or pituitary tumors (e.g. menin gene).
Activating mutations of Gs have been described in pituitary tumors and recently in kidney tumors. The overexpression of pituitary tumor transforming gene 1
(PTTG1) in renal cell carcinoma has been also recently
described. In addition, data from the National tumor registry of former Yugoslavia suggested 4-fold increased risk
– 61 –
lesion from a pituitary adenoma to help guide future therapy and treatment modalities. RCC metastases tend to be
vascular making total resection difficult. Pituitary radiation or chemotherapy along with adequate hormone
replacement is usually the initial course of therapy.
Prognosis is usually poor due to the aggressiveness of the
primary tumor.
Conclusions: Pituitary metastasis from renal cell carcinoma is rare. Symptomatic chiasmal compression, diabetes insipidus and rarely anterior pituitary hormone
deficiency are the presenting symptoms. Transsphenoidal
resection may be difficult owing to the vascularity of the
tumor. Although prognosis is poor, radiation and /or
chemotherapy should be attempted with adequate hormone substitution. In certain situations pituitary resection
may help in relieving symptoms associated with mass
effect.
nial nerve disturbances were present in this case.
Glucocorticoid support was correctly given. Patient was
subsequently found to have hypopituatarism. We postulate
that the patient only recently became "hypopit" due to lack
of prior symptoms. Currently patient is taking steroids and
L-thyroxine.
Conclusions: Pituitary apoplexy is often a delayed
diagnosis, especially without a prior history of a sellar
lesion. Hyperpyrexia is often present but wrongly attributed to sepsis. Glucocorticoid support therapy should be
given promptly. Initial hormone studies are not the determinant factor in starting steroids. Evaluation of remaining
anterior and posterior pituitary functions is indicated after
the acute therapy in all cases.
Abstract #179
NORMAL UFC IN PATIENTS WITH
BIOCHEMICALLY CONFIRMED CUSHING’S
DISEASE
Abstract #244
PITUITARY APOPLEXY: FEBRILE RED
HERRINGS
Maria Fleseriu, MD, Chris G. Yedinak, FNP,
Johnny B. Delashaw, MD, David M. Cook, MD, and
William H. Ludlam, MD, PhD
Richard W. Pinsker, MD, FACE,
Rajulkumar Parikh, MD, Mehul Patel, MD,
Seyedqumars Mirfendereski, MD, amd Aticul Islam, MD
Objective: To discuss the subtle features of pituitary
apoplexy that could be misdiagnosed as encephalitis/
meningitis or sepsis.
Case Presentation: A 55 year old female came to the
ER with frontal headaches, vomiting, and low grade fever
for three days. For two days, she noted drooping of right
eye. Home medications included theophylline, Tylenol,
and Excedrin. On exam, BP 166/90, pulse 90, temp
103.3F, respirations 20. Patient was drowsy with right eye
ptosis. No obvious field defects were present but patient
not fully cooperative. Neck stiffness was present. Labs
showed WBC 17.3, sodium 129, bicarbonate 16.2, anion
gap 18. Initially, she was treated for bacterial meningitis.
CT and MRI revealed 3.1 cm. sellar mass extending into
the suprasellar cistern mildly compressing the optic chiasm with areas of subacute hemorrhage. Lumbar puncture
revealed no cells and no xanthochromia. Diagnosis of
pituitary apoplexy was made clinically and patient was
started on high dose dexamethasone. Further labs subsequently demonstrated FSH 2.5, LH 0.5, Prolactin 0.0, cortisol 2.47, ACTH <5, TSH 0.13, Total T4 3.27. Patient
underwent successful decompression of an apoplectic
non-functiong pituitary adenoma.
Discussion: Many cases of pituitary apoplexy are
mistaken initially for an encephalitis/meningitis symptom
complex. Often, fever is not attributed to pituitary
apoplexy. More typically, headache, confusion, and cra-
Objective: To retrospectively analyze the sensitivity
of the 24-hour UFC in the diagnosis of Cushing’s disease
Case Presentation: Because the clinical features of
Cushing disease (CD) overlap with those in generalized
obesity, biochemical investigations play an important role
in making the diagnosis. The 24-h urinary free cortisol
(UFC) excretion is widely used to screen for CD but it is
unclear how sensitive the assay is since there is no “gold
standard” in making the diagnosis. In this study, 114
patients who underwent pituitary surgery for treatment of
CD over a 5-year period (11/1/01 to 10/31/06) at OHSU
were retrospectively reviewed and patients were identified
who had both a positive Dexamethasone (Dex)/CRH test
as well as UFC tests that were always in the normal range.
Physical features, history and several other biochemical
tests including midnight salivary and serum cortisol as
well as random blood ACTH and cortisol were used to
make the diagnosis of CD. All cases were reviewed by a
panel of endocrinologists to obtain consensus on diagnosis.
Discussion: Of the 114 patients reviewed, eleven
patients (10%) were noted to have both a positive
Dex/CRH test as well as UFC tests that were always in the
normal range. The median age of this group was 40 (range
18 – 51) and all were female. Median BMI was 37.9
kg/m2 (25.3 – 52.8) and all patients were strongly
“Cushingoid” appearing. All patients had normal renal
function (normal serum creatinine). Median cortisol level
in the Dex/CRH test at 15 min post CRH was 6 mcg/dl
– 62 –
(1.8 – 10); validity of test was confirmed by serum dexamethasone level. The median number of UFC performed
per patient was 9 (2 – 30). The median of the highest UFC
for each patient (expressed as a fraction of the ULN) was
79% ULN (37 - 99). Each patient had IPSS/CSS or had a
macroadenoma. Further confirmation of the presence of
CD was made by one or more of the following: ACTH
staining of tumor and/or post op a.m. cortisol of <= 1
mcg/dl. It is unclear why some CD patients do not excrete
excess cortisol into their urine, but it may be because small
increases in cortisol production at the circadian nadir are
not detected as an increase in UFC. Studies to address this
question are planned.
Conclusions: 114 patients treated for CD at OHSU
over a 5-year period were reviewed. Eleven (10%) of these
patients had both positive Dex/CRH tests and UFCs that
were always normal; these patients were otherwise diagnosed by evaluation of history, physical and other biochemical parameters. We conclude that although the UFC
remains a valuable test for assessing hypercortisolemia,
this test should not be used as the sole criterion to exclude
the diagnosis of CD when clinical suspicion for the disease
is high.
Abstract #252
SYMPTOMATIC PITUITARY METASTASES
FROM RENAL CELL CARCINOMA: A CASE
SERIES
Thottathil Gopan, MD, Amir Hamrahian, MD,
Steven Toms, MD, MPH, and Robert Weil, MD
Objective: To illustrate the clinical features and treatment of 5 patients with metastasis to pituitary from renal
cell carcinoma (RCC)
Case Presentation: Over a 5-year period from 20012006, we treated 5 patients (3 males; median age 61 years)
with large sellar masses and RCC. Of these, 4 patients had
a history of RCC, while in 1 patient, RCC was diagnosed
after sellar mass was discovered. RCC was diagnosed a
median of 14.5 yrs prior to diagnosis of MP (range 1-27
yrs).4 patients had previously developed distant metastases. Clinical presentation included bitemporal hemianopia (3 patients), lethargy (3 patients), headaches (2
patients) and diabetes insipidus (DI) (2 patients).
Panhypopituitarism was present in 4 patients and the other
had deficiency of only ACTH and gonadotropins. High
prolactin was seen in 3 patients. MRI showed enhancing
sellar mass with suprasellar extension and chiasmal compression in all patients. Prominent vascular flow voids
were seen in 2 patients. 3 patients underwent transsphenoidal surgery and pathology showed clear cell carcinoma.
2 patients underwent only stereotactic radiotherapy. 4
patients are alive and 1 patient died due to systemic metastases after a median follow up of 12 months (range 6-36
months).
Discussion: In autopsy series, metastases to pituitary
(MP) are seen in 1-5% of patients dying with known cancer. The commonest primaries are breast and lung. Only
7% of patients have symptoms due to the MP. MP from
RCC is rare and only 13 cases have been reported. MP
from RCC behave differently from those from other primaries. MP from other sites tend to localize to the posterior lobe due to direct systemic blood supply, accounting for
high prevalence of DI in these patients (70%) compared to
hypopituitarism (<25%). However, patients with MP from
RCC tend to have more pronounced hypopituitarism and
chiasmal compression (70%) compared to DI (30%), suggesting involvement of anterior pituitary. 4/5 of patients in
our series had panhypopituitarism and only 2 had DI.
Clinical and radiological differentiation of MP from adenoma is difficult. Presence of DI and severe hypopituitarism suggest MP. DI is seen in only 1% of patients with
pituitary adenomas. Features on MRI that suggest MP
include rapid growth, enhancement on contrast, stalk
involvement, sclerosis and/or erosion of sella and presence
of vascular flow voids. Treatment of MP includes surgical
decompression and stereotactic radiotherapy.
Conclusions: We present the largest reported series
of patients with MP from RCC. Compared to MP from
other primaries, those from RCC cause severe hypopituitarism and visual field deficits whereas DI is uncommon.
MRI shows intense enhancement, vascular flow voids,
erosion of sella and supra and parasellar invasion. Careful
assessment of clinical and MRI findings could help to differentiate MP from adenoma. Combined treatment using
decompressive surgery and stereotactic radiotherapy result
in better outcome.
Abstract #215
PITUITARY GIGANTISM AND THERAPEUTIC
OPTIONS IN CHILDREN
Remberto Cuenca Paulo, Jr, MD,
Salman Kirmani, MBBS, and Aida Lteif, MD
Objective: We report 3 cases of gigantism in children
ages 10-14 years. Treatment modalities for each are
described.
Case Presentation: Case 1 is a 10 5/12 yo boy with
gigantism due to a growth-hormone (GH)- producing
4x2.6cm pituitary adenoma (PA). He underwent
transsphenoidal (TS) debulking surgery, followed by treatment with Octreotide then Sandostatin LAR.
Hypopituitarism was diagnosed post operatively. Gamma
knife (GK) radiosurgery was eventually done due to unre-
– 63 –
sponsiveness to combined medical and surgical treatments. He underwent remission and is doing well 4 years
post-GK surgery. Case 2 is an 11 9/12yo boy with a GHand prolactin-secreting 1cm PA who underwent TS resection, and had normal post-op head MRI but had persistently high random GH levels at 15ng/mL despite
Sandostatin LAR treatment. Bromocriptine was added and
later switched to Cabergoline. Last random GH levels still
high at 9.8ng/mL, but IGF-1, IGF-BP3 levels were normal. Serial head MRIs are stable. He is doing well clinically, with a normal rate of growth on medical
management. Case 3 is a 14 7/12yo boy with a GH-secreting 6.5x7mm PA who underwent TS resection, now doing
well with no further treatment pending post-op evaluation.
Discussion: As in the latest consensus guidelines for
acromegaly management, the first line of treatment for
GH-secreting PA in children is typically TS surgery. This
was done in all 3 cases presented. However, adult data
suggest a remission rate of up to 74% with surgery. In 2 of
our patients, pharmacotherapy was added post-op due to
poor disease control. Somatostatin and dopamine agonists
normalize GH and IGF-1 in about 60% and 10% of adult
cases respectively. Stereotactic radiosurgery (GK), with
its maximized targeting, reduced radiation field scatter and
shorter treatment duration, holds great promise should
radiotherapy be indicated. However, there is limited experience with its use in gigantism especially in children . In
Case 1, along with somatostatin analog use, GK effectively induced remission consistent with the recent consensus
on the criteria for cure of acromegaly. Its long term side
effects include complete/partial hypopituitarism, though
our patient has had this after conventional surgery, prior to
GK radiosurgery. Case 2 is clinically stable but may eventually need further treatment to lower his GH levels. Case
3 clearly needs close post-op follow up as well.
Conclusions: Pituitary gigantism is a rare condition.
Management in children is challenging . There is limited
experience with all different treatment modalities. The
promise of stereotactic radiosurgery (gamma knife) is
demonstrated by its successful use in one of the patients
presented. In addition, IGF-1 receptor blockers are now
available for use as well. Studies on each of these treatment options with longer follow up are needed to assess
their long term efficacy and safety in children.
Abstract #323
TREATMENT OF A NON-FUNCTIONING
PITUITARY MACROADENOMA WITH
OCTREOTIDE
Lisa Rene Hays, MD, Thomas Whittaker, JD, MD,
R. Neil Schimke, MD, and Leland Graves, III, MD
Objective: To report a non-functioning macroadenoma treated with octreotide resulting in tumor shrinkage
and improved vision.
Case Presentation: A 46 year old female presented
with a clinically non-functioning pituitary macroadenoma
with visual field loss. Transsphenoidal surgery was unsuccessful in completely resecting the tumor, and the patient
had persistent visual field loss. Immunohistochemical
staining was positive for gonadotropin producing cells and
chromogranin A. An octreotide scan revealed intense
uptake in the region of the pituitary. Treatment with
octreotide injections 50 mcg subcutaneously thrice daily
was initiated for six weeks in hopes of shrinking the tumor
and improving her vision as the patient was reluctant to
undergo further surgery. The patient tolerated octreotide
well, and therapy was changed to depot octreotide. The
patient had dramatic improvement in her visual field
defecits. The tumor decreased in size by 50% compared to
the post-operative tumor size. The patient remains on
octreotide therapy 20 mg intramuscular once monthly.
Discussion: We reviewed the literature to examine
the response rate of octreotide therapy in non-functioning
macroadenomas and to determine predictors of response.
As many as 30% of patients with non-functioning
macroadenomas have residual tumor after surgery.
Response rates to medical therapy with octreotide vary. In
one study eight out of sixteen patients had improvement in
visual fields. In another three out of four patients had
improvement in visual fields but no change in tumor volume. The improvement may be the result of somatostatin
receptors being present on the retina and optic nerve. In
another study 54%(n=24) of patients had improvement in
visual acuity within four days of treatment. Furthermore
41% of patients had persistent improvement at 2 months
suggesting early response predicts chances of long-term
– 64 –
improvement. The percentage of tumors that shrink with
therapy varies between 0 and 43%. Plockinger et al
showed the degree of uptake by octreotide scan does not
predict response to therapy. However according to
Borson-Chazot et al, a negative scan does predict a tumor
will not respond to octreotide. Immunohistochemical classification does not predict likelihood of response.
Conclusions: Our case demonstrates a patient that
had improvement in her vision and shrinkage of a nonfunctioning macroadenoma after treatment with
octreotide. Historically the response to octreotide is variable, but it provides a possible option for patients that seek
medical therapy for persistent vision impairment or mass
effect after surgery.
Abstract #190
OLFACTORY NEUROBLASTOMA: A RARE
CAUSE OF SIADH
Kimberly Ann Placzkowski, MD, and Neena Natt, MD
Objective: To highlight the association between
Olfactory Neuroblastomas and hyponatremia and to
review the literature on this topic.
Case Presentation: A 49 year old woman presented
elsewhere with an episode of syncope. Evaluation
revealed hyponatremia consistent with syndrome of inappropriate ADH release (SIADH). Investigation did not
reveal an etiology, although a left nasal polyp was incidentally noted on MRI. The patient responded to 1-liter
daily fluid restriction with improvement in her sodium.
Later that year she developed sinus symptoms which
prompted a CT scan that again showed the nasal polyp.
This was resected and pathology revealed an olfactory
neuroblastoma (ON). She was referred to Mayo Clinic for
further management. Her sodium while on fluid restriction
remained within the normal range. She had minimal symptoms and denied nasal congestion, epistaxis or changes in
smell. An MRI showed residual tumor in the left medial
meatus with no bony involvement. She underwent left
medial maxillectomy and ethmoidectomy. Pathology confirmed a 1.5 x 1.0 x 1.0 cm ON, Hyams’ grade 2, with negative tumor margins. Postoperatively, fluid restrictions
were lifted and she maintained a normal sodium with usual
volumes of fluid intake.
Discussion: ON is a rare tumor that develops from the
epithelial lining of the upper nasal septum, superior
turbinates and cribiform plate. Clinically, ON may vary
from an indolent mass to a highly aggressive malignancy
with widespread metastasis. Diagnosis may be delayed as
presenting symptoms, commonly nasal obstruction and
epistaxis, are nonspecific. ON typically spreads locally
and may erode through local bony structures, although dis-
tant metastases are possible. Fortunately our patient had
well-localized disease at diagnosis and a neoplasm was
only suspected based on pathology. Paraneoplastic syndromes are well-established causes of SIADH. The most
commonly associated neoplasm is oat cell lung cancer,
though a variety of malignancies have been implicated.
Since the first case of SIADH documented in ON, only 7
additional cases have been reported. Tumor analysis has
documented arginine vasopressin production by ON tumor
cells. As in our patient, complete resection of these neoplasms has led to resolution of hyponatremia. Adjuvant
radiotherapy is common, however, so monitoring for
future signs or symptoms of pituitary insufficiency is
important.
Conclusions: Olfactory neuroblastoma is a rare, but
pathologically proven cause of SIADH. As in our patient,
SIADH may be the first indication of a paraneoplastic syndrome or malignancy. ON typically leads to nonspecific
symptoms that develop secondary to intranasal obstruction
or bleeding from the enlarging mass. Although ON is rare,
idiopathic SIADH should prompt physicians to at least
consider further evaluation of apparently benign conditions.
Abstract #294
MORSIER SYNDROME: A CLINICAL CASE
REPORT
Sigfrido Miracle-Lopez, MD, FACE, Ilan Shapiro, MD,
Marc Rubinstein, MD, and Alejandro Lichtinger, MD
Objective: To report a Case of Septo Optic Dysplasia
(SOD) or Morsier Sindrome, presenting the clinical, laboratory and imaging findings
Case Presentation: A 23 year old African American
woman presented to the emergency service with polyuria
and hypernatremia, which was unresponsive to desmopressin (DDAVP). At physical exploration, no correlation
age-physical appearance, prognatism and other abnormalities. Hormone lab results confirmed hypopituitarism. CT
scan and MRI reveled absents of septum pellucidum, old
water shed ischemic infract, hypoplasy of the pituitary
gland and a small optic chiasm. Treatment was install to
correct hormonal defiencies, but the management of fluids
and sodium became the main goal to achieve.
Discussion: Reeves first Described septo optic
Dysplasia like a syndrome in 1941. George de Morsier
(1894-1982) described the relation of septo optic dysplasia with absents of the septum pellucidum 1956 , being the
soul back bone of the syndrome. Finally Kaplan et. Al., in
1970 reported “hypopituarism dwarfism, hypoplasia of the
optic nerve and malformation of the prosencephalon ”.
Many authors have describe different variations of the
– 65 –
syndrome , modifying the definition to a triad, best enclosing: Septo optic dysplasia, middle line defects (concerning
in the majority of the cases alteration the septum pellucidum and the pituitary gland) and hypopituitarism, living
a great room for variations, having a wide range of problems enclosed in a single name. To achive a better comprehension of the syndrome, we took the Hellstrom and
Albertsson et al proposal to classified and “better” diagnose the patient .
Conclusions: Detecting a clinical rare syndrome can
give a better prognosis to the patient. A clear etiology or a
familial trend hasn’t been found. Genetic work up demonstrated links to alter HESX1 and other genes as the main
cause of this syndrome, but It hasn’t been consistent in
every case. Hormone replacement therapy is mandatory in
this settings. In our clinical scenario, when the patient
can’t communicate the “alarm” symptom, thirst, we really
stretch to observe for minimal change of behavior.
Abstract #193
COULD SHE HAVE CUSHING'S?
Marium Ilahi, MD, and Andjela Drincic, MD
Objective: To review the literature for the screening
guidelines of individuals with primary hyperparathyroidism for the MEN syndromes.
Case Presentation: The patient is an anxious 55yr old
female nurse who presented to our clinic with a diagnosis
of primary hyperparathyroidism made 2 years ago.She
tells us that she was watching a program on Cushing’s
syndrome on the health channel and wanted to be evaluated.On exam she had a mild cushingoid appearance with no
plethora and minimal supraclavicular or dorsocervical fat
pads, and no striae. At this point there was no clear indication that the patient could have Cushing’s syndrome.
Routine labs were done and she was reassured. She
returned and insisted that she be investigated further. A 24
hour urine for free cortisol was 212.4 ug/day. Two midnight salivary cortisols were 746 & 356nmol/L and ACTH
was 74pg/ml. Pituitary MRI revealed a 8.4mm
hypointense noncontrast enhancing lesion. She underwent
transsphenoid surgery and a diagnosis of pituitary dependent Cushing’s syndrome was confirmed. Her serum cortisol on post-op was 2.8ug/dl.The possibility of MEN 1
arose when it was discovered her father died from an
unusual GI cancer, and direct sequencing of MEN gene of
our patient was negative.
Discussion: Primary hyperparathyroidism is an
exceedingly common endocrine disease more readily discovered with the advent of multichannel screening. Unlike
MEN syndromes which are rare disorders. The question
then arises which patients with hyperparathyroidism
should be screened for MEN. Some authorities believe
that this possibility should be explored in settings of a
family history of hypercalcemia or other endocrine neoplasias or when it occurs in a young adult. It has also been
seen that MEN 1 may present as isolated hyperparathyroidism. An anterior pituitary adenoma is the first clinical
manifestation of MEN1 in less than 10% of familial cases
diagnosed prospectively. Hyperparathyroidism is more
common and present in 90-97% of cases. Direct sequencing of the coding region of MEN1 detects a mutation in at
least 85% of typical families and a much lower percentage
of variant families. Therefore the diagnosis of MEN has
not been excluded in our patient. The question now arises
regarding screening of her relatives. As far as we are
aware there is no one in her family who has signs or symptoms of any endocrinologic disorder. But the need of
screening with calcium and PTH remains.
Conclusions: Primary hyperparathyroidism is a common disorder compared to rarer disorders such as
Cushing’s disease and MEN. Our patient was diagnosed
with Cushing’s disease. Now we must explore the possibility of MEN. And this diagnosis would warrant family
screening. On a literature review there was no clear concise approach to this situation or official recommendations. With the high prevalence of hyperparathyroidism
this question needs to be addressed to help make the right
decisions in patient care.
Abstract #295
DO SNPs IN THE AIP AND MEN1 GENE PREDISPOSE TO FAMILIAL PITUITARY TUMORS ?
Shema Riaz Ahmad, MD, Lauri A. Aaltonen, MD, PhD,
Andrew Parent, MD,
Elise P. Gomez-Sanchez, DVM, PhD, and
Christian A. Koch, MD, FACE, FACP
Objective: To elucidate the pathogenesis of familial
isolated pituitary tumors and to help identify predisposed
family members.
Methods: After DNA extraction from blood in the 55
yo black index patient who suffered from a hormonally
inactive pituitary tumor, we conducted a germline mutation analysis of the AIP and MEN1 genes, using primers
previously reported and available upon request (Vierimaa
et al., Science May 2006).
Results: A 55 yo black man was admitted to the
UMMC with new onset left-sided weakness, recurrent
headaches, and diplopia. There were no MEN-1/Carneycomplex associated features in himself and his family
members. MRI of the brain showed a 5.5 x 3.6 x 4 cm sellar mass. After adenoma resection, final pathology
revealed null-cell tumor, IHC negative for anterior pitu-
– 66 –
itary hormones. FH: pituitary tumor in brother, 1 female
and 1 male cousin. In the AIP gene, the index patient was
heterozygous for two known coding AIP SNPs: exon 2,
silent D44D, rs11822907 (C/T), exon 5, Q228K, rs641081
(C/A). MEN1 gene: heterozygous for SNPs rs11231874
(C/T), rs7949944(C/T) and rs679946(G/T), all located in
the 5’ UTR, homozygous for rs540012(C/C, but T in
Ensembl) in exon 9, and heterozygous for rs2959656
(A/G) exon 10.
Discussion: Pituitary tumors are common with a
prevalence of approx. 22% (Ezzat et al., Cancer 2004).
Their pathogenesis is widely unknown. This is the first
black family reported with non-MEN1/Carney complex
familial isolated pituitary adenomas. The family pattern is
strongly suggestive of autosomal dominant inheritance. In
at least 10% of patients with clinical features of MEN1, no
germline mutations in the MEN1 gene are identified.
Therefore, there is still a remote chance that our family has
an atypical MEN1 variant. In contrast to patients reported
with germline mutations in the AIP gene, our patient and
family members had hormonally inactive pituitary adenomas and SNPs in the AIP gene. SNPs are defined as more
common genetic variation (>1%) and correlate with health
because of their proximity to the disease causing genetic
factor, thereby help identify clinically useful disease associations/susceptibility. AIP directly associates with survivin, an inhibitor of apoptosis, and thereby elevates a
cellular anti-apoptotic threshold (Kang & Altieri, JBC
2006). Menin, the gene product of the MEN1 gene, is
widely expressed and common in proliferating tissues
(Guo & Sawicki, Mol Endo 2001).
Conclusions: There are patients with familial isolated
pituitary tumors and no identifiable germline mutations in
the AIP and MEN1 genes. SNPs in various genes, here in
both the AIP and MEN1 gene, may act amplifying and
thereby increase the predisposition of individuals to develop certain tumors, and in the family reported here, pituitary tumors.
Case Presentation: A 21-year-old woman was studied for bitemporal hemianopsy and prolactin levels of 42
ng/ml (normal < 26.7 ng/ml). The “hook effect” was ruled
out after the patient not only denied having been taken
drugs related with hiperprolactinemia, but also when a
MRI showed a pituitary macroadenoma. The diagnosis of
a non-functioning macroadenoma was sustained until
polyethilenglycol precipitation prolactin values were normalized and any other hormonal secretion abnormality
was confirmed. At her next clinical evaluation, she was 5
weeks pregnant, and surgery was postponed on base (1) of
the patient‘s strong desire to continue her first pregnancy,
(2) considering that surgery put her pregnancy at risk and
(3) the impossibility of another pregnancy after hypophysectomy. We prescribed bromocriptine to her but she did
not tolerate it, and cabergoline 2 mg/week was started. In
twelve weeks a complete decompression of the optic chiasm occurred (Figure 1), with 28.5% tumor size reduction.
After her delivery, she had surgery to remove brain tumor
and histopathology confirmed a non-functioning pituitary
macroadenoma.
Discussion: The size reduction of the pituitary tumor
with the subsequent decompression of the visual fields can
be attributed to two principal mechanisms: first, treatment
direct effect on the macroadenoma, and second, to the
pituitary gland size decrease after treatment. It is possible
that in such a short period both factors contributed beneficially to increase the distance between the tumor and the
optic chiasm. Although the presence of a prolactinoma can
be entertained as a possibility, the normal hormonal
results, the presence of macroprolactin, the adequate
gonadal function and the poor staining in histopathology,
confirm the presence of a non-functioning adenoma.
Conclusions: The treatment with cabergoline helped
to preserve pituitary functions, and fertility as well, in a
young woman with a non-functioning pituitary macroadenoma, regardless that visual compromise was present. In
the appropriate clinical context, cabergoline could be considered as a therapeutic option during pregnancy.
Abstract #399
Abstract #401
CABERGOLINE ACHIEVED QUICK VISUAL
DECOMPRESSION IN NON-FUNCTIONAL
MACROADENOMA DURING PREGNANCY
INVASION IN BONE AND/OR CAVERNOUS
SINUS IN PLURIHORMONAL PITUITARY
ADENOMAS
Daniel Cuevas-Ramos, MD,
Alejandra Ramos-Guifarro, MD,
Francisco J Gómez-Pérez, MD, FACE,
Bernardo Pérez-Enríquez, MD, and Juan Rull, MD
Monica Livia Gheorghiu, MD, Anda Dumitrascu, MD,
Corin Badiu, Assoc Prof, Simona Galoiu, MD, and
Mihai Coculescu, Prof
Objective: To illustrate a case with rapid response
after cabergoline treatment in a pregnant women with nonfunctioning macroadenoma and visual compromise.
Objective: To assess tumor invasion rate and the cerebrospinal fluid hormonal level in patients with plurihormonal pituitary adenomas.
– 67 –
Methods: We studied 138 patients with pituitary adenomas; immunohistochemistry was performed by avidinbiotin method; tumor invasion assessed by computed
tomography or magnetic resonance imaging; anterior pituitary hormones simultaneously sampled in serum and CSF
measured by fluoroimmunoassay in 80 patients.
Results: The patients, aged 16-72 years, diagnosed
between 1985 – 2005, had 66 non-functioning pituitary
adenomas (NFPA), 55 acromegaly (ACM) and 17 prolactinomas (PRM). 52 adenomas (37%) were plurihormonal (PA). The rate of invasion into bone and/or
cavernous sinus was 42% in patients with PA (22/52
patients), and 58% (50/86) in patients with uni/nonhormonal adenomas (UA), p=0.08). Similar rates of invasion
were recorded in PA versus UA NFPA (47% vs 71%),
ACM (32% vs 33%) and PRM (71% vs 60%). A
CSF/serum ratio (R) >1 for at least one pituitary hormone
was recorded in 43 patients (53%). More patients with
invasive pituitary adenomas had R>1 for at least 1 hormone (27/37) compared with patients with non-invasive
tumors (16/43, p=0.002).
Discussion: The rate of invasion into bone and/or
cavernous sinus in plurihormonal adenomas was not significantly different from that recorded in unihormonal or
null cell pituitary adenomas. The rate of invasion only in
the cavernous sinus tended to be lower in the plurihormonal tumors, as compared to unihormonal/null cell ones
(p = 0.051). Plurihormonal tumors with CSF/serum > 1 for
at least 1 hormone were as invasive (5/15) as those with
CSF/serum <1 for every hormone (7/18, p=NS).
Unihormonal or null cell adenomas with CSF/serum ratio
>1 for at least 1 hormone were more invasive (22/33) than
those with CSF/serum ratio <1 for all pituitary hormones
(3/14, p<0.01).
Conclusions: The invasion rate was similar in
patients with plurihormonal pituitary adenomas compared
to unihormonal or null cell tumors, with no regard to pituitary adenoma functional type. A CSF/serum ratio >1 for
at least one pituitary hormone was an indicative of invasiveness only in patients with unihormonal/null cell adenomas.
Abstract #407
PROLONGED SUPPRESSION OF HPA AXIS
FROM TOPICAL BETAMETHASONE &
ITRACONAZOLE
Armand Ara Krikorian, MD, and Hiba AbouAssi, MD
Objective: To describe the prolonged suppression of
the HPA axis from the short-term use of topical
betamethasone and itraconazole.
Case Presentation: A 47 yo lady was referred for a
few months history of progressive weight gain and lower
extremity swelling. She denied headache and visual symptoms. Her energy level was good. Her past medical history was significant for ABPA, for which she was receiving
itraconazole. Her physical examination was remarkable
for central obesity, abdominal striae and lower extremity
edema. Her baseline serum total cortisol was undetectable
(<0.2 microg/dl) and failed to rise significantly after high
dose cosyntropin stimulation (2.4 microg/dl). The same
pattern was observed for her free cortisol, DHEA and
DHEAS. Serum Prolactin, IGF-1, TSH, free T4 were
within normal limits. An MRI of the sella was unremarkable. A review of the patient's medication history revealed
the use of topical betamethasone cream for skin rash for a
total duration of 4 weeks 3 months prior to presentation.
Her serum betamethasone level was 0.9 microg/dl. Two
months post withdrawal of itraconazole, repeat testing
showed complete recovery of her HPA axis and undetectable serum betamethasone levels.
Discussion: History and clinical findings of our
patient led to the conclusion that she developed Cushing
Syndrome (CS) secondary to increased systemic concentration of betamethasone resulting from inhibition of
CYP450 dependent CYP 3A by itraconazole. Topical
preparations, despite minimal absorption, remain a potential source of exogenous glucocorticoids and percutaneous
absorption of topically applied steroids in quantities sufficient to replace endogenous production has been previously documented. CS as a side effect of topical steroids
has been described in both children and adults, mostly
from the use of clobitasol propionate. Itraconazole has
been reported to decrease the systemic clearance of
numerous corticosteroids, leading to increases in the total
area under the plasma concentration-time curve of oral and
inhaled steroids. To the best of our knowledge, our case is
the first to describe CS secondary to combination therapy
of topical betamethasone and oral itraconazole. This is of
particular significance to general practitioners, endocrinologists and dermatologists should be aware of such potential interactions and their deleterious consequences.
Conclusions: The persistence of detectable levels of
betamethasone long after its discontinuation, together with
the clinical presentation of hypercortisolism and suppression of the HPA axis are unique aspects of our case and
underscore the need for monitoring of patients receiving
therapy with topical steroids, particularly when combined
with an inhibitor of cytochrome P450-3A. In an era where
polypharmacy prevails, a thorough understanding of
steroid metabolism my prevent therapeutic misadventures.
– 68 –
Abstract #185
GONADOTROPIN PRODUCING PITUITARY
TUMOR PRESENTING AS PITUITARY
APOPLEXY
Alejandra Nancy Santiago, MD,
Margarita Ramirez Vick, Endocrinology, and
Charles Spetch, Neuropathology
Objective: Earlier published pituitary tumor series
suggested thet gonadotropin producing adenomas were
uncommon.
Case Presentation: A 28 year old man with a history
of progressive left eye blindness since 7 years ago was
admitted to the hospital due to sudden onset of a left
retroorbital excrutiating headache, associated with tonicclonic seizure. Brain CT scan revealed a subarachnoid
hemorrhage, pituitary MRI showed a 5cm x 5cm x 5.3cm
sellar and suprasellar mass with extension into sphenoid
sinus. A pituitary apoplexy was dg. and he was started on
high dose IV steroids. Past medical Hx was unremakable,
except por the left eye blindness. No symptoms suggestive
of pituitary hormone deficiency or excess. Pt.has a 2 year
old child. Pt. was well virilized, without testicular atrophy.
Labs revealed cortoisol AM 1.9, prolactin 0.8 IGF-1 205,
free T4 0.84, total testosterone 219(241-827), free testosterone 32 (40-250), FSH 187.89 (1.4-118.1), LH 3.1 ( 1.59.3), free alpha subunit 3.1(0-.8). Craniotomy was
performed. Pathologic report revealed tumor cells chromogranin and Kermix positive;relatively large areas were
occupied by LH and FSH positive neoplastic cells.
Neoplastc cells were negative for PRL, GH, TSH, ACTH.
Discussion: Despite the fact that clinical dg. may be
difficult due to an inefficient and episodic secretion of
gonadotropin hormone by these tumors wich do not cause
a recognizable syndrome, gonadotroph adenomas has been
recently found to be much more common than previously
thought. The prevalence of gonadotrope adenomas is
unkown and they are more common in men than in
women. An increase level of basal serum FSH concentration in a man who has an intrasellar mass lesion usually
indicates that the lesion is a gonadotroph adenoma.
Testosterone levels are usually low, despite the normal or
increase LH levels, reflecting reduced LH bioactivity or
the loss of normal LH pulsatility.The most common
observed glycoprotein hormone secreted is FSH, this may
be accompanied by an increase in circulating alpha subunit. Visual fiels loss is found in more than 70% of
patients. A history of normal pubertal development, sexual function and fertility in men with hypersecretion of FSH
suggests that the gonadotrope tumor developed spontaneously and did not result from primary hypogonadism.
The initial treatment is surgical resection, transphenoidal
surgery improves vision in most of patients.
Conclusions: Since these tumors are usually not associated with any clinical hormonal manifestation they usuall y become apparent when they grow large enough to
cause a local mass effect. Most pituitary adenomas classified previously as nonfunctioning can be shown to produce small amounts of intact glycoprotein hormones or
their alpha or beta subunits.
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ABSTRACTS – Reproductive Endocrinology
REPRODUCTIVE ENDOCRINOLOGY
Abstract #216
INFERTILITY AND HIRSUTISM IN A YOUNG
WOMAN - AN OVERLOOKED ETIOLOGY
Anshu Sood, MBBS, and Andjela Drincic, MD
Objective: 1.To recognize the various causes of hirsutism. 2.To approach hyperandrogenic state in women in a
stepwise manner.
Case Presentation: A 33 year old female presented with
progressive hirsutism. She was diagnosed with Polycystic
Ovarian Syndrome (PCOS) 13 years ago.She was unable to
achieve fertility despite treatment with Clomiphene and
Metformin. On examination her vitals were normal with BMI
of 34. She scored 24 on the Ferriman and Gallwey hirsutism
scoring scale. She had normal breast development (Tanner 5)
and female-type external genitalia. Laboratory tests revealed
normal electrolytes. Her 24-hour urine cortisol, serum prolactin, total and free testosterone, and thyroid function tests
were normal. Her serum DHEAS was elevated at 536 mcg/dL
(normal 23-236mcg/dl) and DHEA at 16.7 ng/ml (normal 1.97.9ng/ml).An MRI showed a 10mm left adrenal mass.ACTH
stimulation test showed a significant increase in serum 17hydroxyprogesterone from 918 ng/ml to 2170 ng/ml (postACTH) indicating Congenital Adrenal Hyperplasia (CAH). A
genotype analysis revealed CYP21A2 positivity, confirming
21-hydroxylase deficiency. She was started on oral dexamethasone (0.25 mg)and her serum DHEAS level has has
returned to 25 mcg/dL.
Discussion: Hirsutism is excessive terminal hair growth
that appears in a male pattern in a woman. It is indicated by a
score of 8 or more on the Ferriman-Gallwey scale.It is idiopathic in half the women and in the rest hyperandrogenism is
the cause. Hyperandrogenism is most often caused by PCOS.
PCOS being a diagnosis of exclusion, it is important to
exclude other disorders with a similar presentation such as
CAH, Cushing’s syndrome and androgen–secreting tumors.
Late onset CAH accounts for 2.5% cases of hyperandrogenism. Routine testing with the ACTH stimulation test in
women with hyperandrogenic hirsutism will prevent missing
a treatable endocrine lesion (CAH). CAH result from deficiencies, or complete absence, of enzymes involved in adrenal steroidogenesis. 21-hydroxylase (CYP21A2) deficiency is
the most common enzymatic defect, accounting for 95% of
cases. In addition to cortisol deficiency, aldosterone secretion
is decreased in one-third of the patients. Thus adrenal virilization occurs with or without a salt-losing tendency. In adults
with late-onset adrenal hyperplasia, the smallest single bedtime dose of glucocorticoid that suppresses pituitary ACTH
secretion is administered.
Conclusions: The prevalence of polycystic ovaries in
patients with CAH is up to 85%. Elevated androgen levels of
adrenal origin stimulate the excessive growth of small follicles and stroma and inhibit ovulation. Subfertitliy in patients
with CAH is multifactorial and requires endocrine, surgical
and psychological management. Routine testing with the
ACTH stimulation test in women with hyperandrogenic hirsutism will prevent missing a treatable endocrine lesion
(CAH).
Abstract #274
PERRAULT SYNDROME (GONADAL DYSGENESIS
WITH SENSORINEURAL DEAFNESS) IN TWO
SIBLINGS
Jubbin Jagan Jacob, MD, Thomas V. Paul, DNB,
Suma S. Mathews, MS, and Nihal Thomas, FRACP
Objective: To report two siblings with Perrault syndrome
and marfanoid body proportions expanding the spectrum of
the disease.
Case Presentation: The older of the siblings presented
initially with hearing loss related to bilateral Sensorineural
deafness (SND) (Figure 1). A year later she presented with
primary amenorrhea and failure to develop any secondary
sexual characteristics. Investigations revealed elevated
gonadotropins, a normal karyotype and non visualized
ovaries. She was 169cm tall and weighed 56kgs. Her body
proportions were Marfanoid with an arm span of 182 cm and
an upper segment: lower segment (US: LS) ratio of 0.78:1.
She had long slender fingers with a positive wrist and thumb
signs. The eye, neurological and cardiovascular systems were
normal. The younger sibling had been brought to our clinic at
the age of 16 yrs with complaints of primary amenorrhea and
lack of secondary sexual development. She also complained
of a progressive decline in hearing. She was 162 cm tall and
weighed 40kgs with an US: LS ratio of 0.78: 1. She had long
slender fingers, high arched palate and positive thumb and
wrist signs. She also had elevated gonadotropin levels and
normal karyotype and non visualized ovaries. ENT evaluation
revealed severe SND.
Discussion: The presentation of the siblings with primary amenorrhea, underdeveloped genitalia, normal female
karyotype and significant SND was consistent with the diagnosis of Perrault syndrome. The pathogenetic relationship
between ovarian dysgenesis and SND is unclear. SND appears
to be a part of a more widespread neurological involvement
seen in a subset of patients with Perrault syndrome. The other
involvement included mental retardation, ataxia, hypotonia,
weakness, spastic diplegia and epilepsy and severe peripheral
neuropathy. SND may represent the first step of a more widespread neuronal degeneration. Both our patients have no addi-
– 70 –
ABSTRACTS – Reproductive Endocrinology
tional neurological involvement. The findings of abnormal
body proportions noted in our siblings have not been previously reported. Both our siblings had abnormal body proportions with high arched palate and long fingers with positive
wrist and thumb signs. The genetic basis of PS is still unclear.
The disease may represent a heterogeneous group of genetic
disorders with multiple gene defects. Preliminary studies on
the first PS family reported has mapped the defect to the long
arm of chromosome 5.
Conclusions: Perrault syndrome represents a spectrum of
disorders characterized by 46 XX gonadal dysgenesis and
neurological involvement commonly SND. Body proportions
and skeletal features of Marfan’s syndrome not reported previously maybe be part of the extended phenotype or may represent a coincidence. As SND may represent the first step to
more widespread neurological degeneration patients should to
be carefully followed up for development of central and
peripheral neurological deficits.
Abstract #126
46, XX MALE WITH SRY GENE TRANSLOCATION
Ali Abbas Rizvi, MD, FACE
Objective: Among the genetic causes of primary hypogonadism in the adult male, we describe a rare etiology that can
be easily overlooked
Case Presentation: A 33-year-old male was seen for
infertility, azoospermia, and primary hypogonadism with total
testosterone 207 ng/dl (241-827), free testosterone 6.0 pg/ml
(8.7-25.1), LH 23.0 mIU/ml (1.5-9.3), FSH 46.1 mIU/ml 1.68.0), and normal prolactin, estradiol, and thyroid function). He
and his wife had been unable to conceive for 3 years. Onset of
puberty was at age 13, he denied problems with libido or erections, and there was no history of trauma or radiation exposure, or anabolic steroid use. BMI was 29.7 with normal body
proportions, Tanner stage 5 pubic hair and penile development, and small testes with a volume of 5-7 ml confirmed on
scrotal ultrasound . Cytogenetic and fluorescent in situ
hybridization (FISH) studies revealed a male with disomy X
in which one copy of the X was a derivative containing the
sex-determining region of chromosome Y (SRY) on its distal
short arm. The karyotype was 46, X, der (X) t (X;Y) (p22.3;
p11.3) (SRY+) at the 450-band level. This finding was consistent with that of a 46, XX, SRY positive male. Genetic
counseling was offered and testosterone therapy started.
Discussion: 46, XX genotype with male phenotype is a
rare abnormality occurring in one out of every 20,000 males.
It has different genetic causes and resultant variable phenotypic features. 80% are ‘SRY positive’, where the Y chromosome fragment transfers to the short arm of an X chromosome
by unequal interchange between homologous regions during
paternal meiotic division. Clinical manifestations include testicular atrophy, primary hypogonadism, hyalinization of the
seminiferous tubules, azoospermia, and sterility. Less common findings are gynecomastia, cryptorchidism, and hypospadias. Diagnosis may be difficult, delayed, or missed because
most individuals have normal puberty, libido, erections, and
secondary sex characteristics; body proportions, stature, intelligence, and behavior are usually normal; external genitalia
abnormalities (except testes) and sexual ambiguity are seldom
seen; and subjects may not seek care for small testicular size
due to embarrassment or unawareness. XX karyotype in a
male is followed by FISH studies to locate the Y sequences to
distal Xp in metaphase chromosomes, and molecular amplification by Southern blot or PCR analysis to detect the presence
of the SRY gene.
Conclusions: SRY positive 46, XX male genotype is a
rare but important cause of primary hypogonadism, atrophic
testes, and infertility. Most cases are sporadic and may come
to light only later in life during evaluation for infertility.
Clinicians should maintain a high index of suspicion and
request cytogenetic analysis in the appropriate clinical circumstances. Genetic counseling is recommended to discuss
management options and deal address the psychological
impact of the diagnosis on the individual.
– 71 –
ABSTRACTS – Thyroid Disease
THYROID DISEASE
lence in the analyzed group and lower risk of malignancy
in nodules smaller than 10 mm allow to recommend
FNAB of nodules larger than 10 mm
Conclusions: Thyroid ultrasonography isn’t sufficiently predictive for malignancy of thyroid nodules. It
plays important role in qualification of thyroid nodule for
biopsy. Ultrasonography can indicate cases in which fineneedle aspiration of thyroid nodules is likely unnecessary.
This should simplify diagnostic algorithm of nodular goiter and allow to reduce costs of treatment. In the analyzed
group of Polish patient percentage of malignant or suspected cytological evaluation was relatively low
Abstract #184
ROLE OF ULTRASOUND IN PREDICTION OF A
RISK OF MALIGNANCY IN NODULAR GOITER
Maciej Jedrzejowski, MD, Janusz Nauman, MD, PhD,
Barbara Gornicka, MD, PhD,
Magdalena Bogdanska, MD, PhD, and
Ewa Bar-Andziak, MD, PhD
Objective: To assess US features of thyroid nodules
as predictors of malignancy and to establish criteria for
FNAB
Methods: Result of US scans performed on 1005
Polish patients with nodular goiter were correlated with
results of fine-needle aspiration biopsy obtained from
1041 nodules, that allowed to identify risk factors of
malignancy and to establish criteria for fine-needle aspiration biopsy
Results Benign cytological result was established in
867 cases (83,3%), suspected in 33 cases (3,17%), malignant in 20 cases. (1,92%). 11,6% of biopsies were nonconclusive. Multiple regression analysis demonstrated that
independent sonographic risk factors of malignancy are
hypoechogenicity, solid appearance, maximum diameter
of nodule between 2 and 3 cm and younger (<40) age of
patients. Fine-needle biopsy should be considered in case
of all solitary or dominant hypo- and isoechoic nodules
with largest diameter greater than 1 cm and hyperechoic
nodules between 2 and 3 cm, nodules with suspected US
appearance and in the presence of clinical risk factors. In
other cases clinical and sonographic follow-up can be recommended without fine-needle aspiration biopsy
Discussion: Prevalence of thyroid cancer in the analyzed population, lower than reported in the literature (2.930%), can be related to a high prevalence of multinodular
goiter in Poland, that has influence on the diagnostic
process of thyroid nodules. Many previous studies have
shown decreased risk of malignancy in multinodular goiter, but some recent studies don’t support this opinion.
Sonographic feature most predictive for thyroid malignancy was hypoechogenicity, with sensivity and specifity
similar to reported in other studies. Higher risk of malignancy in single nodules and nodules larger than 10 mm
can be confirmed by some but not all studies. Presence of
microcalcifications was of no use in determining the risk
of malignancy, probably because of a low prevalence of
this feature. Role of US in selection of thyroid nodules for
biopsy is well established. Our analysis show that US also
allows to select patients at low-risk, in whom FNAB is
likely unnecessary. This opinion is reflected in some studies and diagnostic recommendations. Low cancer preva-
Abstract #345
GRAVES' OPHTHALMOPATHY- AN IMITATOR
Anjana Myneni, MD, Panchali Khanna, MBBS,
Saleh Aldasouqi, MD, Mark DeLano, MD, and
Ved Gossain, MD
Objective: We present a fascinating case of Orbital
Pseudotumor masquerading as Graves'Ophthalmopathy.
Case Presentation: 59-year-old woman with history
of Graves’ disease, treated with radioactive iodine ablation twenty years prior and subsequently on thyroxine
replacement therapy presented to our clinic with symptoms of bulging and puffiness of her right eye, for two
months. She complained of retro orbital pain, blurring of
vision and excessive lacrimation. These symptoms progressively worsened and also involved her left eye. She
had bilateral proptosis, periorbital swelling and reduced
ocular motility on examination. She denied other symptoms suggestive of thyroid dysfunction and recent thyroid
functions revealed TSH 5.43 mIU/ml, free T4 1.38 ng/dl
and free T3 2.3 pg/ml. Initial impression was Graves’ ophthalmopathy, however an MRI of the orbits was obtained
to rule out other orbital pathologies. The MRI showed evidence of significant inflammatory changes involving the
extra ocular muscles, retro bulbar fat, lacrimal glands,
posterior sclera and subcutaneous pre-septal soft tissues.
The optic nerve and intracranial structures were normal. A
diagnosis of orbital pseudotumor was made.
Discussion: Orbital pseudotumor is a rare disorder,
yet the third most common disease of the orbit. The first
two are Graves’ Ophthalmopathy(GO) and lymphoproliferative disease. Orbital pseudotumor shows significant
inflammatory changes of almost all orbital structures, as
described in our case. It may occur as an acute, sub-acute
or chronic form. Etiology is unknown and pathology consists of chronic inflammatory infiltrates and fibrosis. In
contrast, GO occurs due to deposition of glycosaminoglycans between muscle fibers and adipose tissue. GO is postulated to occur due to antibody production against orbital
– 72 –
tissue and activation of fibroblasts. Involvement of
lacrimal glands, sclerae and inflammatory cell infiltrates
have not been described in GO. In cases where clinical and
radiological picture do not confirm diagnosis, tissue biopsy should be considered. Orbital pseudotumor may
progress, if left untreated, to cause vision loss and diplopia. Intracranial extension has also been described. A short
course of high dose steroids will lead to rapid improvement in almost all patients. Rare cases of steroid resistance
or relapse have been described.
Conclusions: Orbital Pseudotumour is a rare ophthalmologic condition that mimics a variety of pathologic
processes, creating a diagnostic dilemma. We aim to
increase awareness among our colleagues and highlight
the significance of considering this entity as an important
differential diagnosis in patients presenting with ophthalmopathy. A careful history, physical examination and
appropriate imaging are essential in arriving at the correct
diagnosis.
Abstract #301
HASHIMOTO’S ENCEPHALOPATHY TREATED
WITH PLASMAPHARESIS AND
THYROIDECTOMY
Meijuan Zhang, MD, Allan D. Marks, MD, and
Elias S. Siraj, MD
Discussion: HE was fist described in 1966. It is a rare
condition observed in a small percentage of patients with
autoimmune thyroid disease, mostly Hashimoto’s thyroiditis, to a lesser extent, Graves’ disease. These patents
have neurological and/or neuropsychiatric manifestations
of encephalopathy in the absence of other known causes.
This condition generally responds to high dose steroid
treatment. Our patient had a suboptimal response to
steroids, making alternative therapy necessary. The pathogenesis of HE is unknown, although an autoimmune
mechanism is likely. The excellent response of this patient
to plasmapharesis supports an autoimmune etiology.
Previous reports suggest that thyroid antibody titers do not
correlate well with the clinical severity of HE. The definitive cure of HE by thyroidectomy in this patient indicates
a direct association between autoimmune thyroid disease
and HE. It is possible that these patients may harbor some
rare unknown thyroid antibodies that induce encephalopathy, but this remains to be proven. In the mean time, we
support the proposal that this syndrome be referred as
“Encephalopathy associated with autoimmune thyroid disease”.
Conclusions: Encephalopathy can present in association with Graves’ disease. High doses of glucocorticoids,
plasmapharesis and thyroidectomy represent viable treatment options.
Abstract #373
Objective: To report the first case of Graves’ disease
associated encephalopathy, requiring plasmapharesis, and
cured by thyroidectomy.
Case Presentation: A 55 year old women with a past
medical history significant for asthma, hypertension and
depression, presented with clinical and biochemical findings consistent with hyperthyroidism secondary to
Graves’ disease. An elevated TSH receptor antibody level
confirmed the diagnosis. Treatment with PTU was initiated. At the same time, the patient was found to have severe
cognitive dysfunction which persisted even after she had
achieved a euthyroid status. An MRI of the brain demonstrated a non-specific pattern of demyelination in the subcortical frontal and periventricular regions. After ruling
out other possible causes, a presumptive diagnosis of
Hashimoto’s encephalopathy (HE) associated with her
Graves’ disease was made. Treatment with a tapering
course of high dose glucocorticoids led to some, but inadequate improvement. Plasmapharesis instituted 3 times a
week led to a dramatic improvement of her symptoms.
Ultimately, thyroidectomy was performed leading to normalization of her cognitive function, which was maintained until her last follow-up visit 1 year after the
thyroidectomy.
OVERT HYPERTHYROIDISM IN METASTATIC
GESTATIONAL TROPHOBLASTIC DISEASE
Amy Maria Toscano-Zukor, DO, and
Xiangbing Wang, MD
Objective: To report a case of overt hyperthyroidism
induced by high hCG in a woman with metastatic gestational trophoblastic disease.
Case Presentation: A 31-year-old woman was diagnosed with gestational trophoblastic disease (GTD)
metastatic to the lungs and admitted to our institution for
chemotherapy. Two months prior to admission, she began
experiencing weight loss, nausea, vomiting, palpitations,
and clammy skin. Admission laboratory data were as follows: serum hCG > 600,000 mIU/mL, TSH <0.01
mIU/mL (0.35-5.5), free T4 3.09 ng/dL (0.9-1.8), total T3
by radioimmune assay 427 ng/dL (60-181), and thyroid
stimulating immunoglobulins 97% (0-129). On physical
examination, her pulse was 100 bpm. She was thin, had a
non-tender mildly enlarged thyroid gland without bruit or
nodules, and bilateral hand tremors. The remainder of her
examination was unremarkable. Propranolol 40 mg TID
was given for symptomatic treatment; no anti-thyroid
– 73 –
agents were given. She was discharged on propranolol
after completing chemotherapy. Two weeks later, she had
no hyperthyroid symptoms, her pulse was in the 60s, and
she had gained five pounds. Bloodwork revealed a TSH
<0.01 mIU/dL, normal free T4 1.28 ng/dL, normal total
T3 107 ng/dL, and hCG 8275 mIU/mL.
Discussion: Hyperthyroidism has been reported in
patients with GTD as a result of the intrinsic TSH-like
activity of high concentrations of hCG. The management
of overt hyperthyroidism, an uncommon complication of
malignant GTD, is controversial. Methimazole or propylthiouracil have delayed effects, and their potential to
cause granulocytopenia in a patient already receiving
chemotherapy made them unfavorable options in this case.
Furthermore, thyroidectomy and 131I therapy would not
have been good choices for her. Using propranolol to
relieve this patient’s hyperthyroid symptoms while waiting for the hCG levels to be lowered by chemotherapy was
a wise management decision in this situation.
Conclusions: We report a case of overt hyperthyroidism secondary to high hCG levels in a patient with
malignant GTD. Her hyperthyroid symptoms were
relieved and the thyroid hormone levels decreased to normal only two weeks after her first cycle of chemotherapy,
without the addition of anti-thyroid medications. In conclusion, hyperthyroidism induced by elevated hCG in
metastatic GTD can be safely treated by lowering hCG
levels with chemotherapy, while reducing symptoms of
hyperthyroidism with propranolol.
Abstract #163
THE PECULIARITIES OF CARDIAC COMPLICATIONS OF THYROTOXICOSIS IN NIGERIANS
Anthonia Okeoghene Ogbera, MBBS, FMCP,
Isiba Abiodun, MBBS, and
Fasanmade Olufemi, MBBS, FWACP
Objective: The study sets out to determine the incidence and the scope of the cardiovascular complications
that occur in thyrotoxicosis
Methods: Patients with clinical and biochemical evidence of thyrotoxicosis were evaluated for features of cardiac morbidity.The presence of arrythmias, hypertension
and features of heart failure were sought for.Laboratory
investigations included Free T3, T4, TSH, C-Xrays, ECG
and echocardiography.
Results Of a total of 103 subjects with thyrotoxicosis,
28(27%) had cardiac complications (TC) thus giving an
incidence rate of thyrocardiac disease as 27%. The M:F
ratio was 1:5. Mean age of the (TC) group was
40.8±14.6yrs and the non-TC group was 39.3.±12.6yrs.
The age range in years of the TC and non-TC group were
12-69 and 13-73 respectively. P values for this data were
> 0.05 In the TC group, Atrial fibrillation (AF) was seen
in 7 (25%), heart failure (HF) in 12 (42%) and hypertension in 15(53%). AF precipitated HF in 5(42%) of those
presenting with HF.Bradycardia was seen in one subject.
Echo features noted were dilated heart wall ,impaired systolic function, reduced ejection fraction and fractional
shortening in some subjects with HF.
Discussion: The incidence rate of the cardiac complications of thyrotoxicosis at 27% is much higher than in
previous Nigerian reports. Though cardiac complications
of thyrotoxicosis have been reported to be common in the
elderly, this report shows that it occurs in the young as
well as the old- the mean age of occurrence of cardiac
complications of thyrotoxisis being 40.8 years. Mean age,
BMI and weight of the subjects with with cardiac complications were comparable to those without cardiac complications. There was no significant differences in these
indices. All the subjects with cardiac complications of thyrotoxicosis had overt features of thyrotoxicosis. There was
a female preponderance in all three stated cardiac complications as opposed to reported male predilection . Sinus
rhythm was restored within 3 months on beta blockers and
carbimazole in those with AF and without HF.
Bradycardia may be a presenting feature of thyrotoxicosis.
Hypertension is the predominant cardiac complication
noted and this was followed by heart failure.As opposed to
Western reports, diastolic and systolic hypertension
occurred at about the same frequency. A common precipitant of heart failure was AF.
Conclusions: This report has emphasized the importance of thyrotoxicosis as a cause of cardiac morbidity and
mortality in Nigerians with thyrotoxicosis.It has also
shown that cardiac complications occur even in the young
and with a predilection in females.In Nigerians, cardiac
complications of thyrotoxicosis occur in the elderly usually accompanied by florid clinical features of the disorder.These complications are readily reversible if there is
timely optimal treatment of the underlying thyrotoxicosis.
Abstract #278
OUTCOMES FOLLOWING FIXED DOSE I-131
THERAPY FOR GRAVES’DISEASE(GD)AND A
LOW IODINE DIET
Jubbin Jagan Jacob, MD, Regi Oommen, MD,
Charles Stephen, PhD, and Mandalam S. Seshadri, PhD
Objective: To study the clinical outcomes in terms of
thyroid functions and overall cure rates at 3 and 6 months
after fixed dose I-131 therapy for Graves’ disease with an
iodine restricted diet.
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Methods: Consecutive adult patients with GD
planned for I-131 therapy were block randomized either to
receive instructions regarding dietary iodine restriction or
no advice prior to fixed dose (5 mCi) I-131 administration.
Urinary iodine excretion rates were assessed at 3 & 6
months to document adequate iodine restiction in diet.
Data was analysed using SPSS V 11.0 (Chicago IL USA)
software at the end of 6 months regarding development of
hypothyroidism, requirement of L-T4 and cure of hyperthyroidism at 3 and 6 months.
Results Forty seven patients (13M & 34F) were
assessed, 2 were excluded and 45 were randomized (Cases
24 & Controls 21) in the study. 39 patients completed the
study and were included in the final analysis. Baseline
data was comparable (Table 1). Median Urinary Iodine
concentration was 115 and 273 mcg/gm creat (p= 0.001)
among cases and controls respectively. Outcomes at the
3rd month were as follows (cases & controls): Euthyroid
(10&6:p=0.24), Hypothyroid (3&5:p=0.38) and
Hyperthyroid (7&8: p=0.64). Outcomes at six months
were as follows (cases & controls): Euthyroid
(10&5:p=0.12), Hypothyroid (3&5:p=0.38) and
Hyperthyroid (7&9:p=0.43). Of the hypothyroid patients 5
(cases 1 & controls 4: p = 0.13) required thyroxine
replacement. Thirteen patients were considered cured
among the cases compared to 10 among the controls
(p=0.43.
Discussion: The increased incidence of autoimmune
thyroid disease among genetically susceptible individuals
with increasing dietary iodine has been demonstrated both
epidemiologically and experimentally. This study did not
reveal any statistically significant difference by restricting
iodine in on the short term outcome of patients following
radioactive iodine therapy for Graves’ disease. A trend for
better cure rates and decreased requirement for levothyroxine replacement therapy at 6 months was observed with
iodine restriction; this was not statistically significant.
This trend, though not significant because of the small
sample size maybe related to the increased antigenicity of
thyroglobulin with excess iodine moieties. The ongoing
autoimmune process would accelerate the development of
hypothyroidism in a subset of patients and also result in
residual thyrotoxicosis in a second subset. The overall
cure rate with 5 mCi of 131I in this study was only a disappointing 51%. The dose used in this study was much
lower than conventional fixed dosing regime. A larger
sample size with a higher dose of 131-I might have given
different results.
Conclusions: There was no statistically significant
difference in the outcome of patients with dietary iodine
restriction following 131I therapy for Graves’ disease but
a trend towards better cure rates and decreased requirement for levothyroxine (L-T4) was observed.
Abstract #233
HYPOTHYROID MYOPATHY WITH
UNUSUALLY HIGH SERUM CREATINE KINASE
LEVELS (CPK)
Jasleen Kaur Duggal, MD, Sarabjeet singh, MD,
Paari Dominic, MD, and Charles Barsano, MD
Objective: Report an African-American male who
first presented with myopathy,markedly elevated serum
CPK secondary to hypothyroidism.
Case Presentation: We report a case of a 63-year-old
African-American male patient who presented to our institution with fatigue, swelling of the upper and lower
extremities .Physical examination was pertinent for a
lethargic and slow gentleman with sinus bradycardia of 58
beats/min,non-pitting edema and delayed relaxation of
deep tendon reflexes.He had markedly elevated serum creatine phosphokinase (CPK) concentration of 6014(normal=22-269 IU/L).and high aldolase. Review of the
patients records showed consistently elevated CPK levels,
ranging in between 2000 and 4000 IU/L.High CPK on a
previous visit was attributed to statin-induced myopathy.
Progression of symptoms with persistently elevated muscle enzymes after discontinuation of the statin led to further investigation and a diagnosis of hypothyroidism (TSH
>37 IU).The patient responded well to levothyroxine therapy with prompt resolution of symptoms within 1 month
and complete normalization of serum free thyroxine and
TSH concentrations.CPK dropped down to a near normal
plateau and remained at that level on followup.
Discussion: Hypothyroidim is responsible for 5 % of
acquired myopathies.The musculoskeletal symptoms of
hypothyroidism are usually less prominent and late occurring than the other symptoms accompanying hypothyroidism ,so it is unusual to see them as the presenting
manifestations of the disease as in this case.The serum
CPK level is the most specific and useful biochemical
marker for monitoring the presence and magnitude of
myopathy. Other enzymes e.g. aldolase, AST, ALT, LDH
,have a complementary role in the absence of hepatopathy.
Our patient had elevated aldolase besides high CPK in the
background of normal liver enzymes which support the
evidence of myopathy resulting in his symptoms.This
patient began taking simvastatin for his hypercholesterolemia 2 years ago and not surprisingly his CPK elevations were attributed to statin-induced myopathy.
Worsening of his muscle aches coincident with the onset
of symptoms of hypothyroidism and an increasing CPK
concentration for 3 months after discontinuation of simvastatin led to diagnosis of hypothyroidism.Statin-induced
myopathies tend to resolve within a month after discontin-
– 75 –
uing statin.The EMG and muscle biopsy are not specific
for diagnosis.
Conclusions: 1.The symptoms and signs of myopathy
including an elevated CPK can sometimes be the initial
and /or most prominent manifestation of hypothyroidism.
2.Patients developing myopathy when taking statin therapy may be having underlying hypothyroidism which
should be tested. 3. Once hormonal reposition is started,
there is gradual resolution of hypothyroid symptoms and
thyroid function demonstrating that the myopathy is
reversible with good prognosis.
Abstract #199
INTERFERON INDUCED THYROID DYSFUNCTION IN A PATIENT WITH HEPATITIS C
Sahibzada Latif, MD, Anjana Myneni, MD,
Saleh Aldasouqi, MD, Ved Gossain, MD, and
Amir Azeem, MD
manifestation in patients treated with IFN alpha and ribavarin. In patients presenting with hyperthyroidism,
Graves’ disease like manifestation is the least common
form while destructive thyrotoxicosis has been more commonly observed. They can be differentiated by radioactive
iodine uptake or by measuring TSI levels. In our patient,
both elevated TSI and low radioiodine uptake were
observed, making this case a more puzzling diagnostic
dilemma for determining the type of hyperthyroidism. Her
precipitous course towards permanent hypothyroidism is
also unusual.
Conclusions: Pretreatment screening is recommended for all patients in whom IFN therapy is considered.
Concern about thyroid dysfunction need not be a contraindication to IFN therapy. However patients treated
with interferon and ribavarin should undergo routine
screening for thyroid disease. In general, discontinuation
of interferon therapy is seldom required.
Abstract #413
Objective: We report a unique case of Interferoninduced thyroid dysfunction with a rapidly progressing
course towards hypothyroidism.
Case Presentation: The patient is a 41-year-old
woman with hepatitis C, who was started on IFN-alpha
and ribavarin one month prior to consultation. Her pre
treatment TSH was 4.8-mIU/L. She presented with palpitations, tremors and weight loss. On physical examination
the thyroid was enlarged and tender without nodules or
bruit. Her thyroid function tests (TFTs) revealed TSH <
0.01, normal free T4, elevated T3 with positive thyroid
stimulating immunoglobulin (TSI), thyroglobulin and
thyro-peroxidase antibodies. Treatment with atenolol and
methimazole was started for suspected Graves’ disease
based on positive TSI. Further work up with a thyroid
uptake and scan showed decreased iodine uptake (methimazole was stopped for at least one week prior to the scan)
which is suggestive of thyroiditis. Repeated thyroid function tests (TFTs) after 8 weeks of methimazole treatment
revealed a TSH >150 and very low levels of T3 and T4.
Both methimazole and atenolol were discontinued and follow up TFTs after few weeks revealed persistent hypothyroidism. Subsequently patient was started on
levothyroxine treatment.
Discussion: Autoimmune thyroid dysfunction has
been described as an extra hepatic manifestation of chronic hepatitis C infection, and this disorder can be exacerbated by IFN alpha. Positive thyroid antibodies with
normal TFTs is the most common finding in patients treated with IFN alpha, while thyroid dysfunction has been
described in less than 15% of cases. Thyroid dysfunction
may present as hypothyroidism, destructive thyrotoxicosis
or Graves’ disease. Hypothyroidism is the most common
POSITIVE THYROID CANCER FDG-PET SCANS
ARE RELATED TO AN ADVERSE OUTCOME
Donald Bodenner, MD, PhD, Carolyn Redman, BA,
Brendan Stack, MD, and Paul Spring, MD
Objective: We asked whether there is a significant
difference in several clinical variables between postoperative PET positive and PET negative scans in thyroid cancer patients.
Methods: The records of 30 patients with a history of
thyroid cancer who had received a PET scan postoperatively were reviewed. Clinical variables abstracted from
each patient's record included PET results, imaging, I-131
avidity, thyroglobulin, diagnoses, and disease progression.
The progression interval was defined as the length of time
between the PET scan and the most recent imaging.
Results PET positive scans showed significantly more
progression than did PET negative scans. The average
PET positive progression interval was 9.78 months and the
PET negative progress interval was 12 months. Of the
PET positive patients, 45% demonstrated progression as
opposed to 20% of the PET negative patients. Of the 38
evaluable PET scans, five were false-positive and one was
false-negative. Tall cell and sclerosing variant of papillary
thyroid cancer were associated with positive FDG-PET
uptake.
Discussion: Although patients with well differentiated thyroid carcinoma (WDTC) generally have an excellent
prognosis a small subset of patients will do poorly.
Staging methods have been developed as general prognostic indicators, but there is currently no standardized
method of identifying virulent tumors in individual
– 76 –
patients. WDTC are radioiodine avid and exhibit high
FDG-PET uptake less often than poorly differentiated carcinomas, such as insular or anaplastic thyroid carcinoma,
types generally associated with a reduced survival rate.
Our results suggest that thyroid cancer patients with a positive FDG-PET scan after their initial surgery will have
faster disease progression than FDG-PET negative
patients and that more aggressive variants of WDTC are
often FDG-PET positive. This would imply that FDG-PET
may be useful as a staging tool. We also corroborate others finding that FDG-PET positivity is inversely related to
radioiodine avidity.
Conclusions: FDG-PET positive patients progressed
more than two times the progression rate of FDG-PET
negative patients. High FDG-PET uptake was associated
with more virulent forms of well differentiated thyroid
cancer and varied inversely to iodine avidity.
Abstract #380
oral thyroid replacements are Celiac disease,
Psuedomalabsorption (failure on part of the patient to take
the medication) and interference with intestinal absorption
with other drugs. The patient described here had no celiac
disease, was compliant and took the thyroid supplements
on an empty stomach, under supervision, with no interference from other drugs. Literature review showed very few
reported cases of selective thyroid hormone malabsorption
in the absence of celiac disease, pseudo-malabsorption or
drug interference. A good response to parenteral thyroid
replacement was documented in these cases. In our clinical scenario too the patient appeared to have some
response to intravenous thyroid replacements during hospitalization, while she remained refractory to oral treatment and did not respond adequately to intramuscular
injections.
Conclusions: This is a rare case where the oral thyroid hormone therapy was not effective necessitating the
use of parentral thyroid hormone replacement.
HYPOTHYROIDISM REFRACTORY TO
THYROID HORMONE SUPPLEMENTATION
Abstract #140
Krithi Bangalore Ramesh, MD, and
Opada Alzohaili, MD FACE
PRIMARY HYPERTHYROIDISM IN
ASSOCIATION TO HYPEREMESIS
GRAVIDARUM
Objective: We present an unusual case of hypothyroidism that was refractory to oral thyroid hormone supplementation.
female with a history of hypothyroidism on very high
doses of oral levothyroxin, was seen for persistent symptoms of hypothyroidism. Labs showed a high TSH of 58.8
and a low Free T4 of <0.2 despite compliance with daily
levothyroxin of 300mcg/day. Trials were done in the
office under direct supervision with different formulations
of oral levothyroxin and also single high dose L-thyroxin
1000mcg on different days. Free T4 level was measured at
one, two, three and four hours after the administration of
medications. Free T4 remained undetectable. Supervised
trials with oral T3, cytomel, thyrolar and armour thyroid
also failed to suppress TSH and raise serum thyroid hormone levels. A work up for malabsorption syndromes was
negative. The patient however reported a significant
improvement in her symptoms when she was given intravenous thyroid replacements during a short period of hospitalization. A trial with 300mcg of intramuscular thyroid
injection was done in office, which raised the serum thyroxin levels only mildly.
Discussion: Hypothyroidism is well controlled in
compliant patients with adequate doses of oral thyroid
hormone supplements. In a minority of patients, an adequate response to thyroid hormone replacement is not
observed.The most common explanations for failure of
German Velasco, MD, Munira Siddiqui, MD,
Sonia Jauhar, MD, and Edward Colt, MD
Objective: To illustrate the significance of controlling
hyperthyroidism in reproductive-age women to avoid
complications in pregnancy.
Case Presentation: A 29 year-old woman with 10
weeks of pregnancy presented to the ED with a 10 day history of nausea and intractable vomiting. She reported
weight loss of 30 lbs over the last 6 months. She was found
to be dehydrated, tachycardic, but normotensive. An initial
diagnosis of HG was made (quantified B-human chorionic gonadotropin (B-hCG) 118,000 mIU/ml) and she was
admitted to the hospital for IV hydration and anti-emetic
therapy. Additional data showed decreased levels of thyroid stimulating hormone <0.03 mU/mL and elevated levels of free thyroxine (3.2 ng/dL) and free triiodothyronine
(5.5 ng/dL). Upon further history and evaluation, it was
found that she had been diagnosed with primary hyperthyroidism 8 months prior to admission; however, was not
taking any anti-thyroid medications. She was then started
on treatment for hyperthyroidism in the setting of HG with
propilthiouracil (PTU) 100mg per mouth q8h with frequent monitoring of thyroid function tests (TFT’s), PTUinduced side effects and fetal distress. HG resolved and
PTU therapy and pregnancy continued without complications.
– 77 –
Discussion: This case illustrates the significance of
controlling hyperthyroidism in women of reproductive age
to avoid complications during pregnancy. The assessment
of elevated TFT’s during pregnancy and pregnancy-associated conditions such as HG and gestational trophoblastic
disease (GTD) can be more challenging. These conditions
can further increase TFT’s by increasing the levels of BhCG promoting a transient hyperthyroidism which may
not require anti-thyroid medications. However, the presence of primary hyperthyroidism or symptomatic hyperthyroidism even in the setting of HG or GTD should be
treated in order to prevent complications with the pregnancy.
Conclusions: Although the management of hyperthyroidism is fairly well known by general practitioners and
internists, additional challenges are seen in the setting of
pregnancy, HG or GTD requiring a multidisciplinary
approach from obstetricians, endocrinologists and general
practitioners. Recognition of abnormal thyroid function
and its correction is key for the outcome of a healthy pregnancy.
Discussion: A search of the literature has revealed
only one other case report of a similar complication of
radioactive iodine therapy for thyroid disease. While a
direct relationship is not certain, it is quite likely that the
radioactive iodine was the causative agent. Additionally,
this patient was taking immunosuppressive agents. What,
if any, affect the patient's immunosuppresed state or medications may have had is uncertain.
Conclusions: This case describes a very rare, but
potentially serious complication of radioactive iodine therapy. While the patient in this case had Graves' disease,
parapharyngeal edema may be a complication of radioactive iodine therapy for other forms of thyroid disease. A
complaint of shortness of breath, stridor, or significant
neck discomfort must be taken seriously in patients with
thyroid disease who were recently treated with radioactive
iodine.
Abstract #305
FEVER AND SUBACUTE THYROIDITIS:
MISSING THE BOAT
Abstract #347
Richard W. Pinsker, MD, FACE, Naeem Chaudhry, MD,
Prachi Dharia, MD, Kaushik Doshi, MD, and
Manuel Gonzalez, MD
AN UNUSUAL COMPLICATION OF
RADIOACTIVE IODINE THERAPY FOR
GRAVES' DISEASE
Michele L. Ledoux-Pascucci, DO, and
John T. O'Brian, MD, FACP, FACE
Objective: To describe an unusual complication of
radioactive iodine therapy for the treatment of Graves' disease.
Case Presentation: A 53 year old female with a history of rheumatiod arthritis, hypertension, and osteoporosis was seen for treatment of Graves' disease. The patient
had been receiving methimazole 10mg twice daily; as well
as alendronate, methotrexate, and infliximab. The patient
desired definitive treatment for Graves' disease. The
patient received 29.4 mCi of 131-Iodine. Three days after
completing treatment, the patient developed dyspnea and
stridor. She was evaluated in the emergency room with a
CT scan of the neck that revealed marked prevertebral and
parapharyngeal edema with posterior impression on the
oropharynx. The edema extended from the nasopharynx to
the thyroid gland. There was also fascial edema in the
neck and strap muscles. The thyroid was enlarged but not
edematous or inflamed. The patient was treated with intravenous steroids and did not require airway intervention.
She was transitioned to oral steroids and a repeat CT scan
revealed improvement of the edema. She slowly recovered
and had persistant pain and inflammation in her strap muscles for 14 days after the therapy.
Objective: To demonstrate two consecutive cases
where fever was followed by a lengthy workup before subacute thyroiditis was identified.
Case Presentation: Two cases were seen on the
endocrine service consecutively with significant similarities. Case#1: A 47 year old female was admitted with
seven days of flank pain, malaise, and fever spiking as
high as 103 degrees F. Urine exam was essentially negative. WBC 10.3. Pancultures were negative. CT of
abdomen and pelvis with contrast were negative. After a
few days patient complained of neck pain and endocrine
consult called. At consult, thyroid appeared about 50
grams and was exquisitely tender, pulse 100 with sweaty
skin and fine tremors. Neck uptake could not be done
because of contrast. Free T4 2.7, TSH <0.05, ESR 86 and
TG 97 with antibodies present. Patient dramatically
improved with propranolol and ibuprofen. Pain and fever
ceased. Six weeks later Free T4 0.7 and TSH 3.91. Case
#2: A 61 year old male had two weeks of painful swallowing, weight loss, one week fever up to 102 F. Upper GI
endoscopy was negative. CT neck with contrast was negative. Thyroid was about 40 grams and tender. Free T4
3.5, ESR 97, TG 105 with antibodies. All symptoms disappeared with same Rx.
Discussion: Subacute thyroiditis typically presents
with malaise, neck pain, and fever. Initially, patients present with typical signs of hyperthyroidism. On exam, the
– 78 –
thyroid is usually tender and patients are uncomfortable
with pressure. Unfortunately, the diagnosis of fever often
leads to a backwards approach of making the diagnosis. In
our first case, the patient had flank pain and fever, leading
to a sepsis workup. When thyroiditis was considered, the
prior contrast use negated a neck uptake. Clinically, the
diagnosis was fairly obvious, and treatment with an
NSAID and beta-blocker rapidly led to improvement. In
the second case, "dysphagia", weight loss, fever, and age
led to erroneous consideration of a neoplasm and contrast
again negated possibility of neck uptake. Clinical diagnosis and same treatment prompted rapid resolution, including the swallowing disorder and gain of weight lost.
Conclusions: Subacute thyroiditis must always be
considered when the classical symptoms are present.
However, fever, advanced age, and unrelated symptoms
may delay the diagnosis of this easily treated illness as
illustrated in our two consecutive consultative cases.
Abstract #283
PAPILLARY THYROID CARCINOMA IN
PATIENTS YOUNGER THAN TWENTY YEARS
OLD
Sheng-Fong Kuo, MD, and Jen-Der Lin, Professor
Objective: Controversies remain regarding to treatment methods and cancer staging for papillary thyroid
cancer (PTC) in young patients.
Methods: From January 1977 to June 2006, patients
younger than 20 years old were included and retrospectively studied. They are divided into disease-free and nondisease-free status at the end of follow-up. We try to find
the prognostic factors and the correlation between cancer
stage and disease status.
Results Totally 77 patients younger than 20 years
were retrospectively studied. The follow-up periods were
one month to 27 years with an average of 10.4 years. Two
patients died of thyroid cancer during the follow-up period; one of the patients died of brain metastasis and the
other died of airway obstruction. Patients undergoing total
thyroidectomy has better outcome than patients not undergoing total thyroidectomy. The younger age and the larger primary tumor size are related to the persistence of
disease in this study. Besides, clinical stage suggested by
DeGroot other than TNM stage issued by American Joint
Committee on Cancer (AJCC) could make better distinction between patients with disease-free and those ended up
with non-disease-free status in this study.
Discussion: Papillary thyroid carcinoma (PTC) is not
common in patients below 20 years old. In this study, the
goal of treatment of PTC is disease eradication, and recurrence-free survival which is a desirable status in children.
Our results show that larger tumor size or younger age is
related with non-disease-free status in PTC patients
younger than 20 years old and patients underwent total
thyroidectomy had a better prognosis than patients without
total thyroidectomy. However, further study is needed
because that perhaps not enough case numbers in our
study. Although there is no statistical difference, clinical
stage has better correlation with disease status in these
patients than TNM stage because all non-disease-free
patients are classified as stage III or IV, and none are in
stage I or II. However, five patients who are classified as
stage I according to TNM stage are actually in non-disease-free status, including one patient died from airway
obstruction. In our opinion, it is not objective that all
patients younger than 45 years old are grouped into one
stage by TNM stage, regardless of local tumor invasiveness.
Conclusions: The prognosis of young patients with
papillary thyroid cancer is not worse. The treatment outcome might be better in Patients undergoing total thyroidectomy than patients not undergoing total
thyroidectomy. The age and the primary tumor size are
related to the persistence or absence of disease in these
patients. Clinical stage other than TNM staging might be
another good alternative for PTC patients younger than 20
years old.
Abstract #391
FDG-PET POSITIVE THYROID
INCIDENTALOMAS: A MOTLEY CREW
Anjali Bhagra, MBBS, Sumit Bhagra, MBBS, and
Vahab Fatourechi, MD
Objective: PET positive thyroid incidentalomas
remain a diagnostic challenge as they represent a heterogenous group.
Case Presentation: Unilateral PET positivity in
Hashimoto’s thyroiditis: A focal PET abnormality was
incidentally detected in the right thyroid lobe (fig. 1a) in a
48 year old woman. Thyroid ultrasound showed a 1.5 centimeter hypervascular nodule corresponding to palpable
nodularity in the right thyroid lobe (fig. 1b). Fine needle
aspiration (FNA) of the nodule was benign and consistent
with Hashimoto’s thyroiditis. Bilateral PET positivity in
Hashimoto’s thyroiditis: Diffusely enhanced FDG uptake
was detected in both thyroid lobes in a 63 year old man
(fig. 2a) who was otherwise euthyroid, clinically and biochemically. Thyroid ultrasound and elevated thyroperoxidase antibodies were consistent with a diagnosis of
Hashimoto's thyroiditis (fig. 2b). Papillary cancer in PET
positive thyroid incidentaloma: A 63 year woman’s PET
scan showed focal positivity in the inferior pole of left thy-
– 79 –
roid lobe (fig. 3a). Thyroid sonography revealed a vascular, hypoechoic 1 cm nodule in the left thyroid lobe with
dense amorphouse calcification (fig. 3b). FNA cytology
was consistent with papillary thyroid cancer.
Discussion: Fluoro-2-deoxyglucose (FDG)-positron
emission tomography (PET) imaging delineates areas of
increased metabolic activity by producing a map of FDG
uptake. FDG-PET imaging has emerged as an accepted
modality for detection, staging and surveillance of a wide
variety of malignant tumors. Approximately three percent
of PET scans have incidentally detected abnormalities in
the thyroid gland. Thirty percent of incidentally detected
PET positive thyroid nodules are cytologically malignant
in some series. However, a variety of benign conditions
including autoimmune thyroid disease, inflammatory and
granulomatous processes, benign follicular neoplasms and
Hurthle cell adenomas may be PET positive. Unilateral
PET positivity warrants a cytological diagnosis. Fine needle aspiration (FNA) cytology is not needed in the presence of known autoimmune thyroid disease with bilateral
PET positivity. FNA should be considered in other situations based on clinical presentation, sonographic characteristics and risk factors.
Conclusions: PET positive thyroid incidentalomas
encompass both benign and malignant pathologies.
Approximately one-third of all incidentalomas harbor
malignancies. FNA is warranted for unilateral PET positivity. FNA should be considered in other cases based on
clinical presentation, sonographic characteristics and presence of risk factors. FNA is perhaps not needed for incidentalomas in the setting of known autoimmune thyroid
disease and bilateral PET positivity.
Abstract #104
STRATIFYING FOLLICULAR THYROID
CANCER RISK GROUPS USING PTNM STAGING
Jen-Der Lin, MD, Tzu-Chieh Chao, PhD, MD,
Yu-Yao Huang, PhD, MD, Miaw-Jene Liou, MD, and
Chuen Hsueh, MD
died of thyroid cancer for stage I to IV, respectively. Of
the 214 patients, 35 (16.4%), 85 (39.7%) and 94 (43.9%)
were defined as belonging to the low, moderate and highrisk groups at the time of surgery, respectively. None of
the case in low-risk group died, and all achieved diseasefree status. In the moderate and high risk groups, 2.4%
(2/85) and 27.7% (26/94) died of thyroid cancer. The moderate and high risk groups underwent near total thyroidectomy and 131I therapies, and 15 of 107 cases (14.9%) died
of thyroid cancer, while, 18 (16.8%) had persisted nondisease-free status at the end of the study period.
Discussion: Limited information was available on the
application of pTNM staging to risk prediction for follicular thyroid cancer. Defining follicular thyroid carcinoma
risk at the time of surgery is important for determining the
surgical procedures and follow-up 131I therapy. As in this
investigation, T1 (pTMN) patients in stage I as the low
risk group were followed without cancer mortality and
remained disease-free for nearly ten years. Compared with
the 5th edition of UICC, increase in tumor size from 1 cm
to 2 cm in T1 patients without local invasion and distant
metastasis did not influence cancer mortality. This study
illustrated more cases in advanced TNM stages II and IV
but fewer in stage III compared with previous report which
combined the data from primary thyroid tumor of papillary and follicular thyroid carcinomas.In this study, a total
of 18.2% (39/214) presented with distant metastases. This
ratio was lower than reported recently by Benbassat et al.
(21%). Bone and lung were the main locations of metastases. 53.8% of the distant metastatic cases died of thyroid
cancer. High risk group patients with distant metastases,
aggressive surgical treatment were not improved survival.
Conclusions: Low risk group of follicular thyroid
cancer defined by pTNM staging in T1N0M0 was with
good prognosis. Early diagnosis and prompt therapy for
the moderate and high risk groups are mandatory.
Abstract #325
THE EFFECT OF THYROIDITIS ON STAGING IN
DIFFERENTIATED THYROID CANCER
Objective: The aims are to determine cancer specific
survival, follow-up status for different pTNM stages and
stratify different risk.
Methods: A retrospective study enrolled a total of 214
follicular thyroid cancer patients, including 167 women
and 47 men, receiving surgery and followed-up treatment
at a single medical center. Low risk of follicular thyroid
cancer was defined as pT1N0M0. High risk was classified
as in stages II to IV.
Results Following mean follow-up of 9.6 years,
among four groups categorized by pTNM staging, 2.5%
(3/120), 21.9% (7/32), 5.6% (1/18) and 52.3% (23/44)
Dima Diab, MD, and Mario Skugor, MD
Objective: To study the effect of coexistent
Hashimoto's thyroiditis on staging in patients with differentiated thyroid cancer.
Methods: We conducted a retrospective study of 90
patients, 19 men and 71 women, with differentiated thyroid cancer, who presented to Cleveland Clinic from
December 2005 to August 2006. We determined diagnosis
of thyroiditis by history or histopathology and stage of
cancer by the TNM classification system.
– 80 –
Results Of the 90 patients with differentiated thyroid
cancer, 11 patients (12%) had coexistent thyroiditis. The
age range of this subgroup was 22 – 72 years (mean age ±
SD, 53 ± 13 years). Ninety-one percent of these patients
had stage I or II disease, and none had stage IV disease. Of
the remaining 79 patients, aged 22 – 91 years (mean age ±
SD, 58 ± 15 years), only 68% had stage I or II disease,
while 20% had stage IV disease.
Discussion: There is some evidence in the literature
that coexistent Hashimoto’s thyroiditis with differentiated
thyroid cancer may be associated with a lower tumor
stage. It has also been suggested that the presence of
chronic inflammation within the thyroid may slow down
the progression of the cancer and inhibit metastatic dissemination, resulting in an improved disease-free survival.
In our study, patients with coexistent thyroiditis were 35
% more likely to have a significantly lower cancer stage
than patients without thyroiditis. Furthermore, stage IV
disease was exclusively found in the group of patients
without thyroiditis, accounting for a significant proportion
of the cases studied. We are currently in the process of
analyzing approximately 300 more medical records of
patients with differentiated thyroid cancer who presented
to Cleveland Clinic within the same period of time.
Conclusions: These data suggest that coexistent thyroiditis with differentiated thyroid cancer may be a good
prognostic indicator associated with a lower tumor stage.
The impact of coexistent thyroiditis on long-term outcome
needs to be further evaluated.
Abstract #145
SMALL CELL CARCINOMA OF THE THYROID A CASE REPORT
Alvin Ng, MBBS, Siok Bian Ng, MBBS, FRCPA, and
Cora Yuk Ping Chau, MBBS, FRCPA, FHKCPath
Objective: To describe the clinical course of a case of
primary thyroid small cell carcinoma and review its diagnostic difficulties.
Case Presentation: A 66 year old Chinese man presented with an enlarging painless neck mass over weeks
with voice hoarsening.Examination revealed a hard,irregular non-tender thyroid mass.CT confirmed a 7.6x4.4cm
thyroid mass with cervical lymphadenpopathy.FNA
showed malignant oat cells. Excision biopsy showed histology of a small cell neuroendocrine carcinoma.
Imunohistochemistry was positive for cytokeratin AE1/3,
thyroid transcription factor-1 and synaptophysin.Focal
weak staining for carcinoembryonic antigen was present.
There was no expression for calcitonin, chromogranin,
thyroglobulin and leukocyte common antigen and adrenocorticotrophic hormone. Pulmonary and extrapulmonary
small cell carcinomas in a location outside the thyroid was
exhaustively excluded. He was treated with a regime of
etoposide and cisplatin and radiotherapy. After 4 cycles of
chemotherapy and completion of radiotherapy,the mass
shrank to 2.0x1.8cm with reduction in cervical lymphadenopathy. However after initial response, disease progressed with multiple hepatic, splenic and adrenal
metastases.He died after 12 months.
Discussion: The current WHO histological classification of thyroid carcinomas does not include small cell carcinomas. Studies in the 80s to early 90s using
immunochemistry showed that most reported small cell
carcinomas of the thyroid were in fact non-Hodgkin’s
lymphomas.In one series,re-evaluation of 68 previously
diagnosed small cell carcinomas/lymphomas, 63 were
identified as NHLs of B-cell origin, 2 as lymphomas of
uncertain lineage and 2 as large cell lymphomas. There are
also variants of anaplastic carcinoma and medullary throid
carcinoma with small cell morphology. The immunohistochemical marker of medullary thyroid carcinomas is calcitonin which anaplastic tumors lack. Metastases from small
cell carcinoma of lung are not uncommon.Nuclear staining
of thyroid transcription factor-1 is useful in identifying the
pulmonary origin of metastatic non-small cell carcinomas.
However, it is not specific for pulmonary small cell carcinomas,with 80% of both pulmonary and extrapulmonary
small cell carcinomas being positive. It is also expressed
in thyroid tumours of follicular cell origin. Thus the TTF1 positivity in our patient does not help in distinguishing
site of origin or primary cell type.
Conclusions: We propose that the following criteria
be fulfilled to diagnose a true primary small cell neuroendocrine carcinoma of thyroid.A:No clinical evidence of a
primary extra-thyroidal small cell carcinoma.B:No clinical evidence or family history of MEN2 or medullary thyroid carcinomas.C:Morphologic features of an oat-cell
type neuroendocrine carcinoma.D: Immunophenotype: 1)
lack of expression for lymphoid markers 2) lack of expression for calcitonin 3) expression of epithelial and/or neuroendocrine markers.
Abstract #287
THYROTOXICOSIS HEART DIESEASE IN A 48
YEAR-OLD NIGERIAN WOMAN
Ayotunde Oladunni Ale, MD
Objective: To document the presence of cardiovascular complication of Thyrotoxicosis (TS).
Case Presentation: This is a case report of a 48 yearold woman that essentially describes the clinical, biochemical and sonographic features of TS and its cardiac
complicatins. RESULT Clinical features: Body Mass
– 81 –
Index of 21.03 kg/m2; Goitre; Bilateral pitting pedal
edema, wide pulse deficit of 30; elevated jugular venous
pressure and S3 gallop. Biochemical results of Thyroid
function test: T3 = 4.6 T4 > 200 TSH < 0.3 Sonographic
features: Chest X-Ray- Cardiothoracic ratio >50%,
Biventricular cardiac enlargement and prominence of
upper lobe pulmonary vessels. ECG – Sinus tachycardia,
Atrial premature complexes and poor R-wave progression.
ECHOCARDIOGRAPY STUDIES: showed systolic dysfunction with ejection fraction.{EF}
Discussion: This is a 48year-old woman with no previous history of cardiac morbidity presenting in heart failure. The Echo studies showed systolic dysfunction with
EF of < 45% consistent with heart failure. TS is shown by
this case report to lead to systolic dysfunction. The thyroid
hormones act on the heart by two principal mechanisms.
The direct action of thyroid hormones influences the force
of contraction of the heart muscle. While a slight increase
in plasma hormone levels increases the force of contraction, large excesses decrease the strength of heart beats as
a result of increase in protein catabolism in the heart tissue. Similarly, the indirect action of thyroid hormones
potentiates the chronotropic and inotropic effect of circulating catecholamines.
Conclusions: Thyrotoxicosis is an important cause of
heart disease in blacks. More emphasis should therefore be
placed on thyrotoxicosis as a significant cause of heart
failure.
Abstract #385
INSULAR THYROID CARCINOMA: A RARE
FORM OF CANCER
Ana Maria Lugaro, MD, and Marielsa Rabelo, MD
Objective: To report a case of insular thyroid carcinoma, an infrequent form of thyroid cancer.
Case Presentation: Case of a 36 y/o woman who
came to us on 5/03 due to a left thyroid nodule detected by
herself on palpation. A 2.2 x 2.0 cm hypoechoic nodule,
predominantly solid, was confirmed to be in the lower
pole of the left thyroid lobe with a sonogram. The patient
refered fatigue and weight loss. Denied family history of
thyroid cancer or radiation exposure. The patient was clinically and biochemically euthyroid. The biopsy of the nodule was compatible with follicular neoplasia for which
was sent for surgery. It came out positive for insular thyroid carcinoma. Immunostain was positive for TTF-1 but
negative for calcitonin, chromogranin, synaptophysin,
CEA, and thyroglobulin. Total thyroidectomy was then
completed. Post surgery whole body radioiodine scan
(WBS) showed remnant functioning thyroid tissue in the
thyroid bed that has persisted after two courses of I 131
(100 and 150 mCi). The last I 131 therapy was given after
A Tc 99 Sestamibi revealed the same unique lesion as the
radioidine study. The patient has remained in levothyroxine with TSH suppresion. Tg and anti Tg are negative.
Discussion: Insular thyroid carcinoma (ITC) is the
best characterized group of poorly differentiated thyroid
cancers. This category include carcinomas of follicular
thyroid epithelium that retain sufficient differentiation to
produce scattered small follicular structures and some thyroglobulin, but generally lack the usual morphologic characteristics of papillary and follicular carcinoma. The ITC
is characterized by a distinct nesting pattern, formation of
small follicular lumina leading to a cribiform configuration, small size, and uniformity of the tumor cells, necrosis, and a focally peritheliomatous pattern of growth
(tumor cells around blood vessels, with necrosis of tumor
cells farther away from vessels). There is histologic heterogenicity. The follicular origin is usually confirmed by
stainning positive to thyroglobulin. The presence of well
differentiated and/or anaplastic components within ITC
have been frequently reported. These supports the hypothesis that this type of cancer represents an intermediate
entity in the dedifferentiation of well differentiated cancer
to anaplastic. It is believed that these tumors have intermediate biological aggressiveness and response to
Radioidine.
Conclusions: Even though these tumors have been
classified in a group of more aggressive biological activity, our patient did not presented with metastasis. Nor have
arised during three years while on TSH suppression. It has
characteristics, behavior, and WBS of differentiated cancer despite of a negative immunostain for thyroglobulin. I
believe that no consensus for therapy can be established
for these tumors. Every case need to be evaluated individually based on the clinical picture and imaging findings.
Abstract #351
GRAVES DISEASE, COMPLICATED BY
THYROID STORM, IN PATIENT WITH HIV
Kateryna Komarovskiy, MD, Seshadri Das, MD, FACE,
and Joseph Ng, MD
Objective: To discus presentation of Graves disease,
complicated by thyroid storm, in the patient with HIV.
Case Presentation: A 47 y/o African-American male
was admitted with severe thyrotoxicosis to the Intensive
Care Unit (ICU) in January 2006. He complained of
severe nausea, hand tremor, headache. He also had exophthalmos, tachycardia, fever of 104° F, and leukocytosis.
Infectious causes of fever were excluded by negative
blood, urine, and cerebrospinal fluid cultures. One year
earlier he was diagnosed with Graves disease and failed to
– 82 –
follow up with treatment. 5 years ago he was diagnosed
with HIV-1 and since than has been on highly active antiretroviral therapy (HAART)-lopinavir/ritonavir, zidovudine/ lamivudine and efavirenz. He had no changes in his
medications and denies personal or family history of thyroid disease. His laboratory results are presented in attachment.In the ICU, patient developed atrial fibrillation that
was converted with diltiazem. His condition was stabilized; radioactive iodine ablation was performed as an outpatient procedure with subsequent significant
improvement in symptoms.
Discussion: Patients with HIV are not commonly
diagnosed with Graves disease. On the contrary, HIV
patients treated with HAART more commonly develop
subclinical hypothyroidism. The pathogenesis of Graves
disease includes secretion of interleukins 4 and 5 by CD4T2 helpers that mediate production of antibodies against
thyroid cells. In patients with HIV, the incidence of
Graves disease is described in the context of immune
reconstitution syndrome (IRS) after initiation (9-48
months) of HAART due to a 2-4 times elevation in CD4+
T-cell counts with inappropriate activation against thyroid
cell receptors. IRS is usually manifested by deterioration
of the patient’s clinical condition and activation of silent
opportunistic infections as a result of an exuberant inflammatory response. In our patient, no significant changes in
CD4 T lymphocyte count or outbursts of opportunistic
infections were identified over a period of 3 years, yet he
developed complicated autoimmune disease, previously
described only in patients with IRS.
Conclusions: Our case suggests that patients with
HIV may develop Graves disease later in the course of
immune system recovery. Without appropriate therapy
they can progress to complications such as thyroid storm,
despite the absence of IRS and suppressed T- lymphocytes. Therefore, we suggest screening and appropriate
treatment for patients on HAART for thyroid disease who
exhibit signs suggestive of thyroid dysfunction to prevent
complications, such as severe thyrotoxicosis.
Abstract #109
THYROTOXIC PEROIDIC PARALYSIS
Saba Khayal, MD
Objective: To describe a case of a 50 y/o male with
recurrent episodes of weakness in the presence of abnormal thyroid function tests
Case Presentation: A 50 y/o white male was diagnosed with Hypokalemic Peroidic Paralysis in the past. He
presented to the clinic c/o muscle cramps and weakness.Also c/o tiredness. Taking potassium would improve
his symptoms. He had to take a leave of absence from his
work.He usually got the symptoms after he ate lunch and
sweet foods like candy. Execrcise and stress would precipitate his symptoms.Past history included HTN and
HLP. He is a nonsmoker, did not use alcohol,is married
with children. No family h/o peroidic paralysis. On exam
deep tendon reflexes were diminished . Medications
included potassium and lisinopril. Review of labs from 2
months prior showed a TSH of 0.37 and FT4 of 1.96.2 yrs
back they were WNL.He had not received any antithyroid
treatment in the past.Nerve conduction studies were negative.W/U of Cushing's, Hyperaldosteronism and
pheochromocytoma was negative.Other labs were within
normal limits. He was advised to take a low carbohydrate
diet.Methimazole 20 mg daily was prescribed. At F/U
after 1 month his symptoms of weakness had improved
cinsiderably. His labs continued to be WNL
Discussion: TPP is a potentially lethal complication
of hyperthyroidism. It is seen mostly in male pts of Asian
descent but is being increasingly seen in the west.Muscles
affected may be asymmetrical. Sensory, bowel, bladder
function not affected.Total paralysis of the respiratory,bulbar and ocular muscles has been reported.Precipitating
factors include, heavy meal, carbohydrate rich meals,
etoh, exercise and stress.Hypokalemia is the hallmark during an acute episode. Mild elevation of thyroid hormones
is seen as in our patient.EKG changes of hypokalemia can
be seen. The defect involved is increased Na/K-ATPase
pump activity. This causes massive shift of potassium
from the extracelluar into the intracellular
compartment.Thyroid hormones increase Na/K-ATPase
pump activity. Pts with TPP have an exaggerated insulin
response during oral glucose challenge, hence the association with carb-rich meals.Catecholamines also increase the
pump activity. During acute paralysis immediate supplementation with KCL is warranted which can be given orally or i.v.Oral or i.v propranolol can also be used.
Treatment of hyperthyroidism is the mainstay of therapy.Pts should be advised to avoid high-carb meals.
Conclusions: TPP should be considered in a pt of
usually,but not exclusively an Asian male, who presents
with weakness.Symptoms are brought on by a precipitating event like a high carb meal.It may be difficult to diagnose if the Clinician does not think about it since low
potassium is seen only during acute episodes.TFT's consistent with hyperthyroidism are seen. This is an important
clinical entity since it resolves with treatment with antithyroid medications.Potassium should be given during an
acute attack
– 83 –
Abstract #386
BENIGN THYROID GOITER PRESENTING WITH
TRUE VOCAL CORD PARALYSIS
malignancy. Therefore, the surgeon should identify and
preserve the recurrent laryngeal nerves to allow for functional recovery after surgery.
Abstract #148
Naifa Busaidy, MD, and Cynthia F Yazbeck, MD
Objective: To present benign goiter causing vocal
cord paralysis and review causes of recurrent laryngeal
nerve palsy by thyroid masses.
Case Presentation: 49 y/o woman came to MDACC
for evaluation of a large goitrous mass with right true
vocal cord paralysis. The patient had pain and compressive symptoms with hoarseness. She denied radiation
exposure. She had previously been intubated for several
surgeries without complications. Exam and CT neck
showed a goiter 5.9 cm with encasement of the trachea and
compression of the esophagus. U/S revealed a large goiter
extending into the mediastinum and prominent lymph
nodes in the anterior jugular area. FNA revealed
Hashimoto’s thyroiditis in the goiter and reactive lymphoid hyperplasia in the lymph node. Videostroboscopy
demonstrated significant impairment in right true vocal
fold mobility. The left side was mobile and compensating
to achieve glottic approximation. The patient an extended
total thyroidectomy with superior mediastinal and right
neck dissection. Pathology revealed Hashimoto’s thyroiditis, adenoma and a hyperplastic node. She did not develop
hypoparathyroidism. After surgery, the patient’s voice
returned to normal and her true vocal cord paralysis completely resolved
Discussion: We present here a rare case of benign
thyroid disease presenting with true vocal cord paralysis.
Large substernal goiters have been described and are frequently associated with compressive symptoms (airway
and dysphagia), but recurrent laryngeal nerve palsy is rare.
Development of vocal fold paralysis when thyroid disease
is present is strongly suggestive of thyroid cancer and this,
therefore, typically implies necessary surgery. There have
been very few other case reports of paralysis being caused
by benign disease and typically there is a good chance of
functional recovery postoperatively in these cases, as in
this lady. Our patient also had no difficulty with previous
intubations despite tracheal encasement and esophageal
compression. The presence of vocal cord paralysis should
not automatically cause one to assume malignancy. Here
in we review the literature of all reported cases of benign
thyroid disease causing vocal cord paralysis and review
the differential, the workup and common prognostic factors.
Conclusions: Unilateral recurrent nerve involvement
occurs infrequently in the presence of benign disease and
generally is thought to herald malignancy. Nevertheless,
such a finding with a goiter does not necessarily indicate
ACUTE SUPPURATIVE THYROIDITIS (AST)
COMPLICATED WITH MEDIASTINAL ABSCESS
Negah Rassouli, MD, Zulekha Hamid, MD,
Palak Choksi, MD, and Vitaly Kantorovich, MD
Objective: To report a case of AST caused by
Methicillin Resistant Staphylococcus Aureus (MRSA) and
thyrotoxicosis.
Case Presentation: A 43-year–old African American
female with end stage renal disease, presented with fever,
dysphagia, odynophagia and neck pain for 4 days. On
examination, she had tachycardia and a symmetrically
enlarged thyroid gland with significant tenderness over the
left thyroid lobe. Her distal tendon reflexes were brisk.
Laboratory studies showed pronounced leukocytosis and
ESR of 140 mm/hr. Her TSH was 0.09 µIU/ml (normal
0.55-3), free T4 5.4 ng/ml (0.58-1.64), and free T3 24
pg/ml (2.3-4.2). Anti-thyroid peroxidase and thyroglobulin antibodies were normal. Thyroid ultrasound (TUS)
showed diffusely enlarged thyroid gland with multiple
hyper- and hypo-echoic areas, while CT and MRI scans
demonstrated an abscess, progressively extending into
retropharyngeal space and upper mediastinum. Fine needle aspiration (FNA) showed destructive leukocytic thyroiditis, while both FNA and peripheral blood cultures
grew MRSA. Intravenous antibiotics and beta-blocker
were started and she underwent urgent surgical drainage
with significant clinical improvement. Subsequently, her
hyperthyroidism improved.
Discussion: AST is a rare disorder, mostly seen in
pediatric population in association with piriform sinus fistula. The most common bacterial causes are staphylococci
and streptococci species. It can be difficult to distinguish
AST from subacute thyroiditis (SAT): both associate with
tender thyroid gland, fever, leukocytosis, and increased
ESR. In the absence of underlying thyroid disease, thyroid
function tests (TFT) are usually normal in AST, but show
a fluctuating pattern in SAT. Our case showed a severe
destruction of thyroid gland, resulting in a TFT pattern
similar to SAT. Positive FNA cultures confirmed diagnosis of AST. While TUS is helpful for initial diagnosis, CT
or MRI imaging is essential for assessment of infection.
Parental antibiotics are the mainstay of treatment.
Potential complications include formation of abscess with
extension and rupture into retropharyngeal and mediastinal areas, compression of vital organs, sepsis, and vein
thrombosis. Planned surgical drainage is necessary for
– 84 –
failure to response to intravenous antibiotics. When there
is a rapid progression of the disease with signs of compression or mediastinal spread, urgent surgical intervention is mandatory.
Conclusions: Patients with AST usually present with
neck pain, evidence of systematic inflammatory response
and normal TFT. Nevertheless, our case was unique
because of thyrotoxicosis on presentation and severe
destructive AST, which rapidly evolved into abscess. This
case demonstrated that a high index of clinical suspicion is
necessary for timely diagnosis of this potentially devastating disease. Rapid and appropriate intervention would prevent fatal outcome.
Abstract #293
THYROXINE MALABSORPTION SECONDARY
TO OCCULT CELIAC DISEASE
T4 dosages necessary to maintain a euthyroid state, suggesting the inability to absorb ingested T4 during active
celiac disease. As the pathogenesis of celiac disease has
become better understood, an increasing number of cases
with atypical presentations are being diagnosed. Thus,
occult, asymptomatic disease may be another cause of T4
malabsorption in the gut. Serologic screening for celiac
disease in compliant patients with autoimmune thyroiditis
requiring high or increasing T4 doses should always be
considered.
Conclusions: The diagnosis of celiac disease should
be suspected in patients with autoimmune thyroiditis and
hypothyroidism, requiring higher than expected doses of
thyroxine. This case illustrates that celiac disease, even
when occult or asymptomatic, may reduce T4 absorption
in the gut resulting in symptomatic hypothyroidism.
Abstract #177
Mae Sheikh-Ali, MD, Tyler Lydell Hanson, MD,
Hossein Gharib, MD, MACP, MACE
NEPHROTIC SYNDROME INDUCES PROFOUND
RISE IN TSH & L-THYROIXINE
REQUIREMENTS
Objective: We report a patient with autoimmune
hypothyroidism with increasing T4 requirement.
Evaluation revealed occult celiac disease.
Case Presentation: A 39-year old woman with 6
years of autoimmune thyroiditis and hypothyroidism was
referred for persistent serum TSH elevation > 250 mIU/L
despite increasing thyroxine (T4) doses. She complained
of fatigue, poor concentration, cold intolerance, and a 30
pound weight loss over the last two years. She reported
normal bowel movements with no other GI complaints.
She had a history of asthma and iron deficiency anemia,
presumed secondary to duodenal AVM. She took brand
T4 (Levoxyl) 150 mcg regularly at midnight, 3 to 4 hours
after taking iron tablets, and was not on other medications
known to interfere with T4 absorption. On examination,
weight was 50 kg, she appeared hypothyroid, and thyroid
gland small, firm with no nodules. In July 2006, while on
thyroxine 100 mcg/day, serum TSH was 255 mIU/L and
FT4 0.4 ng/dl (0.8-1.8). T4 dose was increased to 150
mcg/day; by October serum TSH was 268 mIU/L, FT4 0.4
ng/dl, and TPO antibodies 233 IU/mL (n <20). Further
studies including IgA tissue transglutaminase >250 U (n
<20) and EGD with biopsies confirmed the diagnosis of
celiac disease.
Discussion: Linkage between celiac disease and
autoimmune endocrine disorders, including autoimmune
thyroiditis, is well documented. This case demonstrates
profound hypothyroidism refractory to high doses of T4 in
the setting of occult celiac disease. Orally administered T4
is primarily absorbed in the jejunum and proximal ileum,
both of which are affected in celiac disease. It has been
reported that commencement of a glutin-free diet lowers
Sameer Stas, MD, and David W Gardner, MD
Objective: To identify nephrotic syndrome as a potential cause of increasing levothyroixine requirements in
patients with hypothyroidism
Case Presentation: A 23 year-old white female, diagnosed with Graves’ disease 6 years ago was treated successfully with I131 ablation followed by levothyroixine
(LT4).Since then, TSH was normal except for a short time
when treatment was interrupted for financial reasons and
TSH rose to 347 mu/ml.In 2006, she developed symptoms
of hypothyroidism and a TSH of 102 while taking a maintenance dose of LT4 (0.15 mg QD).She denied taking any
other pills.LT4 increased to 0.3 mg QD, but TSH rose to
308 and serum FT4 and FT3 decreased to 0.58 (RR 0.71.85) ng/dl and 0.5 pg/ml (RR 2-4.2), respectively.Total
rT3 was also low at 19 pg/ml (RR 90-350).TPO antibodies were negative.Simultaneously, she was diagnosed with
nephrotic syndrome (NS) due to membranous glomerulonephritis associated with retroperitoneal fibrosis of
unknown etiology.She had a significant loss of thyroid
hormones in the urine, as estimated by a total T4 (TT4) of
3.9 mcg/dl and a total T3 (TT3) of 29 ng/dl.Improvement
in proteinuria due to immunotherapy was associated with
lower LT4 requirements and normalization of both thyroid
hormones and TSH.
Discussion: This is a case of a woman with post-I131
ablation hypothyroidism who became very resistant to
treatment (with recurrence of clinical and biochemical
hypothyroidism) in conjunction with the development of
NS. TSH remained high despite a large replacement dose
– 85 –
of LT4. At the same time, urinary thyroid hormones were
elevated. Normally, only minimal amounts of T4 and T3
are found in urine due to limited filterability of the hormone-binding protein. In NS, significant urinary T4 and
T3 excretion occur due to TBG and TTR loss along with
albumin. Also, there are major links between the serum
albumin and serum TT4 and TT3. Most patients with a
normal thyroid who develop NS have normal or slightly
abnormal thyroid tests. But, in severe cases of NS, primary hypothyroidism can occur even without thyroid disease.
Also, patients with primary thyroid failure who take LT4
and develop NS rarely present with increased LT4 requirements. Interestingly, the increased requirement of LT4
preceded the clinical diagnosis of NS. The magnitude of
TSH elevation when the patient had NS and was taking
levothyroixine was comparable to TSH elevation when
NS was not present but the medication was not taken.
Conclusions: Most patients with nephrotic syndrome
have normal thyroid function tests. However, cases of profound hypothyroidism may occur in patients with severe
NS or in patients of limited thyroid reserve. Exogenous
thyroid hormone usually does not correct hypothyroidism
due to continuous urinary loss. Furthermore, improvement
in proteinuria results in lower requirements of thyroid hormones.
Abstract #251
HYPERTHYROIDISM & THYROIDITIS IN SAME
PATIENT BEFORE PAPILLARY CARCINOMA
Lee Pletts Goscin, MD, PhD, Cecilia Artigas, BS, and
Cori Chase, BS
Objective: To report 2 cases of Hashimoto's
Thyroiditis and Hyperthyroidism occurring in the same
woman who subsequently had papillary carcinoma.
Case Presentation: Case !: A 33-year-old woman
presented with hair loss and a thyroid nodule 1 year after
pregnancy. Both TSH and free T4 were elevated. TPO
Antibodies were increased. Ultrasound showed a MNG.
Thyroid uptake and scan elevations of 44% were consistent with Hyperthyroidism. Eleven months later the
enlarging nodule was papillary carcinoma with metastatic
lymph nodes. Case 2: This 45-year-old woman had MNG
about forty grams for 8 years that was labeled as
Thyroiditis. Her aunt had Graves' disease. However, the
thyroid scan had elevated uptake of 11% at 24 hours. A
cold nodule contained Hurthleoid cell changes. TSH was
suppressed and free T4 was elevated. She was treated with
PTU for 3 months until free T3 was low and symptoms
changed. Several courses of Levothyroxine were tried
with mixed results. TPO Abs and TG Abs were elevated.
Discussion: Thyroid autoimmune disease can be portrayed as a spectrum of idiopathic myxedema without goiter to Hashimoto's Thyroiditis to Euthyroid Graves'
(without goiter) to Graves' Thyrotoxicosis. Review of the
literature showed 12 cases of Graves' following
Thyroiditis ranging from 2 months to 8 years. These two
young women had time spans of one year before papillary
cancer with metastatic lymph nodes. The second case has
Hurthleoid cell changes after 7 years.
Conclusions: These two cases as well as several other
patients not presented indicate that Hyperthyroidism similar to Graves' and Thyroiditis occur in the same patient
more commonly than previously reported. The etiology
remains unclear and will be addressed.
Abstract #180
COCCIDIOMYCOSIS OF THE THYROID
PRESENTING AS HYPOTHYROIDISM AND
GOITER
Joseph El Youssef, MD, and Ambika Rao, MD
Objective: To describe a case of coccidiomycosis of
the thyroid gland presenting as hypothyroidism and goiter.
Case Presentation: A 27 year old Hispanic male construction worker with HIV disease for 2 years presented to
the emergency room with hoarse voice, chest pain, shortness of breath and hemoptysis. He was in acute respiratory distress with significant stridor and clear breath sounds.
Chest x-ray showed bilateral, diffuse, reticulo-nodular
infiltrates. Laboratory studies were significant for normocytic anemia (hemoglobin 9.2 g/dl) and hyponatremia
(128 meq/L). Coccidioides serology was positive. During
the hospital course, the patient developed worsening stridor associated with a firm, swelling of the neck. TSH was
elevated (34.9mIU/ml). Ultrasound of the thyroid revealed
only diffuse enlargement. Thyroidectomy was performed
to relieve upper airway compression. Histological assessment of the thyroid tissue revealed evidence of coccidiomycosis replacing the thyroid gland. The patient was
started on amphotericin B therapy. His respiratory status
worsened requiring endotracheal intubation and he
expired two months after admission.
Discussion: Goiter and hypothyroidism due to coccidiomycosis of the thyroid are quite rare, as is stridor as
an acute presentation of goiter. Only four cases of coccidiomycosis of the thyroid gland have been identified antemortem in the literature. It is often an indicator of
disseminated coccidiomycosis in immune compromised
hosts and presenting characteristics may vary considerably. Hypothyroidism, hyperthyroidism and isolated
swelling of the gland have all been described. Acute
– 86 –
development of airway obstruction should prompt investigation for inflammatory or neoplastic infiltration of the
thyroid gland. In this patient, disseminated coccidiomycosis was the cause. As fungal infections of the thyroid gland
are uncommon, optimal treatment remains uncertain and
prognosis is dismal.
Conclusions: Infiltrative coccidiomycosis of the thyroid is a rare and difficult to treat complication of disseminated coccidiomycosis. It is seldom found ante-mortum
and presence of significant stridor in an immunocompromised patient may be suggestive.
Abstract #290
ISCHAEMIC STROKE IN A YOUNG
THYROTOXIC FEMALE
Adeleye Olufunmilayo Olubusola, MD
Objective: To report a case of ischaemic stroke in a
young thyrotoxic female by presenting the history, clinical
finding, and lab evaluation.
Case Presentation: A 36 years old teacher seen with
a day history sudden weakness and slurred speech. Not
hypertensive/DM and has no other risk factors for CVD.2
months preceeding history of features suggestive of thyrotoxicosis. Examination-dysarthria, lt 7th cranial nerve
palsy ,spastic paraparesis {grade 2} diffuse thyroid
enlargement approx.50gm WHO estimation. eye
signs,resting tachycardia 124b/min. B/P 120/70
mmhg.TSH 0.3mu per ml {normal 0.8-2 mu per ml}elevated T4 and T3.
Discussion: Clinical and laboratory finding in this
patient is consistent with thyrotoxicosis. It is interesting to
note that she presented withno evidence of arrythmia
which is the most common predisposing factor to development of stroke in thyrotoxic patients. studies have also
demonstrated that hyperthyroidism predisposes a patient
to hypercoagulable state. Hemodynamic factors, dehydration and stasis of venous blood flow due to goiter may also
contribute.
Conclusions: Thyrotoxicosis should be considered as
a possible actological factor in the development of stroke
in young black females.
Abstract #359
AMIODARONE-INDUCE THYROID DYSFUNCTION RATE IN DIFFERENT PERIOD OF OBSERVATION
Nozima L Kayumova, MD
Objective: Investigated the incidence of amiodaroneinduce thyroid dysfunction in various periods of therapy
Methods: We investigated 65 patients with tachyarrhythmias receiving amiodarone, mean age
43±12years, treatment period was from 2 weeks to 5 years.
The examination consist of thyroid hormons and TSH levels, titres of AbTPO (RIA) and thyroid ultrasonogrephy.
Results Incidence of Amiodarone-induce thyroid dysfunction in iodine deficiency region changes in different
period of treatment average 29, 3% (see attachment).
Amiodarone-induce hyperthyroidism is dominate average
25,2%. Amiodarone-induce hypothyroidism occur in
4,1% and only in patients after 3 months amiodarone management. All patients with amiodarone-induce hypothyroidism had previously thyroid diseases.
Discussion: In 14-18% of amiodarone-treated
patients, there is overt thyroid dysfunction, either amiodarone-induced hyperthyroidism or amiodarone-induced
hypothyroidism. In Europe amiodarone-induce hyperthyroidism seems to be more frequent than amiodaroneinduced hypothyroidism, where in many instances iodine
intake is borderline or moderately deficient (Bartalena L,
2004). In a study of 58 consecutive euthyroid patients
residing in a Dutch region with moderately sufficient
iodine intake, amiodarone-induce hyperthyroidism
occurred in 12.1% of cases and amiodarone-induce
hypothyroidism in 6.9% . In a prospective study carried
out in a moderately iodine-deficient Italian area, amiodarone-induce hyperthyroidism occurred in 2 of 13
patients (15%) and amiodarone-induce hypothyroidism in
5 of 7 patients (71%) who had evidence of Hashimoto’s
thyroiditis before treatment( Enio Martino, 2001).
Conclusions: We found a high incidence of amiodarone-induce thyroid dysfunction, similar to the highest
rates reported internationally. In iodine deficiency region
more then 1 year amiodarone intake lead to development
of amiodarone-associated thyroid dysfunction in 29,3% of
patients hypothyroidism and thyrotoxicosis in 4,1% and
25,2% respectively.
Abstract #405
AMIODARONE INDUCED THYROTOXICOSIS IN
A RENAL TRANSPLANT RECIPIENT
Jennifer R. Pedersen-White, DO
Objective: To report the association between amiodarone use and increased risk of thyroid dysfunction after
renal transplantation.
Case Presentation: P.D is a 67-year-old male with a
history of glomerulonephritis and atrial fibrillation (on
amiodarone) who underwent renal transplantation on
5/18/06. To exclude tacrolimus toxicity (considered
because of high serum creatinine, high normal drug levels
and persistent tremors one month post transplant), renal
– 87 –
biopsy was performed (revealing no evidence of rejection). Tacrolimus, however, was discontinued, and
rapamycin initiated. P.D had no history of thyroid dysfunction and TSH at the time of biopsy was normal. One
month later, he was admitted with fever, nausea and vomiting. He denied palpitations or heat intolerance.
Examination revealed a regular tachycardia and hand
tremors but no exophthalmos, thyromegaly or thyroid tenderness. Thyroid function tests revealed a suppressed
TSH, elevated free T4 and negative TsIg and TPO antibodies. Thyroid US showed a RLL nodule with increased
vascularity. I-123 thyroid scan/uptake did not visualize the
thyroid but documented low uptake of 1% at 4 hours.
Amiodarone was discontinued and propranolol and methimazole were then initiated.
Discussion: Amiodarone is an iodine rich drug used
in the management of supraventricular and ventricular
arrhythmias. Even low doses of amiodarone result in a
massively expanded total body iodine pool. Amiodarone
treatment has been associated with both thyrotoxicosis and
hypothyroidism. Amiodarone induced thyrotoxicosis
(AIT) develops in approximately 3% of treated patients
and can develop, often suddenly and explosively, early or
after many years of treatment. AIT type I is a Graves'- like
disease which responds to methimazole and PTU. AIT
type II is an inflammatory destruction of the thyroid which
responds to corticosteroids. An increase prevalence of goiter and hypothyroidism has been reported in both CKD
patients and in renal transplant recipients. Little is know
about potential thyroid dysfunction in renal transplant
recipients receiving amiodarone therapy. A correlation
between amiodarone therapy before heart transplant and
thyroid dysfunction after transplantation, however, has
been reported. We report a case of AIT which occurred
three months after renal transplantation in a man with no
history of thyroid dysfunction who has been maintained
on chronic amiodarone therapy.
Conclusions: CKD, renal transplantation, and amiodarone use have all been associated with thyroid dysfunction. We report an association between amiodarone use
and the development of AIT after renal transplantation. To
our knowledge, this association has not been previously
reported. Thyroid dysfunction should be anticipated in all
CKD patients receiving amiodarone treatment before and
after renal transplantation. Such patients should have routine thyroid hormone evaluation before and after transplant.
Abstract #292
NORMAL MENSTRUAL CYCLES AFTER
TREATMENT OF SUBCLINICAL
HYPOTHYROIDISM
Lee Pletts Goscin, MD, PhD, Roger Alvarez, BS, and
Mandar Jagtap, BS
Objective: To report a case of restoration of menstruation after levothyroxine treatment of SUBCLINICAL
Hypothyroidism.
Case Presentation: A 40-year old married nursing
student with 2 daughters (ages 10 and 16) had 3 menses
the previous year and none for 6 months. She was not
pregnant and her pap test was normal 2 months previously. She had hair loss, cold intolerance and constipation.
Weight was maintained by diet and vigorous workout for
100 minutes, 5 times per week. Her TSH was 6.351 (0.45.5). Free T4 was 1.0 and TPO Abs were 124 (<30). The
thyroid was full (10-15gm) without palpable nodules.
Levothyroxine was gradually increased to 0.088 per day.
Her energy increased and her moods improved. Her
menses resumed and were normal for 6 months.
Discussion: In 2002, the NHANES III(1) report
examined serum TSH in 13,344 "disease-free" and ethically diverse reference subjects. The reference range of
TSH was 0.45-4.12mIU/L and the mean TSH was 1.4.
Some investigators suggested the upper limit of normal
TSH be 2.5mIU/L. Since 2002 in our small clinical practice of 1200 patients, several patients with secondary
amenorrhea and subclinical hypothyroidism were successfully treated with levothyroxine resulting in normal menstruation and other benefits. A JAMA review article in
2004 (2) analyzed 195 papers from 27 years. Those
authors concluded that data supporting associations of
subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few. This case
report would suggest that following the 2002 NHANES III
report with reasonable clinical judgment and decisions
does make significant differences of long lasting medical
outcomes.
Conclusions: Symptomatic inidividuals with elevated
TSH (3-10) should be given trials of levothyroxine. These
patients would also be a good target population to enroll in
clinical trials. It would be wise to avoid gathering large,
costly, and possibly misleading, sets of data, such as WHI
(3) results as we expand medical knowledge. Logic, expe-
– 88 –
rience, and clinical judgment still have a large place in the
practice of medicine.
Abstract #320
FATIGUE IN PATIENT WITH INCREASED
REQUIREMENT OF THYROID REPLACEMENT
Abstract #152
LEAD TOXICITY AND HYPOTHYROIDISM –
ASSOCIATION OR CAUSATION ?
Amanda Reagan Schiefer, MD, and Diana Dean, M.D.
Sachin Kumar Jain, MBBS, MD, DM, FACE,
Pramila Jyoti, MD, Niti Agarwal, MD, and
Rajneesh Singh, MD
Objective: To report the case of a patient having lead
toxicity and hypothyroidism
Case Presentation: 26-year male working in lead &
lithium battery factory for 5 years, presented with irritable
violent behavior & disorientation. No history of (h/o)
fever/seizures. H/o pain abdomen for 1 month, generalized
weakness & constipation for 3 months. Patient was tobacco chewer, nonsmoker & nonalcoholic. No family h/o thyroid disorders. O/E he was drowsy & confused, vitals
maintained. He was pale, had coarse hair & dry coarse
skin. Thyroid was normal. Deep tendon reflexes showed
delayed relaxation. Rest of the systemic exam was normal.
Investigations showed anemia (hemoglobin:6.3g% & P.S
showing anisocytosis with hypochromia & tear drop cells)
& hyponatremia (sodium 110mmol/l). Liver, kidney functions & iron profile was normal. Thyroid functions s/o primary hypothyroidism (FT3-0.5pg/ml, FT4–0.28ng/dl &
TSH–167.025uIU/ml) (Ref. FT3-0.65-170,FT4-90.0180.0,TSH-0.5-5.0). Ultrasound thyroid was normal.
AntiTPO antibodies were normal (30IU/ml, ref. <40).
Blood lead levels: 88.50ug/dl (ref. <14) & serum lithium
levels were normal. Nerve conduction velocity of peripheral nerves was normal.
Discussion: The patient was diagnosed as
hyponateremia with severe primary hypothyroidism with
lead toxicity. Patient was managed with 3%N saline IV,
Thyroxin and calcium EDTA. Possibility of lead induced
thyroid dysfunction was considered and extensive literature search was done. But, we did not come across any
similar case report or literature attributing hypothyroidism
to lead toxicity.
Conclusions: The patient had severe lead toxicity
with primary hypothyroidisim. However, whether the
hypothyrodism was caused due to lead toxicity or is an
associated finding remains unanswered. We plan to repeat
lead levels & thyroid functions after 3 months. If they are
within normal range, then after discussing the issue with
the patient we intend to stop thyroxine & follow up to see
whether he develops symptoms/signs of hypothyroidism
and thyroid functions remain normal or deteriorate.
Objective: Discuss prevalence of Celiac Disease in
autoimmune hypothyroidism and need to screen patients
requiring increased dose of LT4
Case Presentation: In 1/04, 28 yo WF was diagnosed
with Grave's dz. Initial management was PTU. In 5/04, she
became pregnant. PTU was stopped. In 1/05, she delivered. In 3/05, methimazole was started based on elevated
LFTs thought to be recurring Graves'. In 5/05,
Methimazole was stopped with TSH 0.13. Elevated LFTs
persisted. In 7/05, thyroid uptake was 30% at 6 hrs.
Thyroid ablated with 13mCi of I-131. In 10/05, TSH was
34.5, and LT4 88mcg daily was started. By 2/06, TSH still
high despite increased dose of LT4 to 150mcg daily.
Cytomel 12.5mg daily was added. She was seen at our
institution in 8/06 with marked fatigue. Exam revealed
BMI of 19kg/m2 and barely palpable thyroid. Repeat
TFTs and work up for chronic fatigue was done. Based on
TSH 0.05 and free T4 1.5, LT4 150mcg was continued but
Cytomel was not. Rest of labs were normal except for
TTG IgA of 39.4 and TTG IgG of 123.4(< 20 = normal).
EGD with biopsy showed intraepithelial lymphocytosis
with normal villous architecture. GI confirmed CD and
gluten-free diet started. At 3 month follow up, fatigue was
markedly improved on gluten free diet.
Discussion: It is well known that patients with one
autoimmune disease are more prone to develop another
autoimmune disorder. The prevalence of Celiac disease(CD) in patients with autoimmune thyroid disease is
3.3-4.3%. This is almost 10 X higher than in the general
population. Patients with CD may be clinically asymptomatic with normal labs. However, fatigue is a non-specific symptom of CD and autoimmune thyroid disease.
Malabsorption can also be a presenting symptom of CD.
Physiologic replacement of LT4 is 1.7 mcg/kg/day. Our
patient was on 2.6 mcg/kg/day. An apparent resistance to
LT4 should lead to further evaluation of malabsorption
once drug interactions and compliance have been ruled
out. However, marked fatigue, though non-specific,
should also trigger additional work up for other autoimmune etiologies especially in the hypothyroid patient
requiring a higher than expected dose of LT4. The implications of undiagnosed CD extend not only to malabsorption of medications and essential nutrients but also to the
development of lymphoproliferative disease which is 10 X
higher in these patients.
– 89 –
Conclusions: Upon review of the literature, 3 case
reports have documented CD in patients with autoimmune
thyroid disease due apparent resistance to LT4. Our case is
unique in that CD was diagnosed not only in the hypothyroid patient requiring higher than expected dose of LT4
but also in the work-up of chronic fatigue. Though fatigue
is a non-specific complaint, the threshold to screen for
other autoimmune disorders such as CD should be lower
given the higher prevalence of CD in autoimmune thyroid
patients.
Abstract #398
METHOTREXATE TREATMENT IN RIEDEL
THYROIDITIS: A CASE REPORT AND REVIEW
Brian Ellis Michael, MD, FACE, and
Lewis E Braverman, MD
Objective: To report the successful use of methotrexate in a patient with RT who did not respond to steroid and
tamoxifen therapy.
Case Presentation: A 38 year old black female presented with acute dyspnea and painful thyroidal swelling
in June 2003. She underwent debulking surgery at another
institution and sustained damage to the right recurrent
laryngeal nerve and hypoparathyroidism. Pathology confirmed a diagnosos of Riedel thyroiditis. Pain and airway
symptoms persisted despite institution of thyroid replacement and initiation of corticosteroid therapy. The patient
deveoloped a right sided Horner syndrome and Tamoxifen
therapy was added. Serial CT and ultrasound demonstrated further enlargement of thyroid remnant despite steroid
and tamoxifen treatment and a permanent tracheostomy
was placed with additional surgical complications.
Postoperatively the patent experienced worsening of her
Horner syndrome as well as additional respiratory
embarassment. Therapy with Methotrexate was added to
the treatment regimen after tracheostomy did not fully
relieve symptoms. Follow up CT, and ultrasound showed
regression of thyroidal enlargement. Symptomatic
improvement and resolution of Horner syndrome followed
institution of Methotrexate.
Discussion: Riedel thyroiditis is a rare disorder that
has no consistently satisfactory treatment. Standard therapy after diagnosis is generally high dose corticosteroids
and treatment of hypothyroidism. Several case reports
exist of successful treatment of RT with the drug tamoxifen. This response is thought to be due to the drug's induction of transforming growth factor beta and is not thought
to be due to any effect on estrogen receptors. No studies
comparing various treatment modalities appear to exist
due to the absence of any large published series of patients
affected with this disorder. We describe a particularly
aggresive case of RT that was unresponsive to surgical
decompression, tracheostomy, corticosteroids and the
addition of tamoxifen. The affected individual had severe
morbidity associated with attempts at surgical treatment of
her disease. She developed progressive airway obstruction
and extrathyroidal complications of hypoparathyroidism
and a unilateral Horner syndrome despite standard treatment. When the antineoplastic agent Methotrexate was
added to her treatment regimen, her Horner syndrome
resolved, airway symptoms improved, and imaging studies demonstrated regression
Conclusions: Severe cases of Riedel's thyroiditis can
cause significant morbidity and potential mortality from
thyroidal and extrathyroidal manifestations of the disease.
When an affected individual fails to respond to standard
treatment measures of surgery, corticosteroids, and tamoxifen, little published data exists to guide additional treatment efforts. Adding the anti-neoplastic agent
methotrexate in such a situation may offer significant
amelioration of disease progression in a non-responsive
patient.
Abstract #365
FNAC OF THYROID NODULE: DIAGNOSTIC
ACCURACY AND PITFALLS
Saeed Ahmed Mahar, MD, FCPS,
Akhtar Husain, FRCPath, and Najmul Islam, FRCP
Objective: To evaluate the utility of FNAC in patients
with Thyroid Nodule.
Methods: Records of all patients treated surgically for
thyroid nodule(s) at Aga Khan University Hospital from
Jan 2000 to Dec 2004 were reviewed. The patients who
had pre operative FNAC as first line of the evaluation and
the final post operative histopathology report available
were included in the study.
Results 125 patients (90 female 35 male) had thyroid
surgery. The cytological diagnosis was made according to
following categories: Benign, Follicular lesion, Malignant
and Inadequate sampling. Among 63 “Benign cases”, 57
were benign and 6 turned out to be malignant. Among 44
cases from “Follicular group”, 31 were benign and 13
were malignant. Out of 15 patients from “Malignant”
group, 14 were malignant and 1 was benign. Among three
patients from the “Inadequate sampling group”, 2 turned
out to be benign and one was malignant. The overall
results showed a sensitivity of 98%, specificity of 70%,
and positive predictive value of 91%, negative predictive
value of 93% and diagnostic accuracy of 91%.
Discussion: The aim of this study was to evaluate the
diagnostic accuracy in 125 patients with thyroid nodules
submitted to FNAC and afterwards to surgery.The false
– 90 –
negative FNAC results may occur because of sampling
error or misinterpretation of cytology, and are of great
concern because they indicate the potential to miss malignant lesion. However, it is difficult to calculate the true
frequency of false negative results because only a small
percentage (approx 10%) of patients with benign cytologic findings under go surgery.A false positive cytology
result may in retrospect have resulted in surgical over
treatment for an individual patient.The sensitivity of thyroid FNAC ranges from 65% to 99% and its specificity
from 72% to 100%. In this study, the sensitivity for cytological diagnosis of neoplasia was 98%, specificity of
70%, positive predictive value of 91%, negative predictive
value of 93% and diagnostic accuracy of 91% which is
similar to the experience of others.The advent of ultrasound guided FNA biopsy improved specimen acquisition,
especially in patients with small thyroid nodules or nodule
that are difficult or impossible to detect on physical examination.
Conclusions: We conclude that FNAC is a valuable
and minimally invasive procedure for pre operative
assessment of patients with a thyroid nodule in our setting
as well. FNAC has high sensitivity in picking up malignancy in thyroid and also has high diagnostic accuracy in
the evaluation of thyroid nodules.
Abstract #154
ASCITES AND ABNORMAL LIVER FUNCTION
ASSOCIATED WITH HYPOTHYROIDISM
Veena Watwe, MBBS, and Hamdee Attallah, MD
Objective: To report a rare case of ascites and abnormal liver function in a patient with secondary hypothyroidism
Case Presentation: We report a case of a 54-year-old
female who presented with abdominal distension. PMH
included hypothyroidism, an elevated AST and unexplained ascites. Patient has been amenorrheic since the
1970s and could not breastfeed her last child. She denied
any history of alcohol use. After her last admission for
ascites 6 months ago, she was lost to follow-up and
stopped taking levothyroxine and diuretics. Her exam
revealed a non-palpable thyroid and a tense abdomen with
shifting dullness. Heart, lungs and extremities were normal. On labs, TSH was 1.4 µIU/ml and FT4 was undetectable. LFTs were normal except for an AST of 165 U/L.
CBC and hepatitis serologies were negative. Prolactin,
IGF-1 and gonadotropins were low. Liver was normal on
ultrasound. About 3.5 L of ascitic fluid was removed from
the abdomen with a total protein of 4.8 gm/dl. Fluid cytology, AFB smear and cultures were negative. MRI of brain
showed empty sella. After two months of treatment with
levothyroxine, patient has lost 15 lbs and has had no recurrence of ascites. Her free T4 and LFTs, including AST, are
normal.
Discussion: Ascites is a rare presentation of hypothyroidism and is seen in less than 1 % of newly diagnosed
cases of hypothyroidism. The mechanism of ascites in
hypothyroidism is not known, but increased capillary permeability, extravasation of plasma proteins and lack of
compensatory increase in lymph flow and protein return
rate may play a role. Also, the degradation of proteins is
slow, and it is hypothesized that hyaluronic acid accumulates in skin and has a hygroscopic effect. As in our
patient, an isolated elevated AST and ascitic fluid protein
above 2.5 gm/dl are often seen. While ascites with primary hypothyroidism has been reported, to our knowledge
this is the first reported case of ascites with secondary
hypothyroidism. Our patient’s history suggests Sheehan’s
syndrome with panhypopituitarism. In addition, except for
longstanding amenorrhea, she remained asymptomatic
until about two years ago when her abdominal distension
began. While her presentation is atypical, the literature
indicates that pituitary hormone deficiencies can present
years after Sheehan’s has occurred.
Conclusions: Pituitary hormone deficiencies, including secondary hypothyroidism, can present at different
times and in different ways after pituitary injury from
Sheehan’s. Although rare, ascites as a presenting feature
of hypothyroidism has been reported. We have described
a case of ascites associated with secondary hypothyroidism in a patient with Sheehan’s syndrome. Such
unusual presentations of panhypopituitarism with
Sheehan’s can go unnoticed for years after the initial pituitary injury has occurred.
Abstract #125
SUBACUTE THYROIDITIS AS A CAUSE OF
TRANSIENT PSYCHOTIC BEHAVIOR
Ali Abbas Rizvi, MD, FACE
Objective: To describe the previously unreported
association of subacute thyroiditis and organic psychosis.
Case Presentation: An 18-year-old white male presented with anxiety, palpitations, sleep difficulties, weight
loss, and a history of upper respiratory symptoms and neck
discomfort. He manifested irritability, hostility, paranoid
behavior, accused his friends of conspiring to harm him,
and resorted to physical assault. He was admitted to an
inpatient psychiatric facility where he received antidepressant and antipsychotic medications. He had a slightly
enlarged, symmetric thyroid gland and increased deep tendon reflexes. Blood work revealed a free T4 2.8 ng/dl (0.91.4), a free T3 924 pg/dl (287-455), TSH 0.01 mIU/L
– 91 –
(0.7-6.4), thyroglobulin level 149.0 ng/ml (2.0-35.0), and
thyroid peroxidase antibody titer <10 IU/ml (normal <35).
An iodine I-131 uptake was 1.3% at 6 hours and 0.8% at
24 hours, while a Tc-99m scan showed homogeneously
reduced activity. 10 weeks later the patient felt better and
had gained 9 lbs. Tests revealed a free T4 1.1 ng/dl, free
T3 297 pg/dl, and TSH 13.46 mIU/dl. The patient was
counseled that this hypothyroid phase was likely temporary but he needed continued follow-up.
Discussion: The clinical and biochemical progression
in this patient was compatible with a previous episode of
thyroiditis that had spontaneously resolved, as evidenced
by the clinical features, reduced radioactive iodine uptake,
elevated thyroglobulin level, and spontaneous remission
into a hypothyroid phase. There was no family or personal history of schizophrenia, and the severe behavioral
abnormalities resolved with progressive normalization of
thyroid function. This is the first reported case of the selflimited condition of subacute thyroiditis causing ‘thyrotoxic psychosis’.
Conclusions: Subacute thyroiditis can precipitate features of schizophrenia, mania, psychotic depression and
paranoid behavior severe enough to require inpatient treatment. Clinicians should keep this scenario in mind when
evaluating patients with acute onset of elevated thyroid
function tests and concurrent psychiatric abnormalities.
Abstract #195
GRAVES' DISEASE AND A RUPTURED BENIGN
CYSTIC STRUMA OVARII
Cherrie Mae Cortez Sison, MD, and
Frances Lina C. Lantion-Ang, Clinical Professor
Objective: To report the presentation and treatment of
Graves' disease in impeding thyroid storm due to a ruptured struma ovarii.
Case Presentation: A 38 year old Filipina came in for
3 days of progressive, colicky epigastric pain, postprandial vomiting, and high grade fever. She had salphingooophorectomy for a left ovarian cystic teratoma in 1995.
Graves’disease was diagnosed in December 2004. She had
been on PTU and propranolol since then but thyrotoxicosis persisted. On admission, the patient was agitated,
tachycardic,and febrile. On palpation the abdomen was
rigid with direct and rebound tenderness. Rectal examination revealed marked tenderness. There was posterior cul
de sac tenderness on pelvic examination. TSH was suppressed (0.007 mIU/L, NV 0.3 – 3.8 mIU/L) while free T4
was elevated (30.5 pmol/L, NV 11 – 24 pmol/L).
Transvaginal ultrasound revealed a normal uterus with
thin endometrium, minimal ascites, and an
abdominopelvic mass. PTU per rectum, iodinated contrast,
and dexamethasone were given in preparation for surgery.
Exploratory laparotomy revealed a ruptured cystic ovary.
Histopathologic diagnosis was struma ovarii. The patient
was discharged after 5 days on PTU and propranolol. RAI
was given thereafter.
Discussion: Struma ovarii is an ovarian tumor containing functional or nonfunctional thyroid tissue. They
typically occur as part of a teratoma, but may be encountered with serous or mucinous cystadenomas. In our institution in 2004, out of the 343 ovarian tumors and cysts,
only 3 (0.87%) had a histopathologic diagnosis of struma
ovarii. Since clinical manifestation varies and is nonspecific, most struma ovarii are found during pathologic
examination of an excised pelvic mass. Diagnosis therefore requires a high index of suspicion. Only 22 cases of
the cystic variety of struma ovarii have been reported in
literature. Its rarity makes its identification difficult. Even
rarer is the coexistence of Graves’ disease and struma
ovarii, with only 12 other cases cited. Many of these
patients have either relapsing or uncontrollable thyrotoxicosis. Surgical removal of the ovarian tumor is the primary treatment of struma ovarii, whether with euthyroidism
or thyrotoxicosis. Thyrotoxic cases should be prepared
with antithyroid drugs, sometimes in combination with
beta-blockers. PTU given rectally has been documented in
foreign and local studies to be a viable route of delivery.
Conclusions: A high index of suspicion is necessary
for the diagnosis of struma ovarii, especially in the setting
of coexistent Graves’ disease. Although the exact mechanism of thyrotoxicosis from struma ovarii is unclear, its
presence contributes to hyperthyroidism from Graves’ disease. The diagnosis should be considered in Graves' disease patients who remain thyrotoxic despite adequate
treatment. Surgical removal of the struma ovarii should be
emphasized as part of treatment.
Abstract #159
PULMONARY HYPERTENSION AS INITIAL
PRESENTATION OF GRAVES' DISEASE
Karen Choong, MD, and Geoffrey Modest, MD
Objective: To reinforce the association between
Grave’s disease and pulmonary hypertension, a potentially reversible condition.
Case Presentation: A 40-year-old Haitian woman
with no past medical history presents with a month of
worsening dyspnea and bilateral leg swelling. The diagnosis of heart failure was made from physical exam, CXR
and an elevated BNP of 700PG/ML. Her lab work was
normal except for a thyroid function panel which showed
a TSH of <0.01 uIU/ML, total T3 of 734 NG/DL, T3
uptake of 68.1%, free T4 index of 15.1,Thyroid stimulat-
– 92 –
ing immunoglobulin of 273 and Thyroid peroxidase antibody of >1000 IU/ML. Transthoracic echocardiogram
showed normal left ventricular ejection fraction but dilated and hypokinetic right ventricle. Her pulmonary arterial
systolic pressure was 67mmHg. Subsequent CTPA was
negative for pulmonary emboli. Workup for common
causes of pulmonary hypertension returned negative. The
diagnosis of Graves’ disease with thyrotoxicosis was
made and patient began treatment with methimazole,
propanolol and furosemide. Repeat transthoracic echocardiogram a week later showed improved pulmonary arterial systolic pressure of 41mmHg.Unfortunately,outpatient
follow up had been sparse due to patient noncompliance.
Discussion: Pulmonary hypertension often presents a
grim prognosis despite current medical treatments available. There are currently several case reports in the literature indicating an association between Graves’ disease and
pulmonary hypertension. A prospective Doppler echocardiographic study performed by Merce et al(Am J Med.
2005 Feb;118(2):126-31)found a high prevalence rate of
pulmonary hypertension in patients in the hyperthyroid
group(41%)compared to the euthyroid group(3%).It is
noted that most cases of pulmonary hypertension from
hyperthyroidism achieve complete resolution once a
euthyroid state is attained.Our case report further confirms
the connection between these two conditions.The exact
mechanism of pulmonary hypertension in the setting of
Graves’ is not well known. Hyperthyroidism is known to
cause changes in cardiopulmonary dynamics.In the setting
of Graves disease,several mechanisms have been hypothesized,such as an increase in cardiac output causing
endothelial injury and the possibility of an autoimmune
process leading to endothelial dysfunction.The increase in
cardiac output is felt to cause elevation in pulmonary vascular resistant and subsequent pulmonary hypertension.
Conclusions: In summary, this case illustrates an
unusual presentation of Graves' Disease and emphasizes
the need for health care providers to be vigilant about the
many possible presentations of hyperthyroidism.
Treatment of underlying thyroid dysfunction may lead to
improvement in hemodynamic changes and resolution of
pulmonary hypertension. Therefore, screening for hyperthyroidism in all patients presenting with new onset pulmonary hypertension should be considered.
Abstract #273
GRAVES' DISEASE AS AN IMMUNE
RECONSTITUTION SYNDROME IN PATIENTS
WITH HIV
Suzette Adele Robinson, MBBS
Case Presentation: Case1: A 35 year old African
American female with HIV for 14 years presents with
complaints of insomnia, tremors, palpitations and weight
loss. Examination was significant for thyroid enlargement(40gm). Six years after starting HAART, viral load
was undetectable and CD4 cells increased from 40
cells/uL during the first year of therapy to 594 at time of
presentation. TSH 0.002 IU/ml (0.2-4.7), TT4 16.5 mcg/dl
(5-12), T uptake 45% (23-30), free T4 index 7.4 (1.9-5.6).
Radioactive iodine uptake was 66% @ 24 hours with uniform uptake on scan imaging. Patient was initially treated
with PTU followed by radioactive iodine therapy. Case2:
A 41 yr old African American female on HAART since
diagnosis of HIV for five years. She had no symptoms
suggestive of hyperthyroidism, however had enlarged thyroid (40-60gm). TSH <0.002 IU/ml (0.2-4.7), FT4 3.2
ng/dl (0.8-1.8), TT3 470 ng/dl (72-177). CD4 cells
increased from 64 to 783 and viral load undetectable.
Radioactive iodine uptake was 72% @ 24 hours and scan
showed uniform uptake.
Discussion: Graves' Disease is associated with
immune reconstitution after initiation of HAART therapy.
Unlike SLE and polymyositis which occurs during the
first six months of therapy similar to that of opportunistic
infections eg TB, CMV retinitis and MAC, Graves'
Disease presents much later. A review of the medical literature shows that Graves' Disease develops 12-36 months
(median time of 20 months) after the initiation of HAART
therapy and 12-19 months (median time of 18 months)
after CD4 cell count rise. Our two female patients of
African American descent presented with Graves' Disease
approximately 60-72 months after starting HAART. This
process occurs in the second phase of CD4 rise, which is
usually a slower but continous phase of production of
naive CD4 T cells of thymic origin. Therapy with HAART
causes an increase in thymic size and hence increased output of naive CD4 cells of the TH2 cell type. Regeneration
of the thymus upon HAART therapy also leads to failure
to delete autoreactive T cell clones, resulting in very high
titres of thymic derived T cells in blood. These considerations may explain the development of Graves' Disease in
the immune restoration phase.
Conclusions: Graves' Disease has been shown to
occur after initiation of HAART therapy. This is associated with immune reconstitution, correlating with increased
thymus size in HIV-1 patients. To date, there are no
reports of Graves' Disease in the HIV-1 positive patient
before the pre-HAART era. Physicians need to be aware
of the possibility of Graves' Disease in any patient infected with HIV-1 on HAART presenting with hyperthyroidism.
Objective: To report the development of Graves'
Disease in two African American females infected with
HIV on HAART.
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Abstract #333
ASSOCIATION OF HYPERTHYROIDISM AND
HYDATIFORM MOLE: ROLE OF HCG
Suchitra V. Zambare, MD, and Paulos Berhanu, MD
Objective: Present a case of molar pregnancy with
hyperthyroidism.Review literature&discuss the mechanism of thyroid stimulation by hCG.
Case Presentation: CC: Severe vomiting. 16yr old F
with severe vomiting, with gradually increasing abdominal pain,fatigue and weight loss of 15 lbs for 3 wks.
PMHx: nothing significant. Social Hx: no smoking, alcohol, drug use or recent sexual activity. Family Hx: nothing
significant ROS: Had dizziness, diarrhea, SOB. No palpitations,tremors or menstrual irregularity. Vitals: T37.2C,
HR100, BP153/78, RR:20, BMI 29 Gen: Pale, no distress.
HEENT: Pallor, no expothalmos, JVPor thyromegaly,
drymm. CVS: S1, S2, Regular, rapid, 2/6 flow murmur.
R/S: B/L clear. Abdomen:normal bowel sounds. Firm
with some distension & tenderness over both the lower
quadrants.EXT: Noedema, tremors. Brisk reflexes. LABS:
Cr. 6mg/dL (.6-1.2) ALT88U/L (<65), AST90U/L <60),
Hb6g/dL, plt178, TSH.004mIu/ml (.3-6), FT4: 1.7ng/dL
(.8-1.8) TT4:37ug/dL (95-12), TT3:273ng/dL (72-177),
BhCG:1, 627, 736mIU/L (<5). USG: 18x7x15cm mass
within the uterus,with enlarged ovaries.CTthorax:Multiple
nodules in the lungs.Uterine evacuation was done and
pathology with cytogenetics showed complete hydatiform
mole.At 4th post evacuation day, falling thyroid (TT4: 22,
TT3: 139) and hCG (13562) levels were noted
Discussion: Marked elevation of serum T4, T3,and
FT4 occurs in some patients with molar pregnancy probably as a result of the action of serum hCG or a thyroid
stimulator which is closely related to serum hCG. Frank
clinical thyrotoxicosis is usually absent,probably due to
relatively low serum T3/T4 ratios,or due to limited duration of thyroid hyperfunction,or due to unknown factors.
hCG is a weak thyrotropin agonist and hCG and TSH molecules have structural as well as receptor homology. In
FRTL-5 rat thyroid cells, hCG increases(cAMP),iodide
transport, and cell growth. No significant relationship is
found between serum hCG and FTI.Suggesting that a hCG
like substance is elaborated by the gestational trophoblastic tissue and is responsible for thyrotoxicosis. In molar
pregnancy and in 1/3 to 2/3 of patients with hyperemesis
gravidarum molecular variants of hCG with increased thyrotropic potency are produced.These are basic molecules
with reduced sialic acid content,truncated molecules lacking the C-terminal tail,or molecules in which the 47-48
peptide bond in the beta subunit loop is nicked. Removal
of the mole or effective chemotherapy of the choriocarcinoma cures the hyperthyroidism.
Conclusions: Assessment of symptoms of hyperthyroidism and thyroid function tests should be done in all
pregnant patients especially if they have hyperemesis
gravidarum. Frank thyrotoxicosis is not common, but
there are known cases requiring short-term antithyroid
treatment. It is imperative that both urine and serum pregnancy test should be done, as cases of Hyperthyroidism
and negative urine hCG in molar pregnancy are reported.
Monitor hCG and thyroid levels post evacuation.
Abstract #134
GRAVES DISEASE WITH SEVERE
HYPOCALCEMIA, CHYLOUS ASCITES AND
CHYLOTHORAX
Naoki Hiroi, MD, Yasunari Sakamoto, MD,
Takamasa Ichijo, MD, Mariko Higa, MD, and
Gen Yoshino, MD
Objective: Graves’ disease is a relatively common
disorder. It is known that patients with hypethyroidism
sometimes suffer from diarrhea and postulated mechanisms for diarrhea with thyrotoxicosis include activation
of beta-adrenergic receptors resulting in intestinal hyperperistalsis and/or the development of secretory diarrhea.
Thyrotoxicosis is a well-described cause of hypercalcemia, however, in this case we observed hypocalcemia
associated with hyperthyroidism, a much rare entity. In
this report we describe a case of hyperthyroidism with
severe diarrhea, hypocalcemia, chylous ascites and chylothorax
Case Presentation: A 50-year-old female was admitted to our hospital because of severe diarrhea, irritableness
and severe pitting edema of the legs. The patient had been
well until 5 years before admission, when a tremor and
tachycardia developed and a diagnosis of Graves' disease
was made. Treatment with methimazole was effective,
however she was often non-adherent with her antithyroid
medication because of improvement of her symptoms. On
admission, a thyroid swelling, exophthalmos, a pleural
effusion and ascites were observed. The results of thyroid
function tests (FT3; 21.5 pg/ml, FT4; 7.17 ng/dl, TSH; <
0.01 ?IU/ml and TRAb; 95.9 %) were consistent with
Graves’ disease. Biochemical analysis of pleural and
acsitc fluid were consistent with chylothorax and chylous
ascites, respectively. Serum calcium, total protein and
albumin were very low. We found protein-losing
enteropathy on 99mTc-dextran scintigraphy. Her symptoms except severe diarrhea, edema, pleural effusion and
ascites disappeared after receiving intravenous drip infusion of fluid replacement, and methimazole and iodine.
Because of malnutrition she was given a high calorie intravenouse infusion. Three month after admission, her pleur-
– 94 –
al effusion and ascites began to improve, as did her diarrhea and hypoalbuminemia.
Discussion: It is known that patients with hyperthyroidism sometimes suffer from diarrhea. No evidence of
inflammatory colitis and Celiac disease were observed in
this case. One possible cause of secretory diarrhea in this
case may be b-adrenergic activation, which can stimulate
active electrogenic secretion. Intestinal hypermortility,
which is a well-known cause of diarrhea in hyperthyroidism, may be caused by increased b-adrenergic responsiveness. Protein-losing enteropathy might be one of the
causes for the sever hypoproteinemia. Usually hypercalcemia in patients with hyperthyroidism was observed,
because T4 and T3 stimulate osteoblast activity. We
hypothesize that this hypocalcemia in our case may reflect
“hungry bone syndrome” caused by severe, prolonged,
untreated hyperthyroidism. Chylous ascites and chylotho-
rax are both relatively uncommon. The most common
causes in adults are disseminated neoplasia and, rupture of
lymphatic vessels, and less frequently it is associated with
cirrhosis. The underlying pathogenesis of the chylous
ascites and chylothorax in this case was not apparent,
although one possible mechanism may be hypertension in
lymphatic vessels caused by portal hypertension.
Conclusions: We present a case of Graves’ disease
with severe diarrhea, chylous ascites and chylothorax. It is
thought that the protracted course of untreated severe
hyperthyroidism led to the development of hypocalcemia
due to hungry bone syndrome, hypoalbuminemia secondary to malabsorption syndrome and protein-losing
enteropathy, and chylous ascites and chylothorax secondary to lymphatic hypertension. This case re-emphasizes the importance of early diagnosis and appropriate
treatment of Graves' disease.
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ABSTRACTS – Other
OTHER
Abstract #160
ATORVASTATIN AND PIOGLITAZONE
EFFECTS ON INFLAMMATORY CYTOKINES
AND LIPIDS
Stanley Andrew Tan, MD, PhD, FACE,
Linda Giles Tan, MD, FACC, and
Lee Stanley Berk, MPH, DrPH, FACSM
Objective: To compare the effects of atorvastatin (A),
pioglitazone (P), and A+P on cytokines in diabetic
patients with hyperlipidemia
Methods:: Group A: 15 diabetic subjects with hyperlipidemia who were on A (40 mg/d) were started on P (45
mg/d). Group P: 15 diabetic subjects who were on P (45
mg/d) were started on A (40 mg/d). Lipid profile, interferon-gamma, tumor necrosis factor-alpha, IL-6, IL-4 and
CRP were measured every 2 mo
Results: IFN-g, TNF-a, IL-6 and CRP were above
normal, but IL-4 was suppressed, in all diabetic subjects
before treatment. In group A, atorvastatin decreased LDL
cholesterol at 2 mo and increased HDL cholesterol at 4
mo; decreased IFN-g and TNF-a in 2 mo, IL-6 and CRP at
4 mo. In group P, pioglitazone increased LDL cholesterol
slightly in 2 mo, then decreased LDL thereafter.
Pioglitazone increased HDL cholesterol at 4 mo;
increased IL-4 and decreased IL-6 at 2 mo, and decreased
IFN-g, TNF-a and CRP at 4 mo. When pioglitazone was
added to group A, and atorvastatin was added to group P,
additive changes in cytokines and CRP levels occurred.
Atorvastatin decreased LDL cholesterol and increased
HDL cholesterol synergistically when added to group P.
Pioglitazone increased IL-4 when added to group A.
Discussion: Th-1 inflammatory cytokines interferongamma (IFN-g) and tumor necrosis factor-alpha (TNF-a)
increase Th-2 inflammatory cytokine interleukin-6 (IL-6),
which in turn stimulates C-reactive protein (CRP).
Inflammatory cytokines and CRP aggravate atherosclerosis. Th-2 anti-inflammatory IL-4 decreases CRP and IFNg. Diabetic patients have increased inflammatory
cytokines and decreased IL-4, which may contribute to the
increased incidence of coronary artery disease.
Atorvastatin decreases LDL cholesterol and increases
HDL cholesterol, and decreases CRP by attenuating the
Th-1 inflammatory cytokines IFN-g and TNF-a, which
also resulted in IL-6 decrease. Pioglitazone also decreases
CRP, but through the Th-2 system by increasing IL-4 and
decreasing IL-6. In the first 2 mo pioglitazone increases
LDL cholesterol slightly but not significantly, and later
decreases LDL cholesterol. Pioglitazone increases HDL
cholesterol. Effects on lipids are accentuated synergistically when atorvastatin is added. Effects on cytokines
occur before the effects on lipids. The combined effects of
A+P on cytokines and CRP are additive. The cytokine
effects and lipid effects thus appear to be independent.
Conclusions: Atorvastatin decreases CRP by attenuating the Th-1 inflammatory cytokines. Pioglitazone
decreases CRP by affecting Th-2, i.e. increasing the Th-2
anti-inflammatory cytokine IL-4 and decreasing the Th-2
inflammatory cytokine IL-6. Combined A+P lower
inflammatory cytokines additively, and optimize lipids
synergistically. Thus atorvastatin and pioglitazone combination is beneficial, and may provide cardiovascular protection for diabetic patients with hyperlipidemia.
Abstract #241
PRIMARY BILIARY CIRRHOSIS IN A PATIENT
WITH KLINEFELTER’S SYNDROME
Madappa Nanaya Kundranda, MD, PhD,
Roshni M. Kundranda, MD, MPH,
Anamaria Massier, MD, Niculina Olariu, MD, and
Luis Llerena, MD
Objective: To report a rare case of primary biliary cirrhosis (PBC) in a male patient with Klinefelter’s
Syndrome (KS).
Case Presentation: A 53 year-old white male presented with abdominal discomfort, nausea, vomiting and
dark colored urine for one week. He had pre-existing
hypothyroidism and rheumatoid arthritis and a family history of hemochromatosis. Physical examination revealed
jaundiced skin, mild gynecomastia, sparse axillary hair
and beard, Tanner stage II pubic hair, small soft testes and
hepatomegaly. Biochemical workup demonstrated a
cholestatic picture, elevated CRP 11.5 mg/dl,
5’Nucleosidase 52 U/L (0-15), positive ANA and antimitochondrial antibody (1:320). Testing for hereditary
hemochromatosis, smooth muscle antibodies and viral
hepatitis were negative. Ultrasound and MRCP showed a
normal hepatobiliary system. A liver biopsy confirmed
early stage II PBC. Hormone assays were as follows:
Testosterone 23 ng/dl (200-1000), Free Testosterone 2.2
ng/dl (40-240), FSH 24.4 mIU/ml (1.4-18.1), LH 11.4
mIU/ml (1.5-9.3). Chromosomal analysis was consistent
with KS (47, XXY). The patient was started on
ursodeoxycholic acid; six weeks later his liver enzymes
returned to the normal range.
Discussion: PBC is a chronic progressive cholestatic
disease with a female predominance; less than five percent
of those affected are males. This disease is characterized
by progressive granulomatous destruction of mediumsized bile ducts, the exact etiopathogenesis of which is
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ABSTRACTS – Other
unknown. Evidence from the literature suggests that
genetic and environmental factors play a pivotal role in the
occurrence of PBC. The presence of Klinefelter’s syndrome in our patient makes this a very rare and interesting
case. In our extensive review of the English literature,
there is only one previous report of PBC occurring in a
patient with KS. Due to its rarity, it is unclear if the association of PBC with KS is causal or coincidental. The
inverse relationship of male hormones to cellular and
humoral immunity has been postulated as a possible cause
for the prevalence of autoimmune diseases in males with
KS. An increase in the degree of monosomy of the X chromosome has been observed in females with PBC. Also, the
presence of monosomy X has been demonstrated in
patients with KS. It could be possible that the presence of
monosomy X in a patient with KS may lead to an
increased susceptibility to develop PBC.
Conclusions: KS with 47, XXY aneuploidy is the
most common disorder of sex chromosomes in humans.
The association of KS with PBC may suggest a common
etiology as both diseases share common immunological
and genetic factors. Since KS has a high prevalence in the
male population and can go undiagnosed, especially in
those who exhibit mosaicism, it may be reasonable to test
all men with PBC for Klinefelter’s syndrome.
Abstract #411
A 10-YEAR OLD WITH RETROPERITONEAL
PARAGANGLIOMA WITH A NOVEL SDHB
GENE MUTATION AND ASSOCIATED
HYPERTENSIVE RETINOPATHY AND
CARDIOMYOPATHY
involvement. Cardiac echocardiogram showed moderately
depressed left ventricular systolic function (ejection fraction ~32%) . CT and MRI studies revealed a left-sided 5x4
cm retroperitoneal mass. Plasma and urine
normetanephrines were elevated, and a diagnosis of paraganglioma was made, despite negative m-[123I] iodobenzylguanidine (MIBG) imaging. Genetic analysis of
identified a heterozygous change of C to G at the 2nd
nucleotide of codon 129 in exon 4 in one copy of SDHB
gene. It is a heterozygous c.386 C>G sequence variant in
the SDHB gene. Following alpha- and beta-blockade, surgical excision of the mass was performed, with pathology
confirming paraganglioma. Rapid resolution of majority
of symptoms occurred after surgery with mild persistence
of psychosis.
Discussion: Paragangliomas are rare slow-developing catecholamine-secreting tumors of neural crest origin.
In the last few years the role of genetic analysis of susceptibility genes such as VHL, RET and SDHx (subunits of
succinate dehydrogenase complex) has been progressively
more well defined. Our case is unusual due to the young
age of presentation of the patient and associated hypertensive retinopathy and cardiomyopathy, which are rare manifestations in children.
Conclusions: This case illustrates the link between
SDHB gene mutations and paraganglioma. Furthermore, it
highlights the importance of screening patients with paragangliomas for associated genetic mutations especially
when the family history is unknown.To our knowledge,
this is the first reported case of paraganglioma due to this
SDHB mutation.
Other
Abstract #378
Vandana Raman, MD, Lefkothea Karaviti, MD
Jennifer Bell, MD, and Luisa Rodriguez, MD
METABOLIC SYNDROME IN TYPE2 DIABETICS
AND HYPERTENSIVE NIGERIAN PATIENTS
Objective: Germ-line mutations in the genes encoding
for the mitochondrial complex II (succinate dehydrogenase complex, SDH) have been linked to familial paragangliomas and apparently sporadic pheochromocytomas.
We report a case of retroperitoneal paraganglioma due to
a novel SDHB mutation in a 10-year old girl with
unknown family history.
Case Presentation: 10 and 3/12 year old female was
admitted due to uncontrolled hypertension. History was
significant for weight loss of 20 pounds, episodic nocturnal palpitations, dyspnea and sweating for 4 months and
psychosis with diagnosis of “schizophrenia” for 9 months
treated with anti-psychotic medications. The patient was
adopted and family history was unknown. On exam,
patient was hypertensive and tachycardic. EKG revealed
high junctional tachycardia. Funduscopic exam revealed
multiple cotton-wool retinal exudates with macular
Felicia Ohunene Anumah, MBBS, MWCP, FMCP,
Fatima Bello-Sani, FWCP, and
Solomon Suleiman Danbauchi, FWCP/DR
Objective: Prevalence/risk factors of metabolic(MS)
syndrome in diabetics, diabetic- hypertensives and hypertensive Nigerian patients
Methods:: Consecutive age/sex matched patients: 40
diabetics, 53 diabetic-hypertensives and 45 hypertensives
attending the diabetes and hypertension clinic were
recruited. 45 normals were recruited as controls.
Anthropometric measurements and fasting blood samples
were obtained for glucose and lipid profile.
Results: The mean ages of the diabetics (DM), diabetic-hypertensives (DM/HT), hypertensives (HT) and the
controls were similar 47.8+8.6,50.7+9.4,50.6+8.0 and
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ABSTRACTS – Other
47.5+10.0 years respectively P> 0.05. The prevalence of
MS in the DM patients was significantly higher 62.5%
than in the HT patients 41.3% P<0.05. DM/HT and DM
patients had similar prevalence of MS 60.4% and 62.5%
respectively, P>0.05. In patients with MS, the prevalence
of low high density lipoprotein-cholesterol (HDL-c) was
significantly higher than elevated Triglyceride (Tg) in the
diabetic groups (DM,DM/HT), 100% Vs 40%, 93.7%
Vs34.4% respectively, P<0.05. However, in the HT
group,the prevalence of elevated Tg was higher than low
HDL-c,though not significant,73.7%Vs57.5%.
Discussion: In this study the prevalence of MS seems
to be quite high across the patient groups, though highest
in the normotensive diabetic group. The higher prevalence
of HDL-c hypocholesterolaemia in the diabetic group may
be more useful in the diagnosis of MS in our patients
whereas, in the normoglycaemic-hypertensives, it is not so
clear. Obesity and insulin resistance conditioned by genetic and acquired conditions have been said to be the driving
force to the development of the components of MS. Our
results suggest the existence of MS among Nigerians,
despite the relatively low plasma lipid concentrations.
Considering the prevalence of DM/HT in Nigerians of
2.2% and 15%, this finding has serious implications in
predisposing individuals to atherosclerotic cardiovascular
disease such as myocardial infarction, which presently has
a relatively low prevalence in our practice.
Conclusions: The prevalence of MS was high in the
various patient groups and highest in DM patients. HDL
was found to be more useful in the diagnosis of MS in DM
and DM/HT patients, while in normoglyceamic hypertensives, elevated triglecerides was also a prominent lipid
abnormality.
woman presented at age 45 with labile hypertension associated with palpitations, head-tightness and sweating. The
24-hour urine norepinephrine was 5 times ULN. MRI
showed a 3 cm GJT. After treatment with phenoxybenzamine, she underwent surgery. Complications were vocal
cord paralysis and increased intracranial pressure.
Approximately one year post-operatively, 24-hour urine
norepinephrine was 6 times ULN and MRI showed a 2 cm
right jugular foramen mass increased from initial postoperative scan. Stereotactic radiosurgery was performed.
Three years later she had biochemical resolution and stable disease on MRI.
Discussion: Glomus jugalare tumors (GJTs) typically
present with hearing loss, tinnitus, cranial nerve deficits,
dizziness, and occasionally thrombus of venous structures.
Catecholamine-producing GJTs may present with the classic headache, sweating, and tachycardia. Catecholamineproducing GJTs comprise only 1% of all GJTs. Little is
known about the behavior of hormone-producing vs nonhormone producing GJTs in terms of their response to different modalities of treatment. Because GJTs involve
major vessels, have proximity to cranial nerves, and have
propensity for intracranial extension, there can be significant morbidity from tumor resection. Although mainstay
of treatment is surgery, stereotactic radiosurgery remains a
promising alternative for non-surgical candidates or in
residual disease although more long-term data is needed.
Conclusions: Stereotactic radiosurgery remains a
promising alternative to surgically unresectable or residual
catecholamine-secreting glomus jugulare tumors.
Abstract #201
EFFECTS OF IMPAIRED FASTING GLUCOSE
(IFG) ON PNEUMONIA OUTCOMES
Abstract #235
CATECHOLAMINE-PRODUCING GLOMUS
JUGULARE TUMORS & STEREOTACTIC
RADIOSURGERY
Alla Khalfin, DO, Chadi Saifan, MD, Asma Ahmed, MD,
Irina Zigelboym, DO, and Mario Castellanos, MD
Andrea Tom, MD, Todd Nippoldt, MD, and
Bruce Pollock, MD
Objective: To describe two cases of catecholamineproducing glomus jugulare tumors (GJTs) treated by
stereotactic radiosurgery.
Case Presentation: An 86 year-old woman with 2year history of syncopal episodes presented with a 4 cm
GJT on MRI. The 24-hour urine norepinephrine was 5
times upper limit of normal (ULN) and fractionated free
norepinephrine was 13 times ULN. She had stereotactic
radiosurgery performed after a month of phenoxybenzamine. Chronic serous otitis media was her only complication. At one year, she has decreased frequency of syncopal
episodes and decreased tumor size on MRI. A 52 year-old
Objective: To examined the effects of IFG on
Community-Acquired Pneumonia outcomes in non-critically ill hospitalized patients.
Methods:: Retrospective study reviewed inpatient
records, coded for pneumonia. Patients were grouped
according to past medical history or the first admission
fasting glucose level. Pneumonia complications were
defined and rates were compared among groups, along
with hospital stay and overall mortality.
Results: A total of 401 consecutive cases were examined, 49% were female. The mean age for all patients was
68.7 +/- 18.43 years. The complication rates were significantly different by group. Group 1, Overt hyperglycemia
consistent with diabetes, (N=215) had a complication rate
of 46.5.9%, (100/215). Group 2, IFG, (N= 73) had a rate
of 39.7% (29/73) and Group 3, Normals, (N= 113) had a
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ABSTRACTS – Other
rate of 26.5% (30/113), Chi Square=0.002. The relative
risk of getting a complication, with any degree of glucose
impairment was 82% above normal subjects. The mortality rate was not significantly different by group, p=0.72
and was as follows: DM 10.8%, IFG= 9.7% and Normals
8.0%. Similarly, length of stay among groups was not significant, p=0.57 ANOVA, although Diabetes Group did
have the longest stay.
Discussion: The literature clearly demonstrated that
hyperglycemia is associated with poor outcomes in hospitalized patients. Glycemic control is essential for the care
of hospitalized diabetics and aggressive therapy of hyperglycemia improves clinical outcomes. Communityacquired pneumonia (CAP) is the sixth leading cause of
death in the U.S. and one of the most common causes of
hospitalization. While, hyperglycemia has been identified
as an independent predictor of adverse outcomes in
patients hospitalized with CAP, the effects of impaired
fasting glucose (IFG) on hospitalized patients have not
been studied. In this study, we examined the relationship
between IFG and CAP outcomes in non-critically ill hospitalized patients. Our results confirm earlier studies, suggesting that overt hyperglycemia have a higher rate of
pneumonia complications in hospitalized patients. In addition, our data show that patients with IFG have complication rates similar to overt diabetics.
Conclusions: Our observation indicates that any level
of hyperglycemia on admission is independently associated with a higher rate of pneumonia complications in noncritically ill hospitalized patients. Currently, data is being
collected to study the effects of optimal insulin therapy on
DM patients and examine group-to-group shifts. However,
we recommend that all patients hospitalized with CAP
should be screened for IFG and any increase in glucose
level should be normalized.
Results: Six patients received insulin glargine and
nine patients received insulin aspart. The groups were
comparable in terms of age, gender, admission A1c, BMI,
and creatinine clearance. Mean±SD blood glucose in the
glargine group was 128±16.2 mg/dl (range 106-148) and
in the aspart group 126±8.3 mg/dl (range 105-134)
(p=0.82). Mean daily dose of insulin was 12.1±1.8U in
glargine group and 10.0±2.0U in the aspart group. There
were no episodes of hypoglycemia in either group.
Discussion: Tight glucose control with insulin infusion in the post-operative period is associated with
reduced mortality and reduced infections in cardiac
surgery patients. While there are several good protocols
for insulin infusion, there is no satisfactory protocol for
transition to subcutaneous insulin. Most diabetic patients
need both basal and prandial insulin for optimal glycemic
control. However, data are not clear for non-diabetic
patients. Some physicians treat with basal and prandial
insulin, some treat with only basal insulin, and still others
prefer only prandial insulin. Theoretically, glucose levels
are high due to the stress of acute illness and basal insulin
alone should be able to counter the effect of stress hormones and keep blood glucose in an acceptable range. Our
study proves this hypothesis to be true and finds it unnecessary to give multiple insulin injections to these patients.
Our sample size was small and the results will need to be
confirmed in larger studies. If confirmed by further studies, once daily insulin glargine may be used for transition
to subcutaneous insulin in stress hyperglycemia patients,
thereby simplifying the treatment and saving nursing time.
Conclusions: Once daily insulin glargine is as effective as three times daily preprandial insulin aspart for transition from intravenous to subcutaneous insulin in cardiac
surgery patients with stress hyperglycemia.
Abstract #384
Abstract #175
ROLE OF MRI IN LOCALIZING
HYPERFUNCTIONING PARATHYROID TISSUE
TRANSITION FROM INTRAVENOUS TO
SUBCUTANEOUS INSULIN IN STRESS
HYPERGLYCEMIA
Vanitha Singaram, MD, Joel Schnure, MD, and
Rose Christian, MD
Varsha Vimalananda, MD,
Merri Pendergrass, MD, PhD, and Rajesh Garg, MD
Objective: To compare basal versus prandial insulin
for transition from intravenous to subcutaneous insulin in
cardiac surgery patients.
Methods:: 15 non-diabetic patients with stress hyperglycemia following cardiac surgery were randomly transitioned from intravenous insulin to either once daily insulin
glargine or three times daily preprandial insulin aspart.
Mean blood glucose values over the next 3 days were
compared in the two groups.
Objective: To stress the role of MRI for pre-operative
localizaion of parathyroid adenoma when sestamibi and
Ultrasound are not helpful
Case Presentation: We report a case of 66 year old
woman who was referred for mild hypercalcemia. She had
fatigue, myalgia and low bone mass on DXA scan. Labs
showed calcium of 11.1, phosphorous of 3.2, intact PTH
of 124 suggestive of primary hyperparathyroidism. She
elected to undergo surgery for her parathyroid adenoma.Ultrasound revealed normal thyroid anatomy and no
well defined enlargement of the parathyroids were identi-
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ABSTRACTS – Other
fied.Sestamibi scan did not localize any hyperfunctioning
parathyroid tissue. MRI with contrast revealed a 6 x 11
mm nodule in the posterior lobe of left thyroid gland. The
mass was hypointense on T1 and hyperintense on T2 and
enhanced with contrast.She underwent minimally invasive
surgery and was noted to have a discrete parathyroid
enlargement adjacent to esophagus on left side below thyroid gland. Tissue weighed 820gms. and measured 1.8 x
1.2 x 0.7 cm. Her intraopertive PTH fell from 185 to
41.She has had normalization of her calcium and resolution of her diffuse myalgia and fatigue.
Discussion: Primary hyperparthyroidism is a clinical
condition caused by an excessive secretion of parathyroid
hormone. It affects 1 in 700 patients in US. Enlarged
parathyroid glands with elevations in ionized serum calcium and intact PTH characterizes this disease. It is caused
by single parathyroid adenoma in 80-85% of patients,
parathyroid hyperplasia in 10-15%, multiple adenomas
and parathyroid carcinoma in 2-3%. Surgical removal of
the abnormally functioning tissues is the treatment of
choice. The classic bilateral neck exploration has an estimated failure rate of 5-10%, a reliable diagnostic technique for preoperative localization may be beneficial.
Recent reports support pre-operative localization to
decrease operative times, amount of dissection and surgical complications.Detection often requires both a functional and anatomic study. Review of literature showed the
sensitivity and specificity of MRI similar to sestamibi
scan. MRI has been shown to be better than sestamibi in
detection of hyperplastic glands and cases where sestamibi
is negative.
Conclusions: We understand that both functional and
anatomical studies are important and if done together
improve sensitivity. Sestamibi is the first step given its
lower cost and high positive predictive value. We recommend MRI in those cases in which nuclear study is negative as a second attempt to localize parathyroid pathology.
Abstract #414
ISOLATED HYPOPARATHYROIDISM;
DIAGNOSIS AND PRGNOSIS
Kiran Siddique Choudhry, MBBS,
Lefkothea Karaviti, MD, and Vandana Raman, MD
Objective: Autoimmune Hypoparathyroidism (HP)
can present as an isolated entity or as part of the triad of
hypoparathyroidism, adrenocortical failure and candida
dermatitis. However, when hypoparathyroidism exists in
the absence of other autoimmune findings, it creates a
diagnostic and prognostic dilemma. We looked at different
laboratory investigations to assess prognosis of patients
with isolated hyporarthyroidism.
Case Presentation: An 11-year-old Somalian male
presented to the ER with seizures and tetany. He was diagnosed with severe hypocalcemia and treated accordingly.
Evaluation revealed low calcium, high phosphate, undetectable Parathyroid hormone and low Magnesium. There
was no other evidence of polyendocrinopathy on the physical examination. The phenotype was not consistent with
pseudohypoparathyroidism. Laboratory work up was negative for adrenal and antiparathyroid antibodies. A subsequent work up revealed a positive AIRE profile.
Discussion: The incidence of hypoparathyroidism in
males is lower and later in age as compared to female in
autoimmune polyendocrinopathy syndrome. It is uncommon to have this degree of the hypoparathyroidism without other endocrinopathies. The absence of the antibodies
urged us to consider that genetic workup to establish a
cause of hypoparathyroidism.
Conclusions: Any case of hypoparathyroidism
should include genetic testing for AIRE gene for diagnostic and prognostic implications. Having this knowledge
empowers the healthcare providers to monitor for other
components of this syndrome. Furthermore, as the mode
of inheritance of APS I may be dominant, genetic testing
in the family members is warranted.
Abstract #141
MONTHLY IBANDRONATE SHOWS IMPROVED
PERSISTENCE VS WEEKLY
BISPHOSPHONATES
Keith E. Friend, MD, Stuart Silverman, MD,
John Sunyecz, MD, Mark Cziraky, PharmD, and
Sara Poston, PharmD
Objective: To examine medication persistence among
women receiving monthly ibandronate vs weekly bisphosphonates (BPs) at 9 months.
Methods:: Patient data were collected from a large,
managed-care database accessed through HealthCore, Inc.
Eligible women were aged 45 years and older and filled at
least 1 pharmacy claim for a BP starting April 1, 2005.
Persistence was evaluated based on defined grace periods
between prescription refills.
Results: Longitudinal data from of 4,548 women
were available for this analysis. At 9 months, 213 women
received monthly ibandronate and 4,335 women received
weekly BPs. Of patients receiving monthly ibandronate,
60.1% were osteoporosis medication-naïve, 19.7% were
BP-naïve, and 20.2% had switched from another BP dosing regimen. At 9 months, 41.3% for patients receiving
monthly ibandronate were persistent and 33.4% of patients
receiving weekly BPs were persistent (P=0.003). Cox
regression analyses were used to control for potential con-
– 100 –
ABSTRACTS – Other
founders. After controlling for age, copay, and comorbidities users, monthly users were found to be 31.0% more
likely to be persistent than weekly BP users (Hazard ratio=
0.69, 95% CI: 0.58-0.83, P<0.0001).
Discussion: Medication persistence among women
treated for postmenopausal osteoporosis has remained
suboptimal but may be improved by a once-monthly BP
regimen. This analysis demonstrates that, at 9 months, significantly more patients in the monthly ibandronate cohort
were persistent compared with the weekly BP cohort.
Additionally, after controlling for potential confounders,
monthly users demonstrated an increased likelihood of
persistence. This study suggests that a monthly regimen
may improve persistence with osteoporosis therapy.
Conclusions: In this early post-launch 9-month
analysis, women on monthly ibandronate were more persistent compared to women on weekly therapy. Improving
long-term persistence may lead to improved clinical outcomes (such as reduced risk of fractures) for women with
osteoporosis. Longer follow-up of this cohort is ongoing.
are not the same among patients of different ethnic backgrounds. A dry, hacking coughs might develop in 3-20 %
patients treated with an ACEI. Several studies that looked
at a specific ethnic group, including African-American,
Caucasians (New Zealand) and Chinese (Hong Kong) had
found disproportionately higher incidence among the
Chinese and African-Americans. The exact mechanism of
cough related to ACEI use is unknown at present time.
Several substances that are degraded by ACEI, including
kinins, substance P, prostaglandins or thromboxane, may
be important. Our preliminary data indicates that cough is
more common in Asians treated with ACEIs. Genetic
backgroud might be important for ACEI-related cough
among different ethnic groups.
Conclusions: The overall prevalence of ACEI related
cough was 3-5 times higher in Asians compared to that of
Caucasians and African-Americans. We suggest that when
treating Asian hypertensive or diabetic patients with
ACEIs, patients should be educated for possible side
effects of cough or be considered for an alternative class
of medications, such as ARBs, as first line therapy.
Abstract #207
PREVALENCE OF ACEI-RELATED COUGH
AMONG DIFFERENT ETHNIC GROUPS
Abstract #387
CENTRAL DIABETES INSIPIDUS AS AN INITIAL
MANIFESTATION OF NEUROSARCOIDOSIS
Xiangbing Wang, MD, PhD, FACE,
Arlene Perkins, MD, and Yong Q Lin, MD
Objective: To investigate the prevalence of coughs as
a side effect of ACEIs among the different ethnic groups
in NJ.
Methods:: In this retrospective study, we used a
designed survey form to collect data including the patient’s ethnicity and whether a cough developed during therapies with ACEIs. Chi-Square tests for significance among
groups. A P<0.05 is selected as significant level.
Results: From the 1100 reviewed charts, 159 patients
were documented to be on an ACEI treatment. Among
them, 18 patients developed an ACEI related cough
(11.2%). Caucasians had a prevalence of 5.17% (3/58),
African-Americans had a prevalence of 8.51% (4/47),
Hispanics had a prevalence of 14.3% (3/21) and Asians
had a prevalence of 24.2% (8/33). The prevalence of ACEI
related cough was found significantly higher in Asians
compared to Caucasians and African-Americans; 24.2%
vs. 5.2% (p< 0.01) and 8.51% (P<0.05), respectively.
Hispanics might also have higher prevalence but did not
reach significant level compared to Caucasians and
African-Americans (P>0.05) and might be due to insufficient patients for meaningful conclusion at present time.
Discussion: Angiotensin converting enzyme
inhibitors (ACEIs) are widely used for the treatment of
hypertension (HTN), congestive heart failure (CHF) and
diabetes mellitus (DM). However, their side effect profiles
Praveena Gandikota, MBBS, Uma Borate, MD,
Somnath Ghosh, MD,
Catherine Anastasopoulou, MD, FACE, and
Arthur Chernoff, MD, FACE
Objective: To recognize Diabetes Insipidus as the
neuroendocrine manifestation of sarcoidosis.
female with history of biopsy proven sarcoidosis was
admitted with change of mental status and left hemiparesis. MRI of the brain showed bifrontal vasogenic edema
with extra axial enhancing pathologic process and a
prominent enhancing pituitary stalk. Given the patient’s
history of sarcoidosis, the presentation was thought to be
consistent with neurosarcoidosis. Accordingly, the patient
was started on steroids after which she showed significant
improvement in mental and functional status. Soon after
the steroids were tapered, she developed polyuria (>4liters
of urine/day), nocturia and polydipsia with urine specific
gravity of 1.002 and urine osmolality of 125. Diabetes
mellitus was ruled out. Calcium levels were within normal
limits. Diabetes insipidus secondary to neurosarcoidosis
was considered the most likely etiology. She maintained a
normal serum sodium and osmolality because of appropriate access to water. She was started on desmopressin and
showed dramatic improvement of her symptoms. The
patient required the use of desmopressin for 6 months.
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ABSTRACTS – Other
Discussion: We hypothesize that our patient developed central diabetes insipidus as a manifestation of neurosarcoidosis. The bifrontal enhancement, especially the
prominent pituitary stalk and the resolution of polyuria
with desmopressin provide strong support to this consideration. Neurosarcoidosis is uncommon. It is seen only in
5-15% of cases of sarcoidosis.Neurosarcoidosis can have
varied and non specific presentations making the diagnosis difficult and challenging. Diabetes Insipidus as a neurological manifestation of sarcoidosis is rare and has been
described in occasional case reports. The exact incidence
is unclear. According to a European review, it is seen in
25% of the patients with neurosarcoidosis. Corticosteroids
are used as the first line of treatment with neurosarcoidosis despite the absence of randomized double blinded studies. With respect to Diabetes Insipidus secondary to
neurosarcoidosis, case reports have described that recovery is slow and prolonged with patients needing long term
use of desmopression. Corticosteroids have been reported
to cause initial symptomatic improvement but complete
recovery from Central Diabetes Insipidus was uncommon.
Conclusions: This case underscores the importance
of consideration of Diabetes Insipidus as a neuroendocrine
presentation in the right setting and the possibility of
recovery. The recovery most likely reflects the response of
neurosarcoidosis to steroids.
back as following: iPTH was 9.3 pg/ml (normal 14-72
pg/ml); PTHrP was less then 0.2 pg/ml (normal < 2.0
pg/m); 1-25 vit.D was 128 pg/ml (normal 15-75pg/ml);
25-Vit.D was 28 mg/ml (normal 20-57mg/ml) and urine
and serum electrophoresis were negative.
Discussion: Hypercalcemia is seen in many hospitalized patients. There are multiple causes of hypercalcemia,
but in this case, having just 1-25 Vit.D level elevated
prompted us to screen the patient for possible granulomatous diseases and malignancies. Basing on all work up,
reviewing his prior records, which showed normal calcium
level six months ago, as well as reviewing his history and
medications and ruling out all other causes, the patient’s
hypercalcemia was attributed to his topical calcitriol that
he used for the last four months for psoriasis prior to this
event.
Conclusions: Our case is one of the few cases
described in the literature of topical calcitriol induced
hypercalcemia. It showed that it is not a benign medication
especially in the elderly population and calcium levels
should be monitored closely to prevent the dangerous side
effects.
Abstract #188
ELEVATED 24-HR URINE 5-HIAA LEVELS IN A
PATIENT EATING BANANAS
Abstract #111
Mirna Maldonado, MD, and
Vilma M Rabell, MD, FACE
SEVERE HYPERCALCEMIA CAUSED BY THE
TOPICAL USE OF CALCITRIOL
Svetlana Fomin, MD, and Melissa Young, MD
Objective: To describe an unusual case of severe
hypercalcemia secondary to the topical use of calcitriol.
Case Presentation: This was a 76-year-old male with
a past medical history of CVA and Psoriasis who was
admitted to the hospital because of elevated calcium level
as highest as 16.4 mg/dl on the routine blood work. Upon
admission, the patient denied abdominal pain, constipation, and muscle weakness. His medication list included
Warfarin which was used for anticoagulation and topical
Calcitriol which was started four months ago by his dermatologist as apart of the treatment for psoriasis. His
physical exam was unremarkable. There were no ECG
changes. His blood work on admission was significant for
Calcium 16.0 mg/dl, Albumin 3.1 g/dl, Phosphorus 4.1
mg/dl, BUN 20 mg/dl and Creatinine 1.1 mg/dl. While
waiting for the rest of his blood tests, his topical calcitriol
was held and the patient was treated with hydration along
with loop diuretics and one time intravenous biphosphonates. His calcium levels improved and remained within
normal limits after treatment. His other blood tests came
Objective: To report a case with symptoms of carcinoid syndrome and elevated urine 5-HIAA related to large
ingestion of bananas.
Case Presentation: A 76-year-old man with peptic
ulcer disease, COPD, HBP, Alzheimer disease and
prostate cancer on brachytherapy was evaluated because
of a 1-month history of watery diarrhea not related to
meals. On the same period of time he presented frequent
nausea associated to profuse sweating, and pallor affecting
the face and neck. The pallor lasted 0.5 to 1 hr. He presented frequent dry coughing for the past 2 years, and 10
pounds weight loss in the past one year. He denied abdominal pain or cramping, hypotension, headaches, and leg
edema. He had poor appetite and he was used to eat at least
8 bananas per day. He never smoked. There was no family history of malignancy including thyroid gland. His
treatment included memantine, donepezil, clonazepam,
formoterol, lansoprazole and amlodipine. On physical
exam, he was with bradycardia (HR-52 bpm)and BMI of
21.5. He was with slow talking but the rest of the physical
exam was unremarkable. Laboratory data showed no
abnormalities on electrolytes, hepatic function and CBC.
A 24-hr urine collection for 5-HIAA levels showed 10.9
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ABSTRACTS – Other
mg(normal, <=6.0 mg/24 hr). After discontinuing the
bananas in the diet, a repeated test for 5-HIAA showed 3.3
mg/24 hr.
Discussion: The classic carcinoid syndrome includes
flushing, diarrhea, right-sided heart failure, bronchial constriction and increased urine levels of 5-hydroxyindoleacetic acid(5-HIAA). Some patients display only one
or two of the above features. Other symptoms related to
the syndrome are weight loss, sweating and pellagra-like
skin lesions. Patients with carcinoid tumors usually have
urine 5-HIAA levels of 15 to 60 mg/24 hr. Foods including avocado, banana, chocolate, coffee, eggplant, pecan,
pineapple, plum, tea and walnuts can produce false- positive results in the urine test. Drugs including acetaminophen, fluorouracil, guaifenesin, levodopa, methamphetamine, methocarbamol, phenmetrazine, reserpine
and salicylates can produce false- positive test results.
Drugs such as corticotropin, chlorpromazine, heparin, isoniazid, methyldopa, monoamine oxidase inhibitors, phenothiazine and promethazine can cause false-negative
results in the test. On this patient, the diarrhea resolved by
itself, the cough could be explained by COPD and the
weight loss was related to poor nutrition. Banana is wellknown to give false-positive results in the urine 5-HIAA
assay and it was confirmed on this patient.
Conclusions: This case emphasizes the importance of
physical examination and a complete history including
foods and drugs in a patient with elevated urine 5-HIAA
levels before considering any imaging technique.
Abstract #115
Δ (CC-WC): CHEST CIRCUMFERENCE MINUS
WAIST CIRCUMFERENCE = POOR MAN’S
DEXA?
Mitali Vaidya, MBBS, DD
Rakesh Parikh, MBBS, DD, FCPS
Radha Lachhiramani, MSc, and Dip Clin Dermat, MBBS
Objective: To assess sarcopenia relative to adiposity(which predisposes to insulin resistance)by measuring
new anthropometric parameter
Methods:: In 108 type 2 diabetics(57 males),we measured CC(Chest Circumference) at the level of nipples in
males(M)and infra mammary in females(F), and
WC(Waist Circumference). We made a record of Blood
Pressure,HDL,TG,LDL and CAD.DEXA(Dual Energy X
ray Absorptiometry) was performed in 28 patients (18
males).
Results: p<0.05 for all results.Mean values:WC
96.5cm(F)and 92.8 cm (M),CC 87.1cm (F) and 92.1cm
(M), (CC-WC) -9.3cm (F) and -0.67cm (M). As per
NCEP/ATP III definition, Metabolic Syndrome (MetS)
was present in 92% (F) and 67.8% (M). By IDF criteria,
MetS was present in 86% (F) and 50% (M). By DEXA,
50% females were obese (TBF > 33%) and 41% male
were obese (TBF > 25%). CC shows a positive correlation
(r = +0.82) with both Lean Body Mass (LBM) and Fat
Free Mass {LBM + Bone Mineral Content (BMC)}. (CCWC) negatively correlates (- 0.73)and WC positively co
relates (+0.578) with DEXA estimation of TBF (Total
Body Fat). Neither (CC-WC) nor WC correlated with
clustering of MetS parameters.In females, TBF greater
than 33% was the cut off beyond which the risk of MetS
appears to increase.No such cut off was observed in males.
Discussion: The chest of humans comprises the following muscles: pectorals, latissimus dorsi, serrati, infrascapularis and rhomboids. Caucasians are naturally
endowed with more muscle mass. The inherent propensity
of Asians to develop insulin resistance and/or metabolic
syndrome has been attributed to relative sarcopaenia. To
assess the same, we propose a simple clinical tool- a measure tape assessment of the chest circumference (at to provide a representative sample of generalized muscular
development. That of the waist is a surrogate marker of
adiposity. The difference between the two is fairly reflective of the relative constitution of body fat and muscle
.Greater the difference (CC-WC) –- either due to a relatively larger chest and/or a smaller waist –- reflects a
lower TBF%, and vice versa. This simple clinical measurement provides a fair idea of both body fat content and
distribution. We aspire to promote the reflection of sarcopenia by this novel method.We also postulate that
apparently lean individuals (BMI and WC within normal
range)can be ‘metabolically obese’, because of deficient
muscle mass. The shortoming of this pilot project was the
lack of BMI/weight as comparative variables.
Conclusions: WC,known to reflect adiposity, correlates well with TBF. The new anthropometric measurement CC correlates very well with the total muscle mass
of the body,as ascertained by DEXA. It also correlates
positively with non fat mass. This is perhaps a reflection
of the fact that the chest is a representative musculoskeletal region of the body, and such non-adipose tissue is protective. (CC-WC) also correlates with adiposity. NCEP
criteria,as opposed to IDF, identify greater number of subjects with MetS.
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ABSTRACTS – Other
Abstract #214
Conclusions: This rare disease is important to identify because therapy is imperative and allows for an otherwise satisfactory outcome and prevention of the sequelae
of hypocalcemia.
HIDDEN CALCIUM:
PSEUDOHYPOPARATHYROIDISM
Mayurkumar Dineshbhai Bhakta, MD,
Michael Whitaker, MD, FRCPC
Abstract #150
MULTIPLE ENDOCRINE NEOPLASIA TYPE I
Objective: To highlight a case of pseudohypoparathyroidism with classic clinical, laboratory and radiology
evaluations.
Case Presentation: Patient was a 25 year old male
who presented with a 3 minute witnessed grand mal
seizure that resolved without intervention. There was no
precipitating illness or recent change in medications.
Patient had a history of two grand mal seizures in the past,
each associated with extremely low serum levels of calcium. He had been on calcium replacement therapy but
recently had become non-compliant. On admission, vital
signs were stable and physical exam was significant only
for a positive Chvostek’s sign. Relevant laboratory findings: calcium 4.9 mg/dl (8.9-10.1), phosphorus 4.8 mg/dl
(2.5-4.5, biointact parathyroid hormone 159 pg/ml (1167), total 25-hydroxy vitamin D level – 16 ng/ml (25-80).
Computed tomography of the head showed dense calcifications throughout both cerebral hemispheres and basal
ganglia and electrocardiogram showed prolonged QT
interval. Based on the above examination, our patient was
felt to be a classic presentation of pseudohypoparathyroidism, a syndrome of deficient end organ response to the
PTH stimulus.
Discussion: Pseudohypoparathyroidism is an autosomal dominant genetic disease with variable penetrance
and a prevalence of 3.5 per 1 million patients. Various
forms of the disease exist, with type 1a having the most
striking phenotypic features. The deficient response is due
to PTH receptor mutations in multiple tissues prohibiting
normal organ response to the stimulus which would usually include increased calcium mobilization from the bones
and increased calcium resorption and decreased phosphorus resorption in the kidneys. Furthermore, PTH usually
stimulates the conversion of 25-hydroxy vitamin D to
1,25-dihydroxy vitamin D, which facilitates the intestinal
absorption of calcium. The lack of response to PTH leads
to the classic laboratory exam of elevated phosphorus with
low calcium and variable 1,25 dihydroxy vitamin D levels.
The patient presentation is variable and usually related to
the severe hypocalcemia. Radiologic exam of the brain
may show calcifications in the basal ganglia and cerebral
hemispheres, the etiology of which is unknown. Treatment
is calcium and vitamin D replacement in the form of
calcitriol, and with compliance there are little clinical
sequelae.
Niti Agarwal, MD, Pramila Jyoti, MD,
Ajay Ajmani, MD, DM
Objective: To present the case of a patient who had
primary hyperparathyroidism, pituitary macroadenoma
and multiple lipomas.
Case Presentation: 29 yr male with H/O nephrolithiasis & polyuria of 12 yr & father dying of renal stones. No
other significant history. He had acromegalic facies/skin
tags/decreased body hair/expressive galactorrhea & many
nontender subcutaneous firm nodules (FNAC s/o lipoma).
Rest general & systemic exam was normal. He had normal
hemogram, liver & kidney functions. S.calcium (T)
11.00,10.2mg/dl & Ionised 1.48mmol/L, Phos.
3.2,3.2mg/dl, Albumin 4.5mg/dl, Vit D 12.96ng/ml &
PTH 173pg/ml. 24h Urine exam: polyuria (5,4.5L) & high
calcium (260,282mg). X-Ray: nephrolithiasis. Stones calcium oxalate. X-Ray hand/skull/chest/ECG: normal. USG
Parathyroid (Pthd): lt lower pole pthd adenoma. USG: B/L
renal calculi. Pthd Scan: adenoma in lt lower pthd. S. glucose (F)
94mg/dl, 2h PP 111mg/dl, Prolactin
159.94ng/ml, testosterone 3.12ng/ml, FSH 2.79mIU/ml,
LH 5.69mIU/ml, FT4 1.38ng/dl, TSH1.589uIU/ml, cortisol 11.23 (8 am) & 3.43ug/m l(8 pm). GH nonsuppressible
(basal 5.00,60m 4.23,120m 4.94ng/ml) & IGF-1
367ng/ml. MRI: ant. pituitary macroadenoma with
suprasellar extension, no chiasmal compression. No e/o
gastrinoma
Discussion: The patient had primary hyperparathyroidism with multiple gland involvement (multiple adenomas), pituitary macroadenoma secreting prolactin and
growth hormone. There was no evidence of pancreatic
tumour. Patient also had multiple lipomas and significant
family H/O renal calculi. The complex constituting the
Multiple Endocrine Neoplasia type I. Patient refused any
surgical interventions because of apprehensions that his
father also died of surgical procedure for similar complaints. He is at present on long acting somatostatin 20µg
once a month & advised very regular follow up for present
problems as well any for any new complaints in future.
MEN 1 is an autosomal dominant syndrome involving
presence of tumors of two or more endocrine glands
among parathyroid, anterior pituitary and pancreatic islets.
– 104 –
ABSTRACTS – Other
MEN syndromes are characterized by multiplicity involvement of multiple tissues, presence of multiple foci
within a tissue and cells with capability to secrete one or
more peptide or amines.
Conclusions: Our patient had Multiple Endocrine
Neoplasia type I.
Abstract #254
PASIREOTIDE (SOM230) IN CARCINOID
TUMORS, ACROMEGALY AND CUSHING'S
DISEASE
Joan Glusman, MD, Bo Gao, PhD, and
Karen McBride, PhD
the short treatment period, significant reduction in pituitary tumor volume was observed in patients with
acromegaly. Pasireotide is also being evaluated as a treatment for Cushing’s disease, for which there is currently no
approved medical therapy. Results presented here from a
15-day study suggest that pasireotide has potential as the
first directed medical therapy for Cushing’s disease.
Conclusions: These data show that pasireotide is a
promising new treatment for symptoms of metastatic carcinoid tumors refractory or resistant to octreotide,
acromegaly and may have potential as the first directed
medical therapy for Cushing’s disease.
Abstract #151
Objective: To evaluate the efficacy of pasireotide
(SOM230) in metastatic carcinoid tumors, acromegaly and
Cushing’s disease.
Methods:: Pasireotide has been evaluated in Phase II
studies in patients with metastatic carcinoid tumors refractory or resistant to octreotide LAR, patients with de novo,
persistent or recurrent acromegaly and patients with de
novo, persistent or recurrent Cushing’s disease. New data
have become available.
Results: In patients with metastatic carcinoid tumors
refractory or resistant to octreotide LAR, pasireotide
effectively controlled diarrhea and flushing in 25% of
patients. In a 16-week study of 3 different pasireotide
doses in 59 patients with de novo, persistent or recurrent
acromegaly, pasireotide effectively controlled GH or IGFI levels (GH <=2.5 ug/L or normalized IGF-I levels for
age/sex-matched controls) in 56% of patients, and controlled both GH and IGF-I levels by the same criteria in
39% of patients. Significant reduction (>20%) in pituitary
tumor volume was seen in 39% of patients. Preliminary
results in Cushing’s disease showed urinary free cortisol
levels (UFC) decreased in 95% of patients (n=21) with de
novo, persistent or recurrent Cushing’s disease.
Pasireotide was well tolerated.
Discussion: Pasireotide is a novel, multi-ligand
somatostatin analogue that binds with high affinity to four
of the five somatostatin receptor subtypes (sst1,2,3 and
sst5). This unique binding profile offers potential therapeutic benefits in traditional diseases treated with somatostatin
analogues,
such
as
acromegaly
and
gastroenteropancreatic neuroendocrine tumors, as well as
potential new indications, such as Cushing’s disease. The
results presented here demonstrate that pasireotide is an
effective treatment for the severe symptoms of carcinoid
syndrome in patients with metastatic carcinoid tumors
refractory or resistant to octreotide LAR, as well as in
patients with active acromegaly, including those resistant
to prior surgery or medical therapy. Furthermore, despite
A CASE OF AUTIOMMUNE POLYENDOCRINE
SYNDROME TYPE II
Niti Agarwal, MD, and Pramila Jyoti, MD
Objective: To present the case of a patient who had
type I diabetes mellitus, immune mediated hypothyroidism and IgA Nephropathy.
Case Presentation: 37 yr male diabetic for 7 years,
poorly controlled on insulin presented in DKA. On evaluation, GAD 65 antibodies (ab) were elevated (> 30U/ml,
ref. value <1.0) while islet cell ab & anti insulin ab were
negative. He had history of generalized weakness, constipation, slow mentation & appeared depressed. He had
grade1B firm goiter. His thyroid functions showed primary hypothyroidism (FT3-0.9pg/ml, FT4-0.6ng/dl & TSH54uIU/ml)
(Ref.
FT3-0.65-170,
FT4-90-180,
TSH-0.5-5.0). Anti-TPO ab were elevated (278IU/ml)
(ref. 0-40).On routine investigations, patient was found to
have microscopic hematuria. 24 h urine showed subnephrotic proteinuria (1.5&2g). Rest all biochemical
investigations were normal. The fundus examination was
normal. Histopathology & immunofluorescent staining
patterns on kidney biopsy were consistent with IgA
nephropathy. 8:00 am cortisol was 8ug/dl & showed a normal rise to 21ug/dl on ACTH stimulation. There was no
history of malabsorption & serum antiendomyesial ab
were absent. S.calcium levels were normal (9.6, 9.1 &
9.2mg/dl).There was no family history of
endocrinopathies.
Discussion: Autoimmue polyendocrine syndrome
type II (AIPGES II) is a syndrome complex having atleast
two of the following: primary adrenal insufficiency,
Graves’ disease, autoimmune hypothyroidism / thyroiditis, type I diabetes mellitus, primary hypogonadism, myasthenia gravis or celiac disease. Vitiligo, alopecia, serositis
and pernicious anemia occur with increased frequency.
AIPGES II more common of the immunoen-
– 105 –
ABSTRACTS – Other
docrinopathies, has presentation in adulthood and has
familial aggregation. So, this patient having type I diabetes and autoimmune hypothyroidism had two described
endocrinopathies with IgA nephropathy (also an immune
mediated disease).Patient should be under close follow up
because other endocrine manifestations may develop over
a period of time.
Conclusions: Our patient had type II autoimmune
polyendocrine syndrome.
Abstract #117
“THE FAT FIT VERSUS THE LEAN LAZY”:
THIS CENTURY’S THEORY OF RELATIVITY
Rakesh Parikh, FCPS, DD, MBBS,
Mitali Vaidya, DD, MBBS,
Radha Lachhiramani, MSc, and Dip Clin Dermat, MBBS
Objective: To illustrate through 2 patients the role of
sarcopenia(relative to adiposity)predisposing to diabetes
and metabolic syndrome
Case Presentation: 1)A 38 year old gentleman,
recently diagnosed type 2 diabetes mellitus (T2D) and
dyslipidaemia {(high triglycerides at 357 mg/dl despite
glycemic control,and low High Density Lipoproteins
(HDL) at 37 mg/dl}, has a strong family history of diabetes and cardiovascular disorders(CVD). Primary and
other secondary dyslipidemias were ruled out.He satisfies
criteria for metabolic syndrome (MetS). His Body Mass
Index (BMI) is normal at 20.5 kg/m2. He does not have
central obesity because his waist circumference(WC) is
only 80 cm. His chest circumference (CC) is 81 cm. On
Dual Energy X ray Absorptiometry(DEXA), he is obese as
his total body fat (TBF %)percentage is high at 26.9 (cut
off for abnormality is > 25%, while the normal range is
10-20 % for males). He is being aggressively treated by
me for his T2D and dyslipidemia. 2) A 52 year old
male,has hypertension (BP 140/90 mm Hg)and low HDL
(39 mg/dl)along with a strong family history of diabetes
and CVD. His blood glucose is 100 mg/dl. His BMI is 21
kg/m2, WC 86 cm and CC is 81 cm.He has been told by
his physician that he is in perfect health.
Discussion: Both these subjects are not obese by conventional criteria (BMI and WC), and yet have MetS.
They have 3 factors in common that may predispose them
to insulin resistance (IR) :1) sedentary lifestyles 2) relatively less muscle mass compared to adipose tissue 3)
Family History (FH). This case series aims to illustrate A)
that positive FH, poor Exercise capacity and deficient
Muscle mass are significant contributors to an individual's
propensity to develop diabetes and or metabolic syndrome. B) Such patients appear lean as they fail to meet
criteria for obesity or central adiposity, but on DEXA they
still have excess body fat C) They are metabolically obese,
despite not qualifying to be obese by current anthropometric parameters. D) CC is fairly low in them, as is the
general case with Asian races vis a vis Caucasians. It may
be possible that if one has excess fat, (s)he may antagonise
the metabolic consequences of the same by
possessing/acquiring adequate lean body mass. Hence, the
theory of relativity between muscle and fat. E) There are
obese people who, even with strong FH of cardio-metabolic conditions, ward off T2D/CVD because they are
physically active. They are the 'Fat Fit'.
Conclusions: Chest of humans comprises predominantly musculoskeletal tissues.Caucasians are naturally
endowed with more muscle.The inherent propensity of
Asians to develop IR and/or MetS has been attributed to
relative sarcopaenia.To assess the same,we propose a simple clinical tool-a measure tape assessment of CC to provide a representative sample of generalized muscular
development.WC is a surrogate marker of adiposity.The
difference(CC-WC)is fairly reflective of the relative constitution of fat and muscle
Abstract #308
A CASE OF BENIGN SYMMETRIC
LIPOMATOSIS---CAN TZDS BE OF BENEFIT?
Liqun Song, MD, and Agustin Busta, MD
Objective: We report a case of benign symmetric lipomatosis (BSL) and discuss whether thiazolidinediones
(TZDs) can be a treatment option.
Case Presentation: A 56 y/o female, with a history of
HIV since 1986, peripheral neuropathy and obesity, was
referred for the evaluation of Cushing’s syndrome. Her
HIV therapy was initiated with Zidovudine (AZT) after a
Pneumocystis Carinii Pneumonia (PCP) infection in 1999.
Protease inhibitors were added since 2002. She noticed her
upper arms and face “getting bigger” in 2000. The patient
suffered from a significant weight gain(from 200 Lbs to
350 Lbs)since 2004. The patient had an abnormal distribution of fatty tissue symmetrically around the face, shoulders, arms and thighs, and a “buffalo hump”. Laboratory
tests revealed normal glucose, HbA1c and lipid panel; normal liver, renal function and thyroid function; normal 24
hour urine free cortisol and overnight dexamethasone suppression test; mild elevation of uric acid (5.8 mg/dl); CD
4 count of 273, and HIV viral load of < 50 copies/ml. She
had a leptin level of 46 ng/ml (adult female:4.125.0ng/ml) and adiponectin of 4mcg/ml(adult female
whose BMI>30:4-22mcg/ml). OGTT showed normal glucose levels but high insulin levels (peak of insulin:81.2
mIU/ml).
– 106 –
ABSTRACTS – Other
Discussion: BSL is a rare disorder, characterized by
symmetric accumulation of unencapsulated lipomata at
neck, shoulder girdle, upper arms, and thighs, giving
patient a characteristic “pseudoathletic” appearance. The
etiology of the disease is poorly understood. Surgical
removal is the only successful treatment, although relapses may occur. Dietary weight loss is unsuccessful in
majority of cases. It has been postulated that BSL represents a primary, specific disease of adipose tissue, possibly a failure of adipocyte differentiation. In vitro and in
vivo experiments revealed a defect of catecholamine-stimulated lipolysis in the fatty tissue of BSL patients. TZDs
are a class of compounds that improves insulin sensitivity,
acting as ligands for PPAR-gamma;, which is highly
expressed in adipose tissue and has been shown to play an
important role in adipocyte differentiation. Adiponectin,
adipose-specific protein, is known to correlate negatively
with insulin resistance in patients with obesity and type 2
diabetes. This patient’s hyperinsulinemia and low
adiponectin level suggest insulin resistance.TZDs might
promote the adipocyte differentiation and reduce insulin
resistance in patient with BSL.
Conclusions: Benign symmetric lipomatosis
(Launois- Bensaude Syndrome) is a rare syndrome which
is not well understood. TZDs may be useful therapeutic
option in this condition, but studies are needed to demonstrate if they can be beneficial.
Abstract #329
VITAMIN D LEVELS, REJECTION AND DIABETES IN LIVER TRANSPLANT PATIENTS
Mae Sheikh-Ali, MD, Shon Meek, MD, PhD,
Lina Aguirre, MD, Barry Rosser, MD, and
Andrew Keaveny, M.D.
Objective: To determine whether low vitamin D preliver transplant (LT) is associated with rejection or diabetes within 1 year post LT
Methods:: This is an ongoing retrospective analysis
of 491 LTs performed at the Mayo Clinic Jacksonville
between 01/2004 -12/ 2005. Exclusion criteria: No pre-LT
vitamin D level, vitamin D treatment, renal failure, death
within 1 year of LT and prior history of kidney or liver
transplant.
Results: Of 68 patients thus far reviewed, 34 (mean
age 54 y, 9 [26%] women, 25 men [74%], BMI 29.9
kg/m2) met inclusion criteria. Their 25-OH vitamin D
level was 15.8 ± 6.6 ng/mL (mean ± SD). There was a
trend towards lower vitamin D levels in patients with
greater severity of acute liver rejection. Vitamin D levels
were: 17.9 ± 8.6 in those with no rejection (n=7); 16.2 ±
5.4 in those with mild (first) rejection (n=18); and 13. 6 ±
7.5 in those with moderate to severe (first) rejection (n=9)
developed post LT. Of the 22 patients without pre-LT diabetes mellitus (DM) at 1 year, 9 (41%) developed DM and
13 (59%) did not, There was no association between low
vitamin D and the presence of DM at one year, with vitamin D levels of 16.8 ± 6.4 and 16.2 ± 8.3 in the two
groups, respectively.
Discussion: There is a growing body of literature supporting the role for vitamin D in immune regulation
through effects on cytokine production and secretion.
Several investigators have demonstrated that vitamin D
receptor ligands induced dendritic cells to acquire tolerogenic properties that favor the induction of regulatory T
cells, which mediate transplantation tolerance. There is
also evidence that vitamin D metabolism affects the risk of
DM. Norman AW et al., noted that vitamin D deficiency
resulted in decreased insulin secretion. In 2004, the third
National Heath and Nutrition Examination Survey found
an association between vitamin D status and DM.
Furthermore, animal studies have also suggested a protective effect of vitamin D on the development of DM. We
designed an ongoing retrospective analysis of 491 LT
patients to investigate further the role of vitamin D in
immune regulation and development of DM. Our preliminary data in 34 patients suggest that low vitamin D levels
may be associated with the severity of acute liver rejection, but not necessarily with DM. Larger numbers of
patients which we are currently accruing will allow further
analysis of these relationships.
Conclusions: These preliminary results suggest that
low pre-LT vitamin D levels may predispose to a greater
severity of the first acute liver rejection episode. There is
no evidence thus far that low pre-LT vitamin D levels are
associated with post-LT DM. Findings of an association
between low vitamin D levels and the severity of acute
liver rejection or DM post-LT would have important clinical implications.
Abstract #368
MANAGEMENT OF SIADH WITH TOLVAPTAN:
A SUBANALYSIS FROM THE SALT TRIALS
Suzanne Myers Adler, MD, Joseph G. Verbalis, MD,
John Ouyang, PhD, Cesare Orlandi, MD, and
Frank S. Czerwiec, MD, PhD
Objective: This report describes the efficacy & safety
of tolvaptan in chronic hyponatremia in the SALT trials’
SIADH patient subgroups.
Methods:: SALT-1 &-2 were randomized, well-controlled trials in non-hypovolemic hyponatremia (serum Na
<135mEq/mL). 447 patients were randomly assigned to 30
days of oral tolvaptan or placebo at 15mg titrated to
– 107 –
ABSTRACTS – Other
30/60mg as needed. Serum Na was assessed at baseline to
d30 and 7d after stopping therapy (d37).
Results: SALT-1 & 2 included 179 patients with
SIADH (tolvaptan=86, placebo=90, 3=no treatment). In
SIADH tolvaptan was superior to placebo for: (1) change
in the average daily AUC for serum sodium concentration
between baseline to day 4 & to day 30, (2) mean serum
sodium change at each time point, (3) time to normal
serum sodium, & (4) percent of patients with normal
serum sodium levels at day 4 & day 30 (P<0.001 each).
The maximal mean serum sodium change from baseline
was on day 30 (8.5 vs. 2.9mEq/L for tolvaptan & placebo,
respectively, P=0.001); differences between treatment
groups were lost after stopping tolvaptan (day 37). Fewer
patients required fluid restriction on tolvaptan (5%) than
placebo (22%) (P=0.001). Common side effects were
increased thirst, dry mouth, and increased urination.
Discussion: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by
hyponatremia in the setting of low plasma osmolality.
Binding of arginine vasopressin (AVP) to renal V2 receptors induces aquaporin-2 water channel insertion into the
apical membrane of collecting duct cells, which stimulates
free water reabsorption and antidiuresis. AVP V2 receptor
antagonists such as tolvaptan can block AVP-stimulated
water channel insertion and thereby cause increased excretion of solute-free water, which may be beneficial in the
treatment of SIADH. The SALT-1 and SALT-2 trials were
randomized, double-blind, placebo-controlled interventional studies in euvolemic and hypervolemic hyponatremia; demographic characteristics were similar in the
pooled treatment groups, and the studies were conducted
without mandated fluid restriction. The SALT trials
demonstrated that once daily oral tolvaptan significantly
improved serum sodium in patients with chronic hyponatremia of diverse origin (CHF, cirrhosis, SIADH), and was
effective in increasing serum sodium concentrations
specifically in the SIADH patient subgroups. Tolvaptan
use in acute hyponatremia has not yet been studied.
Conclusions: In the randomized, double-blinded,
placebo-controlled SALT-1 and SALT-2 trials evaluating
the safety and efficacy in the treatment of hyponatremia,
tolvaptan was well tolerated and produced a rapid, sustained, and clinically relevant correction of serum sodium
in patients with SIADH, which was reversible upon cessation of therapy. Tolvaptan therefore shows great promise
for the treatment of chronic hyponatremia due to SIADH.
– 108 –
ABSTRACTS – Author Index
Adrenal Disorders
Author
Bhagra, Anjali
Bhagra, Sumit
Borg, Walter P.
Bruder, Jan M
Butler, Paula
Butler, Paula
Cakan, Nedim
Chee, Cheng Ean
Choksi, Palak
Cigliano, Augusto
Ciltea, Daniel
Cosma, Mihaela
Dahia, Patricia
Dey, Lucy
Diab, Dima
Duggal, Jasleen Kaur
Faas, Fred H
Faiman, Charles
Garovic, Vesna
Grant, Clive S
Grossman, William
Hamid, Zulekha
Hamrahian, Amir H
Jani, Rucha
Jech, Marion
Khoo, Teck-Kim
Kumar, Deepak
Massier, Anamaria
Mitre Calderon, Naim
Pinyero, Mercedes
Pittock, Siobhan
Rassouli, Negah
Saadeh, Sermin A
Singh, Sant P
Siperstein, Allan E
Siraj, Elias
Soares-Welch, Cacia V
Taylor, Harris C.
Tripathy, Devjit
Veloski, Colleen
Young, William F
Young, William F.
Diabetes Mellitus
Author
Abdul-Ghani, Muhammad
Aiello, Vito
Akbar, Daad
Albisser, Anthony Michael
Aldasouqi, Saleh
Alhaj, Buthina
Alhaj, Buthina
Ali, Ahmad
Alzohaili, Opada
Amatruda, John
Arastu, Mohammad
Arbab, Tarig Sayed Mustafa
Bailey, Timothy Silleck
Bays, Harold
– 109 –
Abstract No
Page
390
390
101
316
225
194
416
105
143
225
225
275
316
194
324
225
143
324
390
275
324
143
324
316
316
105
105
364
279
245
279
143
416
225
324
245
275
364
316
245
275
105
4
4
2
4
7
6
5
2
3
7
7
7
4
6
6
7
3
6
4
7
6
3
6
4
4
2
2
1
1
3
1
3
5
7
6
3
7
1
4
3
7
2
Abstract No
Page
355
338
354
304
346
353
354
330
377
318
232
327
392
204
24
10
23
15
9
20
23
31
13
16
12
29
25
18
Diabetes Mellitus (Cont.)
Author
Bergenstal, Richard M.
Boyne, Michael S
Brock, Birgitte
Brunelle, Rocco
Bulchandani, Deepti
Bulchandani, Deepti
Burke, Gordon
Butler, Paula
Button, Eric
Chandra, Piyush
Charatz, Seth
Chernoff, Arthur
Chernoff, Arthur
Choong, Karen
Ciltea, Daniela
D'Agostino, Giovanni
DeFronzo, Ralph A.
DiMarco, Paul
Dmuchowski, Carl
Dmuchowski, Carl
Edelson, Gary
Eledrisi, Mohsen
Eledrisi, Mohsen
Elias, Zeinab Abdulla
Espinosa, Ikna
Fasanmade, Olufemi Adetola
Fein, Seymour
Fein, Seymour
Fleres, Mattia
Fonseca, Vivian Andrew
Frias, Juan P
Gadeela, Nitesh
Gavin, Laurence A.
Goldberg, Ronald B.
Gore, Ashwini P
Goscin, Lee Pletts
Guadiani, Vincent
Guevara-Aguirre, Jaime
Guevara-Aguirre, Jaime
Guevara-Aguirre, Marco
Guevara-Aguirre, Marco
Hamburg, Mitchell S
Hammoud, Jamal
Ikem, Rosemary
Jani, Rucha
Johnston, Jann
Jones, Michael
Jones, Michael
Jurado, Gustavo A
Kazlauskaite, Rasa
Keating, Donald
Khanna, Panchali
Kim, Young Nam
Kolawole, Babatope
Konrady, Tara
Koren, Michael
Krimskaya, Marina
Lachhiramani, Radha
Lachhiramani, Radha
Lam, Amy
– 110 –
Abstract No
Page
239
208
356
296
191
282
272
170
296
418
108
394
402
171
170
338
355
264
409
204
377
354
353
327
110
181
412
410
338
409
296
346
299
204
173
264
299
360
302
302
360
282
346
203
355
341
204
409
110
110
299
346
394
203
282
341
272
137
118
272
33
21
32
16
27
18
31
19
16
11
20
27
32
21
19
10
24
29
10
18
13
23
20
29
22
26
14
24
10
10
16
9
34
18
23
29
34
28
13
13
28
18
9
17
24
14
18
10
22
22
34
9
27
17
18
14
31
11
26
31
Author
Lee, Chee Y
Lervang, Hans-Henrik
Leung, Alicia
Lunceford, Jared
Lush, Cameron
Madsbad, Sten
Malkani, Samir
Martinez, Ramon E.
Marur, Surendra
Matboli, Shadia
Mathur, Sandeep Kumar
McDonnell, Marie E.
Molina, Marjarie
Munasinghe, Rajika
Mustafa, Mahmoud
Myneni, Anjana
Nachnani, Jagdish S
Nanda, Sudip
Nowkike, Maria
Nunlee-Bland, Gail
Odeniyi, Ifedayo Adeola
Odonkor, Wolali
Ogbera, Anthonia O
Ohwovoriole, Efe
Ojofeitimi, Ebenezer
Olaitan, Banji Abiodun
Otaibi, Munera
Parikh, Rakesh
Parikh, Rakesh
Parkes, Robert
Perrild, Hans
Pinto, Miguel E.
Poretsky, Leonid
Provenzano, Vincenzo
Ramesh, Krithi Bangalore
Rehmani, Rifat
Rehmani, Rifat
Rooth, Kathryn
Rosenberg, Daniel
Rosenstock, Julio
Saavedra, Jeannette
Saavedra, Jeannette
Sakal, Saad
Sanchez, Matilde
Saura, Gabriella
Schneider, Doron
Semega-Janneh, Mariam
Shah, Nalini
Sharma, Lokender
Sodhi, Vikram
Sodhi, Vikram
Solimen, Domingo Pait
Stein, Peter Paris
Strange, Poul
Strange, Poul
Tong, Jenny
Topiwala, Shehzad
Topiwala, Shehzad
Trence, Dace L
– 111 –
Abstract No
Page
394
356
110
318
296
356
108
272
383
354
418
171
355
377
353
346
191
232
330
330
181
330
181
181
203
420
353
118
137
208
356
375
272
338
383
377
354
353
264
173
409
360
302
304
318
338
173
330
118
418
118
137
196
318
412
410
326
118
137
326
27
32
22
16
16
32
20
31
19
23
11
21
24
13
20
9
27
12
31
31
26
31
26
26
17
25
20
26
11
21
32
30
31
10
19
13
23
20
29
23
10
28
13
15
16
10
23
31
26
11
26
11
33
16
14
24
28
26
11
28
Author
Truitt, Kenneth
Truitt, Kenneth
Tulloch-Reid, Marshall
Udayasankar, Jayalakshmi
Unachukwu, Chioma Nwaonu
Uplinger, Nadine
Uplinger, Nadine
Usdan, Lisa S.
Vaidya, Mitali
Valle, Gabriel
Velinova, Sylvia
Villena, Arturo
Villena, Jaime E.
Vilsbøll, Tina
Walsh, John Thomas
Warrier, Rahul
Weide, Lamont G
Wilks, Rainford A
Williams-Herman, Debora
Wright-Pascoe, Rosemarie A
Yamanouchi, Toshikazu
Zanzmera, Paresh Haribhai
Hypoglycemia
Author
Accacha, siham D
Angulo, Moris
Asa, Sylvia L
Berber, Eren
Boron, Anna
Castro-Magana, mariano
Chaudhry, Afshan Afzal
Davidson, Michael B
Davidson, Michael Benjamin
del Rosario, Marc
Elizundia, Fernando
Faiz, Shazia
Ferro, Linda
Gopan, Thottathil
Gopan, Thottathil
Gupta, Manjula
Ionica, Nicoleta
Kaliebe, Olga
Kulaga, Mark
Lazaro Ligaray, Kenneth Patrick
Miracle-Lopez, Sigfrido
Perez, C. Elisa
Reddy, S. Sethu K
Rennert, Nancy J
Shapiro, Ilan
Silverberg, Alan Bernard
Siraj, Elias
Soni, Sonia
Turcu, Adina
Vega, Lyzbeth
Wagh, Arati
Zak-Aptekar, Monika
Zambito, Gerardo
Zimmerman, Robert
– 112 –
Abstract No
Page
409
204
208
326
342
394
402
171
137
264
110
375
375
356
392
341
191
208
318
208
296
334
10
18
21
28
15
27
32
21
11
29
22
30
30
32
25
14
27
21
16
21
16
9
Abstract No
Page
291
291
271
271
350
291
291
135
271
164
103
122
350
271
135
135
350
122
350
217
103
122
271
350
103
217
135
164
350
103
164
291
103
135
36
36
38
38
36
36
36
38
38
35
35
37
36
38
38
38
36
37
36
37
35
37
38
36
35
37
38
35
36
35
35
36
35
38
Lipid Disorders
Author
Choksi, Palak
Dean, Diana S
Faas, Fred
Hamid, Zulekha
Hanrahan, Brian William
Rassouli, Negah
Swiglo, Brian Alan
Metabolic Bone Disease
Author
Al-Dabagh, Hiba
Al-Dabagh, Hiba
Ali, Ahmad
Allende, Myriam Z
Anderson, Susan
Archer, Juanita
Archer, Juanita A.
Armas, Laura Anne Graeff
Barr, Charles
Barr, Charles E
Basaraba, Ioana
Beary, John F
Binkley, Neil
Binkley, Neil
Boca, Ioan
Bolognese, Michael A.
Bonnick, Sydney Lou
Borretta, Giorgio
Brown, Jacques P
Cesario, Flora
Chertow, Bruce
Chicea, Liana
Chow, John T.
Clarke, Bart L.
Cosman, Felicia
Darbie, Lynn
Delmas, P. D.
Derman, Richard
Drincic, Andjela
Emkey, Ronald D
Erickson, Lori A.
Fleseriu, Maria
Friend, Keith
Friend, Keith
Friend, Keith E.
Friend, Keith E.
Gianotti, Laura
Grant, Clive S.
Grauer, Andreas
Grauer, Andreas
Grima, D.
Gurevich, Yuriy
Guy, Jeffrey A.
Hamoudeh, Eyad
Haque, Salma
Harley, Carolyn
Hochberg, Marc
Ioachimescu, Adriana Gabriela
Jameson, Brian Craig
– 113 –
Abstract No
Page
314
306
314
314
352
314
306
40
40
40
40
41
40
40
Abstract No
Page
246
210
284
317
332
246
210
222
286
300
240
349
319
307
240
289
319
249
349
249
237
240
114
322
319
349
408
286
222
289
114
240
297
307
319
288
249
114
315
303
303
393
169
237
243
286
300
187
422
51
49
53
43
44
51
49
54
50
55
55
49
52
45
55
52
52
49
44
49
48
55
51
46
52
44
56
50
54
52
51
55
54
45
52
47
49
51
48
42
42
53
43
48
45
50
55
50
42
Metabolic Bone Disease (Cont.)
Author
Klemes, Andrea Beth
Koltun, William
Kwagyan, John
Lange, J. L.
Lange, Jeffery
Lewiecki, E. Michael
Lewiecki, E. Michael
Licata, Angelo
Lindsay, R.
Lloyd, Errol
Loftus, Kelly Ann
Maldonado, Mirna
Martens, Mark
Miller, Paul
Miller, Paul D
Miller, Paul D
Moses, Arnold M
Mulloy, Anthony
Newton, Marisha
Newton, Marisha
Nunlee-Bland, Gail
Nunlee-Bland, Gail
Nwokike, Maria
Odonkor, wolali
Osterman, Juraj
Pasquale, Margaret
Pia, Anna
Piziak, Veronica Kelly
Poretsky, Leonid
Poston, Sara
Rabell, Vilma M
Rabelo, Marielsa
Recker, Robert
Russell, Darrell A
Sathananthan, Airani
Schenck, John B.
Schnell, Dan J
Scruggs, Michangelo
Sebba, Anthony
Sederati, Farhad
Semega-Janneh, Mariama
Shaker, Joseph
Shastri, Bhavin Rajendrabhai
Silverman, S. L.
Silverman, Stuart
Silverman, Stuart L
Ste-Marie, Louis-Georges
Sun, Lu Amy
Tassone, Francesco
Teodoru, Cristina
Terris, David J
Thompson, Gary A
Thompson, M.
Wang, Susan
Watts, Nelson B.
Weissman, Peter N.
Wermers, Robert A.
Yaqub, Abid
Zaidi, Mone
– 114 –
Abstract No
Page
349
288
246
408
303
297
286
187
408
210
332
317
288
297
300
289
422
332
210
246
284
246
284
284
169
303
249
300
393
286
317
317
307
315
322
169
315
210
307
289
284
218
218
408
319
300
349
315
249
240
332
315
303
169
408
307
114
237
297
44
47
51
56
42
54
50
50
56
49
44
43
47
54
55
52
42
44
49
51
53
51
53
53
43
42
49
55
53
50
43
43
45
48
46
43
48
49
45
52
53
47
47
56
52
55
44
48
49
55
44
48
42
43
56
45
51
48
54
Obesity
Author
Aston, Chris
Balian, Arax Ara
Jackson, Rhett
Krikorian, Armand Ara
Lancaster, Andrew Darien
Madigan, Elizabeth A
Pasalar, Parvin
Rad, Morva Tahmasbi
Stephens, Lancer
Pituitary Disorders
Author
Aaltonen, Lauri A
AbouAssi, Hiba
Ahmad, Shema Riaz
Badiu, Corin
Choksi, Palak U
Choong, Karen
Coculescu, Mihai
Cook, David M
Cuevas-Ramos, Daniel
Cuevas-Ramos, Daniel
Delashaw, Johnny B
Drincic, Andjela
Dumitrascu, Anda
Faas, Fred
Fleseriu, Maria
Galoiu, Simona
Gheorghiu, Monica Livia
Gómez-Pérez, Francisco J
Gómez-Pérez, Francisco J
Gomez-Sanchez, Elise P
Gopan, Thottathil
Graves, Leland
Hamid, Zulekha
Hamrahian, Amir
Hays, Lisa Rene
Ilahi, Marium
Iqbal, Saima
Islam, Aticul
Kazlauskaite, Rasa
Kazlauskaite, Rasa
Kirmani, Salman
Koch, Christian A
Krikorian, Armand Ara
Leung, Alicia
Lichtinger, Alejandro
Lteif, Aida
Ludlam, William H
Manni, Andrea
McCauley, Robert Andrew
Miracle-Lopez, Sigfrido
Mirfendereski, Seyedqumars
Natt, Neena
Parent, Andrew
Parikh, Rajulkumar
Patel, Mehul
Paulo, Jr, Remberto Cuenca
Pérez-Enríquez, Bernardo
– 115 –
Abstract No
Page
395
339
395
339
395
339
370
370
395
58
57
58
57
58
57
57
57
58
Abstract No
Page
295
407
295
401
205
198
401
179
399
389
179
193
401
205
179
401
401
389
399
295
252
323
205
252
323
193
236
244
236
167
215
295
407
167
294
215
179
174
174
294
244
190
295
244
244
215
399
66
68
66
67
61
59
67
62
67
60
62
66
67
61
62
67
67
60
67
66
63
64
61
63
64
66
61
62
61
60
63
66
68
60
65
63
62
59
59
65
62
65
66
62
62
63
67
Pituitary Disorders (Cont.)
Author
Pérez-Enríquez, Bernardo
Pinsker, Richard W.
Placzkowski, Kimberly Ann
Ramirez Vick, Margarita
Ramos-Guifarro, Alejandra
Ramos-Guifarro, Alejandra
Rassouli, Negah
Rider, Nicholas
Rubinstein, Marc
Rull, Juan
Rull, Juan
Santiago, Alejandra Nancy
Schimke, R. Neil
Shapiro, Ilan
Spetch, Charles
Toms, Steven
Utset, Manuel
Velinova, Silviya
Villabona, Carmen Vanessa
Villabona, Carmen Vanessa
Weil, Robert
Whittaker, Thomas
Yedinak, Chris G
Reproductive Endocrinology
Author
Drincic, Andjela
Jacob, Jubbin Jagan
Mathews, Suma S
Paul, Thomas V
Rizvi, Ali Abbas
Sood, Anshu
Thomas, Nihal
Thyroid Disease
Author
Abiodun, Isiba
Agarwal, Niti
Aldasouqi, Saleh
Aldasouqi, Saleh
Ale, Ayotunde Oladunni
Alvarez, Roger
Alzohaili, Opada
Artigas, Cecilia
Attallah, Hamdee
Azeem, Amir
Bar-Andziak, Ewa
Barsano, Charles
Berhanu, Paulos
Bhagra, Anjali
Bhagra, Sumit
Bodenner, Donald
Bogdanska, Magdalena
Braverman, Lewis E
Busaidy, Naifa
Chao, Tzu-Chieh
Chase, Cori
Chau, Cora Yuk Ping
Chaudhry, Naeem
Choksi, Palak
– 116 –
Abstract No
Page
389
244
190
185
389
399
205
174
294
389
399
185
323
294
185
252
167
236
236
167
252
323
179
60
62
65
69
60
67
61
59
65
60
67
69
64
65
69
63
60
61
61
60
63
64
62
Abstract No
Page
216
274
274
274
126
216
274
70
70
70
70
71
70
70
Abstract No
Page
163
152
345
199
287
292
380
251
154
199
184
233
333
391
391
413
184
398
386
104
251
145
305
148
74
89
72
76
81
88
77
86
91
76
72
75
94
79
79
76
72
90
84
80
86
81
78
84
Thyroid Disease (Cont.)
Author
Choong, Karen
Colt, Edward
Das, Seshadri
Dean, Diana
DeLano, Mark
Dharia, Prachi
Diab, Dima
Dominic, Paari
Doshi, Kaushik
Duggal, Jasleen Kaur
El Youssef, Joseph
Fatourechi, Vahab
Gardner, David W
Gharib, Hossein
Gonzalez, Manuel
Gornicka, Barbara
Goscin, Lee Pletts
Goscin, Lee Pletts
Gossain, Ved
Gossain, Ved
Hamid, Zulekha
Hanson, Tyler Lydell
Higa, Mariko
Hiroi, Naoki
Hsueh, Chuen
Huang, Yu-Yao
Husain, Akhtar
Ichijo, Takamasa
Islam, Najmul
Jacob, Jubbin Jagan
Jagtap, Mandar
Jain, Sachin Kumar
Jauhar, Sonia
Jedrzejowski, Maciej
Jyoti, Pramila
Kantorovich, Vitaly
Kayumova, Nozima L
Khanna, Panchali
Khayal, Saba
Komarovskiy, Kateryna
Kuo, Sheng-Fong
Lantion-Ang, Frances Lina C
Latif, Sahibzada
Ledoux-Pascucci, Michele L.
Lin, Jen-Der
Lin, Jen-Der
Liou, Miaw-Jene
Lugaro, Ana Maria
Mahar, Saeed Ahmed
Marks, Allan D
Michael, Brian Ellis
Modest, Geoffrey
Myneni, Anjana
Myneni, Anjana
Nauman, Janusz
Ng, Alvin
Ng, Joseph
Ng, Siok Bian
O'Brian, John T.
– 117 –
Abstract No
Page
159
140
351
320
345
305
325
233
305
233
180
391
177
293
305
184
292
251
345
199
148
293
134
134
104
104
365
134
365
278
292
152
140
184
152
148
359
345
109
351
283
195
199
347
104
283
104
385
365
301
398
159
199
345
184
145
351
145
347
92
77
82
89
72
78
80
75
78
75
86
79
85
85
78
72
88
86
72
76
84
85
94
94
80
80
90
94
90
74
88
89
77
72
89
84
87
72
83
82
79
92
76
78
80
79
80
82
90
73
90
92
76
72
72
81
82
81
78
Thyroid Disease (Continued)
Author
Ogbera, Anthonia Okeoghene
Olubusola, Adeleye Olufunmilayo
Olufemi, Fasanmade
Oommen, Regi
Pedersen-White, Jennifer R.
Pinsker, Richard W.
Rabelo, Marielsa
Rao, Ambika
Rassouli, Negah
Redman, Carolyn
Rizvi, Ali Abbas
Robinson, Suzette Adele
Sakamoto, Yasunari
Schiefer, Amanda Reagan
Seshadri, Mandalam S
Sheikh-Ali, Mae
Siddiqui, Munira
Singh, Rajneesh
singh, sarabjeet
Siraj, Elias S.
Sison, Cherrie Mae Cortez
Skugor, Mario
Spring, Paul
Stack, Brendan
Stas, Sameer
Stephen, Charles
Toscano-Zukor, Amy Maria
Velasco, German
Wang, Xiangbing
Watwe, Veena
Yazbeck, Cynthia F
Yoshino, Gen
Zambare, Suchitra V.
Zhang, Meijuan
Other
Author
Adler, Suzanne Myers
Agarwal, Niti
Agarwal, Niti
Aguirre, Lina
Ahmed, Asma
Ajmani, Ajay
Anastasopoulou, Catherine
Anumah, Felicia Ohunene
Bell, Jennifer
Bello-Sani, Fatima
Berk, Lee Stanley
– 118 –
Abstract No
Page
163
290
163
278
405
305
385
380
180
148
413
125
273
134
320
278
293
140
152
233
301
195
325
413
413
177
278
373
140
373
154
386
134
333
301
74
87
74
74
87
78
82
77
86
84
76
91
93
94
89
74
85
77
89
75
73
92
80
76
76
85
74
73
77
73
91
84
94
94
73
Abstract No
Page
368
151
150
329
201
150
387
378
411
378
160
107
105
104
107
98
104
101
97
97
97
96
Other (Continued)
Author
Bhakta, Mayurkumar Dineshbhai
Borate, Uma
Busta, Agustin
Castellanos, Mario
Chernoff, Arthur
Choudhry, Kiran Siddique
Christian, Rose
Czerwiec, Frank S.
Cziraky, Mark
Danbauchi, Solomon Suleiman
Fomin, Svetlana
Friend, Keith E.
Gandikota, Praveena
Gao, Bo
Garg, Rajesh
Ghosh, Somnath
Glusman, Joan
Jain, Sachin Kumar
Jain, Sachin Kumar
Jyoti, Pramila
Jyoti, Pramila
Karaviti, Lefkothea
Karaviti, Lefkothea
Keaveny, Andrew
Khalfin, Alla
Kundranda, Madappa Nanaya
Kundranda, Roshni M
Lachhiramani, Radha
Lachhiramani, Radha
Lin, Yong Q
Llerena, Luis
Maldonado, Mirna
Massier, Anamaria
McBride, Karen
Meek, Shon
Nippoldt, Todd
Olariu, Niculina
Orlandi, Cesare
Ouyang, John
Parikh, Rakesh
Parikh, Rakesh
Pendergrass, Merri
Perkins, Arlene
Pollock, Bruce
Poston, Sara
Rabell, Vilma M
Raman, Vandana
Raman, Vandana
Rodriguez, Luisa
Rosser, Barry
Saifan, Chadi
Schnure, Joel
Sheikh-Ali, Mae
Silverman, Stuart
Singaram, Vanitha
Sodhi, Vikram
Sodhi, Vikram
Song, Liqun
Sunyecz, John
Tan, Linda Giles
– 119 –
Abstract No
Page
214
387
308
201
387
414
384
368
141
378
111
141
387
254
175
387
254
150
151
151
150
414
411
329
201
241
241
115
117
207
241
188
241
254
329
235
241
368
368
117
115
175
207
235
141
188
414
411
411
329
201
384
329
141
384
117
115
308
141
160
104
101
106
98
101
100
99
107
100
97
102
100
101
105
99
101
105
104
105
105
104
100
97
107
98
96
96
103
106
101
96
102
96
105
107
98
96
107
107
106
103
99
101
98
100
102
100
97
97
107
98
99
107
100
99
106
103
106
100
96
Other (Continued)
Author
Tan, Stanley Andrew
Tom, Andrea
Topiwala, Shehzad
Topiwala, Shehzad
Vaidya, Mitali
Vaidya, Mitali
Verbalis, Joseph G.
Vimalananda, Varsha
Wang, Xiangbing
Whitaker, Michael
Young, Melissa
Zigelboym, Irina
– 120 –
Abstract No
Page
160
235
115
117
115
117
368
175
207
214
111
201
96
98
103
106
103
106
107
99
101
104
102
98

Table of Contents 2007 ABSTRACTS

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