Document 6427306

Transcription

Document 6427306

ABSTRACTS
ism and AI. APS-2 consists of AI, autoimmune thyroid diseases and/or type 1 diabetes mellitus. Autoimmune thyroid
diseases associated to other autoimmune diseases (excluding AI and/or hypoparathyroidism), define APS-3. The different combinations of autoimmune diseases not included
in the previous groups are characteristics of APS-4.
Conclusion: This case illustrates the importance of
making an early diagnosis of AAI in the right context of
clinical and laboratory data. In addition, the presence of
other endocrine gland insufficiencies should prompt an
evaluation for APS. Clinicians should be aware of these
particular syndromes to avoid the presence of unrecognized endocrine disorders and their complications.
ADRENAL DISORDERS
Abstract #100
A CASE OF ACUTE ADRENAL INSUFFICIENCY
AND HYPOTHYROIDISM: AUTOIMMUNE
POLYGLANDULAR SYNDROME?
German Velasco, MD, Andrew Weinberg, DO, and
Spyros Mezitis, MD, PhD
Objective: To illustrate the acute presentation of adrenal insufficiency (AAI) in a patient with hypothyroidism
with an overview of autoimmune polyglandular syndromes
(APS).
Case presentation: A 29 year-old male with a history
of hypothyroidism presented to his PMD complaining of a
3-week history of lower extremity weakness, muscle pain
and exertional dyspnea. He had a syncopal episode associated with hypoglycemia (43 mg/dL) and was sent to the
ED. His physical examination was significant for hypotension. Laboratory data showed hyponatremia (127 meq/L)
and hyperkalemia (7.0 meq/L) with no changes on electrocardiogram. A random cortisol level was 0.1 mcg/dL. A
suspected diagnosis of AAI was made and he was treated
with intravenous hydration and dexamethasone. A cosyntropin stimulation test (250 mcg) showed a low ACTH
response, confirming the diagnosis of AI. Additional data
included a TSH of 4.72 micro IU/mL, free-T3 223 pg/dL,
T4 5.7 mcg/dL, negative adrenal antibodies, and a CT scan
of abdomen/pelvis showing markedly diminutive adrenal
glands. He also developed anemia with normal iron studies,
negative autoantibodies, and an upper endoscopy significant for mild chronic gastric inflammation. Consequently,
he received oral hydrocortisone and, upon stabilization of
his vital signs and electrolyte abnormalities, he was discharged without complications.
Discussion: AAI can be a challenging diagnosis; however, the presence of autoimmune disease (e.g. hypothyroidism) should prompt a suspicion of the diagnosis in the
right clinical context. APS consist of multiple endocrine
gland insufficiencies associated to autoimmune disease.
Currently 4 types have been described. APS-1 is characterized by presence of chronic candidiasis, hypoparathyroid-
Abstract #101
UTILITY OF THE GLUCAGON STIMULATION
TEST IN THE EVALUATION OF PATIENTS
SUSPECTED TO HAVE PHEOCHROMOCYTOMA:
A CASE REPORT
Krupa Doshi, MD, Dima L. Diab, MD,
Emmanuel Bravo, MD, and Amir H. Hamrahian, MD
Objective: To demonstrate the utility of the glucagon
stimulation test (GST) in confirming the diagnosis of pheochromocytoma (PC).
Case Presentation: A 55 year-old male was found to
have a 3.2 cm left adrenal incidentaloma with an attenuation value of 13 HU on non-contrast CT scan during workup of chronic diarrhea. He denied history of hypertension
or symptoms of palpitations, diaphoresis, headaches or
weight gain. Biochemical data was as follows: plasma free
metanephrines (MN) 1.01 nmol/L (normal <0.5), urine
total MN 1536 µg/24 hr (140-785), serum norepinephrine 265 pg/mL (80-520), serum epinephrine 124 pg/mL
(10-200) and urine total catecholamines (CA) 105 µg/24
hr (26-121). Multiple BP measurements were consistently
below 120/64 mm Hg. He underwent a GST in which
epinephrine and norepinephrine values increased from
271 pg/mL (at baseline) to 6236 pg/mL (at 120 seconds)
and from 462 pg/mL (at baseline) to 1978 pg/mL (at 120
seconds) respectively. His BP rose from 98/69 mm Hg at
baseline to 181/86 mm Hg at 120 seconds. At that time,
––
ABSTRACTS – Adrenal Disorders
he looked pale and complained of headache and lightheadedness, which lasted for a few minutes. He subsequently
underwent a successful adrenalectomy and pathology was
consistent with PC.
Discussion: The diagnosis of PC is made by measurements of 24 hour urine or serum CA and MN levels.
Urine total MN >1800 µg/24 hr, serum total CA >2000
pg/mL or plasma free MN exceeding 3-4 times the upper
limit of normal in the appropriate clinical setting are diagnostic of PC. When clinical suspicion for PC is high but
serum or urine CA and MN levels are non-diagnostic,
additional testing is necessary. Clonidine suppression test
(CST) is used in patients with elevated serum CA or MN
levels. However, this test may be associated with significant hypotension in normotensive patients. GST may be
of value in such circumstances but the literature regarding
its usefulness is controversial. Young (Eur J Endocrinol
1997; 136:28) reported no utility with the use of the GST
in over 500 patients suspected to have PC who had normal
urine CA excretion. Grossman et al. (Hypertension 1991;
17:733) reported positive GST results in 25 of 31 patients
with PC, 8 of whom had normal baseline plasma CA levels.
The result of the GST in our patient suggests that this test
may be useful in confirming the diagnosis of PC in normotensive patients with an equivocal biochemical work-up
for PC.
Conclusion: GST may be of value in normotensive
patients suspected to have PC with a biochemical workup not in the diagnostic range for PC. Appropriate patient
selection is an important factor to maximize the utility of
this test.
pressed by low and high dose dexamethasone, Magnetic
Resonance imaging showed an adrenal tumor which was
removed surgically and patient became normotensive after
surgery with restoration of normal blood glucose, cortisol, ACTH and urinary metanephrines. follow up of the
patient showed complete resolution of the hypertension,
and hyperglycemia on no medications.
Conclusion: Pheochromocytoma is a rare cause of
hypertension that should be sought in patients with severe
hypertension, and it can produce ACTH in addition to
catecholamines
Abstract #103
CUSHING`S SYNDROME DUE TO ECTOPIC
ACTH-PRODUCING PHEOCHROMOCYTOMA
Khalil M Alsoutary, MD, FACE, Riad
��
Sulaimani, MD and
Hani Alassad, MD
Objective: To report a 31 year female patient who
presented with Cushing’ s Syndrome, new onset Diabetes
Mellitus and hypertension that proved to be due to ectopic
ACTH secretion by a pheochromocytoma.
Methods: A 31 year female was admitted to our hospital with polyuria, polydypsia, weight loss of 15 kgs and
difficult to control hypertension for last 3 months. Result: Glucose was 35.8 mmol/l, K 2.9 mmol/l,
serum cortisol 2280 nmol/l(normal 138-690), ACTH level
568,, urine metanephrines 35763 nmol/24 hrs (normal 2501200).Biochemical profile showed high metanephrine and
normetanephrine, and high morning cortisol level not suppressed by low and high dose dexamethasone, Magnetic
Resonance imaging showed an adrenal tumor which was
removed surgically and patient became normotensive after
surgery with restoration of normal blood glucose, cortisol,
ACTH and urinary metanephrines.
Case Presentation: A 31 year old Saudi female, presented with polyuria, polydypsia and weight loss of 15
kgs over the last 3 months, associated with blurred vision,
severe muscle weakness, palpitation, weakness and shortness of breath, but no nausea or vomiting. She had bilateral loin pain and frothy urine. Her menses were regular till
the last six months. She was diagnosed to have diabetes 6
months ago and was started on treatment with Metformin
and diet. Her blood sugar readings were all high in the last
3 months. 2 years before, she had proteinuria of 2.5 gms
in 24 hrs urine collection and kidney biopsy performed
which showed mesango-proliferative glomerulonephritis.
She was treated with prednisolone 30 mgs tapering to 10
mg daily and mycophenolate 500 mgs bid. She was also
receiving simvasatatin for dyslipidemia
Abstract #102
CUSHING SYNDROME DUE TO ECTOPIC
ACTH PRODUCING ADENOMA
Khalil M Alsoutary, MD, FACE, Riad Sulaimani, MD and
Hani Alassad, MD
Objective: To report a 31 year female patient who
presented with Cushing’ s Syndrome, New onset Diabetes
mellitus and hypertension that proved to be due to ectopic
ACTH secretion by a pheochromocytoma.
Methods: A 31 year female was admitted to our hospital with polyuria, polydypsia, weight loss of 15 kgs and
difficult to control hypertension for last 3 months.
Result: Glucose was 35.8 mmol/l, K 2.9 mmol/l,
serum cortisol 2280 nmol/l(normal 138-690), ACTH level
568,, urine metanephrines 35763 nmol/24 hrs (normal 2501200). Biochemical profile showed high mwtanephrine and
normetanephrine, and high morning cortisol level not sup––
echolamines. In this patient BP returned to normal and is
still normal without medication after adrenalectomy.
Physical Examination: Patient was obese BMI 39
kg/m2, Bp 210/130 mm Hg, rounded face with acne, no
hirsutism or hyperpigmentation, wide violacious striae
over the abdomen, lower limbs showed multiple bruises,
Fundoscopy showed grade 1 hypertensive changes( AV
narrowing), peripheral pulses intact, jugular venous pulse
not raised. Heart sounds normal with an ejection systolic
murmer 2/6 over the aortic area. Liver was palpable 4 cm
below coastal margin, nontender, and spleen not palpable.
Lower limbs showed bilateral pitting edema. Laboratory
Investigations: CBC: WBC’s 6200 /ml, hemoglobin 13.8
gm/dl, HbA1C 9.2.Urinalysis showed protein 3+, glucose
3+-24 hrs urine protein 8.76 gms, Na 138 meq/l, K 2.8
mmol/l, Cl-94, HCO3 33 mmol/l Urea 5.2 mmol/l, creatinine 56 mmol/l. Arterial blood gases: pH 7.49, pCO2
38.5, pO2 84, O2 sat. 97% on room air, Serum Cortisol
280mmol/l (normal 138-690) at 8.00 AM ACTH 568 pg/ml
(normal 9-52 at 08 :00 AM) 24 hrs urine metanephrines
35763 nmol/24hrs (normal 250-1200) Normetanephrines
13751 nmol/24hrs (normal 750-2000) 11 deoxycortisone
120 nmol/l (normal <13.8).Low dose dexamehasone:
High dose dexamethasone 8 mgs 1 dose at 12 midnight.
Radiological Investigation: CT scan of lungs-Normal
MRI of pituitary gland: normal size and enhancement.
MR Imaging of the abdomen showed a well-defined,
round shaped mass in the paravertebral area, suggestive
of an adrenal tumor-fig.1. Hospital Course: Her high
blood pressure was difficult to control even with 4 medications-Atenolol 100 mg, valsartan 160 mg, Amlodipine
10 mg/dl and KCL supplement. After the diagnosis was
established with the result of metanephrines and failure of
suppression of cortisol on both low and high dose dexamehasone, patient was prepared for surgery with IV fluids
and phentolamine, On December 13, 2004 she underwent
open Right adrenalectomy. Pathology: Grossly showed
7.0X3.5x4.0 cm with a polypoid mass 4.5x5.0 cm-its cut
section showed a gray soft appearance. Fig.2 Microscopic
section: Hyperplastic adrenal gland with a general nodular appearance with cortical cells of varying appearance,
some of these cells have vaculated cytoplasm. Sections of
the adrenal mass show a tumor of well defined nests separated by well vascularized stroma. Mitotic figures were
uncommon. The cytoplasm has a granular appearance. IHC
for chromogranin stain and synaptophysin are strongly
positive. Findings were suggestive of pheochromocytoma.
Patient improved dramatically after adrenalectomy with
complete normalization of BP and hyperglycemia without
medication Conclusion: Pheochromocytoma is a rare cause of
hypertension that should be sought in patients with severe
hypertension, and it can produce ACTH in addition to cat-
Abstract #104
BRONCHIAL CARCINOID SECRETING ACTH:
A CASE OF MISDIAGNOSIS
Saba Khayal, MD, and Brandy Panunti, MD
Introduction: Cushing’s Syndrome (CS) due to ectopic production of ACTH remains a major diagnostic challenge to the endocrinologist.
Case: A 27 y/o male presented to his internist with
40 lb wt. gain in the past year, uncontrolled HTN and
darkening stretch marks. Diagnosis of CS was established
after an overnight 1 mg dexamethasone suppression test
and elevated 24 hour urinary free cortisol. ACTH was194
pg/ml. MRI pituitary was normal. After inferior petrosal
venous sampling, he underwent transsphenoidal pituitary
resection. Pituitary pathology was normal. After surgery
ACTH level was 234 pg/ml and serum cortisol was 50 µg/
dl. Patient continued to have s/s of hypercortisolism. He
was referred to Endocrinology.
Reviewing the results of his petrosal venous sampling: ACTH levels from the peripheral vein, left petrosal
sinus and right petrosal sinus were 135, 109 and144 pg/ml
respectively before CRH stimulation. ACTH levels post
CRH stimulation from the peripheral vein, left petrosal
sinus and right petrosal sinus were 130, 146 and 143 pg/
ml respectively. The central to peripheral ratios for ACTH
were less than 2:1 baseline and less than 3:1 after CRH
stimulation, findings not consistent with pituitary or central
CS. Patient underwent CT thorax/abd/pelvis, a bronchial
adenoma was seen. An octreotide scan was positive in the
same area. Biopsy of the lesion was consistent with neuroendocrine tumor. Patient underwent resection of the adenoma. It stained positive for ACTH secreting cells. After
surgery, ACTH levels were undetectable. He improved
clinically.
Discussion: Ectopic ACTH syndrome comprises 1020% of the cases of CS. The classic description of the ectopic ACTH syndrome was made by Grant Liddle in the early
1960’s and was based on a series of patients who mostly
had malignant tumors. More recently, the ectopic ACTH
syndrome has been recognized with increasing frequency
with benign tumors specifically carcinoids. Benign versus
malignant lesions typically present in a more subtle clinical
manner. Plasma ACTH levels are strikingly high in ectopic
CS, usually greater than 200 pg/ml. Inferior petrosal sinus
sampling after CRH stimulation is a reliable test to dif––
ferentiate between pituitary ACTH CS and ectopic ACTH
CS. A central to peripheral ACTH ratio of ± 2 basal and
± 3 after CRH administration is consistent with pituitary
ACTH syndrome(which was not the case in our patient).
Once diagnosis is established, the next step is CT thorax/
abd/pelvis. Octreotide scan is another important diagnostic tool for tumor localization. Iodinated or indium -111labeled octreotide scanning has been used more recently.
Management includes treatment of the underlying lesion.
Conclusion: It is important to differentiate between
the various etiologies of CS since the treatment modalities
are different.
normalization of her blood pressure. A repeat cosyntropin stimulation test performed two months later when the
patient was off MA and steroids was normal.
Discussion/Conclusion: Though adrenal insufficiency has been reported as a side effect of MA, it is not
well recognized in clinical practice. Also with the widespread use of MA, adrenal insufficiency may present as
subtle and diverse presentations. It is important for the clinician to recognize adrenal insufficiency in patients of MA
especially with its widespread use in the geriatric population. Though some authors have recommended that routine
steroid replacement at the time of MA commencement may
be the safest course of action, we recommend that during
periods of illness patients receiving MA should receive
empiric therapy with stress doses of corticosteroids. Also,
when discontinuing chronic MA therapy, it should be gradually tapered off as well the HPA axis tested to confirm
normalization.
Abstract #105
MEGESTEROL ACETATE ASSOCIATED
ADRENAL INSUFFICIENCY
Deepti Bulchandani, MD, Jagdish S Nachnani, MD,
Alpesh Amin, MD, and John May, MD
Abstract #106
Objective: Megesterol acetate (MA) is a commonly
used drug in the malnourished geriatric population to promote weight gain. Adrenal insufficiency is a well documented adverse effect of Megesterol acetate. We present a
case with megesterol induced severe adrenal insufficiency
presenting as mental status change, weakness, and ventilatory respiratory failure. Given the challenge of clinically
recognizing adrenal insufficiency in this patient population it is important for clinicians to be alert for this adverse
effect when using or even considering Megesterol therapy.
Case Presentation: The patient is an 80 year old
female admitted for dyspnea. Prior to this presentation, she
had a general decline in physical function associated with
some weight loss and anorexia consistent with failure to
thrive and was started on MA in an effort to stimulate her
appetite. Her portable chest Xray was within normal limits
and neurologic examination was consistent with generalized weakness and cognitive impairment. The rest of her
examination including room air oxygen was within normal limits. During her hospital stay, she developed worsening delirium and dyspnea with hypotension. The patient
was subsequently transferred to the ICU and electively
intubated. Bronchoscopy did not reveal any signs of infection and she continued to oxygenate well on the ventilator.
During her stay she underwent an extensive neurological
workup including an EEG and MRI and EMG which failed
to reveal a cause. A cosyntropin test showed the presence
of adrenal insufficiency. MA was at this time discontinued and steroid replacement with dexamethasone was
initiated. The patient did improve subsequent to this with
INABILITY TO CONCEIVE IN NON-CLASSICAL
CONGENITAL ADRENAL HYPERPLASIA
Ramya Smita Vedula, DO, and
Anne Marie VanHoven, MD
Objective: To describe fertility treatment failure in
women with Non-classical congenital adrenal hyperplasia
(NCCAH).
Case: A 29 year old female presents seeking to
become pregnant. She had menarche at age 14 but noted
her periods were never regular. In 1999 she was started on
an oral contraceptive which regulated her menstrual cycles
until she stopped in August of 2005. She had intermittent
periods thereafter but was not able to conceive despite trying for 6 months. A reproductive endocrinologist was consulted in July 2006, who made a diagnosis of polycystic
ovarian syndrome and prescribed metformin, without benefit. The patient has gained 20-25 pounds over the past 2
years, reports no significant stress in life, no hirsutism but
some facial acne for which she was using topical acne treatments. In addition, there were no headaches, galactorrhea,
eating disorders, excessive exercise, or signs and symptoms of hypo or hyperthyroidism. Physical exam showed a
5’4” woman, weight of 154lbs and BMI of 26, well appearing and in no distress. No hirsutism, acne, thyromegaly,
acanthosis nigricans, abdominal stria, or bruises. The rest
of the exam was within normal limits. Laboratory data
obtained included normal levels of insulin, SHBG, DHEA
sulfate, TSH, prolactin and glucose. Total testosterone was
––
elevated at 70, LH of 11, FSH of 5 and 17-hydroxyprogesterone was 491. An ACTH stimulation test showed a base
line 17-hydroxyprogesterone of 178 and a stimulated 17hydroxyprogesterone of 5815. Based on the clinical history, presentation and lab values, a diagnosis of NCCAH
was made and the patient was started on dexamethasone to
induce ovulation. Despite 3 months of dexamethasone, the
patient has not had a menstrual cycle. Fludrocortisone was
recently added. Genetics was consulted for preconception
counseling.
Discussion: Non-classical congenital adrenal hyperplasia (NCCAH) is a mild enzymatic defect of 21-hydroxylase that results in a delay of symptoms until after puberty.
It is often diagnosed as polycystic ovarian syndrome
(PCOS). In women affected with NCCAH desiring pregnancy, a trial of dexamethasone is initiated to induce ovulation. Since the doses of glucocorticoids needed to suppress
ACTH can cause signs and symptoms of glucocorticoid
excess during long term treatment, the treatment is often
worse than the disease. As a result, dexamethasone is used
mostly for fertility.
Conclusion: Since NACCH seems to trigger a PCOS
like physiology, patients have difficulty with fertility
despite glucocorticoid replacement. Concurrent treatment
with dexmethasone, fludrocortisone and metformin has
been of no benefit, aggressive fertility treatments maybe
needed.
ADRENAL CARCINOMA PRESENTING AS
TYPE 2 DIABETES MELLITUS
Chest radiograph showed canon ball shadows suggestive
of metastasis. CT Scan abdomen revealed left adrenal mass
with metastasis in liver & retroperitoneal lymph nodes.
FNAC from lesions of liver was suggestive of metastasis
from adrenal carcinoma. She was diagnosed as a case of
functioning adrenal carcinoma (Cushing’s syndrome) with
multiple metastases. Patient refused for chemotherapy and
lost to follow-up after 2 visits.
Discussion: Adrenal carcinoma is an uncommon
tumor. Most patients present with nonfunctioning tumors
and clinical manifestations are related to tumor growth or
with an incidentally found adrenal mass detected on radiographic imaging performed for a different reason. Adrenal
carcinoma may cause Cushing’s syndrome in 8% of cases.
Adults with hormone-secreting adrenal carcinoma usually present with Cushing’s syndrome alone, or a mixed
Cushing’s and virilizing syndrome with overproduction
of both glucocorticoids and androgens. Fewer than 10%
present with virilization alone. This patient had poorly
controlled diabetes mellitus since diagnosis that prompted
endocrine evaluation for the cause of diabetes mellitus.
Conclusion: Adrenal carcinoma is a rare tumor with
very poor prognosis. Presentations of Cushing’s syndrome
can be varied, and patients can present across a range of
disciplines. Early consideration of the diagnosis increases
the possibility of successful treatment in cases of persistently uncontrolled diabetes mellitus; a thorough endocrine
work-up should be instituted including imaging studies to
diagnose early adrenal tumors. The most important and
consistently observed determinants of improved survival
are localized tumors, complete surgical resection, and
tumor grade.
Simmi Dube, MD, VK Sharma, and TN Dubey
Abstract #108
Abstract #107
Objective: To report a case of adrenal carcinoma who
presented as poorly controlled type 2 diabetes mellitus.
Case Presentation: 42 years obese female admitted
with complaints of type 2 diabetes mellitus for last 2 years
and amennorrhoea, proximal muscle weakness, acne and
boils since 3 months. She informed that in spite of having diet control, regular exercise and good compliance to
anti-diabetic treatment, her diabetes mellitus is poorly controlled. Physical examination revealed hypertension, moon
facies, buffalo hump, easy bruising, folliculitis, acne, hirsutism, proximal muscle weakness and tenderness over
bones. Complete haemogram and renal function tests were
normal. Fasting Blood glucose– 380 mg %, Post meal blood
glucose- 415 mg%, Serum sodium – 134 meq/L, Serum
Potassium – 3 meq /L, Serum ACTH – 05pg/ml, Serum
cortisol – 45ug /dl, Serum DHEA sulphate – 550ug /dl.
CUSHING SYNDROME CAUSED BY A
NEUROENDOCRINE CORTISOL
PRODUCING TUMOR
Maria Alejandra Ramos Guifarro, MD,
Juan Manuel Rios, Alfredo Reza Albarrán,
Esperanza Valentín, Edgar Avendaño, Arturo Ángeles,
Edgardo Reyes, Francisco J Gómez-Pérez, and Juan Rull
Objective: To present a case of Cushing’s syndrome
caused by a cortisol producing tumor with neuroendocrine
histological characteristics.
Case Report: A 19 year old female presented for consultation with a 10 month history of weight gain, increased
facial hair and purple striae in abdomen and legs. Five
months earlier she had been diagnosed with Cushing syn––
Clinical Presentation: A 19 year old, G1P0 at 30
weeks gestation, presented with high urine and plasma
metanephrines (PM). She had a family history of MEN2A, and was found to have a RET gene mutation at the
time of her sister’s diagnosis (index case). She underwent
prophylactic total thyroidectomy at age 13, and pathology
showed medullary thyroid cancer. Evaluation for pheo
prior to surgery was negative. She was lost to follow up
(FU) until 6 years later, when she was next evaluated for
pheo. Exam demonstrated normal BP without orthostasis,
a healed necklace scar, non-palpable thyroid and a gravid
abdomen. Despite being asymptomatic, both urine and PM
were elevated three fold. Serum calcium, calcitonin and
TSH were normal. An MRI of the abdomen revealed a 2.5
x 3.5 cm lesion in the left adrenal gland, hypointense on T1
and hyperintense on T2 weighted images, consistent with
pheo.
The patient was started on Phenoxybenzamine 10 mg
BID, and referred to high-risk OB. She did well during
the remainder of her pregnancy and underwent an elective
Caesarean-section at 39 weeks, with delivery of a healthy
infant. Six weeks later, she underwent an uneventful laparoscopic left elective adrenalectomy (EA). Pathology
revealed pheo with capsular invasion. She is currently
doing well on LT4.
Discussion: Pregnancy related pheo is rare, and if
unrecognized, is associated with maternal and fetal mortality up to 50%. Cardiovascular collapse, uteroplacental
insufficiency, fetal hypoxia and death have been reported. Antenatal recognition significantly reduces these complications, and if diagnosed in late pregnancy, appropriate management becomes crucial. EA is usually recommended
before 3rd trimester, however, specific guidelines for
management in late pregnancy are lacking. Our case was
unusual in that the diagnosis was made late in pregnancy
precluding elective surgery. Management with a- adrenergic blockade alone resulted in an uneventful pregnancy. Hence, a conservative approach with careful monitoring in
an asymptomatic patient may be appropriate, if diagnosed
in late pregnancy.
Conclusion: Once the diagnosis of MEN-2A is confirmed, routine surveillance for pheo is recommended to
avoid catastrophic outcomes, including those associated
with pregnancy. FU screening for pheo despite left adrenalectomy is necessary in our patient, as the risk of developing pheo in the contralateral gland is 50% in 10 years. Finally, in MEN-2A patients, imaging studies in addition to
biochemical testing, are appropriate as many of these cases
can be clinically silent.
drome and an abdominal CT showed a left adrenal adenoma. At diagnosis her urinary cortisol was 1216 mcg/day,
with a plasmatic cortisol level of 34.26 mcg/dl; serum
ACTH was 19 ng/dl. A laparoscopic left adrenalectomy was
performed and pathological report was a neuroendocrine
tumor adjacent to a hypotrophic adrenal gland. Her symptoms diminished for a couple of months, but then returned;
a new CT scan showed a solid mass located between the
rectum and the uterus, 6x6 cm in diameter, with extension
to both ovaries and multiple nodules inferior to the spleen.
She underwent a laparotomy for tumor removal, but due
to tumor burden only biopsy specimens were removed.
The pathology report was consistent with neuroendocrine
tumor cromogranin+, synaptophysin+, ACTH-.Post-op she
received chemotherapy (etoposide, cysplatin ),mitotane 3
mg per day and ketoconazole 600 mg/day. On a follow-up
scan 10 months later, only 4 small nodules of less than 2
cm were observed and a new laparotomy was performed to
remove all visible tissue; the pathology report was similar.
After her last surgery she developed an adrenal crisis, she
is now receiving 30 mg a day of cortisone therapy and florinef 0.5 mg a day.
Discussion: In this patient, Cushing’s syndrome due
to ectopic ACTH secretion was not demonstrated; furthermore, ACTH levels were low and staining for ACTH was
negative. Histologically, it was compatible with a cortisol
secreting neuroendocrine tumor. There have been reports
of adrenocortical carcinomas with positive neuroendocrine staining, although this is extremely unusual; it is even
rarer to find a cortisol producing carcinoma with neuroendocrine histology.
Conclusion: Adrenocortical and neuroendocrine
tumors can overlap in clinical, biochemical, histological
and inmunostaining markers. The hypothropic adrenal tissue found adjacent to the neoplastic tissue and the clinical
response to medical treatment suggest that the origin of the
tumor is neuroendocrine and not adrenal.
Abstract #109
MANAGEMENT OF PHEOCHROMOCYTOMA
(PHEO) PRESENTING IN LATE PREGNANCY AS
PART OF MEN-2A SYNDROME
Sonia Gajula, MD, and
Lilamani Romayne G Kurukulasuriya
Objective: To discuss the outcome of conservative
management of pheo diagnosed in late pregnancy.
––
Abstract #110
Abstract #111
ADRENOCORTICAL CARCINOMA PRESENTING
WITH RESISTANT HYPERTENSION AND
HYPOKALEMIA
BILATERAL ALDOSTERONE-PRODUCING
ADENOMA. THE USEFULNESS OF CONTINUOUS
ACTH STIMULATION DURING BILATERAL
ADRENAL VENOUS SAMPLING AND
18-HYDROXYCORTICOSTERONE
MEASUREMENT
Abdullah Hanna-moussa, MD, Khurshid Khan, MD, and
Stephen Brietzke, MD
Objective: To recognize the different presentations of
adrenocortical carcinoma (ACC).
Case presentation: 33 year old male presented with
uncontrolled hypertension, hyopkalemia, weight loss, and
lower extremities edema. Three months prior to his presentation he was diagnosed with DM and his BP was markedly elevated while on multiple medications. A CT scan of
the abdomen demonstrated 7.5 cm right adrenal mass, with
liver and lung masses. Blood work showed potassium 2.6
mmol/L, CO2 35 mmol/L. His Am cortisol post overnight
1 mg dexamethasone was 31.2 mcg/dl, aldosterone, PRA
were normal, 24 h urine metanephrine was normal, 24 h
urine free cortisol 1221 mcg/d(normal<60mcg/d), DHEA
4.6 ng/mL (1.9 - 7.6 ng/mL), ACTH 3 pg/mL. He under
went Laparoscopic right adrenalectomy with, excisional
biopsy of liver mass, which showed ACC with and liver
metastases. His post surgery course was complicated by
refractory hypertension treated with IV medications and
ketoconazole 200 mg TID, a subsequent MRI of the brain
showed brain metastases.
Discussion: ACC presents with excess cotrisol production in approximately 60% of cases, with a median survival of 18 months. Our patient presented with hypertension,
weight loss without other common presenting symptoms
(weakness, anorexia, nausea, vomiting, and myalgia) with
normal DHEAs which when elevated is a clue for ACC.
Severe hypokalemia is common and is more likely caused
by grossly elevated cortisol secretion, activating the mineralocorticoid receptor. Clinical features of Cushing’s syndrome are often missing because the rapid development
of ACC. The role of tumor debulking in the presence of
metastatic disease is a matter of debate. Incomplete resection is associated with a poor prognosis, however, tumor
debulking may help to control hormone excess. Mitotane
is the treatment for inoperable tumors, metastatic disease
and after incomplete resection. Chemotherapy is an option
in advanced ACC.
Conclusion: ACC is a rare malignancy. It can present
in different ways and can progress rapidly, high index of
suspension can lead to early diagnosis and potentially better outcomes.
Farnoosh Farrokhi, MD, Fariha Shad, MD,
Javier Clemente, MD, and
Luis A. Llerena. MD, FACP, FACE
Objective: To present a case of bilateral aldosteroneproducing adenoma (APA) and work up to differentiate it
from Idioapthic hyperaldestronism (IHA).
Case presentation: 35-year-old female was admitted
to the hospital with weakness, severe non-induced hypokalemia, and hypertension (HTN). Routine lab work was
unremarkable. Hyperaldosteronism was suspected due to
persistent hypokalemia. Despite of high doses of potassium replacement, her potassium was 2.4 meq/L. Cortisol,
ACTH, catecholamines and metanephrines were normal.
DHEA-S was upper normal. Plasma aldosterone concentration (PAC) persistently elevated (over 50 ng/dl) (nl.
4.5-35.4), with suppressed plasma renin activity (PRA)
(below 0.4 ug/L/hr) (nl. 0.5-1.8). Although PAC did not
change significantly from supine to upright position, it was
not suppressed after high sodium diet and saline over load
test. 1.6 and 1.0 cm nodes were noted on the Ct scan in
the left and right adrenal respectively. Bilateral APA was
suspected. Adrenal venous sampling during continuous
ACTH infusion showed very high levels of aldosterone (A)
(10890 ng/dl) and18-oH corticosterone (18-OHC) (23600
ng/dL) in the left adrenal vein. Aldosterone to cortisol ratio
(A/C) of 384.8 (nl. Less than 4). In the right side also A
and 18-OHC were high (1891 and 6660 ng/dl respectively)
with A/C ratio of 25.2. The A in vena cava was only 81 ng/
dl and the A/C ratio 1.08. Patient was started on spironolactone with excellent control of HTN and hypokalemia. She
no longer required potassium supplements.
Discussion: Bilateral adrenal APA has been reported
in only few cases, and it is always a challenge to differentiate from IHA. Adrenal vein sampling obtained during
a continuous ACTH infusion has proved to be useful in
localization of the tumor. Measurement of 18-oH corticosterone can help in differentiating APA from IHA, as 18-oH
corticosterone is not as high in IHA.
Conclusion: Although we don’t have the pathological confirmation, the secretion of very high levels of aldosterone and 18-oH corticosterone in this patient are highly
––
Discussion: We present a case of iatrogenic CS due
to the administration of intra-articular triamcinolone. Previous reports have focused on frequent and/or larger
doses of intra-articular or intralesional glucocorticoids. Due
to slower absorption modest doses of intra-articular doses
of triamcinolone acetonide have been regarded as less likely
to cause CS than systemic administration of other glucocorticoids. Following an administration of a routine dose
at a routine interval of triamcinolone our patient developed
profound adrenal axis suppression and clinical CS.
Conclusion: Intra-articular injections of even modest
amounts of high potency steroids can cause iatrogenic CS. We recommend careful monitoring of the adrenal axis in
patients receiving these injections.
suggestive that the tumor in both sides of the adrenals
are APA not IHA. The good response to spironolactone
strongly favors the diagnoses of APA. Unilateral adrenalectomy would not have corrected the problem and bilateral
adrenalectomy would have increased morbidity.
Abstract #112
IATROGENIC CUSHING’S SYNDROME
FROM INTRA-ARTICULAR INJECTION OF
TRIAMCINOLONE ACETOMIDE
Michael Gardner, MD, Rebecca Kelly, MD, Richard
Lugar, MD, David Gardner, MD
Objective: To recognize intra-articular injection of
high potency steroids as a potential cause of iatrogenic
Cushing Syndrome (CS).
Case Presentation: A 40 year old female was referred
for a rapidly increasing Cushingoid appearance. She had
initially presented for follow up of low back pain about 6
weeks prior to referral and was noted to have thrush which
was treated with nystatin. A month later she had gained 32
pounds with a rounding of her face. Also, Serum ACTH,
24 hour urine free cortisol, and 8am serum cortisol, were
all below the limits of detection. Upon presentation to our
clinic, she was noted to have a round plethoric face, prominent supraclavicular/dorsocervical fat pads, mild proximal muscle weakness, centripetal obesity and purplish
abdominal stria. Repeat labs showed ACTH <2pg/mL (658pg/mL) and 8am cortisol of 0.7mcg/dL (6.7-22.6mcg/
dL). TSH, LH, FSH, and prolactin were normal. A cosyntropin stimulation test (CST) (0.25mg IM) was performed.
Baseline (10am) cortisol was 1 mcg/dL, ½ hour 5.4 mcg/dL
and 1 hour 6.9 mcg/dL. Iatrogenic and factitious CS were
investigated. Further discussion with the patient revealed
injections of 40mg triamcinolone acetonide on two occasions, 7 and 4 weeks prior to referral, into the sacroiliac
joints under fluoroscopic guidance. Direct contact with
all of the patient’s physicians confirmed that no other steroids had been administered within the last year. Urine
spectroscopy for synthetic glucocorticoids (Mayo Medical
Laboratory Rochester MN.) was performed 2 months following the last injection and showed the presence of only
triamcinolone acetonide at a level of 0.17 mcg/dL with
detection of no other synthetic glucocorticoids. Followup CST 4 months after the last injection, showed normal
baseline (7.2 mcg/dL) and stimulated cortisol levels (28.1
mcg/dL at 1 hour). Baseline ACTH levels had also recovered to 5pg/ml.
Abstract #113
FROM HEMATOLOGY TO ENDOCRINOLOGY:
CUSHING’S SYNDROME PRESENTING AS
PERSISTENT LEUCOCYTOSIS AND
ADRENAL MASS
Asma Sohail Khan, MD, and Uzma Khan
Objective: To recognize the variability in the presentations of Cushing’s syndrome, including its effects on
hematologic indices.
Case Presentation: A 34 year old female presented
to endocrinology service as a referral by the hematology
service. One year prior to this she had presented to her PCP
for new onset HTN, at which time routine blood work had
shown leucocytosis. Her HTN was treated, no infection
could be identified as a cause of her high WBC count and
she was referred to the hematology service. Hematological
workup was negative for any pathology, including JAK-2
mutation for polycythemia vera, BCR-ABL mutation for
chronic myelogenous leukemia and a normal erythropoietin level. A CT scan of abdomen was done as part of her
evaluation and revealed a 3.2 x 2 cm left adrenal mass with
35 HU on pre contrast phase images. On presentation she
gave history of weight gain of 60 pounds in the last 2 years,
but accelerated weight gain of 16 pounds in 2 weeks prior
to presentation, swelling of legs, fatigue and easy bruising.
Exam revealed a BP of 124/90, acne, bruising of skin and
skin colored stretch marks. There was no buffalo hump or
supraclavicular fat pad. Lab work revealed WBC count of
18.9 thousand/mm3, granulocyte count of 15.6, lymphocyte count of 2.20 and an eosinophil count of 0.90.We suspected Cushing’s syndrome. 24 hour urinary free cortisol
(UFC) was 271.8mcg (normal <60), salivary cortisol at 11
pm on two occasions was > 0.55 mcg/dl (normal 0.05-0.17),
––
rated very long chain fatty acids in this condition results
in cerebral demyelination, peripheral nerve abnormalities,
adrenocortical and testicular insufficiency. Our patient had
adrenomyeloneuropathy which is the most common phenotype of X-ALD. He had adrenocortical insufficiency
which is a feature seen in 90% of males with cerebral
ALD and 70% of patients with AMN. Virtually all affected
men have manifest or subclinical testicular insuffiency.
Nonetheless, about 20% of the ALD patients remain free of
overt neurologic disability and half of these have “Addison
only” phenotype with isolated adrenocortical dysfunction.
Several studies have disclosed that a possibly substantial
percentage (4-63%) with Addison’s disease in fact may
have “Addison only” phenotype of ALD as was seen with
the initial presentation of our patient. The risk for developing future neurological involvement remains high as
described above, nonetheless, some of them may escape
until much later in life.
Conclusion: X- ALD is probably an under diagnosed
disease and adrenocortical insufficiency may be the only or
the initial manifestation. It is important to be aware of the
relatively high incidence in so called idiopathic Addison’s
disease and clinical presentation of variants of X -ALD as
it is an inherited disease and may result in severe disability
or death.
ACTH was < 2pg/ml with serum cortisol of 20.7mcg/dl.
Cushing’s syndrome of adrenal origin was diagnosed. Patient underwent laparoscopic removal of the adrenal mass
and is currently doing well on hydrocortisone Discussion: Diagnosis of Cushing’s syndrome continues to be challenging. It becomes even more difficult
when confronted with an unusual presentation. Exogenous
glucocorticoids are known to cause leucocytosis, but very
few cases of endogenous Cushing’s syndrome presenting
with leucocytosis have been reported in the literature.
Conclusion: This case is unique in that the patient’s
initial presentation and workup was for leucocytosis. She
lacked typical stigmata of Cushing’s syndrome initially. It
has been postulated based on the lack of clinical cases, that,
leucocytes and lymphocytes are less sensitive to endogenous over production of glucocorticoids. Only one case
with high total WBC count in CS due to adrenal mass is
reported in the literature. Further studies need to be done to
assess whether CS of adrenal origin has a higher incidence
of leucocytosis than Cushing’s disease.
Abstract #114
ADDISON’S DISEASE ASSOCIATED WITH
SPASTIC PARAPLEGIA : AN ADULT VARIANT OF
X-LINKED ADRENOLEUKODYSTROPHY
Abstract #115
Deepa Taneja, MBBS, Kim Green, Lisa Tannock,
Dennis Karounos, and L.R. Reynolds
SMALL CELL LUNG CANCER WITH SIADH
AND ECTOPIC ACTH PRODUCTION
TREATED WITH MITOTANE
Objective: X-linked adrenoleukodystrophy (X-ALD)
is an inherited disorder of peroxisomal metabolism that
is characterized by accumulation of saturated very long
chain fatty acids. A more indolent variant with adult onset
is called adrenomyeloneuropathy (AMN). In developed
countries, where tuberculosis is not a common cause of
adrenal insufficiency, 40% of male patients with Addison’s
disease have in fact the biochemical defect of ALD.
Case Presentation: A 41 year male was admitted with
acute infection requiring high doses of glucocorticoids. He
had been diagnosed with adrenal insufficiency at 20 year
of age following episodes of lightheadedness, blurry vision
and syncope. He also had a tanned skin that was initially
attributed to excessive sun exposure. Later, he developed
numbness accompanied with slowly progressive sensorimotor weakness in lower limbs. This was followed by
sphincter disturbances and sexual dysfunction. He was
finally diagnosed with adrenomyeloneuropathy nine years
later.
Discussion: X-ALD is a rare disease with a prevalence of 1 in 200,000 male births. Accumulation of satu-
Tanyanan Tanawuttiwat, MD,
Tasma Harindhanavudhi, MD,
Raquel Marguerite Añel, MD, Tahira Yasmeen, MD,
Dan Mihailescu, MD, and Ghassan Zalzaleh, MD
Case Presentation: A 46-year-old woman with stage
IV small cell lung cancer presented to the office with fatigue
and lethargy. On physical examination, she was hypertensive, cachetic, hyperpigmented, and hirsute. Laboratory
studies showed hypoosmolar hyponatremia with a serum
Na of 115 mEq/L (normal, 135-145 mEq/L) and a calculated
serum osmolality of 238.6 mOsm/Kg (normal, 275-300
mOsm/Kg). Her blood urea nitrogen and creatinine were
normal. She was then admitted to the hospital. A few days
later, serum Na was still low at 131 mEq/L, serum osmolality was 274 mOsm/Kg and urine osmolality was high at
328 mOsm/Kg. Given her euvolemic status, a diagnosis of
syndrome of inappropriate antidiuretic hormone secretion
(SIADH) was made and fluid restriction was initiated. Her
––
Eight years later patient presents with labs results suggest hyper secretion of the adrenal glands, ( Cushing’s Syndrome) also a CT scan of the adrenal glands revealed a
plump medial limb of the left adrenal gland, and an MRI
of the pituitary showed a punctuate enhancement within
the right aspect of the gland. The Patient also presents pigmented lesions on her left lower lip, lower eyelids, face,
palms, back and buttocks. These findings were thought
to be suggestive of Carney complex. By Family history
patient’s mother had a history of myxomas, patient’s
brother was diagnosed with Carney Complex, and patient’s
daughter also has Cushing’s syndrome. On April 2007
another stroke like event, patient seeks help on the NIH
again were she had bilateral adrenelectomy on June 2007. Patient was hospitalize at St Luke’s Memorial Hospital
in Ponce, Puerto Rico three months ago because of shortness of breath and chest pain, and all cardiac workup were
negative.
Discussion: Carney’s Syndrome is an autosomal
dominant transmitted multisystem tumorous disorder characterized by myxomas (heart, skin, and breast), spotty
skin pigmentations, endocrine tumors (adrenal, testicular, thyroid, and pituitary), and peripheral nerves tumors
(schwannomas). Approximately 150 affected patients are
known worldwide.
Conclusion: This patient already had couple of the
most prevalent clinical manifestation as spotty skin pigmentation, and Cushing syndrome. Also her first CVA was
caused by one the most serious components of the syndrome cardiac myxoma.
serum Na eventually normalized. She had severe hypokalemia with serum potassium of 1.5 mEq/L (normal, 3.5-5
mEq/L). Further evaluation revealed a markedly elevated
morning serum cortisol of 122.5 μg/dL (normal, 6-23 μg/
dL), 24-hour urine free cortisol of 2703.8 μg/dL (normal,
<45 μg/dL ), and random plasma ACTH level of 543 pg/dL
(normal, 9-52 pg/dL). Renin and aldosterone levels were
normal. She was diagnosed with Cushing’s syndrome
from ectopic ACTH production. She was started on ketoconazole 200 mg thrice daily for her hypercortisolism. She
initially had a good response but her morning serum cortisol increased to 70.7 μg/dL despite titration of ketoconazole
to 400 mg thrice daily. Aminoglutethimide was considered
but was no longer available in the market. Medical adrenalectomy was then induced with mitotane 500 mg every
12 hours. Morning serum cortisol dramatically dropped to
24.9 μg/dL. After a few weeks though, it increased to 118
μg/dL even after mitotane was increased to the maximum
dose of 1000 mg every 12 hours. Addition of metyrapone
was considered but the patient decided to enroll in hospice
and died soon after.
Discussion: Two of the major endocrine paraneoplastic manifestations of SCLC are SIADH (5-10% of patients)
and ectopic ACTH production (3-7%). The concurrence of
both is extremely rare with only six cases reported to date.
Ketoconazole is used as medical therapy for Cushing’s
syndrome. It is effective and has a favorable side effect
profile. Mitotane is an adrenocorticolytic drug that is used
to achieve medical adrenalectomy. Conclusion: Our case report illustrates that although
rare, concurrent SIADH and ectopic ACTH production
from SCLC may happen. If first-line therapy fails, consideration should be given to combination therapy with a
first-line agent and mitotane.
Abstract #117
DIRECT RENIN INHIBITOR (DRI) EFFECT ON
GFR AND USE IN RENAL ARTERY
STENOSIS SCREENING
Abstract #116
CVA AS THE FIRST EVENT OF
CARNEY’S SYNDROME
Harold Thomas Pretorius, MD, PhD, Nichole Richards,
and Michael Harrell
Rafael Espinet, MD, and Luis Raul Ruiz Rivera, MD
Objective: A new method using a nuclear camera and
a direct renin inhibitor (DRI) to screen for renal artery stenosis (RAS) in hypertensive patients and to measure the
otherwise generally DRI increased glomerular filtration
rate (GFR).
Methods: Same-day basal and 1 hr post 150-300 mg
oral Aliskiren (Tekturna) renography used 10-25 mCi Tc99m-DTPA intravenous for split GFR with a nonlinear
relation of renal activity to GFR corrected for body surface
area. Camera sensitivity was corrected using an attenu-
Objective: This is a very rare syndrome and it helps
me complement my medical knowledge to help patients
improve her chance of survival and quality of life.
Case presentation: This is a case report of a 45 year
old Hispanic woman who had at the age of 33 years a cerebrovascular event. Emboli from a cardiac myxoma caused
the CVA for which she underwent surgery. At that time the
patient also had hyperpigmented freckles on her face and
chest.
– 10 –
ation coefficient 0.12/cm, with lateral views for simple
measure of renal depth.
Results: In 9 of 11 patients Tekturna increased GFR
by 10% to 60% (p < 0.05). Both patients with either split
GFR increased insignificantly by Tekturna had RAS at
renal angiography and in one, BP stabilized after renal
angioplasty. The only Tekturna side effect was increased
BP to 208/104 for < 2 hrs in one RAS case. Decreased
GFR expected in affected kidneys from a Goldblatt mechanism may occur with Tekturna; however, we also found
RAS when GFR did not significantly increase as it does in
normal kidneys, with or without concurrent renin angiotensin aldosterone system (RAAS) inhibition. Inaccurate
results typical of captopril renography with concurrent
RAAS inhibitor therapy are avoided with Tekturna renography, which has been accurate in clinical follow-up,
not only with concurrent angiotensin converting enzyme
inhibitors or angiotensin receptor blockers, but also with
thiazides and alpha or beta or calcium blockers.
Discussion: Initial studies of DRI show potential
for renal protection; however, the potential of captopril
renography never materialized, not only due to technical aspects of earlier GFR calculations, but also because
of severe and sometimes fatal side effects, especially in
patients with RAS. All RAAS inhibitors are contraindicated in pregnancy and may cause hyperkalemia, particularly in diabetics and with combined RAAS inhibitor use. Nonetheless, if the present study results including straightforward, reproducible measure of split GFR, as well as
only minor side effects are confirmed in further studies,
then DRI renography may be widely used in the future.
Conclusion: Tekturna, the first widely available
DRI, shows promise for nuclear camera based measure
of split GFR in a same-day basal and stimulated study,
not only for its potential therapeutic increase in GFR; but
moreover, in diagnostic screening for the increasing number of patients with RAS.
Case Presentation: A 44 year old African American
male presented with signs of chronic heart failure and
symptoms of proximal muscle weakness, easy bruising, and poor wound healing for a prolonged period. He
also gave a history of progressive swelling of his abdomen, weight gain, decreased libido, persistent fatigue and
depression for over a year. He had no typical symptoms of
a pheochromocytoma, no palpitations, syncopal episodes
or diaphoresis. The diagnosis was confirmed by biochemical screening with elevated 24 h Urinary free cortisol of
369.0µg/dl with morning ACTH level less than 5.0 pg/ml,
a negative catecholamine screen, and a cortisol level that
was not suppressed by high dose dexamethasone suppression test. CT scan of his abdomen and pelvis showed
multiple bilateral lobular adrenal masses causing diffuse
enlargement of adrenal glands with benign appearance.
Histopathological examination following a bilateral adrenalectomy revealed marked enlargement of both adrenal
glands with macronodular hyperplasia.
Discussion: AIMAH accounts only for less than 1%
of all cases of Cushing syndrome and it is characterized by
multiple yellow adrenal macronodules within hyperplastic
internodular cortex. Most cases are sporadic; few can be
familial autosomal dominant transmission. It has typical
histological findings and has been reported to exhibit aberrant expression of gastric inhibitory peptide, vasopressin,
catecholamine, luteinizing hormone, Human Chorionic
Gonadotropin, leptin and/ or 5-OH tryptamine receptors.
Conclusion: Identification of aberrant adrenal receptors offers potential novel pharmacological therapy, but
adrenalectomy remains the treatment of choice with preoperative medical therapy to lower cortisol levels in some
cases. Cost restrictions limited our ability to perform receptors analysis.
Abstract #119
PRIMARY ADRENAL LYMPHOMA
Abstract #118
Rene J. Harper, MD, and Carlos Isales, MD
ADRENOCORTICOTROPIC HORMONE
INDEPENDENT MACRONODULAR
ADRENAL HYPERPLASIA (AIMAH)
Objective: We discuss a case of adrenal insufficiency
and enlarging bilateral adrenal masses.
Case presentation: A 60 y/o female presented with
weakness, anorexia, nausea, vomiting, abdominal pain,
and weight loss of 20 pounds. She had been hospitalized
two months PTA for pneumonia requiring mechanical
ventilation, and had experienced hypotension and bleeding from a Mallory-Wise tear requiring vasopressors and
blood transfusion. During this previous hospitalization a
random cortisol at 3:40 AM was 22 mcg/dL and peaked
Claudine G Meyer, MD, Almond Drake III, MD, and
Sylvester Odeke, MD
Objective: To present a rare and often unrecognized
cause of Cushing syndrome and review its pre-operative
management.
– 11 –
at 18 mcg/dL sixty minutes after Cosyntropin. A CT scan
at that time showed bilateral adrenal masses (right 3.6 x
2.5 cm and left 3.1 x 2.5 cm), extensive alveolar opacities, bilateral pleural effusions, subcentimeter lymphadenopathy in the paratracheal, retroperitoneal and paraaortic
regions, and an enlarged spleen measuring 14.5 x 5 x 11
cm. She received IV steroids for adrenal insufficiency and
was prescribed oral steroids on discharge. On admission
she reported noncompliance with oral steroids. Her blood
pressure ranged from 81-90 mmHg systolic and 44-60
mmHg diastolic with pulse readings of 80s-90s per minute.
There were no palpable lymph nodes, hyperpigmentation,
weakness or signs of dehydration. Her abdomen was diffusely tender with a palpable spleen; other physical exam
was normal. A random cortisol at 9:00 AM was 3 mcg/dL
and peaked at 2 mcg/dL sixty minutes after Cosyntropin.
A CT scan now showed markedly enlarged adrenal masses
with central necrosis (right 8.7 x 9.6 x 10 cm and left 7.2
x 4.5 x 8.4 cm), retroperitoneal lymphadenopathy (largest
2.2 cm) and multiple, small low-attenuation spleen lesions.
She had negative PPD and HIV tests, normal tumor markers and 21-hydroxylase antibodies < 1 U/mL. Diffuse large
B-cell lymphoma was confirmed by CT-guided biopsy of
the left adrenal mass and a bone marrow biopsy did not
show tumor involvement. She received 6 cycles of chemotherapy (R-CHOP). A CT scan done after the 4th chemotherapy cycle showed a remarkable decrease in size of the
adrenal masses with very little residual tumor, and resolution of pulmonary nodules and effusions, and resolution of
the lymphadenopathy and spleen lesions. A PET scan done
after the 6th chemotherapy cycle showed no evidence of
active lymphoma.
Discussion: Primary adrenal lymphoma is a rare condition that often presents with adrenal insufficiency and
bilateral adrenal masses but usually without peripheral
adenopathy or bone marrow involvement. Prognosis is
poor but remission may be achieved with chemotherapy.
Conclusion: Primary adrenal lymphoma should be
considered in the differential diagnosis of adrenal insufficiency with bilateral adrenal masses.
Abstract #120
HUGE ABDOMINAL MASS WITH SPLITTING
HEADACHES
Marium Ilahi, MD, and Laura AG Armas, MD
Objective: To identify signs and symptoms of pheochromocytomas in order to make a prompt diagnosis and
initiate treatment.
Case Presentation: A 46 yr old male with a history of
palpitations presented to an academic endocrine clinic with
a one year history of severe episodic headaches. These episodes mainly occurred at night and were associated with
pallor, palpitations and nausea. They occurred more commonly when he slept on his right side. The headaches were
so severe he was referred to a neurologist. The neurological workup, including head CT, was normal. During one
of these episodes his wife measured his blood pressure at
200/90 mm HG, though all other documented blood pressures were normal. This was mentioned during follow-up
with his cardiologist for aortic root dilatation. The cardiologist ordered a CT of the abdomen which showed a 14 cm
left adrenal mass. A 24 hour urine for metanephrines was
elevated at 1614 ug and midnight salivary cortisol, renin,
aldosterone and 5-HIAA were all within the normal range.
He was started on phenoxybenzamine and placed on a liberal salt diet and his beta-blocker was titrated accordingly.
He was sent for surgery and the mass was removed with a
maximum dimension of 18 cm and weight of 1450 grams.
Pathology consisted of an encapsulated tumor with no vascular, nerve or capsular invasion. Gene testing for MENIN,
RET oncogene and VHL were all negative.
Discussion: Pheochromocytomas are rare catecholamine secreting tumors which usually present with headaches, sweating and tachycardia. In our patient it is interesting that the tumor was of such a large size and weight.
The diagnosis of pheochromocytoma is often overlooked if
the patient is sent to multiple specialists and all the classic
symptoms are not presented simultaneously. Gene testing
was ordered because of the tumor’s size, though all returned
negative. Currently the patient is doing well and his headaches have resolved. Also repeat 24 hour urine analysis for
fractionated metanephrines and catecholamines have been
normal.
– 12 –
Conclusions: It is not necessary for a patient with
pheochromocytoma to present with the classic symptoms
of headaches, sweating and tachycardia or hypertension.
This diagnosis may be overlooked in individuals who are
referred to multiple specialists for a specific symptom.
With the large size of the tumor it is likely that the pheochromocytoma was missed for a few years which allowed
it to reach it’s final size. Pheochromocytomas may be present in hereditary syndromes which patients may need to
be screened for. It is always important to analyze the big
picture in order to pick up the correct diagnosis.
Recent research has highlighted the role of vascular
smooth muscle cell (VSMC) in hemostatsis. Increased
intracellular calcium promotes VSMC contraction.
Norepinephrine (NE) increases calcium within VSMC by
phospholipase C pathway which activates myosin light
chain kinase causing contraction. NE also activates Rho
kinase, a calcium independent pathway mediating VSMC
contraction. The complex interaction of catecholamines
on VSMC most likely precipitated stroke in our patient.
Selective involvement of cerebral vasculature with sparing
of other vascular beds is secondary to differential distributon of endothelial products in different vascular beds.
Conclusion: Medications that lower intracellular calcium – nimodipine, are antagonist to endothelin – clazosentan or inhibit Rho-kinase – fasudil hydrochloride, are available and may become standard of care to prevent thombotic
injury in hyperadrenergic states.
Abstract #121
STROKE IN PHEOCHROMOCYTOMAENDOTHELIAL AND VASCULAR SMOOTH
MUSCLE CELL DYSFUNCTION
Sudip Nanda, MBBS, Surya Prakash Bhatt, MD,
John Pamula, MD, Santo Longo, MD, and
Thompson H. Dale, MD
Abstract #122
SEVERE IATROGENIC CUSHING’S SYNDROME
AS A RESULT OF CHRONIC USE OF ANTI-RASH
OINMENTS
Objective: Pheochromocytomas cause CNS symptoms through varied mechanisms - uncontrolled hypertension causing intracranial hemorrhage, dilated cardiomyopathy with mural thrombus that embolizes, MEN 2
syndrome with metastasis, NF1 with CNS tumors, Von
Hippel Lindau syndrome with hemangioblastomas, multiple cranial aneurysms, malignant thromboembolization
from metastatic aortic arch involvement.
A patient presented with thrombotic stroke in the
absence of these known mechanisms and we propose a
hypothesis for the same.
Case presentation: A 37 year old female presented
with right sided weakness. Her pulse was 52/minute and
blood pressure was 130/60mm of Hg. She had motor aphasia with right hemiplegia. Head CT revealed dense left
middle cerebral artery infarct. Hemoglobin was 13.4gm/
dL and hematocrit 40.6%. Metabolic panel was normal.
Echocardiogram revealed normal valvular and ventricular
function without mural thrombus. Carotid dopplers were
normal. Hypercoagulable or vasculitic state and systemic
malignancy were absent.
Abdominal evaluation revealed bilateral pheochromocytomas with plasma normetanephrine 14,031pg/ml
and metanephrine 23,136 pg/ml.
Discussion: The patient had a stroke secondary to
pheochromocytomas. Endothelium plays a central antithrombotic role through nitric oxide, prostacyclin and
endothelins. Nitric oxide synthase1 and endothelin1 are
preferentially distributed in the CNS.
Edgar Avendaño, MD, Ma Alejandra Ramos,
Esperanza Valentin, Elva Cardenas,
Francisco Gomez-Perez, and Juan Rull
Objective: To present a case of severe iatrogenous
Cushing´s syndrome due to an abuse of skin ointments.
Case report: We present a female patient, who at consultation referred a 17 year history of skin problems that
started after she underwent a c-section. After medical evaluation for a papuloeritematous rash in her legs and arms she
was prescribed a cream bethametasone formulation with
symptom relief. She referred that if she discontinued use
of the cream, symptoms recurred so she continued to apply
the medication every five minutes, using up to 30g every
two days. Her family noticed that her weight increased progressively and her skin was red, they also noted she became
isolated, stayed home, stopped working or doing chores
around the house because she spent all her time applying
the cream every 5 minutes. At consultation
she weighed
2
128 pounds with a BMI 26 Kg/M , BP 180/110 Pulse 88x´.
She was emotionally labile with a moon face, buffalo
hump, violet striae in her abdomen, arms and legs. Her skin
was red, thin with telangiectasias and presented a generalized scaly pustular dermatosis. Cushing’s syndrome, erythrodermia due to Candida albicans infection, and obsessive
compulsive disorder were diagnosed; she was hospitalized
for treatment and steroid weaning. At admission her serum
– 13 –
cortisol was 0.77ng/ml, Na 133 mmol/l, K 3.79 mmol/l,
glucose 140 mg/dl, triglycerides 588 mg/dl and total cholesterol 422 mg/dl. She refused to discontinue cream use
complaining of extreme irritation and itching so she was
given a glycerine based cream and prednisone with dose
reduction. Five months later her cortisol has risen to 7.56
ng/ml and is well controlled on NPH insulin.
Discussion: We present a woman with a pshychiatric
illness who developed Cushing’s syndrome due to chronic
exposure to a steroid containing ointment. Her case is particularly interesting because of the prolonged exposure and
intensity of her clinical manifestations.
Conclusion: Extreme iatrogenous cushing’s syndrome can occur from the exposure to any form of steroids.
Treatment of these patients is complex and it is important
to convince the patient that continuing to use steroids will
preclude a cure.
– 14 –
ABSTRACTS – Diabetes Mellitus
Several reasons including genetic factors could explain
these differences.
Conclusion: Insulin resistance may not be related
to hypertension in Nigerian type-2 diabetic patients.
However, larger studies are required to define the relationship between blood pressure and insulin resistance in
African populations.
DIABETES MELLITUS
Abstract #200
RELATIONSHIP BETWEEN ARTERIAL BLOOD
PRESSURE AND INSULIN RESISTANCE IN
TYPE 2 DIABETIC NIGERIANS.
Abstract #201
Adamu Girei Bakari, MBBS, FWACP, and
Geoffrey C. Onyemelukwe
PROGNOSTIC INDICES OF DIABETES
MELLITUS MORTALITY
Objective: Cardiovascular disease especially hypertension is commoner among type-2 diabetic patients than
the general population. Several reasons have been advanced
to explain the higher prevalence of hypertension among
type-2 diabetic subjects including the commonality of such
risk factors as obesity and sedentary life styles in the aetiology of both conditions. Furthermore, it has been suggested
that insulin resistance could be the unifying mechanism
for these observations. However, racial factors seem to be
important in the role of insulin resistance in the aetiology
of cardiovascular disease. Although extensive literature has
been generated on the possible role of insulin resistance in
the aetiology and sustenance of hypertension among type-2
diabetic subjects else where, there is paucity of such data
among Africans generally and Nigerians in particular.
Methods: Blood Pressures were measured using standard methods while insulin resistance scores were derived
using the homeostasis model assessment method.
Results: Forty type-2 diabetic patients and 36 healthy
control volunteers were studied. Of the diabetic patients,
13(32.5%) were hypertensive, and 27 (67.5%) were normotensive. The mean insulin resistance scores were
respectively 1.96 +1.04 (range 0.49 - 2.92) among diabetic-hypertensive individuals and 2.28 + 1.89 (range 0.39
- 7.6) among normotensive-diabetic patients. The difference between the two groups were however not significant
statistically (p = 0.5350). Furthermore, there is no significant relationship between mean arterial blood pressure and
insulin resistance (r =+ 0.087, p>0.5)
Discussion: The homeostasis model assessment
method is cheap, simple, and relatively non-invasive and
has been revalidated as a reliable method to assess insulin resistance in clinical practice. In this study there is no
significant relationship between mean arterial blood pressure and the HOMA-IR score. This is contrary to observations in western societies where it has been observed that
insulin resistance correlates with blood pressure and other
cardiovascular risk factors. This observation is however
consistent with earlier findings in blacks and Pima Indians.
Anthonia Okeoghene Ogbera, MBBS, FMCP, FACE, and
Chinenye Sonny
Objective: To document the patterns of diabetes mellitus morbidity and mortality, length of hospital stay (LOS)
and also to determine the prognostic factors affecting fatal
outcomes of DM hospitalization.
Methods: A study carried out for a one-year period
(January –December 2006) in a tertiary hospital in SouthWest Nigeria. Subjects with diabetes mellitus (DM) were
prospectively studied after admission to the medical wards
to assess their short term outcome which was defined as
death. This was facilitated by gleaning information at frequent intervals from the Wards’ Registers. Case fatality and
crude death rates were computed and the prognostic factors
for fatal outcomes were determined. The total mortality,
causes of death, associated complications and duration of
hospital stay were noted. Test statistics included chi test,
logistic regression and Students t test. Results: A total of
1,327 subjects were admitted to the Medical wards for the
duration of the study and DM related admissions made up
206 (15%) of these with a case fatality rate was 33 (16%) .
The commonest reasons for DM admission were hyperglycaemic emergencies (HE) -88 (40%) and hypertension 44
(21%). The commonest causes of deaths were hypertensive
emergencies documented in 15 (46%) and DM foot ulcers
(DFU) in 10 (30%) of the subjects. DFU and cerebrovascular disease (CVA) had the highest case fatality rates of
28% and 25% respectively. The mean (SD) and range of
duration of LOS of DM admissions were 23(17) days. That
for DFU - 51(27) days - was higher than that of DKA, CVA
and hypertension admissions and this difference was statistically significant (p values of <0.05 ). DFU, CVD and
having Type 2 DM rather than Type 1 DM were highly
predictive of fatal outcomes. The odds ratio and 95% CI
for these factors were 4.5 (1.5-12.7), 3.0 (0.9-9.92 and 2.1
(0.7-14) respectively.
– 15 –
Discussion: An overwhelming majority (94%) of
the DM related deaths occurred in those with Type 2 DM
and having Type 2 DM had a prognostic impact on DM
death. HE were found to be the commonest reasons for DM
related admissions and deaths. DFU which was the second commonest cause of death had the highest case fatality rate. The dismal data on DFU outcomes are resultant
effects of late presentation, erroneous traditional beliefs
and high costs of treatment. The significance of DFU as
contributory to a high disease burden is attested to by the
findings of prolonged hospitalization.
Conclusion: The unacceptable high burden of DM
in this report is caused largely by factors that are potentially remediable. Patient education is key to reducing the
adverse sequelae of DM.
to be healthy enough to stand in line from the early morning hours to receive services. Therefore, patients with significant health or mobility problems would likely not have
attended the health fair.
Conclusion: Despite the selection bias in our study, it
is apparent that 18 months after Hurricane Katrina ravaged
the city of New Orleans, the QOL of patients with diabetes
remains suboptimal.
Abstract #203
ELECTROCARDIOGRAPHIC ABNORMALITIES
IN PERSONS WITH TYPE 2 DIABETES IN
KADUNA, NORTHERN NIGERIA
Fatima Bello-Sani, MBBS, FWACP, and
Felicia Ohunene Anumah, MBBS, FNMCP
Abstract #202
Objective: Diabetes mellitus is the commonest endocrine disorder in Nigeria. Type 2 Diabetes Mellitus (T2DM)
is associated with increased cardiovascular risk, in part
due to accelerated subclinical atherosclerosis primarily
from dyslipidaemia. Ischaemic Heart Disease (IHD) is a
very important chronic complication of diabetes mellitus
the most prevalent among cardiovascular diseases and a
major cause of morbidity and mortality. This study sets out
to determine the most frequent electrocardiographic abnormalities in persons with T2DM in Kaduna (a sub-urban
environment).
Methods: 150 consecutive persons with T2DM & 150
controls were recruited from the diabetes clinic of ABUTH
Kaduna for the study. Relevant history and physical examination findings were recorded in a protocol. The variables
studied were: gender, age, smoking habit, physical activity, and waist circumference, and BMI, blood-pressure.
Resting electrocardiogram was recorded and abnormalities grouped according to the classification: ST-Tsegment
changes, left ventricular hypertrophy (LVH), conduction
defects. Serum lipids were also compared.
Results: The mean age of the diabetics & controls
were not statistically significantly different (50.5±9.9yrs vs.
51.1±10.3yrs) respectively. 50% were females. Body mass
index (BMI) and the waist circumference were statistically
significantly higher in diabetics [(BMI 27.89±1.78Kg/
M2,Wc 96±10.2cm) than controls (BMI 24.22±1.51Kg/
M2,Wc 86±6.5cm) p<0.05]. 62% of diabetics were hypertensive. 20% of diabetics and 1.5% of control subjects in
this study had electrocardiographic evidence of IHD, while
7% of diabetics had LVH respectively. 71% of persons with
type 2 diabetes in this study had dyslipidaemia (p<0.05).
Conclusion: The various resting 12 lead electrocardiographic findings among persons with type 2 diabetes in
QUALITY OF LIFE IN DIABETES PATIENTS IN
NEW ORLEANS: 18 MONTHS AFTER KATRINA
Teck-Kim Khoo, MD, and Steven Smith, MD
Objective: To evaluate the quality of life (QOL) in
diabetes patients in New Orleans.
Methods: In August 2005, Hurricane Katrina pummeled southern Louisiana, causing total failure of infrastructure including healthcare. In 2007, the Mayo Clinic
was invited to participate in the New Orleans Health
Recovery Week, a free medical fair jointly organized by
the city and nonprofit organizations. Because of the high
numbers of diabetes patients in the area, diabetology support was specifically requested. Our team included 2 diabetologists, joining 17 other volunteer physicians from across
the country. Patients were invited to complete the EuroQol
EQ-5D Health State Questionnaire, a validated brief multiattribute, preference-based measure of health status. This
was calculated into a utilities score of 1 (in best health) to
-1 (worse than death). In addition, a Visual Analog Scale,
with values from 0-100 was used. This was compared to
a baseline population based score from Olmsted County,
Minnesota.
Results/Discussion: Amongst the patients seen by the
two diabetologists, 162 patient surveys were completed, of
which 7 were omitted from analysis because of incomplete
answers. 155 patient surveys were used for analysis. The
New Orleans population had a utilities score of 0.76, in
comparison to Olmsted of 0.81 (p=0.004), while the VAS
was 65 for New Orleans versus 73 (p<0.0001). Although
there is a significant difference between the scores of both
groups, the real difference is presumed greater as there is
likely a selection bias in this study; patients surveyed had
– 16 –
this study reflects non-specific features of cardiovascular
diseases in general.
The most frequent electrocardiographic abnormalities
in type 2 diabetes in this study are ST-T segment depression, left ventricular hypertrophy.
Ischaemic heart disease is emerging fast in developing
poverty stricken environment like ours and should be routinely looked for.
Hypercholesterolaemia and female gender are the
strongest and most frequent factors associated with IHD.
PGCP 0.9ng/ml or 0.32nmol/L) have been used, most studies conclude that there is a high degree of concordance,
ranging between 86 and 89% between c- peptide levels and
type of diabetes. BCP and PGCP particularly PGCP have
also been found to predict the need for insulin treatment in
T2DM (PGCP ≤1.8ng/ml).In this study, 2 of the study subjects clinically diagnosed with type 2 diabetes had PGCP
<1ng/ml, and had a lean phenotype thus suggesting a possible misclassification. Further characterisation with antibody testing would have been beneficial in these patients.
Ten of the subjects had PGCP values which suggest a need
for insulin therapy.
Conclusion: Post Glucagon C- peptide levels are useful in reclassifying subjects clinically defined as type 2 diabetes mellitus in Nigeria.
Abstract #204
BASAL AND POSTGLCAGON C-PEPTIDE
LEVELS IN NIGERIANS WITH TYPE 2
DIABETES MELLITUS
Adekemi Olabisi Coker, MBBS, Olufemi Fasanmade, and
Efedaye Ohwovoriole
Abstract #205
PERFORMANCE OF AMERICAN DIABETES
ASSOCIATION QUESTIONNAIRE AMONG
NIGERIANS
Objective: To study basal C- peptide (BCP) and post
glucagon C- peptide (PGCP) levels in Nigerians with type
2 diabetes mellitus.
Research Design and Methods: A total of 40 subjects
with type 2 diabetes and 20 control subjects were recruited
from the Lagos University Teaching Hospital. BCP and 6minute PGCP were determined in all subjects.
Results: Mean ±SEM BCP of 2.0±1.1ng/ml and
1.8±0.7 ng/ml in controls and subjects with diabetes was
comparable. Mean ±SEM post glucagon c- peptide (PGCP)
and increment in c-peptide from basal was lower in subjects with diabetes compared with the control subjects
(2.9 ± 0.22 versus 5.6 ± 0.5 and 1.1± 0.2 versus 3.6±0.32
respectively) p<0.05 and p<0.01. Among the subjects with
diabetes, 2 had PGCP levels less than 1ng/ml and mean
increment in c-peptide was 0.03 and –0.06 ng/ml while
10(25%) had PGCP < 1.8ng/ml.
Discussion: Determination of fasting or basal c- peptide (BCP) and stimulated c-peptide (with glucose or glucagon) levels have been used to determine pancreatic β- cell
secretory activity. The c-peptide (CP) response to glucagon
correlates well with the stimulated response to mixed meals
or other stimulus commonly used to characterize endogenous insulin secretion and has the advantage of a shorter
duration and simple standardization. Clinical utilities of
c-peptide tests include determining whether pancreatic βcell function shows concordance with the clinical classification of diabetes into type 1 and type 2 diabetes. Although
different thresholds for BCP (0.6ng/mLor 0.2nmol/L and
Abdullah Ndaman Adamu, MBBS
Objective: To evaluate the performance of American
Diabetes Association Questionnaire among people with
systemic hypertension in Nigeria.
Methods: Between January and May 2004, screening
for type 2 diabetes was conducted among people known
to have systemic hypertension who were regular attendees
of cardiology and nephrology clinic of Lagos University
Teaching Hospital using American Diabetes Association
Questionnaire (ADAQ). Oral glucose tolerance test was
carried out on all the subjects as a gold standard to establish the diagnosis of diabetes.
Result: A total of 207 patients were recruited and 131
of the subjects participated in the whole exercise, giving a
participation rate of 63.28%. The subjects were classified
into :- 0.7% No Risk (0-2), 29.00%High Risk (0-9) and
67.17% Diabetes (>10) based on ADAQ.ADAQ yielded
a sensitivity of 100%, specificity of 71.96%, positive predictive value of 44.44% and negative predictive value of
100%.
Conclusion: ADAQ performed relatively well among
the high risk people with systemic hypertension. A little
modification of it to suit racial and socioeconomic differences of people will go a long way in improving its performance for universal use to screen for diabetes.
– 17 –
Abstract #206
Abstract #207
DIABETES AND AUTOIMMUNE
THYROID DISEASE
DIABETIC AND NON DIABETIC SALIVA
ALPHA AMYLASE ACTIVITY INCREASED IN
ACID MEDIA
Aly Abdel Latif Abbassy, MD, FACE,
Ibrahim Abdel Rahman, MD,
Mohamed Kamal Ghetany, MD, Hazem Shokry, and
Nahed Baddor
Tarig Sayed Mustafa Arbab, MD, MSc, DIC
Objective: To study pH changes during saliva alpha
amylase activity in diabetic and non diabetic subjects in
relation to glucose yielding. Explain mechanism of action
and occurrence of DKA.
Methods: 750 fresh saliva samples were collected
from 200 diabetic and 50 non-diabetic subjects. All subjects were fasting over night for 12 hours. Glucose oxidase
testing was used to detect amylase activity. Three identical 10 mls samples of fresh well-prepared saliva were
accepted from each patient for the study. One sample from
each subject was used as marker and tested for pH changes
and sugar hourly for 24 hours. Each second and third study
samples were tested initially for pH and sugar content; 1
ml of flour powder was added in each second sample (250
flour sample). 1 ml of sucrose was added in each third
sample (250 sucrose samples). pH changes together with
sugar readings were tested hourly in each study sample for
24 hours.
Results: 750 (250 marker + 250 flour + 250 sucrose
study sample) fresh saliva samples of non diabetics and
diabetic patients showed pH of 9 to 7 on immediate testing.
250 marker samples showed no significant change in pH
and zero sugar reading for 24 hours. 235 flour, 223 sucrose
study samples showed decrease in pH 5 >, in association
with glucose detection in samples. 2 flour and 2 sucrose
samples showed decrease in pH from 9 to 7 in association with glucose yielding within 24 hours. 8 isolated flour,
11 isolated sucrose diabetic samples, 4 same patient flour
and sucrose diabetes samples, 5 flour and 14 sucrose non
diabetic samples showed decrease in pH 5 > without glucose yielding in 24 hours (absent amylase activity). Zero
non diabetic samples, same subject showed absent amylase
activity for both flour and sucrose. Decrease in pH in study
samples was noticed to be associated with increase in glucose yielding. 92% of study samples showed decreased pH
5 > in association with high glucose readings (250 – 500
mg/dl or more).
Discussion: Significant but nonspecific elevations of
amylase can be seen in DKA (Diabetes Care 26:3193-3194,
2003). Similarity between DKA and this study in terms of
increased acidity in the presence of elevated serum amylase, and in association with high glucose from degradation
of disaccharides / polysaccharides particles that could exist
Objective: There is a well known strong association
between type1 diabetes (T1D) and autoimmune thyroid
diseases (AITD) but not between type2 diabetes (T2D) and
AITD.
Methods: To study the correlation between both types
(type 1 and type 2) and autoimmune thyroid disorders;
80 diabetic patients (40 T1D “20 males and 20 females”
and 40 T2D “20 males and 20 females”) and 20 control
subjects were studied. All cases were subjected to history
taking, clinical examination with a special emphasis on
thyroid examination. Estimation of fasting plasma glucose,
HbA1c, plasma C-peptide, GAD65 autoantibodies, antiinsulin antibodies(AIA), TPO antibodies, Anti-Tg, thyroid
stimulating immunoglobulin(TSI), FT3, FT4 and TSH
were done in addition, Ultrasound-guided fine needle aspiration biopsy to confirm or exclude the presence of thyroid
pathology.
Results: Revealed significantly elevated BMI, Cpeptide in T2D (confirming IR) than T1D and controls.
Anti-GAD and AIA were only positive in T1D. TSH was
significantly higher in T1D (50%) than T2D (15%), AntiTPO and Anti-TG were significantly lower in T2D than
T1D. BMI was positively correlated with age, C-peptide.
Anti-GAD and AIA were negatively correlated with Cpeptide. Anti-TPO and Anti-TG were positively correlated
with TSH. HbA1c was positively correlated with rT3 but
negatively correlated with T3. Atrophic and Hashimoto’s
thyroiditis were only detected in T1D with positive AntiTPO and Anti- TG.
Conclusions: Increased prevalence of AITD in T1D.
Subclinical hypothyroidism is more common in T1D than
T2D that may contribute to the high frequency of symptomatic hypoglycemia in these patients. Autoimmune
thyroid antibodies are commonly present in patients with
Anti-GAD antibodies. Anti-GAD and AIA are only positive in T1D confirming the role of autoimmunity in its
pathogenesis.
– 18 –
in slightly larger amounts in the blood of diabetic compared to non diabetic subjects (persorption phenomenon
- Gerhard Volkheimer).
Conclusion: Saliva alpha amylase activity should be
determined in relation to pH media. Saliva alpha amylase
is active in acid media. Correction of stomach pH and or
abnormal amylase activity could help treat / prevent diabetes and obesity.
Discussion: Our results show that the prevalence of
vitamin D insufficiency in patients with diabetes seen in
a tertiary referral center is extremely high (74.2%). More
than half of the subjects in our series were clearly deficient,
whereas only about one-fourth had levels considered optimal. Women, patients younger than age 50 years, and those
with poorer glycemic control (HbA1c >7%) had somewhat
lower levels of 25-OH vitamin D. Although the correlation
with these factors was not statistically significant, it may
have clinical importance in a selected population such as
ours.
Conclusion: Vitamin D deficiency is highly prevalent
in patients with diabetes treated in a specialty Diabetes
Center. Possible etiologies should be investigated and therapy guidelines formulated for appropriate management.
Abstract #208
ASSESSMENT OF VITAMIN D STATUS IN
PATIENTS SEEN IN A SPECIALTY
DIABETES UNIT
Kanakasabai Narasimhan, MD, and Ali Rizvi, MD
Abstract #209
Objective: To assess vitamin D status and analyze the
presence and degree of vitamin D deficiency in patients
with type 2 diabetes seen in a specialty diabetes unit.
Methods: We collected data on 97 patients with type 2
diabetes seen in an ambulatory setting in the Diabetes Unit
of an academic institution. The following parameters were
collected over an 18-week period: serum calcium, serum
creatinine, estimated glomerular filtration rate (eGFR),
HbA1c, and 25-OH vitamin D. Patients who had advanced
concomitant chronic disease or obvious malnutrition, stage
5 kidney disease, known vitamin D deficiency, osteoporosis, or derangements of calcium-parathyroid metabolism
were excluded. Data was entered into a Microsoft Excel
spreadsheet for analysis.
Results: The study included 39 men and 58 women
(63 Caucasian, 33 African American, and one Asian) with
an average age of 55 years. The mean serum calcium was
9.46 mg/dl (reference range 8.6 to 10.2), mean serum creatinine was 1.06 mg/dl (reference range 0.5 to 1.3), average glycosylated hemoglobin (HbA1c) was 7.52%, and the
majority (77/97, or 79%) had eGFR values greater than 60
ml/min. The average 25-OH vitamin D level was 23.3 ng/
ml, with the lowest being 7 and highest 68. The mean values were low in both men (24.4 ng/ml) and women (22.6
ng/ml). Values were slightly lower in younger patients:
thus, the mean 25-OH vitamin D level in patients <50 years
(n=34) was 22.9 ng/ml, in patients aged 50-59 years (n=31)
it was 25.8 ng/ml, and in persons ≥60 years (n=30), 23.5 ng/
ml. The mean 25-OH vitamin D was 24.3 ng/ml in patients
with HbA1c ≤7% (n=44) and 22.54 ng/ml in those with
HbA1c >7% (n=53). 49 patients (50.5%) had values of ≤20
ng/ml (“deficient”), the values in 23 patients (23.7%) fell
in the 21 to 29 range (“relatively insufficient”), and only 25
patients (25.7%) had levels ≤30 (“sufficient”).
AN ASSESSMENT OF LIMITED JOINT MOBILITY
OF THE HAND IN BLACK AFRICANS WITH
DIABETES MELLITUS AND NON DIABETICS
Rosemary Temidayo Ikem, MD, Innocent Ikem, MD,
Matthew Olaogun, and Bola Ola, MD
Objective: Limited Joint Mobility (LJM) has been
described in type 1 diabetic patients. Similar abnormalities
are also frequently seen in adult diabetes mellitus (DM)
patients. The purpose of this study is to further characterise
LJM using quantitative goniometric measurements among
type 2 diabetic patients.
Methods: Seventy-six patients with type 2 diabetes
and 63 normal controls (non DM subjects) matched for age
and sex were purposively selected for this study. Visual
clinical examination and quantitative goniometric assessment of DM and non DM controls were done. The LJM
was graded using the criteria of Silverstein et al. Glyceamic
control and proteinuria were also assessed.
Results: Our study found a prevalence of 26.3% LJM
among type 2 DM patients compared with normal controls
with 4.8% LJM. Subjects with LJM within the control
group were significantly older than those with LJM within
the DM group (p<0.05). Prayer sign was present in 11.8%
of DM patients compared with 4.8% of control. The flattening sign demonstrated by the inability to flatten their
hands on a flat surface was found to be more in DM patients
10.5% compared 4.8% in the control group. Stage II LJM
with 18.4% prevalence was the commonest followed by
stage III (7.9%) among DM patients. In our patients, poor
glyceamic control was found in 85%, using Fasting Plasma
Glucose (FPG) and 70%, using 2hpp.
– 19 –
Conclusion: We conclude that black Africans with
type 2 DM only have moderately severe cases of LJM.
Abstract #211
Abstract #210
ASYMPTOMATIC BACTERIURIA IN PATIENTS
WITH DIABETES MELLITUS IN ILE-IFE,
SOUTH-WEST NIGERIA
QUALITY OF LIFE IN NIGERIANS WITH
DIABETIC FOOT ULCER
Rosemary Temidayo Ikem, MD, A O Aboderin, MD,
Babatunde Odetoyinbo, and Babatope Kolawole, MD
Rosemary Temidayo Ikem, MD, Innocent Ikem, MD, and
Bola Ola, MD
Objectives: To investigate the prevalence and associates of asymptomatic bacteriuria (ASB) in a sample of
Nigerian diabetic patients.
Method: This is a cross-sectional descriptive and
analytic study of consecutive diabetic patients attending
the diabetes clinic of the Obafemi Awolowo University
Teaching Hospital (OAUTHC), Ile-Ife, South-West
Nigeria. Patients were recruited from the Wesley Guild
Hospital and Ife State Hospital, both units of OAUTHC,
Ile-Ife, Nigeria. 135 diabetic patients and 57 non-diabetic
patients (as control). Demographic parameters of participants were recorded. Significant bacteriuria was determined for each of the mid-stream urine specimen obtained
from all the subjects. Organisms isolated were identified
and evaluated for antibiotic susceptibility patterns.
Results: There was a significant difference in the
prevalence of ASB in the two groups. Prevalence of ASB
was 16% and 3.5% in the diabetic patients and control
respectively (p=0.03). Demographic parameters except
age were not related to the presence of ASB. ASB was
found in 54.4% of diabetic patients with poor glycaemia
control compared with 2.9% in diabetics with good glycaemia control (p=0.006). Organisms associated with ASB
were Staphylococcus aureus, Klebsiella sp, Escherichia
coli and Enterococcus faecalis, however the most predominant was Staphylococcus aureus. These organisms
were largely resistant to the common antibiotics tested
such as cotrimoxazole and gentamicin but susceptible to
nitrofurantoin
Conclusions: The prevalence of ASB is high in diabetic patients and poor glucose control can be considered a
predisposing factor.
Objective: Diabetic foot ulcer (DFU) has a severe
negative effect on health related quality of life of individuals with diabetes and existing knowledge about these
factors in DFU patients is scarce in sub-Saharan Africa.
The purpose of this study was to determine if there was a
relationship between depression, Health Related Quality of
Life (HRQoL) and cognitive functioning in Nigerian DFU
patients.
Methods: Thirty nine diabetic patients, including 21
with foot ulcers (focus group) and 18 without foot ulcer
but having symptomatic peripheral neuropathy (control
group) as measured by insensitivity to Semmes Weinstein
5.07 (10gm) monofilament, were studied in a cross-sectional setting. All subjects completed WHO Quality of Life
Scale – Brief Version to assess HRQoL, Beck’s depression Inventory (BDI) to assess depression, and Modified
Mini-Mental State Examination (mMMSE) for cognitive
function.
Discussion: Patients with DFU were significantly
impaired in BDI score (p < 0.01) as well as in all domains
of HRQoL. There was no evidence of cognitive impairment
in these patients. Depression correlated with all domains of
HRQoL in them.
Conclusion: Patients with DFU are more likely to
have poorer health related quality of life (HRQoL) than
those without ulcers. Depression is one of the key factors in predicting the outcome of DFU. In DFU patients
it adversely affects HRQoL. Further studies are warranted
to investigate the impact of improved depression management on HRQoL in patients with DFU.
– 20 –
NPH regimens.
Discussion: Long acting insulin is generally avoided
peri-operatively because of risk of hypoglycemia, but we
observed that long acting analog glargine was better than
NPH insulin in basal bolus regimens. However limitation of our study is that it is a single centre observational
study.
Conclusions: There is need of blinded multi centric
studies to prove superiority of long acting insulin analog
containing regimens in pre and post-operative glycemic
control in T2DM patients undergoing major surgery.
Abstract #212
GLYCEMIC CONTROL IN TYPE 2 DIABETES
MELLITUS PATIENTS UNDERGOING MAJOR
SURGERY: COMPARATIVE STUDY OF THREE
S.C. INSULIN REGIMENS
Sandeep Kumar Mathur, MBBS, MD, DM,
Alka Bansal, MD, and Zaffer Yab Khan, MD
Objective: Many different regimens of insulin and
oral drugs have been suggested for metabolic control during major surgery, but pre-operative glucose control with
subcutaneous insulin in semi-urgent situations is logical
and well accepted. Among the several insulin regimens
which is the best is not certain. Therefore we compared
three s.c. insulin regimens in T2DM patients hospitalized
for major surgery.
Methods: 172 T2DM patients hospitalized for
major surgery where it was decided to control hyperglycemia with s.c. insulin because of semi-urgent surgery/oral
drug failure participated in the study. The study design was
randomized comparative observational study. Preoperative
glycemic control was achieved with one of the following
regimens:
1. Pre-mix 30/70 insulin (R/N-0-R/N). 2. R +
NPH. Basal-bolus regular & NPH insulin (R-R-R/N).3. R
+ G. Basal-bolus regular & glargine (R-R-R-G).
Insulin doses were adjusted to achieve fasting and
post-meal glucose values respectively < 120 and < 180 mg/
dl. Intra-operatively they were treated with glucose –insulin – potassium solution. Post operatively same pre-operative insulin regimen was started. These regimens were
compared for following parameters. (1) Time to achieve
glycemic target (2) total daily insulin dose (3) incidence of
hypo and severe hyperglycemia and (4) complications like
renal, infection etc. (5) in hospital mortality.
Results: R + G regimen was associated lesser
dose of insulin (29.53 ± 9.83 vs. 35.67 ± 12.19 & 37.42 ±
13.5 units respectively for regimen 2 & 1 p <0.005), lesser
time to achieve glycemic target (6.75 ± 3.25 vs. 7.37 ± 7.47
& 8.23 ± 6.04 days, p>0.05), lower incidence of hypoglycemia (10.53 vs. 14.81 & 30% p <0.02) and severe hyperglycemia (5.26 vs. 29.63 & 8.33% p <0.005). Incidence of
infection (10.53 vs. 18.52 & 15% p >0.05), renal complications (10.53 vs. 11.11 & 15% p >0.05) and mortality (5.26
vs. 14.81 & 15% p > 0.05) were lower with this regimen,
but the difference was not statistically significant. Pre-mix
30/70 and R + NPH regimens were comparable for most
parameters but hypoglycemia and severe hyperglycemia
were more frequent respectively pre-mix 30/70 and R +
Abstract #213
THE UKPDS RISK ENGINE AS A USEFUL TOOL
FOR CARDIOVASCULAR RISK ESTIMATION
IN A MEXICAN POPULATION WITH TYPE 2
DIABETES MELLITUS
Paloma Almeda Valdes, MD, Carlos Aguilar-Salinas,
Daniel Cuevas-Ramos, Francisco Gomez-Perez, and
Juan Rull-Rodrigo
Objective: To estimate the utility of the UKPDS risk
engine estimating discrimination, calibration, specificity
and sensitivity of the model in a Mexican population with
type 2 diabetes.
Methods: Retrospective study of cases (patients with
coronary heart disease or stroke) and controls (patients
without them) with at least one year follow up, with all the
variables required to calculate cardiovascular risk with the
UKPDS risk engine. Results: Cardiovascular risk was estimated in 436 patients, 215 cases and 221 controls, 217 men
and 219 women. The estimation was repeated when possible. 436 patients had 1 estimation, 433 had 2 estimations
and 289 had 3 estimations. We did not find significant differences between estimations. Mean 10-year coronary risk
was 31%. The estimated 10-year coronary risk was greater
than 20% in 66.7% of the population. There were 260 cardiovascular events: 215 coronary heart disease events and
45 strokes. 101 deaths were documented; in 52 (51.4%)
coronary heart disease was the cause. The discrimination
of the UKPDS model was 0.66 (IC 95% 0.59-0.72) and
calibration was 23.8. The sensitivity for a 10-year estimated risk of 20% was 89% and specificity 36%.
Discussion: Patients with type 2 diabetes have a 2 to
4 fold increased risk for developing cardiovascular disease.
A high proportion of diabetics will develop a cardiovascular event during their life time. The increased cardiovascular morbidity and mortality is due to the coexistence of
multiple risk factors: elevation of total and LDL choles– 21 –
terol, high blood pressure, hyperglycemia, smoking and
low HDL cholesterol. ADA strongly recommends the individual assessment of cardiovascular risk using designed
models. The usefulness of the UKPDS risk engine had not
been evaluated in Mexican population until this study.
Conclusions: The model had moderate discrimination
and poor calibration in this Mexican population. The results
are similar in other studies done in Europe. The UKPDS
risk engine is a useful tool for estimation of cardiovascular
risk in Mexican population with type 2 diabetes.
improvement of insulin sensitivity in insulin resistant subjects. This rare case exhibits an unexpectedly improvement
in glycemic control shortly after using TNF-α inhibitor
despite maintenance of the body weight and diet. A decline
in HbA1c for 1%, 7 months after Enbrel injection along
with significant decline in medication requirement for glycemic control in this patient strongly suggests the TNF-α
blockade impact on glucose metabolism.
Conclusion: This index case emphasizes the importance of TNF-α on management of diabetes type 2.
Cautious should be advised to these patients when start on
anti TNF-α and physicians should be alerted for possible
low blood glucose response.
Abstract #214
SIGNIFICANT IMPROVEMENT IN DIABETES
CONTROL AFTER ADMINISTRATION OF
ENBREL
Abstract #215
DIABETIC CARDIAC AUTONOMIC
NEUROPATHY PROFILE OF WELL
CONTROLLED TYPE 2 DIABETIC SUBJECTS
WITHIN ONE YEAR OF DIAGNOSIS USING
NON-INVASIVE PORTABLE ANSISCOPE
Farnoosh Farrokhi, MD, and Nancy McBride, MD
Objective: To describe a diabetic case with reduced
medication requirement along with improved glycemic
control after receiving Embrel injections for psoriasis.
Case presentation: 59 years old white female with
type 2 diabetes for 17 years returned to the clinic complaining low blood glucose levels and hypoglycemia symptoms
after administration of Enbrel. She has been treated with
twice-daily doses of Metformin 1000 mg, Glyburide 6 mg
and Avandia 4 mg since 2005. In Feb. 2007 she was started
on Enbrel injections 50 mcg 2 times a week for treatment
of psoriasis. Her HbA1c and body mass index (BMI) were
7.9% and 30.99 kg/m2 at that time. She returned to the
clinic in June 2007 stating that after few Enbrel injections
she noticed hypoglycemia symptoms along with decline
in self-measured blood sugars for which she discontinued
the evening doses of all her diabetes medications. On that
visit her Avandia was discontinued, also her HbA1c and
BMI measured to be 7.5% and 29.7 kg/m2 respectively.
Few weeks later, due to continuation of low blood sugar
levels she decreased Glyburide to 3 mg/day. In Oct. 2007
her HbA1c was 6.9% without any change in the BMI. She
denied any change in concomitant medications or diet.
Discussion: Enbrel (Etanercept) is Tumor necrosis
factor α (TNF-α) inhibitor used in treatment of chronic
inflammatory diseases. TNF-α is a proinflammatory cytokine involved in inflammatory and immune responses.
Studies have shown that administration of this cytokine to
culture cells or in vivo to animals impairs insulin action.
Also in humans, acute infusion of TNF-α has shown to
inhibit the insulin stimulated glucose disposal leading
to increase susceptibility to insulin resistance. There has
been debate on the role of anti- TNF-α medications and
Ali Asghar Jawa, MD, MPH, Mumtaz Hasan,
Jawad Zaheer, Muhammad Shahid Jamil,
Tahir Rasool, Muhammad Abu Zafar,
Syed Ali Imran, and Imteyaz Ahmad
Objective: Diabetic Cardiac Autonomic Neuropathy
(DCAN) is associated with high risk of cardiovascular
morbidity and mortality. Portable ANSiscope is a relatively
new device that non-invasively measures the parasympathetic/sympathetic nervous system imbalance in an office
setting. The ANSiscope computes a percentage of dysautonomia from a recording of 571 RR intervals recordings
for patients at rest in supine position. After analyzing, the
ANSiscope generates an ANS index. Based on scoring
described by Bellavere et al, five risk categories have been
identified using the computed ANS Index. Subjects with
ANS index <11%, 11-20%, 21-50%, 51-60 and 61-100%
are classified into Healthy, Early, Late, Advanced and
Most Advanced Diabetic Cardiac Autonomic neuropathy
(DCAN) groups respectively. We investigated prevalence
of DCAN amongst well controlled type 2 Diabetic subjects
within one year of diagnosis.
Methods: All type 2 diabetic subjects with HgbA1c
< 7.0 and diagnosed with type 2 Diabetes Mellitus within
the past 12 months were included in the study. Informed
consent was obtained and subjects were asked to lay supine
comfortably for at least 10 minutes before start of the study.
EKG electrodes connected to the portable ANSiscope were
placed on the chest wall and EKG tracings were recorded
– 22 –
for 5 minutes. ANSiscope analyzed the data and calculated
an ANS Index.
Results: We studied 29 type 2 diabetes subjects, out
of which 18 were female, with a mean duration of diabetes
of 9 months (1- 12), mean age of 51 years(30-73), mean
BMI of 29 (20-42) and a mean hemoglobin A1c of 6.3%
(5.3-7.0). Out of total 29 subjects, 10, 4, 11, 1, 3 subjects
were categorized in Healthy, Early, Late, Advanced and
Most Advanced Diabetic Autonomic Neuropathy Groups
respectively.
Conclusions: Our study clearly indicates that despite
good glycemic control, almost 2/3 rd of recently diagnosed
type 2 diabetes mellitus (T2DM) subjects have some level
of diabetic cardiac autonomic neuropathy. This is alarming and further emphasizes the need for earlier diagnosis
and aggressive treatment of type 2 diabetes mellitus. This
study also underscores the need for identifying other factors that contribute towards such high level of autonomic
dysfunction in subjects with T2DM. We plan to investigate factors and interventions that may reverse or halt the
progression of Diabetic Cardiac Autonomic Neuropathy.
In future studies, we also plan to assess for any correlation between Diabetic Cardiac Autonomic Neuropathy and
microalbuminuria and retinopathy.
p=0.05 for significance. Multivariable linear regression
was then performed separately for T1 and T2 diabetics.
Results: Charts of T1 and T2 diabetics age 18 or older
were reviewed until 200 complete records were obtained.
Exclusion criteria included dialysis and transplant patients.
At least one missing glucose value was noted in 51 of the
first 200 (25.5%) records examined. Only two cases of
glucose <60 mg/dl were documented. T1 diabetic median
preoperative glucose was 233 mg/dl (range 48-444 mg/dl)
and median postoperative glucose was 156 mg/dl (range
93-380 mg/dl). T2 diabetic median preoperative glucose
was 133 mg/dl (range 71-315 mg/dl) and median postoperative glucose was 155 mg/dl (range 55-318 mg/dl). Type
of diabetes (p=0.004), insulin use (p=<0.0001), and oral
medication use (p=0.002) were significantly related to glucose change while all other variables were not. Regression
analysis for T2 diabetics was significant only for insulin
use (p=0.02) which decreased glucose change by 24.6 mg/
dl. No variables significantly predicted glucose change in
T1 diabetics as the regression was confounded by 100%
of all T1 diabetics being on insulin and none on oral
medications.
Discussion: Incomplete perioperative glucose records
were found in 25.5% of the first 200 diabetics examined. Perioperative glucose control in T2 diabetics was reasonable given no specific targets exist. The only predictor of
glucose change in this group was insulin use. Glucose control in T1 diabetics was suboptimal preoperatively, and no
predictors of glucose change were found for this group.
Conclusion: Perioperative glucose management in
our study was not optimal particularly in T1 diabetics. Our
data support the need to develop diabetic perioperative
glucose protocols to ensure proper glucose testing and to
improve perioperative glucose control.
Abstract #216
DIABETIC PERIOPERATIVE BLOOD GLUCOSE
CONTROL: A COMPARISION OF BLOOD
GLUCOSE MEASUREMENTS IN
THE PREOPERATIVE AND
POSTOPERATIVE SETTING
Kelli Karches, MD, MPH, James McCallum, MD, and
Nitasha Bakhru, MD
Abstract #217
Objective: Hyperglycemia in the perioperative setting
is associated with poor surgical outcomes, yet no specific
targets for perioperative glucose management exist. This
study was designed to examine perioperative glucose control and variables that may influence it.
Methods: A retrospective chart review using diagnosis
codes identified 200 Type 1 (T1) and Type 2 (T2) diabetics
who had a general anesthetic surgical procedure at Scripps
Green Hospital between April-September 2006. Variables
examined were pre- and postoperative point of care blood
glucose, type of diabetes mellitus, insulin, oral, or no
medication use, age, gender, BMI, ethnicity, and postoperative hospitalization. Univariate analysis using 2 sample
Wilcoxon tests examined variables with respect to average glucose change (postop-preop) for each group using
ACUTE CHOLECYSTITIS TEMPORALLY
ASSOCIATED WITH INITIATION OF
TREATMENT WITH EXENATIDE
Sri Prakash L. Mokshagundam, MD,
Suresh Lohano, and Vasdev Lohano
Objective: We report a patient with type 2 diabetes
mellitus (T2DM) who presented with abdominal symptoms shortly after the initiation of exenatide (Byetta) therapy and was found to have acute cholecystitis requiring
cholecystectomy.
Case Presentation: A 51-year old South Asian lady
with history of T2DM presented with symptoms of epi– 23 –
during the time frame. Other parameters examined in the
present study included maternal age, delivery date, selfdeclared First Nation status, rural or urban residence and
previous history of GDM. The data were analyzed using
multivariate logistic regression models.
Results: The prevalence of GDM during the 20 year
period was 2.92%. Statistically significant increases in the
prevalence of GDM were detected over the time, from
1.95% in 1985-86 to 3.72% in 2003-04 (p<0.01). The
trend of increase in the prevalence of GDM in Manitoba
sustained after modifications in the diagnostic criteria
of GDM in the Canadian Diabetes Association Clinical
Practice Guidelines. The prevalence of GDM was substantially higher in First Nation women (6.94%) than that in
non-First Nation women (2.36%, p<0.01). The prevalence
of GDM was higher in pregnant women living in rural
regions (3.12%) compared to those in urban areas (2.70%,
p<0.01). The prevalence of GDM in pregnant women who
were ≥35 years old (5.92%) was greater than those <35
years of age (2.60%, p<0. 01). The prevalence of recurrent
GDM in First Nations was 48.12% compared to 42.39%
in non-First Nations pregnant women (p<0.01). Adjusted
odds ratios (95% confidence interval) of GDM for First
Nation status, advanced maternal age and previous history
of GDM were 2.20 (2.00, 2.42), 2.38 (2.24, 2.54) and 25.09
(23.15, 27.19). The adjusted odds ratio for rural residence
was 0.77 (0.74, 0.82), but had an interaction of 1.66 (1.48,
1.86) when associated with First Nation status.
Conclusion: The results of the present study indicate
that the prevalence of GDM increased in Manitoba during
the 20 year time frame. First Nation status, advanced maternal age and a history of GDM are independent risk factors for GDM in Manitoba. Further research to determine
the cause and consequence of the increase in prevalence
of GDM is required (Supported by Canadian Institutes of
Health Research and The Lawson Foundation).
gastric pain, nausea and vomiting after a meal. Her past
medical history was significant for T2Dm, hypertension,
severe pancreatitis in 2003, vitamin D deficiency, and
aspirin induced gastritis. She had been on metformin and
pioglitazone for her diabetes mellitus and was started on
Exenatide 5 micrograms bid, about 1 week before the
episode. Physical examination was significant only for
tenderness in the right upper abdominal quadrant. Liver
function tests, creatinine, amylase and lipase were normal.
Ultrasound of the abdomen showed mild distension of gall
bladder with small amount of sludge. She underwent laparoscopic cholecystectomy the following day. Resected gall
bladder showed acute and chronic cholecystitis with intramural abscesses.
Discussion: Exenatide has been increasingly used
in management of T2DM. A common side effect of the
medication is abdominal discomfort, which is usually mild
and often resolves over time. Recently, however, several
reports of pancreatitis associated with the use of exenatide
have prompted the FDA to issue warning about this potential effect. The mechanisms leading to pancreatitis are
unclear. It is not known whether exenatide increases risk
of cholelithiasis, which could lead to both pancreatitis and
cholecystitis. Gall bladder disease is common in subjects
with obesity and T2DM. However, the temporal relationship between the start of exenatide and the development
of symptoms of gall bladder disease in our patient, raises
possibility of a causative link.
Conclusion: Clinicians using exenatide for the management of diabetes should carefully evaluate any significant abdominal symptoms and consider the possibility of
gall bladder disease. Abstract #218
GESTATIONAL DIABETES IN MANITOBA
DURING A TWENTY YEAR PERIOD
Abstract #219
Naji Jameel Aljohani, MD, Garry Shen, MD,
Brenda Rempel, MD, Sora Ludwig, Margaret Morris,
Kelly McQuillen, Mary Cheang, and Robert Murray
PATTERN OF DIABETES IN
NORTHERN NIGERIA
Objective: Gestational diabetes mellitus (GDM) is
associated with postnatal obesity and type 2 diabetes. We
conducted a retrospective database study to determine the
prevalence of GDM in the province of Manitoba in the
years 1985-2004 and its relationship with advanced age,
ethnicity, rural residence and history of GDM of pregnant
women.
Methods: Manitoba Health collected computerized
data on 324,605 deliveries by 165,969 Manitoban women
Adamu Girei Bakari, MBBS, FWACP, and
Geoffrey C. Onyemelukwe
Objective: Genetic and environmental factors are
known to play significant roles in the pathogenesis and presentation of diabetes mellitus. The pattern of this disorder
may therefore vary from one location to the other depending of genetic factors, other confounding disease conditions and peculiarities in life styles. This report describes
the pattern of diabetes in the sahelian northern Nigeria.
– 24 –
Methods: A 10 year prospective review of cases of
diabetes mellitus seen in a Teaching hospital. Diabetes was
diagnosed and classified using the WHO criteria.
Results: A total of 747 patients with a male to female
ratio of 2.38:1 were seen. Type 2 diabetes mellitus is the
commonest form of the disorder occurring in 575 (77.0%)
of patients. Type-1 diabetes occurred in 117 (5.7%), while
41(5.5%) of patients had secondary diabetes. Chronic Liver
disease was the commonest cause of secondary diabetes
mellitus in this population. Gestational diabetes was found
in 14(6.5%burden of diabetes among the females in this
series. Type 2 diabetes mellitus is the commonest form of
the disorder encountered. On the other hand, chronic Liver
disease was the commonest cause of secondary diabetes
mellitus in this population.
Discussion: As was the case in other studies in
Nigeria, and globally, type 2 diabetes mellitus is the commonest form of diabetes mellitus in this study. Chronic
liver disease was the commonest cause of secondary diabetes in this environment accounting for 36.6%of cases in
the secondary diabetes group. This finding is noteworthy
as hepatitis B viral infection is endemic in this region as
evidenced by Hepatitis B surface antigen (HBsAg) rates.
An HBsAg rate of 40% and 10% has been demonstrated in
children under the age of 5 years and adults above 30 years
of age respectively. The role of liver disease in increasing hepatic glucose output and insulin resistance culminating in glucose intolerance has been extensively discussed.
Further studies on the probable role of hepatitis B Viral
infection in the aetiology of diabetes mellitus are required
especially in HBsAg endemic areas
Conclusion: Liver disease is a significant cause of
secondary diabetes in this environment.
Background: Vitamin B12 deficiency causes peripheral neuropathy in subjects with type 2 diabetes mellitus.
Vitamin B12 deficiency can occur either due to nutritional
deficiency or due to lack of intrinsic factor and subsequent vitamin B12 malabsorption in pernicious anemia.
Additionally, Metformin use in type 2 diabetic subjects has
been associated with nutritional deficiency.
In order to ascertain the type of vitamin B12 deficiency, performing a Schilling test has been the standard
of care. However, Schilling test is a cumbersome and relatively expensive procedure. We decided to test a different
approach. All subjects with biochemically proven Vitamin
B12 deficiency would be supplemented orally with methylated Cyanocobalamin, chemically known as Mecobalamin.
Mecobalamin is the activated form of Vitamin B12 and is
absorbed more efficiently. Subjects would receive 1500
Microgram of Mecobalamin per day orally for 3 months
followed by repeat Vitamin B12 levels measurement.
Those subjects who would remain deficient in Vitamin
B12 will be offered 7 injections of intramuscular supplementation of Mecobalamin given every other day for 14
days. Vitamin B12 levels would be measured again after
three months of receiving intramuscular supplementation
with Mecobalamin. Those subjects who will correct their
Vitamin B12 deficiency by oral supplementation alone will
be labeled as having nutritional Vitamin b12 deficiency.
Those who require intramuscular injections in order to
correct the deficit will be presumed to have pernicious
anemia.
Methods: After obtaining informed consent, we measured vitamin B12 levels in 44 subjects with type 2 diabetes mellitus not taking metformin. 23/44(52%) subjects
with type 2 diabetes mellitus had normal vitamin B12
level and 21/44 (48%) subjects had low vitamin B12 level
defined as Vitamin B12 levels less than < 200 MCG/dL.
10/21 vitamin B12 deficient subjects with type 2 diabetes
mellitus decided not to participate in the intervention phase
and 1 subject expired due to unrelated medical condition.
10/21 subjects with type 2 diabetes mellitus agreed for oral
mecobalamin therapy for 3 months followed by measurement of vitamin B12 levels. If they persistently had low
vitamin B12 levels after 3 months, they would be treated
with intramuscular injection of mecobalamin and Vitamin
B12 levels measured after 3 months of first injection.
Results: 10/10 subjects with type 2 diabetes mellitus
and a mean age of 50 years (35-65) completed the study.
All subjects normalized their vitamin B12 level (> 200
MCG/dL) 3 months after initiation of oral mecobalamin
therapy. Hence none of these subjects needed to be treated
with intramuscular mecobalamin therapy.
Abstract #220
VITAMIN B12 DEFICIENCY IS COMMON
IN SUBJECTS WITH TYPE 2 DIABETES
MELLITUS NOT TAKING METFORMIN AND IS
NUTRITIONAL IN NATURE
Ali Asghar Jawa, MD, MPH, Mumtaz Hasan,
Muhammad Shahid Jamil, Jawad Zaheer, MD
Syed Ali Imran, Ghazanfar Jawa, and
Umair Javaid Chaudhary, MD
Objective: To assess frequency of vitamin B12 in
subjects with type 2 diabetes mellitus. Additionally, we
decided to investigate whether the vitamin B12 deficiency
was due to nutritional deficiency or due to malabsorption
of Vitamin B12 in pernicious anemia.
– 25 –
Conclusions: Our study clearly shows that almost
half of T2DM subjects not taking metformin have Vitamin
B12 deficiency. 1/4th of these subjects have vitamin B12
deficiency that is readily correctable with oral supplementation alone. This is a novel finding and stresses the need
for aggressive and early diagnosis and treatment to avoid
neurological complications of Vitamin B12 deficiency.
Also, it would not be unreasonable to empirically treat type
2 diabetes subjects with signs and symptoms of peripheral
neuropathy with 3 months of oral supplementation with
Vitamin B12 or its activated form, Mecobalamin. respiratory alkalosis which occurs in pregnancy. Fetal IQ
and incidence of fetal congenital heart defects have been
inversely related to ß hydroxybutyrate and FFA levels. Fetal
loss in DKA is caused by decreased uteroplacental blood
flow due to osmotic diuresis leading to volume depletion.
Maternal hypokalemia can lead to fetal hypokalemia leading to myocardial suppression and arrhythmia. Maternal
hypophosphatemia can cause decrease in 2, 3-DPG leading
to impaired delivery of O2 to fetus. Fetal hyperinsulinemia
due to maternal hyperglycemia can cause increase in O2
requirement by stimulating the metabolic pathway.
Conclusion: This case illustrates the need to consider
euglycemic DKA in pregnancy and the deleterious effects
of uncontrolled DM and DKA on the fetus.
Abstract #221
“EUGLYCEMIC” DKA IN PREGNANCY AND ITS
EFFECTS ON FETUS
Abstract #222
Veena Watwe, MBBS, and Hamdee Attallah, MD
ADDITION OF COLESEVELAM HCL IMPROVES
GLYCEMIC CONTROL IN PATIENTS WITH
POORLY-CONTROLLED TYPE 2 DIABETES
MELLITUS WITH SULFONYLUREA-BASED
THERAPY: A POOLED ANALYSIS
Objective: To describe a case of euglycemic DKA in
type 1 DM and effects of uncontrolled DM on the fetus.
Case: A pregnant 26-yr-old African American woman
with longstanding type 1 DM presented at 30 wks gestation
with frequent nausea and vomiting. She has had multiple
DKA admissions due to noncompliance with insulin since
the first trimester. On admission, fingerstick glucoses were
132-150 mg/dl and ketoacidosis was confirmed by the presence of a serum bicarbonate 7, anion gap 21, and ++ ketones
in the serum and urine. No identifiable precipitating factors
for DKA were identified, and the acidosis resolved completely with reinstitution of insulin. Diabetes-associated
complications included overt nephrotic syndrome noted
since the first trimester, pregestational uncontrolled hypertension and longstanding retinopathy. At presentation, BP
= 170/80, RR = 30 and Kussmaul respiration was present.
Other findings included generalized edema with 3-4+ pitting the lower extremities. At 32 5/7 weeks, a 1.3 kg male
infant was delivered by cesarian section with abdominal
situs inversus and congenital hypoplastic left heart syndrome. The baby died at 1 month of age.
Discussion: DKA has been associated with a fetal loss
rate of 9 %, and most DKA episodes occur in second and
third trimester and often despite relatively lower glucose
concentrations. “Euglycemic” DKA, in which diabetic
ketoacidosis appears when glucoses are below 180 mg/dl,
has been described in the literature. Factors contributing to
increased risk of DKA in pregnancy are increasing insulin
resistance due to increase in hormones like HPL, cortisol
and prolactin, decreased GI motility with increased absorption of carbohydrates, accelerated starvation as the fetus
and placenta use up large stores of glucose, lower buffering
capacity with bicarbonate ions due to compensation of the
Vivian Andrew Fonseca, MD, FACE,
Allison B. Goldfine, MD, Kenneth E. Truitt, MD, and
Michael R. Jones, PhD
Objective: Colesevelam HCl (COL) is a bile acid
sequestrant with a new additional indication as an adjunct
to diet and exercise to improve glycemic control in adults
with type 2 diabetes mellitus (T2DM). The glucose-lowering efficacy of COL in patients (pts) with poorly controlled
T2DM (A1C 7.5%-9.5%) was evaluated in 3 randomized,
double-blind studies in which COL was added to metformin (26 wks), insulin (16 wks), or sulfonylurea (SU)-based
therapy (26 wks), respectively, as monotherapy or in combination with other antidiabetic agents. Each of the primary
studies demonstrated a significant reduction in mean A1C
with COL vs placebo (PL) by study end (-0.54%, -0.50%,
-0.54%, respectively; P<0.001 for all). Here we report the
results of a pooled analysis of the efficacy data for all pts
who received SU in the 3 primary studies.
Methods: A total of 653 pts on SU-based therapy
(alone or combined with other oral antidiabetic agents)
were randomized in the primary studies to add-on therapy
with COL 3.75 g/day (n=326) or PL (n=327). Efficacy
endpoints included change from baseline to study end in
A1C and fasting plasma glucose (FPG). In addition, the
proportion of pts who achieved a reduction in A1C≥0.7%
or a reduction in FPG≥30 mg/dL from baseline to study
end was evaluated.
– 26 –
Results: Compared with PL, COL added to SU therapy resulted in significant reductions in mean A1C and
FPG by study end. The mean change from baseline in A1C
was -0.35% in the COL group (mean baseline A1C 8.2%)
vs +0.18% in the PL group (mean baseline A1C 8.3%),
resulting in a treatment difference of -0.53% by study end
(P<0.001). The mean change from baseline in FPG with
COL was -1.4 mg/dL (mean baseline FPG 174.1 mg/dL)
vs +12.2 mg/dL with PL (mean baseline FPG 172.4 mg/
dL), resulting in a treatment difference of -13.6 mg/dL at
study end (P=0.001). In addition, significantly more pts in
the COL group achieved a reduction in A1C≥0.7% (35.0%
vs 16.5%; P<0.001) or FPG≥30 mg/dL (29.1% vs 21.7%;
P=0.029) from baseline to endpoint vs the PL group.
Conclusion: The addition of COL in pts with T2DM
inadequately controlled with SU-based therapy significantly improved glycemic control. Several mechanisms
have been proposed for the glucose-lowering effect of
COL, including reductions in glucose absorption and
effects on glucose metabolism via nuclear receptors in the
intestine and/or liver. The exact mechanism(s) remains to
be confirmed.
obesity (27% were overweight and >65% were obese). Overweight or obese T2DM respondents were significantly less likely to report excellent health (31% and 18%,
respectively), compared with overweight or obese HR
respondents (42% and 30%, respectively), p<0.001. There
were no differences between T2DM and HR groups overall
for ‘contemplating exercising’ and ‘exercising regularly’
but more obese respondents in the T2DM and HR groups
were ‘contemplating exercising’ (20.4% and 20.8%,
respectively), and fewer obese respondents were currently
‘exercising regularly’ (21.4% and 23.3%) than the overweight (9%-13% contemplating and 33%-34% exercising
regularly) and normal weight (8%-9% contemplating and
38%-40% exercising regularly) groups, p<0.001 for each. More obese respondents in both the T2DM and HR groups
attempted weight management (83% and 78%, respectively) than normal or overweight respondents (28%-61%),
p<0.001. However, a larger proportion of obese T2DM
respondents tried to lose (82.7%) or maintain weight
(82.2%), compared with obese HR respondents (78.4%
and 77.6%, respectively), p<0.001.
Conclusions: Differences in attitudes and behaviors
for exercise and weight management within T2DM and
HR groups were largely associated with differences in BMI
category. Obesity had a negative impact on current health,
on the likelihood of exercising regularly, and on weight
management for those with or at risk for diabetes.
Abstract #223
INFLUENCE OF OBESITY ON HEALTH
ATTITUDES AND BEHAVIORS AMONG
INDIVIDUALS WITH OR AT RISK FOR TYPE 2
DIABETES MELLITUS
Abstract #224
AN OBSERVATIONAL STUDY OF THE
GLYCEMIC CONTROL IN HOSPITALIZED
PATIENTS ON ARTIFICIAL ENTERAL FEEDING
Helena W. Rodbard, MD, FACP, MACE,
James R. Gavin III, Kathleen M Fox, and Susan Grandy
Objective: This investigation evaluated the role of
obesity in health attitudes and behaviors for weight management and exercise among individuals with type 2 diabetes mellitus (T2DM) and those at high risk for T2DM.
Methods: Self-reported attitudes toward health, exercise behaviors, and weight management were assessed in
the US longitudinal SHIELD study from the mailed 2004
survey for respondents with T2DM or high risk (HR) for
diabetes defined as >3 of the
following: abdominal obesity,
2
body mass index >28 kg/m (BMI), self-reported diagnosis
of dyslipidemia, hypertension, or history of cardiovascular disease. Respondents
were stratified into 3 categories
2
of BMI (kg/m ): <25 (under/normal weight), 25.0-29.9
(overweight), and >30 (obese). Comparisons across BMI
groups were made using analysis of variance; comparisons
between T2DM and HR were made using chi-square tests.
Results: T2DM (n=3917) and HR (n=5465) were
similar for age (mean=59 years), race (>85% white), and
Fadi Adel Nabhan, MD, Norma Lopez, MD,
Alexandra Reiher, MD, James Sincaroe,
Nicholas Emanuele, and Mary Ann Emanuele
Objective: This study is aimed at evaluating the prevalence of adequate glycemic control in hospitalized patients
on artificial enteral tube feeding (TF) and appropriate insulin management in these patients
Methods: This is an observational study on hospitalized patients at Loyola University Medical Center. We
included patients who were on TF for at least 8 continuous
hours/day. Medical records were reviewed on 5 random
days to assess the blood glucose (BG) measurements of
all eligible patients. Some patients were represented on
more than one day, so we utilized the concept of a patientday, defined as a 24-hour period where a given patient’s
glucose measurements were evaluated. Glycemic control
– 27 –
was considered optimal if BG was 70-180 mg/dL. Primary
outcome was the percentage of BG measurements between
70 and 180 mg/dL.
Result: Seventy-three eligible patients, resulting in
108 patient-days, were studied. Thirty-four patient-days
were on intravenous insulin drips, 17 were on insulin
glargine and the remaining 57 patient-days were either
on no insulin or insulin as needed. Overall, the mean
percentage of BG measurements recorded at target, >180
mg/dL and <70 mg/dl were 83.9%, 14.1% and 1.5%
respectively. Those with a history of DM were less likely
to have BG measurements at target (p<0.002) and more
likely to be hyperglycemic (p<0.014) than those without a
prior history of DM. While on intravenous insulin, 91.3%
of BG measurements were at target compared to 54.1% on
subcutaneous insulin glargine (p<0.001). Among patients
receiving insulin glargine, those with renal failure were
less likely to achieve BG measurements at target than those
with normal renal function (p<0.006) and more likely to
be hyperglycemic (p<0.015). The use of glucocorticoids
and mechanical ventilation were not correlated with the
achievement of target glycemic control. Mean percentage
of BG measurements at target in patient-days on no insulin
or insulin only as needed was 88.4% suggesting their lack
of need for insulin. Discussion: Our data revealed that the overall prevalence of optimal glycemic control in hospitalized patients
receiving TF was high. However, this was mainly noted
in those who were on intravenous insulin drips or those
whose hyperglycemia was so mild that they either did not
require insulin or were only treated with minimal insulin
as needed. Patients who required insulin more consistently but were on subcutaneous insulin glargine achieved
less optimal glycemic control. Since the use of insulin by
intravenous drips may not be practical outside of intensive
care units, more studies to determine the optimal mode(s)
of subcutaneous insulin deliver are warranted. Our study
also showed that a previous history of DM or renal failure were associated with achieving less optimal glycemic
control.
Conclusion: Prevalence of optimal glycemic control
in patients on artificial enteral feeding in our entire study
cohort was high at 83.9%, and was better in those without
an antecedent history of diabetes and with normal renal
function. The use of continuous intravenous insulin administration was superior to subcutaneous insulin glargine.
Abstract #225
CONTINUOUS GLUCOSE MONITORING SYSTEM
AS AN INDICATOR OF GRAFT DYSFUNCTION IN
ISLET TRANSPLANTATION
Lisa Gorn, DO, Raquel N. Faradji, MD,
Shari Messinger, PhD, Kathy Monroy MD,
David A. Baidal MD, Tatiana Froud MD,
Camillo Ricordi MD, and Rodolfo Alejandro MD
Objective: To evaluate the effects of islet transplant
(ITx) on glycemic control via the continuous glucose monitoring system (CGMS) and its utility as an indicator of
graft dysfunction (GD).
Methods: Glycemic control was assessed in 25 subjects with type 1 diabetes:12 underwent ITx and 13 were
controls. Weight, BMI, insulin use, HbA1C, 90min glucose
after a mixed meal tolerance test, and fasting C-peptide/
glucose ratio (CPGR) were followed. Mean interstitial
glucose (MG), standard deviation (SD), glucose variability (GV), and percent time in hyperglycemia (%GT>140
mg/dl), hypoglycemia (%GT <54 mg/dl), and normoglycemia (%GT 54-140 mg/dl) were measured in 72 hr periods
from CGMS in the controls at baseline and ITx group at
3,6,9,12,15, and 18 months after ITx, and analyzed as indicators of GD. Linear mixed model regression assessed if
CGMS findings at the time of GD were significantly different than those at preceding timepoints.
Results: MG and GV were significantly lower in the
ITx group at all times except 3 and 15 months. Compared
to controls, percent time in hypoglycemia was significantly
lower in the ITx group at all times. There was no association between insulin use and time in hypoglycemia in
the ITx group. Time in normoglycemia was increased in
the ITx group at all times except 15 months. Decreased
time in hyperglycemia was significant at 6,9,12, and 18
months in the ITx group. HbA1C, 90min glucose, and
CPGR were significantly improved at all times after ITx.
MG, SD, GV, and %GT>140 mg/dl were indicators of GD,
and increased by 19.4 mg/dl,15.1 mg/dl,19.8 mg/dl, and
19.4% respectively when GD occurred compared to preceding timepoints.
Discussion: CGMS is an indicator of GD with changes
in patterns of glycemia found within 3 months of GD. Use
of real time CGMS should be considered for earlier detection and prediction of GD.
– 28 –
glycemic control (1,5-AG was recently included in the new
International Diabetes Federation guideline for management of postmeal glucose as an emerging technology to
measure PPG). Data from this retrospective analysis indicate that 1,5-AG revealed underlying treatment effects on
postprandial glucose control which were not readily apparent by A1C measurements, confirming the role of 1,5-AG
as a PPG marker.
Conclusion: 1,5-AG may be a useful complement to
A1C to reflect PPG in diabetic patients treated with agents
that target PPG.
Conclusions: Benefits up to 18 months post-ITx were
apparent, regardless of insulin independence, including
decrease in hypoglycemia, maintenance of glucose stability, and increase in normoglycemia. MG, SD, GV, and
%GT>140mg/dl were indicators of GD.
Abstract #226
THE USE OF 1,5-ANHYDROGLUCITOL
(GLYCOMARK) TO MONITOR NEW CLASSES
OF THERAPIES FOR MANAGING POSTMEAL
GLUCOSE IN PATIENTS WITH DIABETES
Abstract #227
Steven Wittlin, MD, Hirotaka Ishibashi, MS,
Eric Button, MS, MBA, Scott Foster, PhD,
Toshikazu Yamanouchi, MD, and Antonio Ceriello, MD
LONG TERM INSULIN INDEPENDENCE AND
IMPROVEMENT OF FIRST PHASE INSULIN
RELEASE AFTER SUPPLEMENTAL ISLET
INFUSION UNDER EXENATIDE TREATMENT IN
SUBJECTS WITH ISLET GRAFT DYSFUNCTION
Objective: To evaluate the use of 1,5-anhydroglucitol
(1,5-AG) to monitor new therapies for PPG.
Methods: Retrospective analysis of clinical drug studies utilizing 1,5-AG.
Results: 1,5-AG has recently been used in clinical
studies with several new classes of therapies for managing postmeal glucose (amylin analogs, glucagons-like peptide-1 [GLP-1] derivatives. dipeptidyl peptidase-4 [DPP4] inhibitors, alpha-glucosidase inhibitors). In the case of
sitagliptin phosphate, a DPP-4 inhibitor, 1,5-AG increased
by 4.45 ug/ml in the sitagliptin group (n=75) compared
with a decrease of 0.33 ug/ml in the placebo (n=76), for a
between-treatment group difference in 1,5-AG of 4.78 ug/
ml (95% CI: 3.76, 5.80; p<0.001) over a 12-week period
and consistent with improvement in PPG control. In a
study with miglitol, an alpha-glucosidase inhibitor, comparing a placebo group (n=84) to a miglitol-treated group
(n=158) over 12 weeks,1,5-AG mean levels did not change
significantly from baseline (4.62 ug/ml) to study end in
the placebo group. In the miglitol-treated group, 1,5-AG
increased from 4.79 ug/ml to 10.46 ug/ml from baseline to
study end, consistent with changes in PPG control. After
4 weeks, the mean 1,5-AG was 9.15 (p<0.001 compared to
baseline levels). Discussion: A1C measurement is a critical component of diabetes management; however, a key limitation of
A1C as a measure of glycemia is the lack of timeliness -- it
does not detect underlying blood glucose excursion levels
in moderately controlled diabetic patients (A1C < 8) as it
is a measurement of mean glucose levels over the longerterm. In contrast, the 1,5-anhydroglucitol (1,5-AG) assay
responds rapidly and sensitively to serum glucose levels
above the renal threshold and has been demonstrated as a
valid marker of postprandial hyperglycemia and short-term
Raquel Noemí Faradji, MD, Thipaporn Tharavanij,
Tatiana Froud, Shari Messinger, Kathy Monroy,
Antonello Pileggi, David A. Baidal, Davide Mineo,
Cristiane Leitao, Pablo Cure, Aleida Saenz,
Andrea Curry, Gennaro Selvaggi, Camillo Ricordi, and
Rodolfo Alejandro
Objective: To assess the effects of Exenatide (EXN)
on supplemental islet infusions (SI).
Methods: SI was performed in 9 subjects with graft
dysfunction after previous islet transplantation under
Edmonton-like protocol. Five underwent SI in 2003 without exenatide (SI-C group) and four received SI under
EXN in 2006 (SI-EXN group). Clinical and metabolic profiles were assessed every 3 months up to 18 months. The
analysis was done by 2-way ANOVA and t-test.
Results: The SI-EXN group had been on this drug
for median time of 171 days (range 155-197) pre-SI without achieving insulin independence (IND). Both groups
had similar baseline characteristics except duration of
graft dysfunction before SI which was longer in SI-EXN
group (664±83 vs 326±93, p=0.03). The SI-C and SI-EXN
groups received a mean of 8713±4714 and 5613±970 IEQ/
kg, respectively (NS). Only 3/5 of SI-C patients achieved
IND for 303, 403 and >1670 days after SI. All subjects in
the SI-EXN group achieved IND for more than 443, 621,
641, 654 days. At 18 months IND was 20% in SI-C group
and 100% in SI-EXN group. Comparing pre and post-SI,
only the SI-EXN group had significantly lower A1C at 3, 6
and 12 months (6.7±0.2, 5.5±0.1, 6.1±0.2, and 6.2±0.8%,
respectively). Mixed meal stimulation index (AUC C– 29 –
within 2½ hours starting at 10 p.m. The CGMS tracing (see
figure) demonstrated that the cumulative effect of these late
night boluses on day #1 lowered his subcutaneous glucose
from 200 at midnight to <40 mg/dL shortly after 2 a.m. on
day #2. When his parents called EMS his measured CGMS
glucose was ~10 mg/dl. Since the patient was otherwise
healthy, we concluded that this case represents hypoglycemic death.
Discussion: The patient had a long standing history
that could be characterized as “zealous perfectionism” to
achieve tight glycemic control. Strenuous evening physical activity predisposed him to nocturnal hypoglycemia. His recent episodes of severe hypoglycemia lowered his
threshold for counterregulation. The Dead in Bed Syndrome
describes a scenario where otherwise healthy young persons with T1DM are found dead in the morning. Autopsies
are unrevealing and the post mortem diagnosis of hypoglycemia is problematic. This syndrome may account for
6% of deaths of patients under age 40 with T1DM. The
literature suggests that death is probably caused by a cardiac arrhythmia. Strategies to prevent this outcome include
increasing glucose targets to raise the threshold for hypoglycemic counterregulation and the use of real-time subcutaneous glucose sensors with alarms for hypoglycemia.
Conclusion: This case may be the first time CGMS has
recorded hypoglycemia resulting in death. Unfortunately
the device he wore did not have a real-time glucose display
or alarms for hypoglycemia which may have prevented this
tragic outcome.
peptide×100/ AUC glucose) was increased at 3, 6, 9 and
12 months (p<0.05). Intravenous glucose tolerance test
(IVGTT) showed significantly increased acute insulin
and C-peptide responses to glucose at 3, 6, 9, 15 and 18
months in SI-EXN group (p<0.05). No significant differences of these parameters were seen pre and post-SI in the
SI-C group. At 18 months post-SI, body weight was not
different from baseline in both groups. No serious adverse
events from EXN treatment were observed.
Discussion: Comparing with conventional SI, adjuvant EXN treatment had better metabolic profiles and longer IND. IVGTT indicated the improvement in first phase
insulin release (FPIR) followed by better glucose control.
This study confirmed better islet function in SI-EXN group.
These changes may be due to prevention of apoptosis and
reduction of islet stressors (decreased glucagon, glucose)
leading to better engraftment.
Conclusion: Supplemental islet infusions under EXN
treatment appear to be beneficial as there is improvement
FPIR and long term graft function that leads to long term
insulin independence.
Abstract #228
HYPOGLYCEMIC DEATH INCIDENTALLY
RECORDED BY CGMS
Robert Jay Tanenberg, MD, FACP,
Christopher Alan Newton, and A.J. Drake III, MD, FACE
Objective: Demonstrate the current and potential uses
of a continuous subcutaneous glucose sensor to detect
potentially fatal nocturnal hypoglycemia T1DM patients
Case Presentation: A 23 year old man with T1DM
for 12 years had recently begun insulin pump therapy to
improve his glycemic control and reduce frequent hypoglycemic reactions. In June 2005, his family called the
EMS for severe hypoglycemia associated with a seizure.
He was treated in the emergency department and released.
His A1C was 6.4% and his nighttime basal rates were
adjusted to prevent further episodes. Despite this change,
he had another severe hypoglycemic episode the next week
and a continuous glucose monitoring system (CGMS,
Medtronic DiabetesÔ) was ordered. Less than 24 hours
after the patient was placed on the monitor, he was found
unconscious by his family at 9 a.m. Unfortunately, with
this episode he did not respond to D50 administered by
EMS and was pronounced dead on arrival in the ED. The
insulin pump and CGMS were removed by the diabetes
nurse. Downloaded data showed the patient worked out
after supper, but took 5 insulin boluses totaling 7.35 units
Abstract #229
EFFECT OF RESVERATROL, A COMPONENT
OF RED WINE, ON GLUT1-MEDIATED
GLUCOSE TRANSPORT
Kimberly Martin, MD, Ming Jing, MD, PhD, and
Faramarz Ismail-Beigi, MD, PhD
Objective: To examine the effect of resveratrol on
Glut1-mediated glucose transport.
Methods: Clone 9 cells, C2C12 cells and human erythrocytes were employed. Resveratrol and 5’-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR)
were added to the culture medium. Resveratrol’s effect on
phosphorylation of AMPK was assayed by Western blot. Glucose transport was measured by cytochalasin B (CB)inhibitable 3-OMG uptake. The effect of resveratrol on
CB binding to erythrocyte ghosts was determined in the
presence and absence of glucose.
– 30 –
Results: Incubation of Clone 9 cells (a rat liver cell
line expressing only the Glut1 isoform) with resveratrol
(0.1 to 500 mM for 1 hr) revealed that AMPK phosphorylation is slightly inhibited at low concentrations and stimulated (1.5 to 2.2-fold) at concentrations of resveratrol above
100 mM. However, the addition of resveratrol to the same
cells markedly inhibited glucose transport (EC50 of ~25
mM), regardless of whether AMPK phosphorylation was
augmented or suppressed. Glucose transport was inhibited while AMPK phosphorylation was stimulated within
1 minute after exposure of cells to 100 mM resveratrol. Addition of 2 mM AICAR, a known stimulator of AMPK
and glucose transport in these and in other cells, to resveratrol-treated Clone 9 cells stimulated AMPK phosphorylation but had no effect on the suppressed rate of glucose
transport. The effect of resveratrol on activation of AMPK
and inhibition of glucose transport was also observed in
C2C12 cells. Addition of resveratrol to human erythrocyte ghosts, which exclusively express Glut1, completely
blocked the glucose displaceable binding of cytochalasin B
to erythrocyte membranes.
Discussion: Resveratrol is a naturally occurring polyphenol found in grapes that has been reported to have cardioprotective, anti-inflammatory, and anticancer properties. More recently, investigations have demonstrated that this
compound stimulates AMPK activity and appears to have
anti-diabetic capabilities through the activation of Glut4mediated glucose transport in skeletal muscle. Our results,
however, demonstrate that resveratrol inhibits Glut1-mediated transport. Further studies are needed to verify these
results using in vivo models.
Conclusions: Our findings indicate that resveratrol
suppresses Glut1-mediated glucose transport by presumably acting directly to inhibit the Glut1 glucose transporter. Given that Glut1 transporters are highly expressed in brain,
retina and placenta, we tentatively recommend that this
agent be used with caution in humans. This work was
supported by the Metabolism Training Program (T32 DK007319) and by DK-061994. – 31 –
Abstract #230
THE GLUCOSE-LOWERING EFFECTS OF
COLESEVELAM HCL IN PATIENTS WITH
TYPE 2 DIABETES MELLITUS INADEQUATELY
CONTROLLED WITH METFORMIN-BASED
THERAPY: A POOLED ANALYSIS
Harold Bays, MD, Kenneth Truitt, MD, and
Michael Jones, PhD
Objective: Colesevelam HCl (COL) is indicated as an
adjunct to diet and exercise for improving glycemic control in adults with type 2 diabetes mellitus (T2DM). This
pooled analysis evaluated the glucose-lowering efficacy of
COL in T2DM patients (pts) inadequately controlled (A1C
7.5%-9.5%) with metformin (MET). Pts were derived
from 3 randomized, double-blind studies wherein COL
was added to MET, insulin, or sulfonylurea, respectively,
administered alone or combined with other oral anti-diabetes agents (OAD). MET was the primary OAD in the
MET study (26 wks) and constituted a concomitant OAD
in the insulin (16 wks) and sulfonylurea study (26 wks). In
these separate studies, the addition of COL reduced A1C
by ‑0.54% (MET), ‑0.50% (insulin), or ‑0.54% (sulfonylurea) vs placebo (PL) by study end (P<0.001 for all).
Methods: In this pooled analysis of the 3 primary
studies, 696 MET pts were assigned COL 3.75 g/day
(n=355) or PL (n=341), in addition to their other anti-diabetes agent(s). Efficacy endpoints in this analysis included
change from baseline in A1C and fasting plasma glucose
(FPG). Additional analyses included the proportion of pts
who achieved a reduction in A1C≥0.7% or a reduction in
FPG≥30 mg/dL from baseline to study end. Lipids and
weight were not analyzed in this pooled analysis. However,
LDL-C was significantly reduced in each of the primary
studies (P<0.001 vs PL). Weight did not significantly
change with COL in any of the primary studies.
Results: Demographic and baseline characteristics
(age, weight, BMI, A1C, and FPG) were comparable
between the COL and PL groups. By study end, A1C was
reduced by ‑0.42% in the COL group while A1C increased
by 0.08% in the PL group, resulting in a placebo-corrected
change from baseline of ‑0.50% (P<0.001). FPG decreased
by ‑4.6 mg/dL in the COL group and increased by 11.1 mg/
dL in the PL group, resulting in a treatment difference of
‑15.7 mg/dL (P<0.001). Furthermore, the addition of COL
to MET therapy resulted in a significantly higher proportion of pts achieving a reduction in A1C≥0.7% (38.3% vs
19.4%; P<0.001) or a reduction in FPG≥30 mg/dL (30.1%
vs 22.0%; P=0.015) from baseline to endpoint vs PL.
Conclusion: COL administered to T2DM pts with
inadequately controlled blood glucose on MET-based therapy significantly improved glycemic control.
Conclusion: Kidney function remained stable after
islet transplantation alone and it continues to be a safe
procedure for treatment of unstable type 1 DM as long as
aggressive treatment of conventional risk factors for diabetic nephropathy is provided.
Abstract #231
UNCHANGED RENAL FUNCTION AFTER
CLINICAL ISLET TRANSPLANTATION
Abstract #232
ACANTHOSIS NIGRICANS IN A SUB-SET OF
TYPE 2 DIABETIC PATIENTS IN AN URBAN
HOSPITAL IN NIGERIA
Cristiane Bauermann Leitao, MD, Pablo Cure,
Shari Messinger, Antonello Pileggi, Oliver Lenz,
Tatiana Froud, Raquel N. Faradji, Gennaro Selvaggi,
Warren Kupin, David Baidal, Thipaporn Tharavanij,
Davide Mineo, Karina Bernetti, Eva Herrada,
Camillo Ricordi, and Rodolfo Alejandro
Akinyele Taofiq Akinlade, MBBS, and
Anthonia Ogbera, MBBS, FACE
Objective: This study is to determine the prevalence of
Acanthosis (AN) and the associated features in our patients
with Type 2 diabetes Mellitus (DM)
Methods: 171consecutive patients drawn from our
Diabetes center were examined for AN and other essential data were obtained through interviewer administered
questionnaires. Primary endpoints were the prevalence of
Acanthosis Nigricans and the accompanying type 2 DM
risk factors
Results and Discussion: The mean age (SD) of the
study subjects was 58 (12) years with a range of 21-85
years. A significant proportion of the patients-70% were
obese. Mean BMI of the study was 28.4kg/m2 with mean
body weight being 74kg (SD 15). The male-female ratio of
the subjects was 1:2. The mean fasting blood sugar (FBS)
of the study was 162.64mg/dl (SD 76.42). The prevalence
of AN in this study was 24% and three-quarters of these
subjects with AN were women. A family history of DM
was seen in 26% of those with AN while 74 % had no family history. This difference was statistically significant (?=
7.9, p<0.01). Mean FBS of those with AN was 174.5mg/dl,
majority 33 (80.5%) of whom are on oral hypoglycemic
agents (OHA) and their mean FBS was 156.1mg/dl. This
is better than the 166.89mg/dl for the 6 (14.6%) patients
with AN but on either insulin alone (9.8%) or both insulin/OHA (4.9%). More than half of patients (53.7%) with
AN are obese while 31.7% are overweight. A small proportion (14.6%) had a normal BMI despite having AN
but no underweight patient had AN. Those with AN have
more of generalized and centripetal obesity as compared
to those without AN and was statistically significant (?=
9.95, p<0.04). Of the obese patients with AN, 18 (81.8%)
are also hypertensive, representing a significant clustering
of the associated features of insulin resistance in our DM
patients.
Objective: To determine the clinical course of kidney
function after islet transplantation and identify clinical,
laboratory and immunosuppressive factors associated.
Methods: A retrospective cohort study was conducted
in 35 subjects submitted to pancreatic islet transplantation
as treatment for unstable type 1 diabetes mellitus (DM).
Demographic, anthropometrical and laboratory data, as
well as immunosuppressive and anti-hypertensive therapy
were recorded. Kidney function was assessed by serum
creatinine and albuminuria and estimated glomerular filtration rate (eGFR) was calculated by MDRD formula.
Results: Overall eGFR remained stable during follow-up. Even subjects with low eGFR and/or microalbuminuria (n=10) at baseline maintained stable values posttransplantation
(61.13±3.25 vs. 63.32±4.36 ml/min/1.73
2
m , P=0.500). Six (20%) normoalbimunuric subjects progressed to microalbuminuria, but sustained macroalbuminuria was not detected. A1c was normal in all patients after
transplant (pre: 7.45±0.11 vs. post: 6.09±0.09%, P <0.001).
A mild increment in LDL-cholesterol levels after transplantation was found (pre: 93.3±3.3 vs. post: 101.6±2.3
mg/dl, P=0.008). BP remained stable during the follow-up
(pre: 121.7±2.3/71.9±1.6 vs. 119.3 ± 1.6/71.5±1.0 mm Hg,
P >0.05), at the expense of increasing the number of antihypertension medications/patient (0.34±0.48 vs. 0.71±0.86,
P=0.002). After multivariate adjustments, age was the only
risk factor for low eGFR (OR=1.78, 95%CI 1.22–2.61).
Similarly, LDL-cholesterol (OR=2.90, 95%CI 1.37–6.12)
and previous microalbuminuria (OR=6.42, 95%CI 1.42–
29.11) were risk factors for macroalbuminuria development. Tacrolimus was a protective factor against macroalbuminuria (OR=0.12, 95%CI 0.06-0.26).
Discussion: The better kidney prognosis found could
be attributed to healthier kidney status at baseline associated with prompt treatment of renal side effects.
– 32 –
Conclusion: The prevalence of AN in DM in this
report is 24%. Its presence is related to generalized and
centripetal obesity, a family history of DM and being
female. Cluster of these factors points to the likely presence of insulin resistance. AN occurring with obesity and
hypertension are prominent features of our type 2 DM
patients. Majority of them are on OHA and have poor glycemic control like other patients with AN on insulin or
insulin/OHA combination; putting them at greater risk for
atherosclerotic cardiovascular disease.
group (7.52 ±0.30 vs. 7.53 ±0.32 [mean ± sem]; p=0.98).
However, when we stratified the hemoglobin A1C categorically adjusting for age, patients in the NSTEMI group
were 3.6 times more likely to have an A1C over 8.0% compared to control patients (p=0.03). We did find a significant
inverse correlation between HDL-C and peak troponin in a
univariate analysis. Conclusion: We found no difference in
the last measured mean A1C in diabetic patients presenting
to the intensive care unit with NSTEMI compared to other
intensive care unit diabetic patients without NSTEMI.
However, when A1C was categorized into those with
‘controlled’ versus ‘uncontrolled’ (cutoff value of 8%),
NSTEMI patients were over three times more likely to
have a high (over 8) hemoglobin A1C value when adjusted
for age. HDL-C was inversely related to the peak troponin
when examined individually.
Discussion: High Hemoglobin A1C as a risk factor
for Acute NSTEMI can be further investigated in large
scale prospective studies. Hyperglycemia as a potential
cause for direct myocardial injury has been studied in animal models and human cell culture lines. Providers should
follow established guidelines for A1C monitoring and A1C targets for therapy. Thiozolidinediones are a class
of drugs which were approved as they improved glucose
control. Recent studies have highlighted their negative
cardiovascular effects. This study raises the question; Can
we really consider blood sugar control and cardiovascular events as mutually exclusive ?There are however some
significant limitations to our study. Our study does not
distinguish between Type 1 and Type 2 Diabetes Mellitus.
Our study does not differentiate the subjects with respect
to the duration of diabetes. The last measured A1C was not
categorized based on the time lag between measurement
and the event. Our study was underpowered in the multiple
linear regression analysis. There were significant number
of persons with renal failure who may have influenced both
the peak troponin as well as the A1C levels.
Conclusion: We found no difference in the last measured mean A1C in diabetic patients presenting to the intensive care unit with NSTEMI compared to other intensive
care unit diabetic patients without NSTEMI. When A1C
was categorized into those with ‘controlled’ versus ‘uncontrolled’ (cutoff value of 8%), NSTEMI patients were over
three times more likely to have an uncontrolled hemoblogin
A1C value when adjusted for age. HDL-C was inverserly
related to the peak troponin when examined individually.
Abstract #233
IS THERE AN ASSOCIATION BETWEEN LAST
MEASURED GLYCATED HEMOGLOBIN (HbA1C)
AND ACUTE NON-ST SEGMENT ELEVATION
MYOCARDIAL INFARCTION IN DIABETIC
INDIVIDUALS?
Prasanna Santhanam, MBBS, Bruce Chertow, and
Todd W. Gress
Objective: Diabetes mellitus (DM) is an independent risk factor for the development of acute myocardial
infarction (AMI). Prior work has revealed an association
between the admission serum glucose and mortality in
patients with AMI. The purpose of the study was to examine if there existed some relationship between the last measured Hemoglobin A1C in the clinical setting (within six
months)and the acute coronary syndrome specifically Non
ST segment Elevation Myocardial Infarction (NSTEMI) in
persons with Diabetes Mellitus.
Methods: We identified 1128 patients admitted to our
intensive care unit between January 1, 2006 and June 30,
2007. Of these, 36 with NSTEMI were found to have a
measured A1C within the last 6 months and comprised our
case group. From the same time period, we selected 42 diabetic controls without NSTEMI admitted to our intensive
care unit with a measured A1C within the last 6 months.
The hemoglobin A1C was divided into those below 8%
(‘controlled’) and those at or above 8% (‘uncontrolled’).
We performed a multiple linear regression analysis simultaneously adjusting for potential confounding variables,
which included age, systolic blood pressure, diastolic
blood pressure, hemoglobin,HDL-Cholesterol, and LDLCholesterol levels.
Results: We found that the mean hemoglobin A1C
in the NSTEMI group was no different than the control
– 33 –
betes7. This study has a prospective component (with support of our local Diabetes Association) and has attempted
to look at the pattern of diabetes in Rivers State. Our study
confirms that diabetes is a health problem in Rivers State,
though rate (0.3%) is much lower than that reported in the
1997 national survey (3.03% Vs 2.2%). However the current study focused on overt diabetes. The few number of
diabetics from some LGAs is probably a reflection of the
awareness level and nearness to the study centres rather
than an actual magnitude of the disease.
The non-availability of facilities for chromosomal/
genetic studies in our environment may have resulted in
inclusion of more ‘Other specific type’ into the ‘Type 2’
category.
The diet of most of the patients consisted of one or
two bulky carbohydrate meals (derivatives of yam, cassava
and maize) eaten with vegetable soup and occasional meat
and fish. Some ate cereals such as beans, rice and bread.
The diet of the elites comprised in addition, animal protein.
No one admitted to more than occasional consumption of
alcohol, and usually on social occasions.
The proportion of type 2 subjects with chronic complications (neuropathy 56.3%; erectile dysfunction 36.3%,
nephropathy 9.2% and retinopathy 7.3%) at diagnoses
reflects the fact that Type 2 diabetes has an asymptomatic
pre-clinical phase which is not benign. This underscores
the need for primary prevention and population screening
to detect the disease early and institute therapy.
Hypertension and diabetes mellitus: Hypertension frequently co exists with diabetes, there is an increased prevalence of hypertension among diabetic patients but there
is also high propensity among hypertensive patients to
develop type-2 diabetes. When occurring together the two
disease entities appear to aggravate one another worsening both the diabetes and cardiovascular end points. Data
from UK Prospective Diabetes Study (UKPDS) revealed
that every 10mm.Hg reduction in the level of systolic BP is
associated with a nearly 12% lower incidence in myocardial infarction, down to a systolic BP level of <120mm.Hg. Progressive lower diastolic BP also reduces CV risk progressively. The Hypertension Optimal Treatment (HOT)
trial showed that number of major cardiovascular events
dropped in line with increasing astringent target diastolic
BP-target. These findings are reflected in the BP-target
for diabetic patients of < 130/80mm of Hg as now recommended by European Society of Hypertension, JNC7
report and American Diabetes Association.
Conclusion: Diabetes mellitus is a substantial health
problem in Rivers State, though crude prevalence (0.3%)
is much lower than that reported in the 1997 national survey (0.3% vs 2.2%) Type 2 diabetes has an asymptomatic
pre-clinical phase which is not benign, considering the pro-
Abstract #234
THE PATTERN OF DIABETES MELLITUS IN
RIVERS STATE, NIGERIA
Sunday Chinenye, MBBS, FWACP,
Doris Uchenna MBBS, FWACP, FMCP,
Chioma Unachukwu BSc, MBBS, FWACP, and
Anthonia Ogbera MBBS, MPH, FMCP
Objectives: To determine the types of diabetes mellitus seen in Rivers State. Ascertain the clinical and biochemical features of our newly diagnosed diabetics.
Methods: Cross-sectional study of people living with
diabetes attending our local diabetes association meetings, and diabetes clinic at the University of Port Harcourt
Teaching Hospital (UPTH) during the period Jan 2001 to
Dec 2005, were recruited with informed consent.
The subjects were old and new diabetics from the
settings above. Physical and biochemical examinations were undertaken to detect the main outcome variables viz: Demographic/ Anthropometrics of subjects,
Hypertension ( Taken as BP ≥140/90mmHg on at least
two different occasions), Neuropathy (Sensory, motor
and/or autonomic) diagnosed by established clinical criteria., Retinopathy (Checked for by fundoscopy, confirmed by an Ophthalmologist), Diabetes mellitus: Defined
as FPG ≥7.0mmol/L and/ or 2 Hour PG ≥11.1mmol/L,
Nephropathy: Frank proteinuria detected with Multistix
test strip or an albumin excretion rate >200µg/ min using
“Micral test” strip on an early morning urine sample was
regarded as demonstrating nephropathy.
Results: A total of 10,518 people living with diabetes
mellitus were seen during the period from the 23 local governments (LGAs) of Rivers State.
There were 5,350 females (50.9%) and 5,168 males
(49.1%) giving F:M ratio of 1.04: 1.
The majority of subjects were adults (93.9%) aged 20
years and above.
830 of the subjects were seen regularly and evaluated
for clinical / biochemical characteristics, modes of therapy and complications on initial presentation (see tables).
These comprised 25 type 1 diabetics (3.0%), 780 type 2
(94.0%), 10 (1.2%) ‘Other specific types” and 15 (1.8%)
with Gestational diabetics.
At diagnosis, the type 2 subjects (780) had the following complications viz: neuropathy 439 (56.3%), erectile dysfunction 283 (36.3%), nephropathy 72 (9.2%), and
retinopathy 57 (7.3%). Discussion: Previous reports on diabetes in our environment were retrospective hospital based studies which
dealt mainly with pattern of foot ulcer and childhood dia– 34 –
portion of new cases with established complications, thus
underscoring the need for primary prevention and population screening to detect the disease early and institute
therapy.
factors found in this study are similar to findings in other
parts of the world with high prevalence of GDM.
Conclusion: The prevalence of GDM among the
study group was 14%. The predominant risk factors for
GDM were multiparity, macrosomia, stillbirth, previous C/
S, glycosuria and hypertension. Most (83%) of the women
found to have GDM had risk factors for GDM.
Abstract #235
PREVALENCE AND RISK FACTORS FOR
GESTATIONAL DIABETES MELLITUS AMONG
NIGERIAN WOMEN
Abstract #236
Andrew Enemako Uloko, MD, Fabian Puepet, FMCP,
Christiana Ukoli, FMCP, and Patrick Daru, FWCOG
MOST NEWLY DIAGNOSED TYPE 2 DIABETES
MELLITUS SUBJECTS MEET INTERNATIONAL
DIABETES FEDERATION 2005 DEFINITION FOR
METABOLIC SYNDROME
Objective: To determine the prevalence of gestational
diabetes mellitus (GDM) and to assess the risk factors
associated with it.
Methods: In a cross sectional study spanning three
months, pregnant women from second trimester upwards
attending the antenatal clinics of the Jos University
Teaching Hospital (JUTH), Jos, Nigeria were consecutively recruited regardless of risk factors for diabetes
mellitus. Relevant bio-data and history of risk factors of
GDM were obtained from each participant via a structured
interviewer-administered questionnaire. Physical examination including anthropometric indices was carried out on
each subject. Urinalysis and a 2-hour 75g OGTT were performed. The WHO diagnostic criteria for GDM was used
to interpret the OGTT. Multivariate analysis using logistic
regression was applied to determine the independent risk
factors associated with GDM. p < 0.05 was considered to
be statistically significant.
Result: A total of 180 pregnant women with a mean
(SD) age of 28.16 (5.23) years, age range 20-45 years participated in the study. Mean (SD) gestational age was 33
(7) weeks. The prevalence of GDM based on the WHO
diagnostic criteria for GDM was 14%. Risk factors for
GDM were present in 83% of the women with GDM. The
predominant risk factors for GDM were multiparity, macrosomia, stillbirth, previous caesarean section, glycosuria
and hypertension. The independent risk factors associated
with GDM were macrosomia [OR = 3.20, (95% CI 1.005
– 9.773) p = 0.04], C/S [OR = 12.42, (95% CI = 2.9252.77) p = 0.001], and systemic hypertension [OR = 12.10,
(95% CI =2.93-49.92) p = 0.001].
Discussion: A GDM prevalence of 14% found in
this study is slightly higher compared to earlier reports of
11.6% by Olarinoye et al in south-western Nigeria, though
the diagnostic methods are different. This prevalence may
also mirror the rising prevalence of diabetes in Nigeria
(2.2% in 1997, 5% projected prevalence in 2005). The risk
Ali Asghar Jawa, MD, MPH, Tahir Rasool,
Muhammad Abu Zafar, Prof., Mumtaz Hasan, MD (S.I.),
Jawad Zaheer, MD, Ghazanfar Jawa, and Syed Ali Imran
Objective: To assess the prevalence of Metabolic
Syndrome amongst newly diagnosed subjects with type
2 diabetes mellitus using the International Diabetes
Federation 2005 definition.
Methods: According to International Diabetes
Federation 2005 definition, metabolic syndrome is defined
as ethnic-specific central obesity (Waist circumference
> 80 cms in females or > 90 cms in males for southeast
Asians) and presence of 2 out of the following 4 risk factors: Systolic Blood Pressure >130 mm Hg or Diastolic
Blood Pressure > 85 mm Hg or known hypertension,
Fasting Blood Glucose > 100 mg/dL or known type 2 diabetes mellitus, Serum Triglycerides > 150 mg/dL or on
lipid lowering medications, or HDL < 50 in females or <
40 in males. We performed a retrospective chart review of
all newly diagnosed type 2 diabetes subjects presenting to
the Hamza Foundation Diabetes Centre from January 1December 31, 2005. 89 new cases presented for new onset
diabetes management. Medical records were reviewed
and baseline data including Height, Weight, BMI, Waist
Circumference, HDL-Cholesterol, Serum triglycerides,
Systolic and Diastolic Blood pressure at the time of presentation were tabulated. All data was analyzed using SPSS
13.0
Results: 64/89 subjects with newly diagnosed type 2
Diabetes Mellitus met International Diabetes Federation
2005 Criteria for Metabolic Syndrome. 50/64 subjects
were female. Mean age was 46 years (30-70), mean waist
circumference was 98 cms (80-120) and mean BMI was
29 (20-40). Biochemical profile of these subjects showed
a mean A1C of 8.8% (5-16), mean HDL-Cholesterol of 39
mg/dL (25-59) and mean Triglycerides of 281 (85-1487).
– 35 –
Discussion: One rare form of fungal sinusitis is
chronic invasive sinusitis that usually takes weeks to
months to develop. Patients usually have visual changes
not associated with fever, chills, nasal congestion or rhinorrhea. Few cases have been reported, most of them have
type 2 diabetes which is relatively well-controlled. They
usually present with orbital apex syndrome characterized
by ptosis, periorbital edema and cranial nerve III, IV and
VI deficits as seen in this patient.
Conclusion: This is the first case of chronic invasive
fungal sinusitis in type 1B diabetes that has been reported
which responded well to treatment. This infection usually
has an indolent course but a poor prognosis. A combination
of medical and surgical treatment is usually required as in
this case.
The Systolic Blood Pressure at the time of diagnosis was
130 mmHg (100-170) and Diastolic Blood Pressure was 84
mmHg (70-100).
Conclusions: The results of this study indicate that
almost 3/4th of newly diagnosed newly diagnosed type 2
diabetics have Metabolic Syndrome as defined by the new
IDF definition. This finding underscores a great need for
earlier detection and treatment of metabolic syndrome
before clinical diabetes develops.
Abstract #237
CHRONIC INVASIVE FUNGAL SINUSITIS IN A
28 YEAR-OLD WITH TYPE 1B DIABETES
Juan Carlos Varon, MD, and Alina Khan Ronal Goldberg
Abstract #238
Objective: To report an unusual case of chronic
invasive fungal sinusitis in a young woman with type 1B
diabetes.
Case presentation: A 28 year old non-obese Asian
woman with type 1 diabetes Mellitus presented to the hospital complaining of progressive right eye pain and frontal
headaches, without fever or chills, as well as diplopia for
approximately one month. The patient was diagnosed with
type 1 diabetes 7 years prior to presentation when she presented with diabetic ketoacidosis. Since then, she had been
on insulin treatment and presented with diabetic ketoacidosis on 2 occasions after stopping insulin for 2-3 months. The
absence of islet cell antibodies, GAD54 autoantibodies and
a low C-peptide level of 0.4 pm/ml with plasma glucose
of 230 mg/dl, confirmed a diagnosis of Type 1B diabetes.
Before presenting to the hospital, she had discontinued her
insulin therapy for 6-7 months but continued to monitor
her diabetes at home and her finger sticks were about 200
mg/dl. On admission, her blood glucose was 660 mg/dl,
but without features of diabetic ketoacidosis. Notable on
physical examination were the presence of right sided ptosis and cranial nerve III, IV and VI paralysis. A CT Scan of
the head and sinuses revealed bilateral sinusitis with bony
destruction, highly suggestive of a fungal infection. The
patient was then started on empiric broad spectrum antibiotics as well as antifungals which may have contributed
to the fact that the culture results were negative. She subsequently underwent endoscopic bilateral ethmoidectomy,
sphenoidectomy and orbital exploration. The histology of
the sinus and bone showed both acute and chronic inflammation as well as dichotomously branching septate hyphae
at 45 o angles which is characteristic of Aspergillus infection. Post-operatively the patient was started on high-dose
liposomal amphotericin-B and oral vorizonazole, with
good response.
INPATIENT HYPERGLYCEMIA MANAGEMENT
AND OUTCOMES
Megan Elizabeth Mcgarvey, MD, Maida Soghikian, MD,
and James McCallum, MD
Objective: Despite the large body of evidence linking hyperglycemia with poor hospital outcomes, there is
ongoing debate about the value of achieving glycemic control targets in the non-ICU setting. We sought to evaluate
glycemic control and outcomes for patients hospitalized in
a non-critical care setting prior to the institution of a basal/
bolus subcutaneous insulin protocol.
Methods: We conducted a retrospective review of all
patients admitted in a one year period to non-critical care
wards. ICD-9 codes were used to identify diabetic and nondiabetic patients at the time of admission, track inpatient
complications, length of stay, total costs of stay, discharge
destination, and mortality rates. Recorded finger-stick glucoses (FSG) were evaluated. All data was subjected to statistical review using both chi square and two-sided T tests.
Results: Fewer patients with diabetes were admitted to the hospital in comparison to non-diabetic patients
(3,021 diabetic vs.13,268 non-diabetic admissions).
Diabetic patients were more likely to be readmitted than
the non-diabetic patients (29% vs. 24%, p<0.0001). 24%
of patients admitted with diabetes had a pre-admission
HbA1C greater than 7%. There was a significantly higher
percentage of the diabetic patients admitted with a diagnosis of infection (24% vs. 16%, p<0.0001) and of cardiovascular complications (19% vs. 9%, p<0.0001). Only 40% of
diabetic inpatients’ FSG values were within the American
Diabetes Association’s (ADA) recommended goal of 70139 mg/dL, while 57% of obtained values were in the
– 36 –
hyperglycemic range and 3% were in the hypoglycemic
range. When compared to the non-diabetic patients, we
found that patients with diabetes more often developed
infection (9.5% vs. 4.5%, p= 0.005) and renal complications (9.1% vs. 5.9%, p=0.05) during their hospitalization.
Fewer diabetics were discharged directly to home (69%
vs. 72%, p<0.0001). Diabetic patients more often were dis
charged home with home health care (15% vs. 13%, p =
0.012). 15% of diabetics vs.12% of non-diabetics were discharged to a skilled nursing facility (p=0.012). There was
no significant difference in inpatient mortality between the
two groups. Patients with diabetes stayed on average a half
a day longer and incurred approximately $1300 more in
hospital cost.
Discussion: Intervention with a standardized insulin protocol may improve glycemic control, and improve
overall patient outcomes.
Conclusion: Our institution was poorly compliant
with ADA guidelines. Compared to non-diabetics, our diabetic patients had poorer outcomes, longer length of stays
and incurred higher costs.
the outpatient A1Cs was 7.778, and the mean inpatient A1C
was 7.711, with a difference of 0.067 (p=0.91). Correlation
of mean outpatient and inpatient A1Cs was 0.68 (p<0.001).
124 (56%) of the admission A1Cs remained in the same
category as the mean associated outpatient A1C, 49 (22%)
dropped to a lower category after admission, and 47 (21%)
rose to a higher category (p<0.01).
Discussion: Although A1Cs have been used to assess
mean glucose levels over three month intervals, A1C is a
time-weighted measure of glycemic control, most influenced by mean blood glucose during the previous 4-5
weeks. We compared admission A1Cs with prior stable
outpatient A1Cs to determine if potential hyperglycemia
from illness in the weeks prior to admission significantly
raised the admission A1C. A1Cs from 60 days prior to
admission were excluded since the inpatient A1C would
assess glycemia over this time period.
Conclusions: Inpatient A1Cs obtained during one
week after hospital admission did not significantly change
from mean stable outpatient A1Cs from the previous year.
Admission inpatient A1Cs may be an accurate indicator
of stable outpatient glycemic control in this population of
patients. Further studies with greater power are needed to
determine if the slight decrease in the mean A1C upon hospital admission is significant.
Abstract #239
THE EVALUATION OF HEMOGLOBIN A1C IN
STABLE DIABETICS PRE AND POST ADMISSION
Abstract #240
Aysha Emily Inankur, MD, and Brian Burke, MD, FACP
EXENATIDE LEADS TO REDUCTION IN LIVER
ENZYMES IN DIABETICS INDEPENDENT OF
WEIGHT LOSS
Objective: To examine the relationship between A1Cs
measured upon hospital admission and stable outpatient
A1Cs measured during the year prior to admission in subjects with diabetes mellitus (DM).
Methods: Medical records of patients with DM admitted onto medical and surgical wards of the Dayton, Ohio VA
Hospital from October, 2003 through October 2007 were
reviewed. Admission A1Cs were included if they were
preceded by two stable outpatient A1Cs. Stable outpatient
A1Cs differed <1.0 and were obtained within a 10 month
period <12 months and >60 days prior to admission.1
A1C levels were standardized by the Diabetes Control and
Complications Trial reference method. Admission A1Cs
were compared to the mean of two prior outpatient A1Cs by
the pared t-test. Outpatient and inpatient values were categorized as <6.00%, 6.00-6.99%, 7.00-7.99%, and ≥8.00%.
Categories were analyzed by the Pearson chi-square test.
Results: During the period of review, 18,908 admissions occurred to medical and surgical wards. Of these
admissions, 6,379 involved a prior diagnosis of DM type 1
or 2. Of this group, 1,922 had an inpatient A1C ≤7 days of
admission. 220 of these inpatient A1Cs were preceded by
≥2 stable outpatient A1Cs as defined above. The mean of
Deepti Bulchandani, MD, Jagdish S Nachnani, MD,
Crystal Eaton, LPN, and Mitchell Hamburg, MD, FACE
Objective: Exenatide is a peptide receptor of the GLP1(Glucagon like peptide 1) receptor which promotes insulin secretion. Raised liver enzymes in diabetics has been
postulated to be due to Non alcoholic fatty liver disease
(NAFLD) which is one of the commonest liver diseases
and has been associated with Type 2 diabetes mellitus(DM)
and insulin resistance. Exenatide has been shown to
reverse hepatic steatosis in the animal model of fatty liver.
However, there have been no studies looking at the association of liver enzymes with the use of exenatide.
Methods: From January 2007 till date, 29 eligible
patients who had completed exetanide for a period of one
year were included in our study. The patients were continuing their sulfonylurea/metformin treatment per their treating endocrinologist. Demographic, anthropometric and
laboratory were retrospectively collected. Paired t test and
Pearson’s correlation coefficient was used for comparison.
– 37 –
A two tailed p value of 0.05 was considered statistically
significant.
Results: There were 29 patients in our study cohort.
The mean age (+/- standard deviation) of the patients was
55.5(8.1) years. 59% of the patients were males. The mean
weight, HgBA1C, AST and ALT was 239 +/- 51 lbs, 8.2
+/- 1.3%, 31.3 +/- 15.6 units/L and 37.5 +/- 16.0 units/L
respectively prior to starting exetanide therapy. 12/29
patients had either AST or ALT > 35 units/L. The mean
decrease in weight at one year was 10. 8 lbs (p=0.005)
and the mean decrease in HgBA1C was 0.7(p=0.001).
The mean decrease at one year in AST was 6.5 units/L
(p=0.04) and ALT was 11.9 units/L (p=0.001) respectively.
There was no correlation with reduction in AST(p=0.51) or
ALT(p=0.50)with change in weight. Out of the 12 patients
with raised liver enzymes, in 7 patients the liver enzymes
returned back to normal.
Discussion: NAFLD has emerged as the most common chronic liver disease in United States. Diabetes has
been implicated as a risk factor in NAFLD. In fact the
commonest reason for aymptomatic raised liver enzymes
in diabetics has been postulated to be NAFLD. In our study
exetanide has been shown to reduce liver enzymes after
one year of treatment. It may possible that this could be an
independent effect of exetanide or it could be secondary to
the loss of weight accompanied with the use of exetanide.
However, it our study, change in weight did not seem to
be correlated with the reduction in liver enzymes and the
effect was probably secondary to the use of exetanide.
Conclusions: In patients with Type 2 DM, exetanide
treatment leads to decrease in AST and ALT along with
a mean reduction of weight and HgBA1C. It is possible
that exetanide may be a possible therapy option in NAFLD
in patients with raised liver function tests though further prospective studies will be needed to delineate that
association.
2007 were reviewed. Patients older than 18 years of age
and confirmed DKA or HHS (according ADA criteria)
were included in this study. Subjects were retrospectively
classified as having type 1 diabetes (T1D), type 2 diabetes
(T2D) irrespective of their insulin use or had new-onset
diabetes. We found 96 episodes of DKA and 9 episodes of
HHS between January 2001 and January 2007 (91.4% and
8.6%, respectively). 61% of the patients were male, the age
(mean ± SD) was 44.7 ± 15.6 years, 57.1% of the patients
had a family history of diabetes, and 55.3% of the patients
had a prior diagnosis of diabetes. In 44.7% of the patients
this was the first manifestation of diabetes. Discontinuation
of treatment was the precipitating factor in 41%, infections
in 17.1% and, an intercurrent illness in 2% of the patients.
No identifiable causes were found in 40% of the patients.
During the six years of the study, only five episodes of DKA
in five T1D patients were observed. The mean ± SD results
of laboratory blood tests were: glucose 496.62 ± 173.14
mg/dL, pH 7.17 ± 0.15, bicarbonate 8.46 ± 6.31 mEq/L,
serum osmolality 304.27 ± 21.07 and, anion GAP 25.72 ±
7.97 mmol/L. 70% of DKA episodes were severe.
Discussion: The incidence of DKA/HHS among T2D
patients has been increasing in the last years especially
among the non-Caucasian ethnicities. Peru has one of the
lowest T1D incidence, this phenomenon could explain
why less than 5% of the DKA episodes were observed in
patients with T1D. Also, it might reflect inadequate availability of primary health care services and be caused by
delayed diagnosis of T2D.
Conclusion: Our study suggests that in countries
were the incidence of T1D is low, a significant proportion of DKA cases occur in patients with T2D, especially
in patients with new-onset disease. Most of these episodes
were severe, and were related to non-compliance in treatment or had no identifiable cause.
Abstract #242
Abstract #241
HYPERGLYCEMIC HYPEROSMOLAR STATE
AND RHINO-ORBITAL MUCORMYCOSIS IN A
PATIENT WITH NEW-ONSET
DIABETES MELLITUS
HYPERGLYCEMIC CRISES IN PERUVIAN
PATIENTS WITH TYPE 2 DIABETES
Miguel E. Pinto, MD, Ximena Guevara, MD, and
Jaime E. Villena, MD
Miguel E. Pinto, MD, Ximena Guevara, MD, and
Jaime E. Villena, MD
Objective: To describe the clinical and laboratory
characteristics of hyperglycemic crises in Peruvian patients
with diabetes.
Case Presentation: The clinical charts at Cayetano
Heredia Hospital (Lima, Peru) of all diabetic patients with
diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS) between January 2001 and January
Objective: To report the case of a man with new-onset
diabetes mellitus who developed hyperglycemic hyperosmolar state and rhino-orbital mucormycosis.
Case Presentation: A 74-year-old man with 2-week
history of polydipsia, polyuria, weight loss, and diplopia
came to the Emergency Service. He had no personal his– 38 –
tory of diabetes. Physical examination showed a swelling
of his left cheek, ocular protrusion and purulent discharge
from his left eye. His vital signs showed a blood pressure
of 150/90 mmHg, heart rate of 90 beats/min, oral temperature of 37.3 ºC, and BMI of 25.5. When he was admitted
to the hospital, the glucose level was 700 mg/dL, serum
bicarbonate was 20.4 mEq/L, arterial pH was 7.40, corrected sodium was 157 mEq/L, potassium was 4.9 mEq/
L, chloride was 106 mEq/L, calculated serum osmolality
was 334 mOsm/Kg, and urine ketones were positive. The
diagnosis of hyperglycemic hyperosmolar state (EHH) was
established, and appropriate medical treatment was started
with IV insulin, hypotonic solutions, and broad spectrum
antibiotics. A CT scan showed cellulitis in the left orbit
with severe swelling of all extra ocular muscles and pansinusitis. Patient underwent aggressive surgical debridement
of the sinuses and nasal cavity, and exenteration of the left
orbit. On histopathologic examination, the orbital tissue
was found to contain a fungus ball with nonseptate hyphae
with right-angle branching, consistent with mucormycosis.
IV amphotericin B was started. Further laboratory working
showed an HbA1c of 14%, microalbuminuria of 292µg/
mg and normal funduscopy. Cultures were positive to
Rhizopus sp. Patient had a favorable glycemic control with
NPH insulin. Oral posaconazole was added because patient
developed renal insufficiency associated with amphotericin
B. Patient was discharged from hospital with no specific
therapy for diabetes, because his glucose level was in the
normal range, and oral posaconazole.
Discussion: Mucormycosis often develops in immunocompromised patients, particularly in patients with
diabetic ketoacidosis. In many cases, this could be the
first manifestation of the disease. The metabolic acidosis offers an added advantage to this fungal infection, the
acidic milieu reduces the binding of iron to transferrin and
thereby a more favourable conditions for fungal multiplication arises.
Conclusion: We report the case of a patient with newonset diabetes mellitus with a rhino-orbital mucormycosis
and hyperglycemic hyperosmolar state. Although mucormycosis is a fatal infection, early diagnosis and aggressive
treatment, that includes surgical procedures, may decrease
mortality.
Abstract #243
RESOLUTION OF DIABETES AFTER
EXTIRPATION OF BENIGN HEPATIC
FIBROHISTIOCYTOMA
Miguel E. Pinto, MD, Ximena Guevara, MD,
and Jaime E. Villena, MD
Objective: To report the clinical evolution of a man
with new-onset diabetes who resolved his disease after the
extirpation of a benign hepatic fibrohistiocytoma.
Case Presentation: A 54-year-old man with a 1-week
history of polydipsia, polyuria, and fever was referred to
our emergency unit. Initial laboratory work-up showed:
glucose of 700 mg/dL, pH of 7.09, bicarbonate of 3.9
mEq/L, and urine ketones were positive. There was no history of diabetes. Diabetic ketoacidosis (DKA) diagnosis
was established and aggressive treatment with IV insulin,
hydratation, and antibiotics was started. Te HBA1c level
was 11.1% Physical examination showed fever and hepatomegaly with a palpable mass in the left hepatic lobe.
The daily insulin requirements were high with an average
over 320 UI/day. Computed tomography showed a heterogeneous mass in the left hepatic lobe. The initial management was difficult because high doses of insulin were
needed (daily average insulin dose of 105 UI, daily average fasting glucose of 252 mg/dL) and fever was persistent
throughout hospitalization (daily average temperature of
38.4 C). After 27 days of hospitalization, extirpation of his
hepatic mass was done. This was a 670 grams encapsulated
mass. Pathologic anatomy was compatible with a benign
fibrohistiocytoma and immunohistochemical stain was positive for glucagon. One day after surgery, fever was gone
and daily average glucose was 95 mg/dL. Patient’s clinical
evolution was favorable and e was discharged from hospital with no specific therapy for glucose control and without
complaints. After four weeks of discharge, patient was with
no antidiabetic treatment and glucose was normal.
Discussion: Fibrous histiocytoma is a pleomorphic
sarcoma composed of histiocyte-like and fibroblast-like
elements. The majority of tumors occurs in the extremities,
retroperitoneum and head/neck. The hepatic location is
extremely rare. In this case, infection of the mass was ruled
out because no necrosis was found in the surgical piece
and cultures were negative. No association with secondary
diabetes has been described in medical literature.
– 39 –
Conclusion: To our knowledge, this is the first case
reported in the English medical literature that describes the
association of a benign hepatic histiocytoma with diabetes. We suggest that probably this mass secretes some substances that impaired insulin sensitivity as a paraneoplasic
syndrome like glucagon.
Conclusion: Overall glyburide appears safe and
effective for the treatment of gestational diabetes mellitus
during the second and third trimester of pregnancy.
Abstract #245
EFFECTIVENESS OF AN INTENSIVE TRAINING
PROGRAM COMBINED WITH INSULIN PUMP
THERAPY
Abstract #244
GLYBURIDE TREATMENT IN
GESTATIONAL DIABETES MELLITUS:
HOW SAFE AND EFFECTIVE
Andrew John Behnke, MD, FACE, Ruth Beel, RN, and
Melissa Benzon, RD
Objective: To examine the effectiveness of an intensive education program in patients with poorly controlled
diabetes mellitus using insulin pump therapy.
Methods: Sixteen (16) patients with diabetes mellitus
were identified as having poor glucose control and requiring
insulin therapy. The majority (9/16) had Type one diabetes. The average Hgb A1C at the beginning of the program
was 8.6. These patients were educated with an intensive
program including multiple office visits and culminating
in a 24-hour continuous physician supervised monitoring
period with insulin pump administration. Levels of glycosylated hemoglobin were monitored before, during, and
up to six months after the education program and insulin
pump starts.
Result: Average levels of Hgb A1C reduced to 7.7%,
7.3%, and 7.3% at the time of the insulin pump administration and 24-hour monitoring period, three months, and
six months later respectively. The percent of individuals
achieving the AACE recommended level of Hgb A1C ( <
6.5 %) increased from a baseline of 6.3% to 14.3% at three
months and 37.5% at six months.
Discussion: Patients with poor glucose control are at
high risk for multiple diabetic complications and may benefit from insulin pump therapy. The combination of insulin
pump therapy with a novel intensive education approach
including a continuously monitored 24-hour period significantly reduced levels of Hgb A1C. A significantly more
number of these individuals met AACE goal levels of glucose control which persisted up to six months after the education period.
Conclusion: In patients with poorly controlled diabetes requiring insulin, the combination of an insulin pump
and an intensive education program significantly reduced
levels of glycemia and resulted in an increase in the number of patients meeting AACE goals of glucose control.
Besa Bushati, MD, Vipul Shah, MD, and
Jann Johnston, MD
Objective: To study the safety and effectiveness of
glyburide in the treatment of gestational diabetes mellitus.
Methods: Retrospective chart review of all patients
with gestational diabetes mellitus (GDM) in endocrine practice in 2005. 58 women were identified. All were instructed
in diet and home glucose monitoring. Glyburide or insulin
were initiated if diet failed to control postprandial glucose
values <120 mg/dl. Choice of therapy was up to patient
preference. Groups were compared for age, weight at first
visit, parity, final hemoglobin A1C (HbA1C), reported
hypoglycemia, mode of delivery, pregnancy complications
and baby weight. Statistical analyses consisted of applying
univariate parametric and nonparametric measures.
Results: 41/58 or 71% patients were treated with
diet only. For the 17 who required pharmacologic therapy,
12/17 (71%) chose glyburide compared to 5/17 (29%) who
chose insulin injections. There was no significant difference between any group regarding parity, weight, age,
pregnancy complications or baby weight. Mean HbA1C:
Diet 5.38 + 0.41%, Glyburide 5.45 + 0.46%, Insulin
5.92 + 0.94% (p-value 0.08). C-section rates were: Diet
9/41 (22%), Glyburide 9/12 (75%), Insulin 3/5 (60%) (pvalue 0.03). Reported hypoglycemia for Diet 5/41 (12%),
Glyburide. 8/12 (67%) Insulin 1/5 (20%) (p-value <0.001).
No severe hypoglycemia was reported.
Discussion: Glyburide for the treatment of GDM
does not appear to be associated with more fetal complications or difference in baby weight. C-section rates were
higher as well as increased episodes of hypoglycemia however this is a known side effect of glyburide and insulin
therapy. Oral glyburide was preferred to insulin injections
and appears to be safe and effective for use in the second
and third trimester.
– 40 –
Abstract #246
Abstract #247
CLINICAL USE OF BRAIN NATRIURETIC
PEPTIDE (BNP) IN PATIENTS WITH TYPE 2
DIABETES WHO ARE TAKING TZD’S
THE RELATIONSHIP AMONG HOMOCYSTEINE,
URINE ALBUMIN/CREATININE RATIO AND
DEGREE OF RETINOPATHY IN PATIENTS WITH
TYPE 2 DIABETES
Andrew John Behnke, MD, FACE
Nanny Natalia Mulyani Soetedjo, MD, Helen C. Tarigan,
and I. Gusti N. Adhiartha
Objective: To examine the clinical utility of Brian
Natriuretic Peptide (BNP) in patients with type two diabetes receiving Thiazolidinedione (TZD) therapy.
Methods: Patients who had Type 2 diabetes and were
receiving TZD therapy with either pioglitazone or rosiglitazone were identified in a clinic setting. Levels of BNP
were measured in 90 consecutive patients. Data were collected regarding levels of glucose control, adverse events
and estimates of cardiac function.
Result: The proportion of patients receiving either
pioglitazone or rosiglitazone was even ( 49 % rosiglitazone
and 51% pioglitazone). Baseline characteristics were similar in both groups. Most patients ( 57%) had reached ADA
goal of Hgb A1C <7.0 and 27 % reached AACE goals
of < 6.5 %. The number of patients having a BNP level
of greater than 100 pg/ml was 6.4%. Significantly more
patients receiving pioglitazone had elevated BNP levels
(62.5 % vs. 12.5 % on rosiglitazone). Patients with elevated BNP levels had had several significant cardiac events
including cardiac bypass and myocardial infarction.
Discussion: Previous studies have demonstrated
the clinical utility of BNP levels in screening patients
with Diabetes for occult heart dysfunction. BNP levels
in patients with type two diabetes receiving TZD therapies were generally lower than 100. Of those that were
elevated, further investigation revealed significant cardiac
dysfunction. More patients had elevated BNP levels if they
were treated with pioglitazone vs. rosiglitazone.
Conclusion: A) TZD therapy in patients with type 2
diabetes is associated with A1C levels at ADA goal rates
in a majority of patients and AACE goals in nearly 1/3 of
patients.
B) Most patients in this study had low levels of BNP on
TZD therapy
C) There were more patients with significantly high BNP
(>100) on Pioglitazone vs Rosiglitazone D) BNP may be used clinically to assist in the management of Type 2 diabetes in patients who are receiving TZD
therapy Objective: Increased plasma levels of homocysteine
(tHcy) considered as independent risk factor for atherosclerotic disease in subjects with normal tolerance. There
are controversies concerning plasma tHcy levels in type
2 diabetes. Whether hyperhomocysteinemia contributes
to the development of diabetic microangiopathy is still
debated. Thus the aim of this study is to evaluate whether
there is relationships among homocysteine, urine albumin/
creatinine ratio (UACR) and retinopathy in type 2 diabetic
patients.
Methods: We observed type 2 diabetic patients who
visited our outclinics between February 2007 and July
2007 who had creatinine serum <1.4 mg/dL, no history of:
cardiocerebrovascular disease, diabetic ulcers, and severe
infection. Urine albumin level was tested by immunoturbidimetry method, urine creatinine level was measured using
Jaffe method and homocysteine level was measured by
fluorescence polarization immunoassay (FPIA) method.
Result: Baseline data for the cross-sectional study
were obtained from 49 patients, between 40 and 79 years
of age. The history of diabetes were between 8 months and
17 years. Their mean tHcy levels are 11.27 (4.15-98.29)
µmol/L. All patients have perifer neuropathy. Mean of
UACR levels are 42 (0.02-724.92) mg/g. Eight patients
have Proliferative Diabetic Retinopathy (PDR), 31 patients
have Non-PDR and 10 patients normal.
Discussion: There are no significant differences
between group with high tHcy (>10 µmol/L) and low
tHcy levels for UACR and stage of retinopathy. No significant correlation between tHcy and UACR, but there are
significant correlation between stage of tHcy and stage of
retinopathy with p<0.01 and stage of retinopathy and stage
of UACR with p<0.01.
Conclusion: Plasma tHcy levels in this study are mild
hyperhomocycteinemia. tHcy and UACR seem to be correlated with stage of retinopathy in patients with type 2
diabetes.
– 41 –
decreased synthesis of gamma-aminobutyric acid, temporary ischemia and hyperviscosity.
Conclusion: Hemiballism is a rare neurologic manifestation of hyperglycemia. Awareness of this association is important, since the movement disorder may be the
sole presentation of a clinically significant hyperglycemia. Additionally, hyperglycemic hemiballism may be reversible with glycemic control.
Abstract #248
A RARE NEUROLOGIC MANIFESTATION
OF HYPERGLYCEMIA: CASE REPORT
OF A PATIENT WITH HYPERGLYCEMIC
HEMIBALLISM
Sara Elisabeth Lubitz, MD, and Julie Probst-Riordan, MD
Objective: To describe a case of hemiballism associated with hyperglycemia
Case Presentation: A 79 year old female presented
with uncontrolled movement of her arm. Exam was significant for flailing of the left upper extremity that ceased
with sleep and worsened with agitation; the remainder of
her neurologic exam was normal. Laboratory evaluation
revealed a glucose of 421 mg/dl, normal anion gap, and
negative urinary ketones. Although the patient had no
known history of diabetes mellitus, HbA1c was 16.1%. CT brain showed high-density material within the right
basal ganglia. MRI was significant for increased T1 signal
and decreased T2 signal within the right lentiform nucleus
without associated mass effect, diffusion restriction, or
susceptible artifact and interpreted as compatible with the
diagnosis of diabetic hemiballism. The patient was treated
with intravenous insulin and neuroleptics. Two months
later her glucose was controlled (HbA1c 6.9%) with lowdose sulfonylurea without resolution of the movement
disorder.
Discussion: Hemiballism is a rare hyperkinetic movement disorder characterized by unilateral, irregular, involuntary flinging movements of the limbs caused by lesions
of the basal ganglia. Hyperglycemic hemiballism was first
described by Bedwell in 1960 in a woman who presented
with arm flailing in the setting of hyperglycemia. As the
blood-glucose abnormality was corrected, the hemiballism
resolved only to recur episodically with lapses in glycemic control. Today, it is largely a neuroradiologic diagnosis
characterized by high signal on T1-weighted MRI images
in the putamen contralateral to the movements, with similar
changes found in the globus pallidus and the caudate. Twothirds of patients also have high signal abnormalities on T2
weighted sequences or densities in the striatum on CT scan. The patients typically are elderly females with no history of
diabetes mellitus who present with involuntary movements
and severe non-ketotic hyperglycemia. The hemiballism
may be the only manifestation of the hyperglycemia. After
correction of the hyperglycemia, the movements usually
resolve in hours to days. However, 20% of patients have
persistent hemiballism. The pathogenesis remains uncertain. Potential etiologies include petechial hemorrhage,
– 42 –
Abstract #249
EVIDENCE THAT NEW SCREENING TESTS
ARE NEEDED FOR SCREENING FOR
TYPE II DIABETES
Lee Pletts Goscin, MD, PhD
Objective: Numerous studies have shown 50% of
patients with first diagnosis of Diabetes 2 have coronary
artery disease (CAD). Complications of Diabetes 2 take
ten years to develop. Eight million people in the U.S.A.
are estimated to have undiagnosed Diabetes 2. Cases with
undiagnosed diabetes are presented.
Case Presentations: Case #1 A 43-year-old, thin
woman had three risk factors for Diabetes. She requested
a glucose tolerance test which showed blood glucose of
195 at two hours. She required daily NSAID or COX II
inhibitors for arthritis. This patient did diet and exercise
for 15 years until she developed Type II Diabetes with a
Hemoglobin A1C of 6.3. In four months of Actos 15 plus
Metformin 500, and a statin, diet, and exercise the patient’s
Hemoglobin A1C is 5.4. Now at 60 years old, she has
four risk factors for CAD: family history, Hypertension,
Elevated LDL and DM.
Case #2: A 55- year-old RN, survivor of breast cancer
has two risk factors for Diabetes with symptoms and Impaired Fasting Glucose. A two-hour glucose tolerance test
shows glucose of 255 at 90 min. and 279 at 120 min.
Case #3: An asymptomatic 58-year-old man had an
abnormal CT of the Coronary Arteries. Cardiac catheterization showed three blocked coronary arteries.. He underwent 3 vessel coronary artery bypass.. His two brothers
died suddenly at ages 52 and 53 within a year apart recently.
His father died at 50 after heart trouble. The patient had no
previous history of metabolic syndrome, high blood pressure, smoking, stress, alcohol. His fasting blood sugar in
this cardiac workup was 180. On day one post surgery the
fasting glucose was 150 and HgA1c was 5.4. His LDL of
117 had been treated for seven years with a statin.
Case #4: An obese (BMI 31) woman age 52 with
fasting blood sugars in the 90s seeks a second opinion of
does she have Diabetes? Another Endocrinologist did a
two-hour glucose tolerance test on her two years ago and
said she did have Diabetes. She has lost approximately 10
pounds, with diet and exercise. Now her fasting blood
sugars is 90 and the HgA1C is 5.4.
Discussion: With Diabetes and Metabolic Syndrome
being risk factors for CAD, should endocrinologists
and primary care physicians be identifying IGT, IFG,
Metabolic Syndrome or DM 2 more aggressively and
sooner to decrease C AD as well as diabetic complications?. An expensive CT of the coronary arteries was the
starting abnormal test which may have saved an asymptomatic patient’s life. These cases represent only the tip
of the iceberg for redefining our standards and methods of
identification of people with Type 2 Diabetes. Also treatment goals may need to be lowered with more aggressive
therapies. Conclusion: These cases support a strong argument that can be made for increased detection of DM in
young people based on clinical suspicion and the number
of risk factors for DM and CAD.
by measuring reflection index (RI), a ratio of the heights
of the diastolic and systolic components of digital volume
pulse (DVP) obtained by using a photoplethysmograph
device.
Results: Mean values of clinical characteristics in
68 selected subjects were, age 49.9±2.0 years, body mass
index 26.1±1.0 kg/m2 and duration of diabetes 7.4±1.0
years. Before study, these parameters as well as glycemic
and other laboratory measurements were comparable in
all 4 groups (control, RG, EN, RG+EN). After 12 weeks,
fasting and post prandial plasma glucose, glycated hemoglobin, fasting insulin and insulin resistance (HOMA-IR),
and systolic and diastolic blood pressure improved significantly (p<0.001) in all subjects treated with RG compared to controls. However in subjects on EN alone, there
were significant improvements in blood pressure levels
but not in glycemic control and insulin levels. In subjects
treated with RG+EN, reduction in heart-brahial (hb) PWV
(-10.1%), brachial-ankle (ba) PWV (-13.7%) and carotidfemoral (cf) PWV (-16.3%) was significantly (p<0.01)
greater than in those on RG alone (hbPWV -8.1, baPWV
-9.4 and cfPWV -11.3%). Similarly, RI has also improved
significantly (p<0.01) in subjects treated with RG+EN than
in those on RG alone (-11.5 Vs.-8.5%).
Conclusion: In spite of no discernible effect of enalapril on glycemia, insulin levels or lipids, it has an additive
effect on the beneficiary role of rosiglitazone in improving the vascular functions in type 2 diabetes. Enalapril in
combination with rosiglitazone was effective in improving
vascular function and to possibly decrease cardiovascular
complications in patients with type 2 diabetes mellitus.
Abstract #250
ENALAPRIL WITH ROSIGLITAZONE
IMPROVES VASCULAR FUNCTION IN TYPE 2
DIABETES MELLITUS
Sreekanth Reddy Reddem, MBBS, Yashmaina Sridhar,
Paturi Bhanu Teja, P. Usharani, P.V. Rao,
and M.U.R. Naidu
Objective: To assess the effect of enalapril therapy
with and without rosiglitazone on vascular function in
patients with type 2 diabetes mellitus in a prospective, randomized, double-blind, controlled, and parallel comparative study.
Methods: Sixty-eight subjects with type 2 diabetes on
stable doses of two oral hypoglycemic agents (metformin
500-750 mg tid and gliburide 5-10 mg bid) attending the
Diabetes Care facility at the Nizam’s Institute of Medical
Sciences University Hospital in Hyderabad, India, were
consecutively recruited. They were randomized into control (n:15), rosiglitazone alone (RG n:17), enalapril alone
(EN n:18) and RG+EN (n:18) groups. All subjects in test
groups received either rosiglitazone 2 mg bid, enalapril 5
mg bid or both, for 12 weeks. This study was approved
by the Institutional Ethics Committee and all patients gave
their written informed consent to participate. Vascular
function was measured by pulse wave velocity (PWV), an
indicator of arterial stiffness using a non-invasive pulse
wave analyzing device. Vascular tone was also quantified
Abstract #251
DECREASED HOSPITAL ADMISSIONS FOR DKA
IN A HIGH RISK PEDIATRIC POPULATION
Mark A. Kummer, MD, and Sandra G. Hudson, ARNP
Objective: Escambia County, Florida is the poorest
county in Florida and the 17th poorest in the USA. After
receiving permission from the IRB, a retrospective review
of hospital readmissions in the under 18 yr age group for
diabetic ketoacidosis was undertaken in May 2006 to assess
the quality of the Pediatric Diabetes Program. In 2004, 62
children with known diabetes were readmitted for ketoacidosis: in 2005, there were 61admissions. This reflects 24
admissions for every 100 children followed in the outpatient clinic.
Methods: This study targeted high risk patients with
the primary goal of decreased hospital admissions over the
– 43 –
next year - July 2006 to June 2007. Patients were identified
as high risk if they had an admission for DKA in the past
year or an hemoglobin A1c above 12% in the clinic. There
was considerable overlap in the groups, but not exclusive. This project was accomplished within the limits of
the clinic without any new monetary support. All patients
from these groups were approached to participate in a high
risk protocol which included: monthly clinic visits, weekly
review of blood sugars, a review with both the dietitian
and diabetes educator, and a visit with the social worker
at enrollment to ensure that the patients had adequate diabetes medications and supplies as well as a review of family concerns. Counseling was recommended to all patients
and families to identify blocks in compliance with treatment recommendations. A case management team meeting of physicians, nurse practitioners, educators and social
worker was held monthly to discuss all current patients and
the need to enroll additional high risk patients.
Results: Upon enrollment, all families and patients
were asked to sign a statement that identified them as being
at high risk for diabetes complications or death from diabetic ketoacidosis. They were asked to commit to the blood
sugar testing, reporting of blood sugars and clinic visits.
During the time of the study, hospital readmissions for
DKA dropped to 41 despite a total increase of patients seeking care. Because of a rise in new diabetes patients attending clinic and the decreased number of hospital admissions,
the rate of admissions per 100 clinic patients dropped to 13
from 24. During the 2nd quarter of 2006, there were 30
patients with an A1c > 12% whereas, in the 2nd quarter of
2007, the number had dropped to 7 patients.
Conclusion: This method has proven effective in
lowering hospital admissions over the short term without significant increase in costs to the clinic or hospital.
Secondary benefits have been improved coordination and
consistency of the care plan for the most complicated
patients and fewer patients with very high hemoglobin
A1c levels in the clinic. Also, a new sick day management
guideline was developed for all clinic patients because of
the effectiveness identified in this high risk group.
thetic deep pain, disturbing sleep and quality of life which
brings the most referrals to some clinics for therapy. It is
called “dying back” axopathy because of its ascendance
overtime from the toes upward. It predicts foot ulcers with
89% sensitivity. But until now there has been no clinical practical grading scale for its quantification which is
clearly needed by the busy clinician (NCNS is not practical in every patient. research grading system exists but
difficult to do in practice). We devised a practical grading
scale, easy to do in the first office visit and every follow
up visit within 2 minutes. This is a report of its practical
application.
Methods: We tested 102 consecutive patients with
the 128 Hz tuning fork. We recorded the loss of vibration
sensation at the first office visit and every follow up visit
at 10 levels from the hip downward: 1-toes and foot bottom (T), 2-mid foot (F), 3-ankle (A), 4-lower third of the
shin (LS), 5-mid shin (MS), 6-upper third of shin (US),
7-Knee(K), 8-thigh (TH), 9-hips (H), 10-above the hip
(AH). All normal sensory vibration patients were termed
NL. Each patient had intermediate outcome measures
(FBS, PPG, HgA1C, etc.) tested before and after therapy
(which included metabolic control, Trazadone, and adjuvant analgesic). Results: At baseline, loss of sensory vibration
was found in 58 patients (56.8%) at the following variable levels: 1-toes: 8(%13.8) 2-foot: 8(%13.8) 3-ankle:
8(%13.8) 4-lower shin: 4(%6.8) 5-mid shin: 8(%13.8) 6upper shin: 4(%6.8) 7-knee: 10(%17.2) 8-thigh: 3(%5) 9hip: 2(%3) 10-above hip: 1(%1.7). Average FBS was 255,
average HgA1C was 9.7% . After therapy, loss of sensory vibration clearly
improved within 2-4weeks and up to 4 months: 12 patients
became normal (NL), 3 were unchanged, 2 became worse.
The other 40 have improved at the following variable
levels:1-toes: 11(%19). 2-foot: 9 (%15.5). 3-ankle:
5(%8.6) 4-lower shin: 4(%6.8) 5-mid shin: 6(%10) 6upper shin: 2(%3). 7-knee: 2(%3) 8-thigh: 0 9-hip: 0 10above hip: 0. Average FBS became 154, HgA1c 7.85%.
Comparing baseline with after therapy for the total group:
FBS decreased 101, HgA1c decreased 1.85%, improvement in sensory vibration by one level was seen in 19
patients (%33), two levels 16 pt’s (%27.5), three levels
4 pt’s (%6.8), four levels 4 pt’s (%6.8), uncertain level
11 pt’s (%19). When looking at any level of improvement it
was seen in 53/58 original patients with neuropathy (91%)
Discussion: The striking improvement seen in most
patients was a very important objective sign to patient
and physician. Patients see improvement correlated with
metabolic control, making patients more committed to
treatment plan. It guides physician in increasing intensity
Abstract #252
HOW TO QUANTIFY DIABETIC
POLYNEUROPATHY
Saad Sakal, MD, FACE
Objective: Loss of vibration sensation is an early sign
in diabetic polynueropathy (DPN), reported in 30% of diabetics by phys. exam,70% by NCVS, as a burning paras– 44 –
levels in the general populace.
Results: 365 complete records of type 2 DM patients
were identified for the period December 2006 to November
2007. Mean HBA1c was 7.78+/- 2.73%. The range of
HBA1c was 4.0% - 16.7%. 208 of the HBA1c results were
> or = 7.0%, representing a level of 57.0% being in poor
control. Less than 5% of the patients were able to do more
than 1 HBA1c tests in the year under review due to financial
constraints. In comparison 10 male and 10 female adults
(volunteers) with normal OGTTs were tested and their
HBA1c ranged from 4.0 -5.8%, the mean being 4.59%.
Discussion: Glycated Hemoglobin is a relatively
expensive test which few patients with DM can afford to
do especially in resource poor countries like Nigeria where
more than 50% of the population lives on less than one
US dollar per day and less than 10% of the population is
covered by health insurance of any kind. Despite limited
resources it is interesting that more than 40% of out-patient
managed type 2 DM patients have good glycaemic control.
Larger local studies require to be carried out to evaluate
the correlation between these HBA1c levels and morbidity
and to see the effect of different pharmacological and non
pharmacological intervention on the HBA1c levels.
Conclusion: Diabetes is a major health burden that
requires strict glycaemic control to prevent complications.
The targets can be achieved with simple and affordable
medication and lifestyle modifications which are readily
available even in resource poor countries. More widespread use of this simple tool is to be encouraged to help
manage DM better.
of therapy. The significant percent of reversible component likely relates to glycemic/metabolic control despite
diabetes duration of years, seems easily documented
as early as 2-4 weeks and descending gradually further
toward the toes reversing the “dying-back” axopathy in a
welcome “living-back” phenomena. we believe this grading scale of sensory vibration (Sakkal Scale) an extremely
easy to do, time saving (less than2 minutes), reproducible,
correlates well with patient symptoms, metabolic control,
easy to document in the chart, to follow up, it improves
communication in research and stimulate patient and physician to improve care. Division to 10 levels (metric system) makes the scale easier to administer. In practice most
patients (86%) will fall in the first 7 grades. Choosing the
absolute loss of vibratory perception for the scale improves
application, avoid inter observers confusion.
Conclusion: Documenting the level of the loss
of sensory vibration in diabetic neuropathy is an objective, accurate, easy to implement, time saving, reproducible clinical grading tool ( Sakkal Scale ) which correlates
well with patient symptoms and metabolic control . It
improves communication in research and clinical care in
most patients with diabetic polynueropathy.
Abstract #253
TYPE 2 DIABETES MELLITUS SUBJECTS
DIAGNOSED WITHIN ONE YEAR MANIFEST
AUTONOMIC DYSFUNCTION SIMILAR TO
THOSE WITH DIABETES OF
LONGER DURATION
Abstract #254
Olufemi Adetola Fasanmade, MBBS, FWACP,
Adekunle Adeyemi-Doro, Anthonia Ogbera,
Sandra Iwuala, and S.B. Bamiro
HBA1C LEVELS IN PERSONS WITH TYPE 2
DIABETES MELLITUS IN LAGOS, NIGERIA
Objective: This cross sectional non interventional
study was carried out to determine the degree of glycaemic
control of patients with type 2 diabetes attending a federal
tertiary hospital in the Lagos metropolitan area of Nigeria
in West Africa.
Methods: All the available medical records of patients
with type 2 diabetes mellitus who had been sent for HBA1c
testing were studied and basic health statistics and levels of
HBA1c were extracted and analysed using Microsoft excel
statistical software. (Tests were done using electrophoresis and the effect of Hemoglobin S noted to be minimal).
Results (NGSP/DCCT calibrated) were expressed as mean
+ SD. The number who were within the levels of good control (</= 7%) were ascertained. A control (non diabetic)
group of volunteers was also tested to ascertain the HBA1c
Olufemi Adetola Fasanmade, MBBS, FWACP,
Adekunle Adeyemi-Doro, Anthonia Ogbera, and
Sandra Iwuala, S.B. Bamiro
Objective: This cross sectional non interventional
study was carried out to determine the degree of glycaemic
control of patients with type 2 diabetes attending a federal
tertiary hospital in the Lagos metropolitan area of Nigeria
in West Africa.
Methods: All the available medical records of patients
with type 2 diabetes mellitus who had been sent for HBA1c
testing were studied and basic health statistics and levels of
HBA1c were extracted and analysed using Microsoft excel
statistical software. (Tests were done using electrophoresis and the effect of Hemoglobin S noted to be minimal).
– 45 –
Mellitus (DM) was defined by the current ADA guidelines
or the need for anti-DM medications, at the time of preLT evaluation, and at 1 week, 4 months and 1 year postLT. Exclusion criteria included: known DM pre-LT, renal
failure prior to LT, prior history of a solid organ transplant, or the initial use of immunosuppressant other than
Tacrolimus.
Result: A total of 122 patients met study criteria. The
overall incidence of NODM post-LT was 95% at 1 week
(n=114), 38% at 4 months (n=38) and 34% (n=37) at 1
year. Intriguingly, of the 35% (n=43) of patients were classified as NODM at both1 week and 4 months post-LT, 85%
(n=35) remained diabetic at 1 year post-LT. The odds ratio
for NODM in subjects with alcoholic liver disease was 8
fold of that autoimmune hepatitis. In univariate analysis
the significant predictors of NODM (p < 0.05) were the
etiology of liver disease, family history of diabetes, severity of liver disease (MELD score), male gender. Age, race
and body mass index were not significantly associated with
NODM.
Discussion: The rationale for identifying NODM at
1 week, 4 months and 1 year post-LT is to account for the
steroid treatment regimen. In general, patients undergoing
LT, receive steroid boluses immediately post-LT, then are
discharged home on a tapering steroid dosage, to be discontinued at 4 months.
Conclusion: Patients undergoing LT are at high risk
for developing NODM. Those who have diabetes at 4
months post LT are very likely to continue to have diabetes
at 1 year. The risks for persistent NODM at 1 year post-LT
include: underlying etiology, notably alcoholic liver disease, family history of DM, male gender and high MELD
score.
Results (NGSP/DCCT calibrated) were expressed as mean
+ SD. The number who were within the levels of good control (</= 7%) were ascertained. A control (non diabetic)
group of volunteers was also tested to ascertain the HBA1c
levels in the general populace.
Results: 365 complete records of type 2 DM patients
were identified for the period December 2006 to November
2007. Mean HBA1c was 7.78+/- 2.73%. The range of
HBA1c was 4.0% - 16.7%. 208 of the HBA1c results were
> or = 7.0%, representing a level of 57.0% being in poor
control. Less than 5% of the patients were able to do more
than 1 HBA1c tests in the year under review due to financial
constraints. In comparison 10 male and 10 female adults
(volunteers) with normal OGTTs were tested and their
HBA1c ranged from 4.0 -5.8%, the mean being 4.59%.
Discussion: Glycated Hemoglobin is a relatively
expensive test which few patients with DM can afford to
do especially in resource poor countries like Nigeria where
more than 50% of the population lives on less than one
US dollar per day and less than 10% of the population is
covered by health insurance of any kind. Despite limited
resources it is interesting that more than 40% of out-patient
managed type 2 DM patients have good glycaemic control.
Larger local studies require to be carried out to evaluate
the correlation between these HBA1c levels and morbidity
and to see the effect of different pharmacological and non
pharmacological intervention on the HBA1c levels.
Conclusion: Diabetes is a major health burden that
requires strict glycaemic control to prevent complications.
The targets can be achieved with simple and affordable
medication and lifestyle modifications which are readily
available even in resource poor countries. More widespread use of this simple tool is to be encouraged to help
manage DM better.
Abstract #256
Abstract #255
DIABETIC AND NON-DIABETIC SALIVA
ALPHA AMYLASE ACTIVITY INCREASED IN
ACID MEDIA
THE INCIDENCE AND RISK FACTORS OF NEW
ONSET DIABETES MELLITUS POST LIVER
TRANSPLANTATION
Tarig Sayed Mustafa Arbab, MD, MSc, DIC
Mae Sheikh-Ali, MD, Lina Aguirre, MD, Shon Meek, MD,
PhD, Rebecca McNeil, PhD, and Andrew Keaveny, MD
Objectives: To study pH changes during saliva alpha
amylase activity in diabetic and non diabetic subjects in
relation to glucose yielding. Explain mechanism of action
and occurrence of DKA. Methods: 750 fresh saliva samples were collected
from 200 diabetic and 50 non-diabetic subjects. All subjects were fasting over night for 12 hours. Glucose oxidase
testing was used to detect amylase activity. Three identical 10 mls samples of fresh well-prepared saliva were
accepted from each patient for the study. One sample from
Objective: 1-To determine the incidence of new onset
diabetes mellitus (NODM) in patients who have undergone
liver transplantation (LT) 2-To follow the progression and
transition of NODM over the first year post-LT 3-To identify risk factors for the development of NODM post-LT
Methods: A retrospective review of 275 LTs was
conducted at the Mayo Clinic in Jacksonville from 2004
to 2005. Patients were followed for 12 months. Diabetes
– 46 –
cose yielding in 24 hours (absent amylase activity). Zero
non diabetic samples, same subject showed absent amylase
activity for both flour and sucrose. Decrease in pH in study
samples was noticed to be associated with increase in glucose yielding. 92% of study samples showed decreased pH
5 > in association with high glucose readings (250 – 500
mg/dl or more).
Discussion: Significant but nonspecific elevations
of amylase can be seen in DKA (Diabetes Care 26:31933194, 2003). Similarity between DKA and this study
in terms of increased acidity in the presence of elevated
serum amylase, and in association with high glucose from
degradation of disaccharides / polysaccharides particles
that could exist in slightly larger amounts in the blood of
diabetic compared to non diabetic subjects (persorption
phenomenon - Gerhard Volkheimer).
Conclusion: Saliva alpha amylase activity should
be determined in relation to pH media. Saliva alpha amylase is active in acid media. Correction of stomach pH and
or abnormal amylase activity could help treat / prevent diabetes and obesity.
each subject was used as marker and tested for pH changes
and sugar hourly for 24 hours. Each second and third study
samples were tested initially for pH and sugar content; 1
ml of flour powder was added in each second sample (250
flour sample). 1 ml of sucrose was added in each third
sample (250 sucrose samples). pH changes together with
sugar readings were tested hourly in each study sample for
24 hours.
Results: 750 (250 marker + 250 flour + 250 sucrose
study sample) fresh saliva samples of non diabetics and
diabetic patients showed pH of 9 to 7 on immediate testing.
250 marker samples showed no significant change in pH
and zero sugar reading for 24 hours. 235 flour, 223 sucrose
study samples showed decrease in pH 5 >, in association
with glucose detection in samples. 2 flour and 2 sucrose
samples showed decrease in pH from 9 to 7 in association with glucose yielding within 24 hours. 8 isolated flour,
11 isolated sucrose diabetic samples, 4 same patient flour
and sucrose diabetes samples, 5 flour and 14 sucrose non
diabetic samples showed decrease in pH 5 > without glu-
– 47 –
ABSTRACTS – Hypoglycemia
HYPOGLYCEMIA
Abstract #301
Abstract #300
TIME FACTOR IN INSULIN OVERDOSE
ADULT NESIDIOBLASTOSIS IN A PATIENT WITH
PAST EVIDENCE OF INSULINOMA
Monica Agarwal, MD, and Steven Elbein
Objective: Hypoglycemia induced by exogenous insulin often occurs accidentally in diabetic patients but many
cases of insulin overdose are self inflicted by depressed
persons with intent of suicide. We report a case of patient
who injected a massive dose of insulin with prolonged
hypoglycemia. Case: 47y/o Caucasian male with depression and
Type 2 diabetes on insulin presented to emergency room
(ER) with low blood glucose. Earlier that night the patient
had injected subcutaneously 11,000 units of Neutral
Protamine Hagedorn insulin in the abdomen. He had purchased 10 ml syringes on the internet. As an hour passed
by after injecting insulin, he changed his mind and decided
that he needed to go to ER. He presented to ER after raising his glucose by drinking pancake syrup. In the ER, his
blood glucose was 48 mg/dL; serum insulin level was 6194
uIU/dL. He received intermittent boluses of D50 and was
started on D10. Over the first 24 hours he required 450
gms of glucose intravenously in addition to generous oral
intake. His blood glucose ranged from 50 to 75 mg/dL. He
required intravenous glucose for eight days. Insulin levels
were measured for nine days. The insulin decay curve was
nonlinear as suggested in the literature.
Discussion: To our knowledge this is the first case
reported of NPH insulin overdose of this magnitude. This
case is unique as the patient injected 11,000 units of NPH
insulin and required intravenous dextrose for eight days. Intermittent hypoglycemia continued for 232 hours. The
serum insulin level was not related with the severity of
the hypoglycemia. The intensity of hypoglycemia seems
to be independent of the dose or the type of insulin, but
the duration of hypoglycemia and dose do appear to be
related. The time course of our patient reflects that relationship. The prolonged hypoglycemia could be related to
delayed absorption from the injection site. The buffering
effect of antibodies present in many diabetic patients may
delay clearance. The case confirms the exceptionally long
half life of insulin in such settings. In insulin overdose the
serum glucose level should be carefully monitored and
glucose infusion rate accordingly adjusted because insulin levels are continuously changing. The patients who
attempt suicide with insulin may repeat the attempt using
the same method so other therapeutic approaches should
be considered.
Eshraq Nazir Aljaghbeer, MBBS, Sant P Singh, MD, and
Ahmad Khraisat Sidney Cruz, MD
Objective: To report a case of recurrent hyperinsulinemic hypoglycemia, secondary to adult nesidioblastosis, in
a patient with previous evidence of insulinoma.
Case presentation: In 1978, a 22 year old woman was
diagnosed with insulinoma. A 2 cm solitary insulinoma was
enucleated and patient remained asymptomatic. In 2002,
she experienced progressive neuroglycopenic symptoms
after meals. In 2003, patient presented to ER unconscious,
plasma glucose was 28mg/dl, insulin 64mIU, proinsulin
28pmol/l, c-peptide 1.1ng/ml and plasma sulfonylurea
was negative. Localization studies were negative for insulinoma, patient underwent partial (80%) pancreatectomy.
Histological examination was characteristic for nesidioblatosis. Post-operative recovery was uneventful. Two months
later, 5 hour OGTT was normal. Subsequently, during
three and a half years of follow-up, the patient remained
euglycemic.
Discussion: Nesidioblastosis is a descriptor of the morphologic findings of B cells associated with hyperinsulinemic hypoglycemia in the absence of an insulinoma. These
morphologic abnormalities include; hypertrophic islets’ B
cells, close association of islet cells with small pancreatic
ducts and an abnormal aggregation of islets. It is the most
common cause of Persistent Neonatal Hyperinsulinemic
Hypoglycemia. In adults, Insulinoma is the most common
cause. A relationship between the hyperfunction pathology conditions of B cell was not identified as yet. Adult
patients with nesidioblastosis characteristically present
with neuroglycopenic symptoms within a short period of
meal ingestion, but have negative hypoglycemic response
to a 72-hour fast. After excluding an insulinoma by imaging studies, selective arterial calcium-stimulation test
(SACST) can be helpful in differentiating nesidioblastosis from insulinoma. Diagnosis requires histopathological
verification. Treatment is operative reduction of the B cell
mass with guidance by SACST.
Conclusion: Nesidioblastosis should be considered in
a patient with previous evidence of insulinoma, presenting
with recurrent hyperinsulinemic hypoglycemia. We raise
the question of a common etiology causes both disorders.
– 48 –
Conclusion: Insulin overdose and suicidal intent
is more common than thought and should be considered
in diabetic patients with unexplained hypoglycemia.
Physicians should be prepared for persistent and recurrent
hypoglycemia. Delay in therapy is an important prognostic
factor.
are not different from a typical insulinoma, the diagnosis,
however, is usually delayed until proinsulin measurement
is made. As in other reported cases, measurements of proinsulin, but not insulin, established the diagnosis.
Abstract #302
RESTORATION OF HYPOGLYCEMIA
AWARENESS AFTER ISLET TRANSPLANTATION
Abstract #303
ABNORMAL EXPRESSION OF THE
PRO-PROTEIN CONVERTASES 1/3 (PC1) AND
PC2 IN HUMAN INSULINOMAS,
THE SO CALLED “PROINSULINOMAS”
Cristiane Bauermann Leitao, MD, Pablo Cure,
Antonello Pileggi, David A. Baidal,
Thipaporn Tharavanij, Davide Mineo, Karina Bernetti,
Raquel N. Faradji, Tatiana Froud, Aleida Saenz,
Camillo Ricordi, and Rodolfo Alejandro
Daniel Cuevas-Ramos, MD, Francisco J. Gómez-Pérez,
Paloma Almeda-Valdés, Xeily Zarate-Diaz,
Alejandro Zentella-Dehesa, Jose Luis Ventura-Gallegos,
Norma Uribe-Uribe, and Juan Rull
Objective: To determine if optimal metabolic control
achieved by islet transplantation has sustained effects on
hypoglycemia unawareness.
Methods: A retrospective cohort study was conducted in 29 subjects followed before and after allogenic
islet transplantation as treatment for unstable type 1 diabetes mellitus. Hypoglycemia unawareness was accessed
through a validated questionnaire (Clarke score; score =
0 if no reported hypoglycemia; score ≥4 = hypoglycemia
unawareness) before and at end of follow-up. A stratified
statistical analysis was performed based on graft function:
off-insulin (n = 8), graft dysfunction (back on insulin and
stimulated C-peptide ≥0.3 ng/ml, n = 13) and graft failure
(stimulated C-peptide <0.3 ng/ml, n = 8, 5.5 ± 6.2 months
after failure).
Results: The hypoglycemia score was lower after
islet transplant (1.11 ± 1.52 vs. 5.41 ± 1.52, P <0.001) and
an increment in the threshold for hypoglycemic symptoms was observed (60.28 ± 7.9 vs. 42.5 ± 18.7 mg/dl, P
= 0.001), as expected. Lower hypoglycemic score values
were correlated with better beta cell function (r = -0.522,
P = 0.004 and r = 0.605, P = 0.001 for stimulated C-peptide and glucose levels, respectively). These results were
sustained even after patient’s stratification based on islet
function (off-insulin–pre: 5.63 ± 2.00 vs. post: 0.00 ± 0.00,
P <0.001; graft dysfunction–pre: 5.31 ± 1.49 vs. post: 1.23
± 1.59, P <0.001 and graft failure-pre: 4.86 ± 1.35 vs. post:
2.14 ± 1.57, P = 0.004).
Discussion: The recovery of awareness found in offinsulin and graft dysfunction groups was predictable and
probably related to islet function. In patients with graft failure it is possible that the due to avoidance of hypoglycemia
during the early post-transplant period lead to reestablishment of alert hypoglycemic symptoms.
Objective: The mechanism of the over production of
proinsulin by proinsulinomas is unknown. Since the normal processing of proinsulin to insulin involves PC1/3
(75%) and PC2 (15%), the aim of the study was to analyze
the expression of PC1/3 and PC2 in one proinsulinoma and
one benign insulinoma.
Methods: Western blot with anti-PC1/3 and anti-PC2
antibodies was done in both islet-cell tumors; and used
normal pancreatic tissue from each patient, from mice and
an islet-cell culture (RINmsf) as control.
Results: Immunoblot in both tumors’ cells detected
specific molecular bands for PC1/3 at 80kDa and for PC2 at
65kDa. An increased expression of PC1/3 (3-fold) and PC2
(15-fold) was detected in both tumors but not in controls.
Interestingly, we found a second specific band expression
for PC1/3 of lower molecular weight (75kDa) only in the
proinsulinoma.
Discussion and Conclusions: The immunoblot results
indicate that in both tumors, the activity of PC1/3 and PC2
is increased. In addition, we found an abnormal expression
of PC1/3 only in the proinsulinoma. It is plausible that a
structural alteration of PC1/3 explains a lower molecular
weight and enzymatic activity of this protein, and therefore a defective processing of proinsulin to insulin. The
decreased activity of PC1/3 is not overcome by the overexpression of PC2 and, the proinsulinoma, in turn, releases
more proinsulin to the circulation. Although the results
need confirmation, the enzymatic abnormality of PC1/3
found in this study seemed to be exclusive of proinsulinomas. If confirmed, a new subtype of islet-cell tumors with
different physiopathology and diagnostic approach should
be considered. Although the clinical behavior and treatment
– 49 –
Conclusion: Stable metabolic control achieved with
clinical islet transplantation restores hypoglycemia awareness and these effects have persisted even after islet graft
failure.
72-h fasting test has been illustrated in some patients with
insulinoma. It is also possible that early in the treatment
of panhypopituitarism and central adrenal insufficiency
with corticosteroid, patients might have relative hyperinsulinemia resulting in misleading 72-h fasting test. An
inconclusive fasting test should be interpreted in the light
of clinical picture.
Abstract #304
RECURRENT HYPOGLYCEMIA IN
HYPOPITUITARISM TREATED WITH
CORTICOSTEROID.
Abstract #305
PROINSULIN-SECRETING ISLET-CELL TUMOR
AS A CAUSE OF ORGANIC HYPOGLYCEMIA,
OUR FOURTH CASE
Tanyanan Tanawuttiwat, MD, Tarita Thomas, MD,
Barnard San Gabriel, MD, Tahira Yasmeen, MD,
Dan Mihailescu, MD, and Joseph Kowalczyk, MD
Daniel Cuevas-Ramos, MD, Francisco J. Gómez-Pérez,
Paloma Almeda-Valdés, Xeily Zarate-Diaz,
Norma Uribe-Uribe, and Juan Rull
Introduction: Fasting hypoglycemia is a serious condition which can potentially cause substantial morbidity
and even death. Frequently, there is difficulty in diagnosis, localization and management due to failure to recognize each of the clinical syndromes. We describe a case of
hypoglycemia related to endogenous hyperinsulinemia in a
patient with panhypopituitarism.
Case description: A 60 years old lady with neurosarcoidosis previously treated with prednisone presented
with generalized seizures associated with hypoglycemia.
Physical examination was unremarkable. Laboratory data
showed low blood glucose. Patient was also found to have
panhypopituitarism. She was treated with stress doses of
hydrocortisone for adrenal insufficiency, followed by levothyroxine replacement. However, she continued to have
hypoglycemic episodes. 72-h fasts revealed a low glucose level of 40 mg/dl with concomitant inappropriately
elevated insulin (7 uIU/ml), pro-insulin (19.5 pmol/L) and
C-peptide (3.7 ng/ml) levels. Similar results were obtained
during a spontaneous hypoglycemic episode 5 days after
admission which also was consistent with endogenous
hyperinsulinemia. Sulfonylurea screen was negative. The
possibility of a coexistent insulinoma was considered.
Abdominal CT scan, MRI, endoscopic ultrasound and
octreotide scintigraphy, were all unable to localize a tumor.
She was transferred to a tertiary center where repeat imaging studies including celiac-splenic angiogram failed to
show any focal tumors. Patient also underwent a second 72h fasting which was reported within the normal limits. She
was discharged home on hydrocortisone and levothyroxine
replacement therapy and so far remained asymptomatic.
Discussion: Insulinoma is the most common cause
of hyperinsulinemic hypoglycemia. A “normal” standard
Objective: To report a case of a proinsulinoma.
Case presentation: a 46-year-old woman was studied
for organic hypoglycemia. The patient had a five year history of dizziness, confusion, seizures and a weight increment of 26 lbs. She underwent a supervised fast that produced symptomatic hypoglycemia (20mg/dl) after 7 hours.
During the entire fast test, insulin, using an ultraspecific
assay, remained lower than 3μU/ml (2.2±0.7) when glucose was <50mg/dl. Urinary sulphonylureas were negative
and C-peptide was high normal (3.3±0.7ng/ml, 0.8-3.9).
Circulating proinsulin was persistently and significantly
high (>200±0.0pmol/L, nl<18) during the test. An abdominal MRI and endoscopic ultrasound confirmed the presence of a 2.5 cm tumor in pancreatic head. The patient
underwent surgical resection. Interestingly, the immunohistochemistry staining for proinsulin was stronger than
insulin inside the tumor.
Discussion: The biological activity of proinsulin is
estimated to be only 5-10% of that of insulin. Nevertheless,
some authors suggest that the hyperproinsulinemic state
amplifies the biological activity of this peptide and, consequently, serum glucose levels decrease. This appears to be
a reasonable explanation for the findings in our patient. We
were surprised that of our last consecutive cases of organic
hypoglycemia, 4 out of 5 appeared to be proinsulinomas.
This fourth case shares similar clinical and biochemical
characteristics of the other three previously reported.
Conclusion: The measurement of proinsulin levels may disclose the etiology of organic hypoglycemia
in patients with islet-cell tumor and normal intact insulin
levels.
– 50 –
puted tomography was performed and found with a small
lesion at the tale of the pancreas. During exploratory laparotomy, a lesion (1.2x0.5x0.7cm) found by palpation and
small portion of the tale of the pancreas (1.5x0.6x0.6cm)
was removed. After the surgery, half hour, and one hour
later the blood sugar levels were138 and 132mg/dL,
respectively. One month after the surgery, a repeat fasting
blood sugar was found on 49mg/dL, insulin 66.2uIU/mL,
and C-peptide 9.4ng/mL, with recurrence of symptoms.
The pathology failed to report any endocrine tumor, but
it did revealed findings consistent with the adult form of
nesidioblastosis. The patient was started in Diazoxide with
improvement in glycemia and symptoms. The possibility
of a more extensive pancreatectomy is being discussed.
Discussion: Nesidioblastosis is the most common
cause of neonatal hyperinsulinemia but is rare in adults
accounting for 0.5-7% of all causes of hyperinsulinemia.
Pathologic findings are primarily islet cell hyperplasia that
is found in close contact with acinar ducts. Our patient’s
history and findings were consistent with these pathologic findings, but they have also been described in nontumor pancreatic tissue of patients with insulinomas. As
the report failed to demonstrate pathologic findings of an
insulinoma, and the patient had recurrence of symptoms
and biochemical evidence of hyperinsulinemic hypoglycemiaafter the lesion was removed, we made a diagnosis of
nesidioblastosis.
Conclusion: Although a very rare disorder in adults,
nesidioblastosis should be considered as a differential
diagnosis when evaluating a patient with hyperinsulinemic
hypoglycemia, even in the presence of a pancreatic mass.
Abstract #306
NESIDIOBLASTOSIS: A RARE CAUSE OF
NONINSULINOMA PANCREATOGENOUS
HYPOGLYCEMIA SYNDROME IN ADULTS
Marielba Agosto, MD, Monica Santiago, MD,
Jose Garcia Mateo, MD, Margarita Ramirez, MD,
Myriam Allende, MD, and Vilma Rabell, MD
Objective: To report a case of an adult male patient in
Puerto Rico with nesidioblastosis.
Case Presentation: A 54-year old man referred after
he was found with a fasting glucose of 40mg/dl during
work up for hypoglycemia. The patient refers that since
one year ago, had been experiencing weight gain, intermittent cold sweats, dizziness, blurred vision, and tumescence, which were relieved with carbohydrates ingestion.
The episodes occurred both at fasting and postpandrially,
and he denies insulin administration. Medical history was
negative for peptide ulcer disease or gastrointestinal surgical procedures, family history was negative for endocrine tumors and physical examination was unremarkable.
Repeated fasting blood sugar 39mg/dL(60-100 mg/dl), with
concomitant insulin levels:24.09uIU/ml(1.9-23 uIU/ml),
proinsulin levels:34.1pmol/L(1.8-18pmol/L), b-hydroxybutarate 0.5 mmol/L (> 2.7mmol/L), C-peptide: 4.4 ng/mL
(1.1-5 ng/mL), a negative serum sulfonylurea screen and
negative serum insulin antibodies. An insulinoma was considered to be the etiology, but abdominal magnetic resonance, computed tomography, and indium octreotide scan
were all negative. An abdominal arteriogram with a com-
– 51 –
ABSTRACTS – Lipid Disorders
experiments have shown competitive inhibition of binding
between HCV and LDL receptor by LDL thus low LDL
actually helps the virus to gain entry into the hepatocyte.
Deficiency of MTP also causes low Apo B and that could
be involved in the pathogenesis of steatosis in chronic
Hepatitis C. No significant difference has been seen in the
levels of triglycerides.
Conclusion: Lower LDL cholesterol and BMI is seen
soon after the HCV infection is diagnosed regardless of
degree of fibrosis. The cardiovascular benefits of this are
still unproven.
LIPID DISORDERS
Abstract #400
UNDETECTABLE LDL CHOLESTEROL IN
DIABETIC WITH HEPATITIS C
Suchitra V. Zambare, MD, and Hamdee Attallah
Objective: To understand the interactions between
chronic hepatitis C and lipid metabolism.
Case-Presentation: A 56-year-old African American
male with Hepatitis C related to prior IV drug abuse was
seen for evaluation and treatment of recently diagnosed
type 2 diabetes mellitus. He was originally on NovoLog
70/30 mix 15 units twice daily and metformin 500 mg
twice a day but experienced repeated hypoglycemic episodes on this regimen. He denied polyuria or polydipsia.
He had loss of appetite, fatigue and weight loss for the last
3 months. Insulin was gradually tapered off because of his
symptoms, and his HbA1c was 6%.
Abstract #401
STATINS IN CLINICAL PRACTICE:
USE OR OVERUSE?
Mohsen Eledrisi, MD, FACE, Analyn Crisostomo,
Omran Joosub, Elsayed Bakry, and Mohammed Sultan
Objective: Statins are commonly prescribed in clinical practice. We aimed at assessing the appropriateness of
prescribing statins by physicians. The guidelines recommended by the national cholesterol education program
adult treatment panel (ATP-III) were used as a quality
control tool to determine if statin therapy was properly
indicated.
Methods: The study was conducted at the National
Guard medical city in the eastern region of Saudi Arabia.
Patients using statins were identified from the pharmacy’s
computerized system of physicians’ prescriptions. Medical
charts of those patients were reviewed and data collected
on, age, sex, medical conditions, LDL-cholesterol levels,
risk factors of coronary heart diseases (CHD), including
family history of CHD, smoking history, and HDL levels,
and indication for initiating statins. Target LDL-cholesterol
levels and need for drug therapy was assessed according to
ATP-III guidelines.
Results: A total of 885 patients were identified.
Patients’ primary diagnosis was as follows: hypertension
77 %, diabetes 13 %, coronary artery disease 1 % and dyslipidemia 9 % (had 0-1 risk factors). Using the ATP-III criteria for initiating drug therapy, statins were appropriately
prescribed for 30 % of patients with hypertension, 95 % of
patients with diabetes, and 100 % of patients with CHD.
All clinical decisions to start statins for patients with the
diagnosis of dyslipidemia were not supported by evidence
(those patients had LDL levels that did not meet the criteria
for drug therapy).
Discussion: Dyslipidemia is well-recognized as an
important risk factor for coronary heart disease. Statins
have shown significant impact on cardiovascular disease
PHYSICAL EXAMINATION: BP:120/ 70, P: 80, R/R:
20, BMI 23.8. Examination was unremarkable except for
the appearance of fatigue and a thin body habitus.
LABS: Electrolytes normal, BUN12mg/dL (7-20), Cr
0.6mg/dL (.6-1.3), Cholesterol 50mg/dL (100-200), triglycerides 12mg/dL(35-160),HDL 26mg/dl (>39) LDL
could not be calculated. Total bili 0.4mg/dL (0-1.5), alk
phos 52u/L (50-185), albumin 3.3g/dL (3.5-5.2), AST 23u/
L (0-60), ALT 40u/L (0-65), Apo-lipoprotein-B < 35mg/
dL (52-109)
Discussion: Studies have reported 5 times higher
prevalence of hypocholesterolemia and hypo-betalipoproteinemia in patients with HepatitisC infection than the general population. The mechanism by which HCV infection
may lower serum cholesterol is not known. Microsomal
Triglyceride Transfer Protein (MTP) is necessary for
assembly and secretion of VLDL cholesterol from the
hepatocytes. It has been demonstrated that hepatic overexpression of HCV core protein causes a marked reduction of MTP activity and results in decreased secretion of
VLDL cholesterol. These are the mechanisms postulated to
explain the lower VLDL and LDL cholesterol production
that can occur with hepatitis C infection. Particles of HCV
exist bound within lipoprotein particles. It is suggested that
the LDL may protect the virus from the inactivating antibodies. Thus a reduction in serum LDL cholesterol may
serve as a defense mechanism against hepatitis C infection.
On the contrary it has been reported that HCV binds to the
LDL receptor in order to gain entry into the hepatocyte and
– 52 –
and are one of the most commonly used drugs worldwide.
The National Cholesterol Education Program adult treatment panel (ATP-III) recommends specified target levels
for LDL-cholesterol that vary according to the patient’s
risk for coronary heart disease. Our data showed that in this
Saudi population, statins were appropriately prescribed for
patients with CHD, CHD equivalent and those at high risk
for CHD (2 or more risk factors). However, in the majority
of lower risk patients (those with 0-1 risk factors) the use
of statins was not supported by evidence.
Conclusion: In this study, clinical decisions were
appropriate to initiate statins in the majority of patients
with diabetes, those with CHD and those with 2 or more
CHD risk factors. However, most patients with 0-1 risk factors were prescribed statins with no justification. Physician
education and focused quality improvement programs are
needed to improve the patterns of statins prescriptions.
Discussion: ABL (Bassen-Kornzweig syndrome)
is a rare autosomal recessive disease. Clinical manifestations result from malabsorption and defective transport of
lipids and fat soluble vitamins (A, D, E, and K). In our
patient ABL presented as a failure to thrive in infancy with
steatorrhea. An unusual feature of this case was that the
patient had no neuromuscular or ocular manifestations,
possibly related to initial compliance with vitamins during childhood. Her family history revealed normal lipid
profiles in both parents indicating an unusual inheritance
of this disorder. Patient had no prenatal care and was noncompliant with vitamin therapy. Vitamin K deficiency
was responsible for the coagulopathy in this patient causing postpartum hemorrhage. Fortunately our patient had a
normal neonatal outcome despite several abnormal fetal
effects reported with fat-soluble hypovitaminosis.
Conclusion: This is the first reported case in literature with life threatening postpartum bleeding in a patient
with abetalipoprotenemia. Expecting patients with ABL
should be counseled. Clinicians should make sure that
laboratory studies (serum retinol levels, coagulation panel)
are normalized and maintained for a favorable pregnancy
outcome.
Abstract #402
ABETALIPOPROTENEMIA WITH
POSTPARTUM HEMORRHAGE
Seema Haq, MD, Mary Baker,
Hal Scofield, and Sadaf Saghier
Abstract #403
Objective: The purpose of this case report is to review
the management of abetalipoprotenemia (ABL) and its
impact on pregnancy and fetal outcomes.
Case Presentation: A primigravid 24-year-old with
history of abetalipoprotenemia presented with early postpartum hemorrhage and hemodynamic instability after
vaginal delivery at 37 weeks of gestation. Infant was delivered at home by midwife with proper delivery of placenta.
Patient denied any history of coagulation disorders, excessive bleeding with surgical procedures, menorrhagia or
being on any medications. Her family history was unremarkable. Physical examination revealed a pale, lethargic,
tachycardic (pulse rate 110 beats/min), afebrile, and hypotensive (BP 70/40 mmHg) patient. Abdomen was mildly
distended and non-tender. Genital examination revealed left
vulvular hematoma at the episiotomy site oozing bloody
serous fluid. Laboratory studies showed INR 7.7 (0.9-1.2),
PT 72.4 (9.5-12), PTT 83.6 (24-34) and hemoglobin 5 gms
(12-16), acanthocytosis and normal platelet count. She had
abnormal lipid and lipoprotein profile consistent with history of ABL. Patient was stabilized with PRBC, IV fluids
and subcutaneous vitamin K. Perineal hematoma was managed conservatively. Infant evaluation was reported normal
by the pediatrician. Patient did well and was discharged
home on modified regimen of fat-soluble vitamins.
HYPERLIPIDEMIA IN SYSTEMIC
LUPUS ERYTHEMATOSUS
Sudip Nanda, MBBS, Rohini Handa, MD, and
Surya Prakash Bhatt, MD
Objective: Premature atherosclerosis is increasingly
recognized in systemic lupus erythematosus (SLE) and
other autoimmune disorders. Hyperlipidemia in SLE is due
to both the disease and its treatment.
We hypothesized that patients with SLE have a high
frequency of hyperlipidemia and aimed to estimate its frequency and determinants.
Methods: 103 consecutive SLE patients fulfilling the
American College of Rheumatology 1997 criteria were
included in this cross-sectional observational study conducted at a tertiary referral center. Patients with diabetes
mellitus; age<16 years; overlap syndromes; pregnancy;
statin use; with other defined causes of hyperlipidemia like
hypothyroidism, liver disease and familial were excluded.
Variables studied included age, sex, BMI, menopausal
status, smoking, alcohol use, nephrotic syndrome, disease duration, and use of steroids and hydroxychloroquine
(HCQ). SLE Disease Activity Index (SLEDAI) assessed
the disease activity with SLEDAI>16 being severe disease.
– 53 –
and beta-blocker use, and disease severity. Nephrotic syndrome was more common in patients with hyperlipidemia
(16.1% vs 2.9%; p=0.03). Severe disease, present in 25%,
was associated with significantly elevated TG (210±118 vs.
154±109 mg/dl, p=0.03). Those on steroids and HCQ had a
lower apo B compared to those on steroids only (81±29 vs.
108±46 mg/dl, p=0.01).
Discussion and Conclusion: Hyperlipidemia is a frequent occurrence in this young, predominantly pre-menopausal cohort of lupus patients. It should be routinely tested
and aggressively treated.
Fasting lipid profile included total cholesterol, LDL-C,
VLDL-C, HDL-C, TG, ApoA and ApoB. Borderline high
for any one of the 5 lipid parameters of the NCEP-ATP III
guidelines was used to define hyperlipidemia.
Results: Mean age was 32.9+10.7SD years. 97(94%)
were females of whom 88.7% were pre-menopausal.
68(66%) patients had hyperlipidemia. 30(44%) had elevated LDL-C, 40(59%) had elevated VLDL-C, 41(60%)
had hypertriglyceridemia and 33(49%) had low HDL-C.
There were no significant differences between those with
hyperlipidemia and those without, in age, sex, presence of
lupus nephritis, duration of disease, oral prednisone HCQ
– 54 –
ABSTRACTS – Metabolic Bone Disease
PREVALENCE OF VITAMIN D DEFICIENCY
AMONG ACUTE HIP FRACTURE PATIENTS IN A
NEW ENGLAND HOSPITAL
hip fractures. History of a previous fracture as a risk factor
for future fractures is still under-recognized in the medical community. Increased awareness can lead to efforts
to modify risk factors including vitamin D deficiency. Identifying and treating these patients with vitamin D may
help prevent future fractures and the significant morbidity
associated with them.
Akta Patel Mukherjee, MD, and Suzanne Rieke, MD
Abstract #501
Objective: To determine the prevalence of vitamin D
deficiency in patients presenting with acute hip fracture in
a New England Hospital.
Methods: This study was a retrospective analysis of 117 patients who presented with acute hip fracture
from November 2004 to January 2006 to Lahey Clinic
in Burlington, Massachusetts. An endocrinology consultation assessed risk factors for osteoporosis including a
25hydroxyvitamin D (25OHD) for all of these patients.
Results: Ninety patients (76.9%) with acute hip fracture were women, and mean age was 80.3 years. With a
25OHD of <30ng/ml, 109 patients (90.6%) presenting with
acute hip fracture were vitamin D insufficient. Seventythree patients (62.4%) were vitamin D deficient, with a
25OHD <20ng/ml. Mean serum calcium was 8.5mg/dl
among all patients. The mean parathyroid hormone level
in the 15 patients assessed was 57.8pg/ml. Fifty patients
(42.7%) reported a history of osteopenia or osteoporosis, and 63 subjects (53.8%) had a history of previous
fracture. Twenty-four patients (48%) with osteoporosis
prior to admission were vitamin D deficient compared to
49 patients (73.1%) without osteoporosis. However, of the
63 patients with a history of fracture, 43 subjects (68.3%)
were vitamin D deficient compared to 30 of 54 patients
(55.6%) without a fracture history.
Discussion: The health consequences of vitamin D
deficiency have been increasingly recognized, including
the greater risk of fractures. Our study demonstrates the
continued high prevalence of vitamin D deficiency among
patients presenting with a hip fracture. The majority of
patients presenting to our hospital with hip fracture, even
with history of a previous fracture, were vitamin D deficient. Patients with osteoporosis or osteopenia were less
likely to be vitamin D deficient, because they are often
advised to start calcium and vitamin D. However, history
of fracture is not identified as an osteoporosis risk equivalent that is aggressively treated with vitamin D. The new
emphasis on fracture risk assessment will help address this
issue and identify patients at high risk of complications
from vitamin D deficiency.
Conclusion: This study reinforces the high prevalence of vitamin D deficiency in patients presenting with
FLUORESCENCE-GUIADED
PARATHYROIDECTOMY IN SECONDARY
HYPERPARATHYROIDISM: FIRST CASE OF
LATIN AMERICA
METABOLIC BONE DISEASE
Abstract #500
Pedro E Morales, MD, Franklin García, MD,
Lavi Jasson, MD, and Monsalve Laura, MD
Objective: Develop the technique of the fluorescence
– guiaded parathyroidectomy in patients with secondary
hyperparathyroidism.
Case presentation: Female patient, 29 years old, with
systemic lupus eritematous since 10 years. Chronic renal
failure since 5 years, with dialysis since 2 years. Se refers
bone pain, 1 year of evolution, and deformation in fingers
of hands. Also, diagnosis of multinodular goiter the last
year. Serum parathormone in 6500 pg/ml, alkaline fosfatase 380 U/L, serum calcium 10.5 mg/L, serum phosphorus 4.0 mg/L. Ultrasound of neck showed thyroid increased
and nodular image suggesting right superior parathyroid
gland. Photosensitization was with 5-aminolevulinic acid,
dose 30 mg/Kg, diluted in 250 cc of water, oral way, 4 hour
before the procedure. The patient stayed in dark room.
We did total thyroidectomy, total parathyroidectomy and
transcervical subtotal timectomy. The surgical procedure
begins with cervicotomy. Then, exposition of posterior
side of thyroid lobules. First, we used white light without
recognize the parathyroid glands. Then, we used blue light
wavelength between 380-440 nm (D-Light System, Karl
Storz Co) by 3 minutes and we can recognize 4 structures
with selective red fluorescence corresponding to 4 parathyroid glands. The pathology analysis showed 4 parathyroid
glands (the same structures identified with fluorescence)
with hyperplasia; the thyroid gland showed adenomatous
hyperplasia; the timic specimen showed not alterations.
The evolution of patient was satisfactory. Only one adverse
effect: skin reaction auto-limited in 10 days.
Discussion: The surgery treatment of secondary
hyperparathyroidism requires the recognition of all parathyroid glands. In some cases, this situation is not easy and
is necessary the use of methods for the localization of the
glands, principally in cases of ectopic tissue. The fluores– 55 –
cence-guiaded parathyroidectomy showed the capability of
recognizes, in selective form, the parathyroid glands. This
technique not requires special training, not uses radiations
and is not necessary expensive equipments, only the surgeons and the blue light source. Also, the 5-aminolevulinic
acid is a natural product, with few adverse effects. This
case is the first fluorescence-guiaded parathyroidectomy
in Latin America. The firsts reports in the world were in
Germany. In the medical literature, there aren’t cases with
this technique in United States.
Conclusion: The fluorescence-guiaded parathyroidectomy in patients with secondary parathyroidectomy is an
effective technique. May be the use of this technique will
be for cases of primary hyperparathyroidism or reoperation
where the anatomy is altered. However, the model of secondary hyperparathyroidism is very good for observe and
study the technique. Finally, this is an important contribution of the region.
Discussion: Based on the above presentation &
investigations patient. was diagnosed as having Primary
Hyperparathyroidism due to parathyroid adenoma but did
not have overt hypercalcemia due to associated vitamin D
deficiency. Patient was operated & left lower parathyroid
gland was removed. Histopathology showed parathyroid
adenoma with other biopsied glands normal. In immediate
post-op period serum PTH-3.28 pg/ml; Trousseau’s sign
positive; serum calcium 7.3 mg/dl; phosphorus 1.4 mg/
dl & ALP 1761 U/L.Patient. was given calcium replacement 3g/d & 60,000 U of 25(OH)vitamin D.Post-operative
day 5- calcium rose to 7.5 mg/dl. After 3 weeks patient
asymptomatic, serum calcium 8.4 mg/dl; phosphorus 3.5
mg/dl; ALP 1699 U/L; PTH 56.5 pg/ml; 25(OH)vitamin
D 46.85 ng/ml; BMD after 4 mth showed improvement
in bone density, yet in osteoporotic range. At 8 mth, pt
could walk without support, climb stairs with no aches &
pains. Serum calcium 8.6 mg/dl; phosphorus 3.6 mg/dl;
ALP 506 U/L; 24 hr. urinary calcium 172.4mg/day.Due
to high prevalence of vitamin D deficiency in India, normocalcemic hyperparathyroidism is not uncommon. This
association leads to more severe bone disease than what
is seen in primary hyperparathyroidism without vitamin D
deficiency.
Conclusion: Our patient is a case of primary hyperparathyroidism due to Parathyroid adenoma of left
lower gland with Vitamin D deficiency, presenting with
normocalcemia.
Abstract #502
NORMOCALCEMIC PRIMARY
HYPERPARATHYROIDISM
Sachin Kumar Jain, MBBS, MD, DM, FACE,
Niti Agarwal, and Ajay Ajamani
Objective: To present a case of Primary Hyperparathyroidism with coexisting vitamin-D deficiency.
Case Presentation: 44 yr old postmenopausal lady
presented with generalized bodyache & backache for
1year,had been wheel chair bound for last 6 months.
History of myalgia, generalized weakness & difficulty in
getting up from lying or sitting position for more than one
year. There is no history of polyuria, flank pain or renal
stone. Examination was normal except bone tenderness
& proximal muscle weakness,much more marked in both
lower limbs. Investigations revealed-normal hemogram,
liver & kidney functions; Serum calcium10.10 mg/dl (8.410.2); Albumin 4.9 g/dl (3.4-4.8); phosphorous 1.5 mg/dl
(2.7-4.5); Serum Alkaline phosphatase 4154 U/l(95-240);
PTH 1447 pg/ml(10-69); ionized calcium 1.39 mmol/l
(1.10-1.38); 24 hr urinary volume-1710ml (800-2500) &
calcium-290.70 mg (100-300); 25(OH) vitamin D was 5
ng/ml (9-37.6); vitamin D challenge given with 60,000 U
weekly and after 4 weeks serum calcium rose from 10.10
to 10.80 with ionized calcium being 1.51mmol/l; X-ray
spine showed osteoporotic changes resulting in multiple
vertebral compressions; BMD evaluation revealed severe
osteoporosis; CT- Neck & 99Tc Sesta MIBI scan showed
adenoma left lower Parathyroid gland.
Abstract #503
HYPERCALCEMIA RESULTING FROM
COMBINED USE OF TERIPARATIDE AND
HYDROCHLOROTHIAZIDE
Arun Kumar Movva, MD, and Arnold M. Moses, MD
Objective: To report a case of substantial hypercalcemia in a patient who was on treatment with teriparatide and
hydrochlorothiazide (HCTZ).
Case Presentation: The patient is a 75yr old female
with history of severe osteoporosis. She could not tolerate oral bisphosphonates or IV pamidronate because of
the side effects. She failed to respond with Miacalcin. Her
bone density continued to get worse based on the DEXA
scans. The pretreatment serum calcium and Vitamin D levels were within normal range. Her bone turnover markers,
phosphorus and PTH were also within normal range. She
was treated with teriparatide after which she developed a
substantial asymptomatic hypercalcemia. The hypercalcemia resolved once the hydrochlorothiazide was substituted
– 56 –
with a nonthiazide antihypertensive medication. Serum
calcium (8.4-10.2mg/dl), Baseline on HCTZ: 9.3, 4-6hrs
after Teriparatide: 12.5, 20hrs after Teriparatide: 11.8,
Off Teriparatide and off HCTZ: 9.6, 5hrs after Teriparatide
and off HCTZ: 10.0.
Discussion: Teriparatide (Forteo) causes hypercalcemia to a modest degree by elevation of the bone turnover
markers. The effect is usually transient. Thiazide diuretics
are known to increase renal calcium reabsorption. They
cause hypercalcemia infrequently because of the compensatory mechanisms. Our case illustrates that patients can be
at risk of developing substantial hypercalcemia when they
are on both medications. To the best of our knowledge such
an association has never been reported before. Further studies delineating the association are needed to be done.
Conclusion: We recommend careful monitoring of
serum calcium levels in patients on thiazide diuretics who
are being treated with Teriparatide.
(4.8%) reported drinking >14 alcoholic/week vs 3.4% of
Eur and 2.5% of US (p<0.0001); women with a fracture
were 0.7, 3.5, 1.8% (p=0.7). Smoking was higher in women
with a fracture (Aus/Can 25%, US 13%, Eur 16%, p=0.03)
vs those without (8.9, 11, 6.9%, p<=0.0001). Those with a
fracture were more likely to use their arms to assist from
sitting (Aus/Can 81%, US 59%, Eur 48%, p=0.6) vs those
without (35, 29, 32%, p<0.0001). Rheumatoid arthritis was
more common in women with a fracture (Aus/Can 26%,
USA 21%, Eur 7.3%, p=0.04) vs those without (10, 12,
7.8%, p<=0.0001).
Conclusion: In this international real-world cohort,
self-reported fracture risk factors varied by region and
fracture history.
Abstract #505
VITAMIN D DEFICIENCY: EFFECTIVENESS OF
WEEKLY ADMINISTRATION OF ORAL 50,000 IU
ERGOCALCIFEROL
Abstract #504
DISTRIBUTION OF RISK FACTORS FOR
FRACTURE IN WOMEN WITH AND WITHOUT
A FRACTURE HISTORY: A REGIONAL
COMPARISON. THE GLOBAL LONGITUDINAL
REGISTRY OF OSTEOPOROSIS IN WOMEN
Donald Bodenner, MD, PhD, and Carolyn Redman
Objective: The aim of the present study was to evaluate the response of vitamin D (vit D) deficient patients (<30
ng/ml) to treatment with weekly doses of 50,000 IU of vit
D2.
Methods: The records of patients with complete data
available who had been treated weekly with 50,000 IU of
vit D for variable amounts of time were retrospectively
reviewed. Clinical variables abstracted from each patient’s
record included: race, sex, age, diagnosis of malabsorption,
vit D levels, and number of vit D treatments.
Results: 48 patients were treated with 50,000 IU
vit D2. The mean age was 70.8 (+/-10.1) years, 45 were
female, and there were 6 African Americans. All patients
were taking greater than 1,000 mg of calcium. In 11
patients (23 %), the treatment course failed to raise the vit
D level more than 6 ng/ml. None of the patients carried
the diagnosis of malabsorption, so these treatment failures
were considered to be secondary to noncompliance. Of the
37 patients that appeared to take the vit D as prescribed, one
treatment course normalized vit D levels (>30 ng/ml) in 29
patients (78% success rate) and two courses were required
in 4 patients for an overall success rate of 89%. True treatment failures where the vit D level increased by more than
6 ng/ml but did not normalize occurred 6 times, however
only in patients severely deficient (2 of 6, 8.0 avg doses of
50,000 IU) or moderately deficient (4 of 6, 8.0 avg doses).
Of the 31 patients successfully treated, the average number
of weekly 50,000 IU doses prescribed for the severely deficient (1-10 ng/dl), deficient (11-20 ng/dl) and insufficient
Nelson B. Watts, MD, FACP, MACE,
Susan L Greenspan, MD, Andrea LaCroix, PhD,
Kenneth Saag, MD, Stuart Silverman, MD,
Ethel Siris, MD, Rebecca Dedrick, MPH, and
Robert Lindsay, MD, PhD
Objective: To compare factors for fragility fracture in
3 regions.
Methods & results: GLOW (Global Longitudinal
registry of Osteoporosis in Women) is a study of women
>=55 recruited by 540 primary physicians in 17 sites in
10 countries. All women in the practice in the prior 2 yr
were eligible. Self-administered questionnaires were used.
Prevalence of risk factors (maternal hip fracture, weight
<125lb/57kg, smoker, arms to assist from sitting, parental
fracture, cortisone, >14 alcoholic units/week, rheumatoid
arthritis) was age-adjusted. In women with a fracture after
45 (n=353, 18%), 17% said their mother had a hip fracture
vs 12% in those without (n=19,767, p<0.01). 29% of women
with fracture reported weight <125lb/57kg vs 16% in those
without (p<0.0001). In women with a fracture, Australians/
Canadians (Aus/Can;19%) and Americans (US;18%) more
often reported maternal fracture vs Europeans (Eur;11%,
p=NS); rates were similar in those without fracture (12, 13,
11%, p<0.001). More Aus/Can without a fracture history
– 57 –
(21-30 ng/dl) patients were 9.3 (+/- 1.6), 9.3 ( +/- 3.5), and
7.2 (+/- 2.7). Vit D levels were elevated outside the normal range (20 to 57 ng/ml) in two patients (91 ng/ml and 61
ng/ml) who remained normocalcemic and asymptomatic.
Discussion: Although vit D deficiency is extremely
common, there are few guidelines for replenishment. This
retrospective review demonstrated that a weekly dosage
regimen with 50,000 IU of vit D successfully treated the
vast majority of compliant patients without toxicity. We
recommend 50,000 IU vit D2 for 9 weeks in patients with
vit D levels less than 21 ng/ml, and 7 weeks for patients
with levels from 21 to 30 ng/ml. This should be followed
by a repeat vit D level and maintenance with at least 800
IU D3 daily.
Conclusion: Weekly 50,000 IU doses of vit D were
safe and effective in treating vit D deficiency, but noncompliance was a major problem. A prospective study will
be required to determine the specific duration required to
adequately treat all patients.
vitamin D supplements. Many of the patients with vitamin
D deficiency were also on low-dose supplements. Only 1
of 18 AA’s had a 25VitD >32 ng/ml. Vitamin D deficiency
and secondary hyperparathyroidism are associated with
metabolic bone disease, myopathy, cardiomyopathy, vasculopathy, and carcinogenesis. Therefore, this high incidence
of deficit could have wide-spread clinical consequences.
Conclusions: These data indicate that vitamin D deficiency is extremely common in older, relatively healthy,
affluent patients being seen in a sunbelt location for generally unrelated problems.
Abstract #507
PARATHYROID STORM
Lisa Young, MD
Abstract #506
VITAMIN D DEFICIENCY IN AN
ENDOCRINOLOGY-LIPID PRACTICE IN
THE SUNBELT
Syeda Sadia Zaidi, MD, and Thomas A. Hughes, MD
Objective: In order to assess the frequency of vitamin D deficiency, we reviewed the charts of all patients
seen in the previous 6 years in the University of Tennessee,
Endo-Lipid private practice office of one of the co-authors
in Germantown, TN (a relatively affluent population). Patients with primary or tertiary hyperparathyroidism (Ca
>11.0 mg/dl), a serum creatinine >2.0 mg/dl, and those
on high-dose vitamin D supplementation (>5000 U/day)
were excluded. A total of 262 patients were included in
this analysis.
Demographics: Average age: 59.9+12.8 (+SD) years
(range: 21-88); 89% Caucasian, 7% African-American;
46% male; serum Ca 9.6+0.5 mg/dl (range 7.8-11.0); serum
creatinine 1.0+0.3 mg/dl (range 0.5-2.0). Twenty-five percent of patients are known to have osteopenia or osteoporosis. The most common diagnoses were: Type 2 Diabetes
(60%), hyperlipidemia (92%), and thyroid disease (28%).
Results & Discussion: Six percent of these 262
patients had severe 25-hydroxy vitamin D (25VitD) deficiency (<10 ng/ml), 32% moderate (10-20 ng/ml), and
35% mild (20-32 ng/ml) deficiency, while 16% were in
the low-normal range (32-40 ng/ml). Only 11% of these
patients had satisfactory 25VitD levels (>40 ng/ml) and
these patients were typically younger and/or on low-dose
– 58 –
Objective: To describe a case of acute renal failure
precipitating a parathyroid storm in a patient with previously diagnosed primary hyperparathyroidism.
Case: A 73 year old African American male was
admitted to the hospital with altered mental status and
abdominal pain. At the time of this admission he had a
serum calcium 21.4mg/dl and a serum iPTH 2872pg/ml.
Past medical history was significant for a 6-year history
of primary hyperparathyroidism and peptic ulcer disease.
Ten days prior, he was admitted with acute renal failure,
his creatinine had increased from a baseline of 1.4mg/dl to
9.4 mg/dl and his serum calcium increased from 12.2mg/dl
to 12.7mg.dl. A presumptive diagnosis of NSAID associated interstitial nephritis was made based on a history of
recent Ibuprofen use and the presence of white blood cells
in sterile urine. His creatinine improved to 3.4mg/dl with
hydration but his calcium continued to rise. Physical exam
revealed an afebrile, elderly black male with normal vital
signs. There was a 2cm by 1.5 cm firm, mobile left sided
neck mass. Serum iPTh which was 875 pg/ml 2 months
prior, increased t0 2872 pg/ml. A prior ultrasound showed
a 1.7 by 1.7 by 1.6 cm possible thyroid adenoma in the left
cervical area and a sestambi scan was also positive in this
area. The patient was aggressively hydrated and furosemide
and calcitonin were added to his regimen. Bisphosphonates
were not used due to his significant renal impairment. The
patient was taken to surgery and a left sided parathyroid
adenoma and a normal left hemi-thyroid was removed.
His iPTH decreased to 49pg/ml and his serum calcium to
9.9mg/dl immediately after the surgery. His postoperative
course was complicated by hypocalcemia, with a nadir ionized calcium of 0.80mmol/l at post op day 5. He responded
to calcium and activated vitamin D supplementation and is
currently normocalcemic off of supplementation.
Discussion: Parathyroid Storm was first described by
Dawson in 19321. It has also been called parathyroid crisis
and parathyroid intoxication. These terms refer to a condition with a very elevated iPTH and serum calcium leading
to clinical complications. The last clinical review suggests
that there have been less than 200 cases reported2. It is
typically caused by sporadic primary hyperparathyroidism
or parathyroid carcinoma. In primary hyperparathyroidism, it is not clear what triggers the rapid increase in iPTH.
Prior case reports have noted an association with a preceding viral illness and dehydration. Renal insufficiency has
been associated with parathyroid storm in 9% of cases3 but
often it is not clear if it is a precipitating event or a complication of the severe hypercalcemia. In this case, the renal
failure preceded any significant changes in his serum calcium or osmolarity. Therefore, it more likely represented a
triggering factor. The mechanism for the rapidly increasing iPTH is unclear. The liver and kidneys degrade iPTH.
In the kidneys, a small amount is degraded after binding
to physiologic PTH receptors. The majority of iPTH degradation occurs after the hormone is filtered through the
glomerulus and metabolized internally by the tubules4.
It is possible that the decreased glomerular filtration lead
to an accumulation of iPTH. The hypercalcemia may also
have been exacerbated by biologically active fragments of
PTH.
Conclusion: This is a case of acute renal failure precipitating a parathyroid crisis.
cose), and a generalized aminoaciduria. Knee radiographs
revealed rickets. The data was consistent with RFS. He
was treated with bicarbonate, calcitriol, and phosphorus
supplementation. Despite hypoparathyroidism and subsequent renal failure, he continued to require phosphorus
supplementation. Hypoparathyroidism and hypophosphatemia persisted after his renal transplantation, but his
rickets resolved. He developed multiple endocrine, renal,
neurologic, and hematologic disorders.
Discussion: Pearson Syndrome (PS), Kearns Sayre
Syndrome (KSS) and Progressive External Ophthalmoplegia
(PEO) are three syndromes associated with a deletion of
mtDNA. Clinical expression of these disorders is broad and
can include anemia, heart disease, pigmentary retinopathy,
cerebellar ataxia, and endocrinopathies such as diabetes
mellitus, growth hormone deficiency, hypoparathyroidism, and RFS. Hypoparathyroidism and congenital heart
defects in the newborn merits an evaluation for DiGeorge
Syndrome. Our patient had a normal chromosome 22q11
analysis. He developed several disorders that have been
previously associated with deletion of mtDNA. As in our
patient, clear delineation between PS and KSS is difficult
since clinical features can overlap or change over time. RFS is caused by a proximal tubulopathy associated with
multiple inherited or acquired disorders. In the context of
mtDNA deletion, it would seem that an intrinsic renal defect
would cause the tubulopathy and renal phosphate wasting. It is striking that the renal phosphate wasting has persisted
despite his renal transplantation and hypoparathyroidism
suggesting that a circulating factor may play a role.
Conclusion: Mitochondrial DNA deletion syndromes
are rare and can result in significant endocrine abnormalities including concurrent RFS and hypoparathyroidism.
Abstract #508
FANCONI SYNDROME AND
HYPOPARATHYROIDISM ASSOCIATED WITH A
MITOCHONDRIAL DNA DELETION SYNDROME
Abstract #509
Remberto Cuenca Paulo, Jr, MD, and
Peter J. Tebben, MD
PAGET’S DISEASE PRESENTING AS
CAUDA EQUINA SYNDROME MIMICKING
A SPINAL TUMOR
Objective: To describe a boy with a mitochondrial
DNA (mtDNA) deletion syndrome associated with hypoparathyroidism and renal Fanconi syndrome (RFS). We
present his clinical, biochemical, radiographic, and genetic
data.
Case Presentation: The patient is a 7 year old boy
with congenital heart defects, pancytopenia, and hypocalcemia discovered shortly after birth. He has had persistent
inappropriately normal or low PTH levels despite hypocalcemia. Physical exam and genetic analysis did not support a diagnosis of DiGeorge Syndrome. Mitochondrial
studies revealed mtDNA deletion. He subsequently developed short stature, hypophosphatemia, hyperphosphaturia,
metabolic acidosis, glucosuria (with normal serum glu-
Daniel Rubin, MD, and Robert Levin, MD
Objective: To describe a case of cauda equina syndrome in a patient with Paget’s disease of bone mimicking
a spinal tumor.
Case Presentation: A 67 year-old man with a history
of Paget’s disease of bone presented with 3 weeks of low
back pain radiating down the left leg and left thigh weakness. CT and MRI revealed diffuse osteolytic and sclerotic
lesions of the spine and pelvis. Additionally, a 6 x 5 x 7
cm bony mass arising from the L3-L5 vertebrae was causing neuroforaminal narrowing and spinal canal stenosis. – 59 –
SPECT bone scan showed increased radiotracer uptake at
multiple sites including the L3-L5 vertebrae. Serum alkaline phosphatase was 1287 U/L (normal 25-100) and serum
calcium was 9.1 mg/dL. CT-guided biopsy of the mass
revealed increased osteoclastic activity and irregular bone
trabeculae consistent with Paget’s disease. Pamidronate 60
mg IV monthly and 2 weeks of high dose corticosteroids
were administered, which temporarily relieved the patient’s
symptoms. One month after corticosteroids were discontinued, the pain and weakness worsened. Electrodiagnostic
testing revealed active denervation of the L3-S1 innervated
muscles. The patient underwent lumbar laminectomy and
partial corpectomy, resulting in modest improvement. Despite a decrease in alkaline phosphatase to 416 U/L after
180mg total of pamidronate, his symptoms again recurred
and the patient underwent a second laminectomy 7 weeks
later. He was given zoledronic acid 4 mg IV when his
alkaline phosphatase climbed to 1068 U/L 5 weeks after
the second surgery.
Discussion: Cauda equina syndrome is a rare complication of Paget’s disease of bone. Multiple mechanisms have been implicated, including
compression of the neural elements by overgrowth of pagetic bone, compression by pagetic intraspinal soft tissue,
and neural ischemia produced by blood diversion or arterial
compression. Symptoms typically progress over months
or years before coming to medical attention. Treatment
options include calcitonin, mithramycin, bisphosphonates,
corticosteroids, and surgery. Recognition of Paget’s disease as the etiology of neurologic dysfunction is important
because medical therapy alone has been shown to be effective in some cases. Furthermore, bisphosphonate therapy
prior to surgery is critical for reducing bone vascularity and
bleeding complications.
Conclusion: Given his unusually rapid progression of
symptoms, this patient underwent two laminectomies. It
is unclear if more aggressive medical therapy would have
enabled delay or avoidance of surgery. Patients must be
followed closely because recurrence is common.
Abstract #510
OSTEODYSTROPHY – A RARE PRESENTATION
IN WILSON’S DISEASE
Simmi Dube, MD, VK Sharma, and TN Dubey
Objective: To report a case of osteodystrophy which is
an uncommon but well documented feature of the Wilson’s
disease.
– 60 –
Case Presentation: A 14 year old male child, was
admitted with the history of difficulty in walking and painful movements of the limbs for 2 years which had progressively worsened and was bedridden for last 2 months. He
had jaundice 3 years back, which recovered in 6 months.
Then, he noticed difficulty in going up and coming down
a staircase and in getting up from the squatting position
with no weakness in distal part of upper and lower limbs.
He had generalized aches and pains, which were aggravated by palpation. Physical examination revealed anemia,
knock knees and mild icterus, firm, non-tender liver 2.5
cm and firm spleen 3 cm. Nervous system examination
revealed tremor and symmetrical wasting with spasticity,
muscle power was grade 2, exaggerated deep jerks of all
the four limbs and flexor planter reflex. Slit lamp examination of eyes showed Kayser-Fleischer ring on both sides.
Complete haemogram and renal functions were normal.
Prothrombin time was 40 seconds. Liver function studies
revealed total serum bilirubin 3.4 mg/dl, SGPT 150 IU/L,
SGOT 100 IU/L, alkaline phosphatase 204 IU/L, serum
total protein 5.5 mg/dl of which albumin and globulin were
3 gm/dl and 2.5 gm/dl respectively. Serum calcium level
was 8 mg/dl. A skeletal survey showed generalized demineralization Serum ceruloplasmin level was 34 mg/dl. The
level of 24 hours urinary copper excretion before and after
750 mg of oral penicillamine were 30 mmol. and 68 mmol
in 24 hrs.respectively. CT scan of brain showed hypodense
area over caudate nucleus extending to the subcortical
area.
Discussion: Neurological features and hepatic
involvement are the presenting manifestations of Wilson’s
disease. The osseomuscular syndrome of Wilson’s disease
is uncommon but well documented presentation and seems
to be peculiar to the Indian subcontinent as maximum
cases so far reported come from India. Several mechanisms
have been implicated in the pathogenesis of osseomuscular
manifestations of Wilson’s disease. They are: a) A genetic
variant of Wilson’s disease b) Secondary to renal tubular
acidosis, renal tubular phosphate leak c) Exhibit hepatic
dysfunction d) Copper-mediated oxidative damage to collagen probably underlies the arthritis
Conclusion: We reported a case of osseomuscular
dystrophy that is a rare presentation in Wilson’s disease.
It highlights that Wilson’s disease should be considered
in the differential diagnosis of rickets and osteomalacia
particularly when rachitic manifestations appear after first
decade.
Conclusion: Risedronate 75 mg for 2 consecutive
days each month appears as effective as the 5 mg daily
dose in reducing the risk of new vertebral fractures in the
first year of treatment.
Abstract #511
REDUCTION OF VERTEBRAL FRACTURE RISK
AT ONE YEAR WITH TWO-CONSECUTIVE
DAYS-A-MONTH RISEDRONATE 75 MG (2CD)
Abstract #512
Nelson B. Watts, MD, FACP, MACE, J. Brown, MD,
G. Kline, PhD, and P.D. Delmas, MD, PhD
A CASE OF HYPERCALCEMIA OF MALIGNANCY
WITH UNIQUE FEATURES
Objective: To use historical control data to investigate
the anti-fracture efficacy of a less frequent dosing form of
risedronate. The antifracture efficacy of new osteoporosis
therapies is usually based on placebo-controlled trials, but
inclusion of a placebo arm in subsequent clinical trials
may be limited by practical or ethical considerations. In
these cases, use of historical controls can be explored as an
interesting alternative. A recent active-controlled study of
risedronate 75 mg for 2 consecutive days per month (2CD)
demonstrated that this regimen increases bone mineral density (BMD) comparable to what is seen with risedronate 5
mg daily, which has proven anti-fracture efficacy.
Methods: To assess the anti-fracture efficacy of this
new regimen, we analyzed fracture data in an active-controlled study of risedronate dosing regimens (the 2CD
study) using matched historical controls from previous placebo-controlled trials. Women in the 2CD study
were matched for age, years since menopause, BMD and
prevalent vertebral fractures, with placebo patients in the
Vertebral Efficacy of Risedronate Therapy (VERT) trials,
forming an historical placebo group. We also constructed
an historical active-treatment group from the risedronate 5
mg daily arm of the VERT trials for comparison with the
5 mg daily (n=613) and 2CD (n=616) treatment groups in
the 2CD study; historical control groups consisted of daily
placebo patients (n=99, matched from 993) and risedronate
5 mg daily patients (n=96; matched from 990) in the VERT
studies.
Results: Over 1 year of treatment, risk of new vertebral fractures in the 2CD group (1.1%) was reduced by
79% relative to the historical placebo group (5.1%) (OR
0.21; 95% CI, 0.05 to 0.88, P=0.016), similar to the 1-year
risk reduction observed in the VERT trials of risedronate 5
mg daily (61-65%). The incidence of new vertebral fractures, assessed for internal validation, was similar in the
three treatment groups: 1.0% in the historical risedronate 5
mg group, 1.5% in the risedronate 5 mg daily group from
the 2CD study, and 1.1% in the 2CD group.
Discussion: The use of appropriate historical control
data provides an approach to the assessment of fracture
effects in osteoporosis trials for which placebo-controlled
data are not available.
Fadi Adel Nabhan, MD, and Alaleh Mazhari
Objective: To report a case of mild and intermittent
hypercalcemia that has lead to the diagnosis of lung cancer. We will also discuss the unique features that are present in
this case.
Case Presentation: A 64 y/o female initially noted to
have mildly elevated calcium at 10.4 mg/dL (8.9-10.3) in
November 2006. Patient’s past medical history was significant for cirrhosis and osteoporosis. She has a smoking
history of 25 pack year. Osteoporosis was being treated
with Risedronate, calcium and Vitamin D2. The patient
was also taking calcitriol but the reason is not known to
us. In Jan 2007 she was evaluated by the liver service and
instructed to stop vitamin D2, calcium and calcitriol due to
her hypercalcemia. She was seen by our service in April
2007 shortly after she had a repeat calcium measurement
that was still elevated at 11.8 mg/dL with an intact parathyroid hormone (PTH) that was suppressed at 9 (10-65). In
reviewing her medications, she was noted to be still taking
calcitriol as she misunderstood the recommendation to stop
it. Calcitriol was thought to be the cause of her hypercalcemia and she was therefore instructed again to stop it and
careful verification was done to ensure that. Repeat calcium level in May and June showed elevated (at 10.6 mg/
dL) and high normal (at 10.2 mg/dL) levels respectively. Given the persistent hypercalcemia even after stopping
calcitriol, The patient had a repeat intact PTH which was
at 21 pg/mL (10-65) and PTH related protein which was
elevated at 2.4 pmol/L (<1.9). 25 hydroxy vitamin D, 1,
25 dihydroxy vitamin D and phosphorus were within normal range. Due to the elevation in PTH r P and especially
with her smoking history, a CT scan of chest was done
and it revealed a 3.2 cm X 3.3 cm left upper lobe mass
with extension into the chest wall and hilum and hilar/
mediastinal lymphadenopathy, multiple liver lesions and
lytic lesion at L3 compatible with metastatic disease. The
patient underwent a CT guided biopsy of lung mass, which
revealed squamous cell carcinoma. The patient continues
to have mild intermittent hypercalcemia with the highest
level being at 10.8 mg/dL.
– 61 –
Discussion: The prevalence of hypercalcemia in
patients with cancer has been reported to be between 20
and 30% and it signifies a poor prognosis. Tumors present in this disease are generally large and readily apparent.
This case has several unique features: the calcium elevation was mild and intermittent, the parathyroid hormone
therefore was not consistently and fully suppressed, and
the hypercalcemia preceded the diagnosis of cancer for
several months. The case was also confounded by the use
of calcitriol which was considered to be the main culprit of
the hypercalcemia and the use of Bisphosphonate which
might have been a factor in attenuating the severity of
hypercalcemia.
Conclusion: It is essential to recognize that in patients
with hypercalcemia of malignancy, the level of hypercalcemia can be mild and intermittent and therefore the level of
intact PTH may vary. Measuring PTH r P could be useful
in making the diagnosis in these patients and this should
be considered especially in patients with high risk for
malignancy.
Month 6, with significant absolute risk reduction of 1.0%
(95% CI: 0.3%, 1.6%).Discussion: The magnitude of the
difference in fracture risk between the placebo and risedronate 5 mg groups increased over time. Relative to placebo,
RIS significantly reduced the risk for radiographic vertebral fracture starting from the first scheduled radiographic
visit at one year. In general, the mean magnitude of the
difference in the fracture risk between the placebo and risedronate 5 mg groups increased over time (from 5.3 % at 12
months up to 8.6%, (95% CI: 5.5%, 11.6%).
Conclusion: The results confirmed reduced risk of
clinical vertebral fracture as early as Month 6 in the risedronate treatment group. Further, risedronate anti-vertebral fracture efficacy, as reflected in absolute fracture risk
reduction, increased over 3 years for both clinical and
radiographic vertebral fractures.
Abstract #514
A CASE OF PAGET’S DISEASE OF THE
BONE WITH A POOR RESPONSE TO
VARIOUS BISPHOSPHATES FOLLOWED BY
A SUBSTANTIAL IMPROVEMENT IN BONE
TURNOVER MARKERS INTO THE MID
NORMAL RANGE AFTER TREATMENT WITH
ZOLEDRONATE
Abstract #513
VERTEBRAL FRACTURE EFFICACY IS
APPARENT EARLY AND IS SUSTAINED WITH
Nelson B. Watts, MD, FACP, MACE,
Christian Roux, MD, PhD, and
Xiaojie Zhou Andreas Grauer
Brijmohan Sarabu, MD, and Arnold M. Moses, MD
Objective: To show the effectiveness of Zoledronate
in a patient with Paget’s disease with a poor response to
other bisphosphonates
Case Presentation: We describe a case of polyostotic
Paget’s disease of the pelvis bilaterally, femur and right
humerus who was referred to our metabolic bone clinic for
further evaluation in 1997. She was diagnosed with Paget’s
disease in 1970 and was subsequently treated with etidronate for four years and then alendronate10mg daily for
several years. She did quite well with this treatment until
1997 when she complained of progressive pain in her right
leg, right hip, low back and both knees. At that time a bone
scan confirmed increased uptake in all her known areas of
Pagetic bone. Bone turnover markers at the time showed
alkaline phosphatase of 852 U/L (ULN 126). She subsequently received four courses of IV pamidronate (each
course 60 mg three times) with some improvement in her
alkaline phosphatase, but never below 239 U/L. She subsequently received risedronate which eventually lowered her
alkaline phosphatase to 89 U/L. She was then lost to follow up for five years. In 2006 she was referred back to our
clinic with worsening left hip pain and was found to have
an alkaline phosphatase of 720 U/L. She was again treated
Objective: To examine the absolute vertebral fracture
risk reduction in the Vertebral Efficacy with Risedronate
Trials (VERT).Treatment with an agent that provides both
early and sustained fracture protection can benefit patients.
Superficial examination of published studies suggests
that the early effect of treatment on vertebral fracture (as
reflected in relative risk reduction) may lessen over time.
Methods: The population included 2442 patients from
VERT-NA and VERT-MN who were treated with at least
1 dose of either placebo or risedronate (RIS) 5 mg daily.
The mean age was 69 and the mean spine T-score was 2.5. Treatment groups were balanced with respect to key
baseline characteristics. Fracture endpoints included clinical vertebral fracture and radiographic vertebral fractures.
Difference in risk of vertebral fractures between placebo
and RIS 5 mg groups was estimated using the difference
of the Kaplan-Meier (KM) estimators at months 3, 6, …
and 36.
Results: The findings for clinical vertebral fracture
were consistent with the rapid onset of risk reduction with
risedronate treatment; relative to placebo, RIS significantly
reduced the risk for clinical vertebral fracture starting from
– 62 –
with risedronate for four months, but did not normalize her
alkaline phosphatase. She was then infused with 4mg of
zoledronate which resulted in a decrease of bone turnover
markers to the mid normal range along with an improvement in her bone pain.
Discussion: Various bisphosphonates have been used
to treat Paget’s disease of the bone. In patients with a poor
response to these agents, Zoledronate may be effective in
normalizing bone turnover markers and improving bone
pain.
Conclusion: This abstract describes a case of Paget’s
disease that was refractory to various bisphosphonates
except for zoledronate which decreased bone turnover
markers into the mid normal range.
failure or anterior pituitary dysfunction were noted. Five
patients had more than one endocrinopathy. Both patients
with adrenal infiltration also had hypothyroidism. Three
patients with diabetes insipidus also had at least one additional gland involved, one with Hashimoto’s thyroiditis,
one with impaired fasting glucose and one with both hypogonadism and diabetes mellitus.
Conclusion: We conclude that ECD may be associated with infiltrative disease of endocrine organs, including the posterior pituitary gland, testes, or adrenal glands.
Thyroid hypofunction and diabetes mellitus may occur,
although these may not be directly related to ECD.
Abstract #515
EFFECTS OF RESIDRONATE AND
PROSTAGLANDIN E2 ON CANCELLOUS AND
CORTICAL BONE IN
HYPOPHYSECTOMIZED RATS
Abstract #516
ERDHEIM-CHESTER DISEASE:
ASSOCIATION WITH ENDOCRINE DISORDERS
Kimberly Ann Placzkowski, MD, and Bart L. Clarke, MD
Mauricio Ernesto Flores, MD, James Yeh, PhD, and
Mariano Castro-Magana, MD
Objective: Erdheim-Chester Disease (ECD) is a rare
systemic disorder characterized by tissue infiltration with
lipid-laden histiocytes. The phenotype is variable, ranging
from benign appendicular bony sclerosis to more diffuse
organ involvement with granulomas and fibrosis. Although
bony involvement is almost universal, solid organ infiltration portends a poorer prognosis.
Methods: We evaluated associated endocrine disorders after reviewing all patients with ECD seen at Mayo
Clinic between 1980 and 2006. A total of 24 patients were
included in our analysis, 92% of whom had biopsy-proven
ECD. The remainder of our patients had clinical findings
consistent with the disease. We have previously shown
decreased bone density (63%) and increased fracture risk
in ECD1. Twelve patients (48%) were identified as having
other associated endocrine disorders.
Results: The most common abnormality was hypothyroidism, with six patients (25%) on L-thyroxine replacement or with an elevated TSH. Two patients had ultrasound
appearance of or antibody-confirmed Hashimoto’s thyroiditis, while the remainder did not have further assessment
of their thyroid disease during their evaluation. Diabetes
insipidus was present in 5 patients (21%), and was diagnosed prior to ECD in all cases. Two patients (8%) had
hyperglycemia, one receiving therapy for diabetes mellitus
and one followed for impaired fasting glucose. One patient
(4%) had adrenal insufficiency, while another was found
to have unilateral adrenal enlargement on imaging with
normal adrenal function. Hypogonadism was documented
in 3 of 15 men (21%), but no cases of premature ovarian
Objective: Whether Risedronate (Ris) as anti-resorptive drug and Prostaglandin E2 (PGE2) as anabolic drug
have an additive effect on bone metabolism in hypophysectomized (HX) rats.
Methods: Fifty female Sprague-Dawley rats were
randomly divided into groups of 10 animals each as follows: Intact, HX, HX+PGE2, HX+Ris, HX+ PGE2+Ris.
All HX rats were supplemented 5 days a week for 4 weeks
with hydrocortisone succinate 100 ug/100gm, thyroxine
2ug/100gm SQ. PGE2 was administered IM at 0.83 mg/kg
(low dose) and Ris was administered SQ at 2.5ug/0.1 ml.
IGF-1 in serum was measured upon sacrifice to assess the
completeness of HX.
Results: HX rats resulted in a significant reduction of
final body weight, tibial and femoral length, femoral bone
area, bone mineral content (BMC), bone mineral density
(BMD), cancellous bone mass of the proximal tibia, total
tissue and cortical area of the tibial diaphysis and IGF-1
when compared with the intact group. Administration of
Ris attenuated HX-induced loss of trabecular bone mass,
femoral BMC and BMD when compared o HX-rats. A low
dose of PGE2 significantly improved cortical and marrow
area of the tibial shaft, trabecular, periosteal and endosteal bone formation rate when compared to intact, HX and
HX+Ris groups.
Discussion: The combination of Ris and a low dose
of PGE2 had an important additive effect on cancellous/
cortical bone when compared to the HX group. However
it was statistically insignificant with intact group. IGF-1
– 63 –
levels remained low throughout the administration of both
drugs.
Conclusion: Further studies using Ris and a high dose
of PGE2 will be necessary to establish additional benefits
on bone metabolism.
Conclusion: These results confirmed the rapid reduction of non-vertebral fracture risk as early as Month 6 with
risedronate. Further, the risedronate anti-fracture efficacy
was sustained through out the remaining study period.
Abstract #518
Abstract #517
THE IMPACT OF RISEDRONATE ON CLINICAL
FRACTURE RISK IN PATIENTS WITH A PRIOR
HIP FRACTURE
EARLY AND SUSTAINED NON-VERTEBRAL
FRACTURE RISK REDUCTION WITH
RISEDRONATE
Andreas Grauer, MD, PhD, Xiaojie Zhou, PhD,
Paul D. Miller, MD, Steven Boonen, MD, PhD, and
Michael R. McClung, MD
Andreas Grauer, MD, PhD, Christian Roux, MD, PhD,
Jonathan D. Adachi, MD, Xiaojie Zhou, PhD,
Nelson B. Watts, MD, and Robert Lindsay, MD
Objective: To evaluate the antifracture efficacy of
risedronate among patients from the HIP Trial who had one
hip fracture at baseline. A hip fracture is a risk factor for
subsequent fractures.
Methods: The analysis population included 5445 subjects from the HIP trial (McClung,MR et al. 2001 NEJM),
aged 70-79 years, with low BMD ( FN T-score <=-2.5
SD). Among these subjects, 339 had experienced a traumatic or an atraumatic hip fracture at some time prior to
the entry into the study (determined via lifetime medical
history). These subjects were treated with either placebo
(PLC) or risedronate (RIS) 2.5mg or 5 mg daily. The incidence of osteoporosis-related clinical fracture, defined by
the occurrence of the radiographically confirmed clinical
vertebral fracture or radiographically confirmed non-traumatic non-vertebral fracture was calculated using KaplanMeier survival estimates over a 3 year period and was compared between PLC- and RIS-treated subjects. Treatments
were compared using log rank test, and the risk ratio and its
95% confidence interval were obtained using a Cox regression model stratified for study.
Results: Subjects’ mean age was 75 years, and their
mean femoral neck (FN) and lumbar spine (LS) T-scores
were -3.1 and -3.2 SD, respectively. Baseline characteristics were well balanced between the 3 treatment groups.
Over the 0-3 year period, the clinical fracture incidences
were 28.4%, 14.9% and 13% for the PLC, RIS 2.5mg and
RIS 5mg groups, respectively.
Discussion: Relative to the PLC group, RIS 5mg and
2.5 mg statistically significantly reduced the risk for clinical fracture over 0-3 year period (p<0.05). The risk ratio of
clinical fracture was 0.5 for both the RIS 5mg and 2.5 daily
groups relative to the placebo group. RIS treatment was
well tolerated in HIP trial.
Conclusion: Risedronate significantly reduced the
risk of clinical fracture among women with postmenopausal osteoporosis who had a prior hip fracture.
Objective: To investigate whether the non-vertebral
fracture risk reduction with risedronate is early and sustained. Previous analyses have shown non-vertebral fractures account for 77% of the osteoporosis-related fractures
and over 90% of costs. Predicting an osteoporosis-related
fracture is not possible. Therefore, treating with an agent
that provides both early and sustained fracture protection
will provide maximum patient benefit.
Methods: The analysis population included 1169
postmenopausal women from VERT and BMD trials with
low BMD (LS T-score <-2.5 SD), who were treated with at
least one dose of either placebo or risedronate 5mg daily.
The mean age of the population was 67 years and 58% of
the patients had at least one prevalent vertebral fracture at
baseline. The fracture endpoint was radiographically confirmed osteoporosis related non-vertebral fracture. Risk
difference of osteoporosis-related non-vertebral fracture
between the placebo and risedronate 5mg groups was estimated using the difference of the Kaplan Meier (KM) estimators from month 3 through 36. The standard error of the
risk difference was approximated by the square root of the
sum of the variance of the KM estimators of the placebo
and risedronate 5mg groups. The upper and lower bound of
the 95% confidence intervals were calculated as the mean
plus and minus 1.96 times the standard error of the estimated risk difference.
Results: Relative to placebo, risedronate significantly
reduced the risk for non-vertebral fracture starting from
Month 6 with an absolute risk reduction of 1.8% (95% CI:
0.4%, 3.3%). The magnitude of the difference in the risk
for non-vertebral fracture between the placebo and risedronate 5mg groups increased during the first 2 years and
remained constant during the 3rd year of the trial with an
absolute risk reduction of approximately 4%.
Discussion: The findings are consistent with the rapid
onset of fracture risk reduction with risedronate treatment.
– 64 –
Abstract #519
Abstract #520
PREDICTORS OF BONE MINERAL DENSITY IN
MEN WITH PRIMARY HYPERPARATHYROIDISM
VITAMIN D DEFICIENCY IN PATIENTS
WITH OSTEOPOROSIS
Giorgio Borretta, MD, Laura Gianotti,
Francesco Tassone, Flora Cesario, and
Giampaolo Magro
Harinder Singh, MD, Satish Karmegan,
Aswatharayan Manandhi, Jyothi Ratti, Kenneth Grant,
Swamy Venkatesh, and Ambika Rao
Objective: In primary hyperparathyroidism (PHPT)
bone involvement is frequent. In women with PHPT it has
been previously reported that menopausal status together
with PTH, calcium levels and renal function are independent predictors of bone density. In male subjects, the impact
of PHPT on bone status is less defined. Aim of the study
was to investigate possible predictors of bone mineral density (BMD) in a series of male subjects affected by PHPT.
Methods: Sixty male patients with PHPT were consecutively studied (age, mean ± SD: 57.9± 14.1 yrs;
Symptomatic /Asymptomatic 32/28; PTH, median and
interquartile levels: 119 and 95.0-228 pg/ml, calcium 11.1±1.0 mg/dl). In all subjects BMI, levels of calcium,
PTH, 25 hydroxy-vitamin D, creatinine and creatinine
clearance and bone mineral density (BMD) at lumbar
spine, femur and distal radius by DXA were evaluated.
Results: A positive association between BMI and
DXA measurement at femoral levels was found (BMIBMD: R=0.52, p<0.004; BMI-T score : R=0.53, p<0.002;
BMI-Z score : R=0.55, p<0.002). On the contrary, neither
PTH, calcium, renal function nor 25-hydroxy-vitamin D
showed significative correlation with BMD levels.
Discussion: BMI resulted a good predictor of BMD
in male patients with PHPT as found in women with
PHPT, confirming the important role of BMI as risk factor for bone damage in osteoporosis of both primary and
secondary origin. On the contrary, biochemical indices of
PHPT as well as renal function did not associate with DXA
measures in male patients, differently from female. These
findings could indicate gender-dependent differences in the
clinical expression of PHPT, particularly at bone level. A
peculiar resistance of male bone to PTH excess in PHPT
could be also hypothesized.
Conclusion: These findings suggest that the clinical management of the modern form of PHPT should be
differently by gender.
Objective: Vitamin D facilitates intestinal absorption
of Calcium, Phosphate, and maintains normal serum calcium and mineralization of bone. Vitamin D deficiency is
not uncommon and may contribute to the development of
osteomalacia and fractures. Purpose of this study was to
find the prevalence of Vitamin D deficiency in osteoporotic patients who were already on the recommended dose
of Vitamin D and calcium. Our observations suggest that
Vitamin D deficiency in patients diagnosed with osteoporosis by DEXA scanning is underdiagnosed. We suggest
Vitamin D levels as part of initial evaluation of patients
with osteoporosis.
Methods: This retrospective chart review study was
conducted at the outpatient endocrinology clinic in Las
Vegas. Study inclusion criteria were as follows; any patient
with osteoporosis diagnosed on DEXA scan who had documented vitamin D levels, irrespective of race, gender, and
age or other underlying diagnoses. 328 charts with diagnosis of osteoporosis were reviewed, of which 71 had documented 25-hydroxyvitamin D levels and were included in
the study. Patients were on Vitamin D 800 IU and calcium
1200 milligrams daily. 25-hydroxyvitamin D level was
checked while patients were assumed to be taking Vitamin
D 800 IU. We also reviewed other risk factors including
family history of osteoporosis, tobacco use, steroid use and
other major pre-existing medical diagnoses.
Results: The average age was 62.2 years and 89%
were females. 60 (84.5%) were Caucasians and 11 (15.5
%) were smokers. Five (7%) had family history of osteoporosis and 2 (2.81%) had osteoporotic fractures in the
past. Thirteen (18.3%) were taking steroids for various
medical reasons. Thirteen (18.3%) subjects were found to
be Vitamin D deficient (<20ng/ml) and 16 (22.5%) were
Vitamin D insufficient (20-30 ng/ml). Seven (9.86%)
patients were hypocalcemic (<9 mg/dL).
Conclusion: Our study demonstrates that many
patients with osteoporosis who were on Vitamin D and calcium had low vitamin D levels, which in turn contributes
to increased risk of fractures. Therefore, all patients with
osteoporosis should have vitamin D levels measured, and
replaced adequately.
– 65 –
compression fracture when an obvious cause such as osteoporosis is not found, even when antecedent trauma can
potentially account for the fracture. Plasmacytomas do not
have the typical manifestations of multiple myeloma and
may not be evident on routine labs and imaging. Therefore
SPEP should be obtained in all cases of suspected pathological fracture.
Abstract #521
VERTEBRAL COMPRESSION FRACTURE
CAUSED BY A PLASMACYTOMA
Sreevidya Kannoorpatti Subbarayan, MD, and
Thomas Moraghan
Objective: To present a case of solitary plasmacytoma
causing vertebral compression fracture.
Case: A 54-year-old-woman developed severe back
pain that radiated along the T10 dermatome, while attempting to lift a 50 lb bag at work. X-rays showed severe compression fracture of the T10 vertebra with marked anterior
wedging and mild osteopenia. MRI of the spine demonstrated a new/non healing T10 compression fracture with
80% loss of anterior height and spinal cord compromise.
The patient was referred to Endocrinology for evaluation
regarding metabolic bone disease. She denied steroid use,
nephrolithiasis, family history of osteoporosis or prior
fractures. She was menopausal and had a 20 pack-year history of smoking. There was no history of sustained weight
loss, night sweats, rash or anemia. Physical exam was
unremarkable except for mild kyphosis. DEXA scan performed a year ago was normal. CBC, 25 hydroxyvitamin
D, intact PTH, calcium, Phosphorus, Alkaline phosphatase, Albumin, Creatinine, LFTs and urine calcium levels
were normal. Repeat DEXA scan showed T-score of -0.5
at the spine and -0.1 at the hip. SPEP showed a minimal
monoclonal IgG spike. Skeletal survey was negative for
lytic lesions. CT of the chest through pelvis demonstrated
no adenopathy or organomegaly. Bone marrow biopsy
showed 1% mature plasma cells. Repeat MRI showed progression of the vertebral lesion with radiological features
worrisome for malignancy. Biopsy of T10 vertebra demonstrated a plasmacytoma.
Discussion: Plasmacytomas are tumors arising from
malignant plasma cells that are histologically identical to
those seen in multiple myeloma. They can occur in bone
or soft tissue as solitary or multiple lesions. Plasmacytoma
is characterized by the absence of osteolytic lesions, anemia, hypercalcemia or renal involvement that is associated
with multiple myeloma. Solitary plasmacytomas of the
bone account for 5% of all patients with plasma cell disorders and commonly involve the thoracic spine. Median
age at diagnosis is 55. Patients usually present with skeletal pain, pathological fractures or cord compression.
Plasmacytomas have a 54% chance of eventual conversion
to multiple myeloma. Tumoricidal radiation is the treatment of choice.
Conclusion: Our case underscores the importance
of considering plasmacytoma as an etiology for vertebral
Abstract #522
HYPERPARATHYROIDISM-JAW
TUMOR SYNDROME
Amanda Reagan Schiefer, MD, and
Vahab Fatourechi, MD
Objective: Discuss the clinical aspects of the rare
genetic disease, HPT-Jaw Tumor Syndrome, and, in particular, report case series with the presenting clinical aspects
seen at Mayo Clinic from 1997 to 2007.
Case Presentation: In 1982, 13 yo female was diagnosed with benign jaw tumor (JT) requiring surgery. In
1988 (age 18), she underwent a right nephrectomy for a
malignant Wilms’ tumor (WT) and multiple hemartomas
with concurrent chemoradiation. In 1993 (age 22), a
second jaw tumor was removed. Both jaw tumors were
benign ossifying fibromas. In 9/1993, she was diagnosed
with hyperparathyroidism (HPT). A left superior parathyroid gland was resected. No evidence of parathyroid carcinoma (CA) was seen on pathology. Her hypercalcemia
resolved. In 1995 (age 26), she underwent hysterectomy
for Mullerian adenofibroma. Her family history was positive for jaw tumors and HPT. In 5/2005, she was seen at
our institution for second opinion with recurrent HPT in
the setting of HPT-JT syndrome. Her calcium was normal
(9.4mg/dL) with low PO4 (2.0 mg/dL) and elevated PTH
167 pg/mL. She underwent cervical re-exploration and
excision of right superior parathyroid adenoma per pathology. Panoramic x-ray revealed multiple mandibular tumors
that were not clinically relevant. In 12/06, repeat biopsy of
right posterior mandibulur tumor revealed benign ossifying
fibroma. In 6/07, a screening MRI of left remaining kidney
revealed solid enhancing mass. She underwent left partial
nephrectomy and was found to have 2 renal mass: oncocytoma and metanephric adenoma. This case prompted a
retrospective review of cases with this diagnosis seen at
Mayo Clinic from 1997 to 2007. The case series consists
of 3 patients (2’s and 1) aged 33-38. All 3 patients have
tested positive for the HRPT-2 mutation. All 3 patients
had HPT with ages at diagnosis of 17, 22, and 28. Only 1
of the 3 cases had JTs and the full blown syndrome.
– 66 –
Discussion: HPT-JT syndrome is a rare genetic syndrome with clinical features that include ossifying jaw
fibromas, HPT, kidney tumors, and uterine tumors. HPTJT was initially identified by Jackson et al in 1958. In
2002, the gene responsible was linked to HRPT2 on the
long arm of chromosome 1. It is inherited in an autosomal
dominant fashion with high but incomplete penetrance. In HPT-JT syndrome, 90% of patients develop HPT, 3035% of patients have JTs, and 10% of patients have renal
cysts with solid renal tumors less common. Parathyroid
carcinoma is seen in 15% of patients. The frequency of
other cancers such as uterine cancer and Wilms’ tumor are
unknown. There are no published surveillance guidelines
for HPT-JT.
Conclusion: Unlike other familial HPT syndromes,
HPT-JT has solitary parathyroid adenomas that recur, not
pluriglandular disease or parathyroid hyperplasia. Also,
unlike “brown tumors” associated with severe HPT, jaw
tumors in HPT-JT are restricted to the maxilla and mandible, lack multinucleated giant cells on pathology, occur
asynchronously with HPT, and do not heal after parathyroidectomy. Renal manifestations can be bilateral renal
cyst or, as in 1 of 3 cases presented here, Wilms’ tumor
with hamartomas followed by benign solid tumors. In
2005, uterine tumors were added to the spectrum. HPT-JT
is a complex syndrome with diverse clinical aspects spanning over a long time with various manifestations. This
can lead to an under recognized syndrome with multiple
medical professionals focusing on only one aspect of the
syndrome at a time without putting the entire spectrum
together as HPT-JT syndrome. Given the increased risk
of tumors, in particular parathyroid carcinomas and renal
tumors (such as Wilms’ tumor), it is important to recognize
those families at risk and perform appropriate screening
surveillance.
MANAGEMENT OF RECURRENT TERTIARY
HYPERPARATHYROIDISM IN A PATIENT WITH
HYPOPHOSPHATEMIC RICKETS
temic rickets at 18 months and started on phosphate and
calcitriol therapy. There is no history of nephrolithiasis,
renal failure, fractures or family history of hypophosphatemia. She developed tertiary hyperparathyroidism at
age 30, treated with subtotal parathyroidectomy. Fifteen
years later she presents with fatigue and worsening bone
pain. On physical exam, height of 4’10”. Laboratory values showed calcium of 10.8 mg/dl, phosphorus 3.9 mg/dl,
PTH 286 pg/ml and Cr 1.5 mg/dl. Kidney ultrasound with
medullary calcinosis. Calcitriol and calcium were discontinued. It was decided that a second neck exploration
should be undertaken to remove the remaining gland to
prevent further nephrocalcinosis. Operative notes from the
surgery were not readily available so efforts to localize the
remaining parathyroid gland were undertaken. Sestamibi
parathyroid scan demonstrated a focal uptake of tracer
overlying the right thyroid gland. Thyroid ultrasound
showed a hypoechoic cystic nodule in the posterior right
lobe. Fine needle aspirate of this nodule was obtained to
differentiate it from thyroid origin. PTH levels of the fluid
were reported > 2500 pg/ml. At the time of referral for surgery, operative notes were found, confirming the remaining gland in the right neck. Removal of the adenoma was
performed with peri-operative auto-transplant to forearm.
Cryopreservation also requested. Patient seen 3 months
after surgery with clinical evidence of graft function, normal serum calcium levels and stable renal function with
decreasing doses of calcitriol and calcium.
Discussion: X-linked hypophosphatemic rickets
(XLH) is the most common inherited form. Tertiary hyperparathyroidism in patients with hereditary hypophosphatemic rickets is rare, reported in the literature in 23 patients.
The treatment is subtotal parathyroidectomy but recurrence
of hypercalcemia has been reported. Treatment with cinacalcet can be considered, but in patients with nephrocalcinosis the treatment should be definitive. Autotransplant
and cryopreservation can be done in efforts to prevent
complications of hypoparathyroidism.
Conclusion: Patients with recurrent hyperparathyroidism in hypophosphatemic rickets should be treated
definitively in those with nephrocalcinosis.
Ana Mendoza, MD, and Mira S. Torres, MD
Abstract #524
Abstract #523
Objective: Tertiary hyperparathyroidism is though to
be a rare complication of patients with hypophosphatemic
rickets treated with lifelong oral phosphate therapy. We
describe a case of a patient with hereditary hypophosphatemic rickets with recurrent hypercalcemia, nephrocalcinosis and worsening renal function
Case Presentation: A 45 year old female was referred
for hypercalcemia. She was diagnosed with hypophospha-
ACUTE RENAL FAILURE PRECIPITATING
PARATHYROID STORM
Lisa Young, MD, and Anup Sabharwal
Objective: To describe a case of acute renal failure
precipitating parathyroid storm.
– 67 –
responded to calcium and vitamin D supplementation and
is currently normocalcemic off supplementation.
Discussion: Parathyroid Storm was first described by
Dawson in 19321. It refers to a very elevated iPTH and
serum calcium leading to clinical manifestations. It is rare.
It is caused by primary hyperparathyroidism or parathyroid
carcinoma. In primary hyperparathyroidism, the trigger
for the rapid increase in iPTH is not known. Renal insufficiency has been associated with parathyroid storm in 9%
of cases3 but often it is not clear if it is a precipitating event
or a complication of the severe hypercalcemia. In this case,
renal failure preceded any significant changes in his serum
calcium or osmolarity. Therefore, it more likely represented a triggering factor. The mechanism for the rapidly
increasing iPTH is unknown. In the kidneys, the hormone is
degraded after binding to physiologic PTH receptors. The
majority of iPTH degradation occurs after the hormone is
filtered through the glomerulus and metabolized internally
by the tubules4. The decreased glomerular filtration may
have lead to an accumulation of iPTH and elevated serum
calcium.
Conclusion: This is a case of acute renal failure precipitating a parathyroid crisis.
Case: A 73 year old man was admitted with altered
mental status and abdominal pain. He had a serum calcium
of 21.4mg/dl, phosphorus 5.5mg/dl and serum intact parathyroid hormone (iPTH) 2872pg/ml. Past medical history
included a 6-year history of primary hyperparathyroidism
and peptic ulcer disease. Ten days prior, he was admitted
with acute renal failure, his creatinine had increased from
a baseline of 1.4mg/dl to 9.4 mg/dl and his serum calcium
increased from 12.2mg/dl to 12.7mg/dl. A presumptive
diagnosis of NSAID associated interstitial nephritis was
made based on a history of recent ibuprofen use and the
presence of white blood cells in sterile urine. His creatinine improved to 3.4mg/dl with hydration but his calcium
continued to rise. Physical exam revealed a 2 cm by 1.5
cm firm, mobile left sided neck mass. Serum iPTH which
was 875 pg/ml 2 months prior, increased to 2872 pg/ml. An
ultrasound showed a 1.7 by 1.7 by 1.6 cm left cervical mass
and a s sestamibi scan was positive in this area. The patient
was treated with hydration, furosemide and calcitonin. The
patient was taken to surgery and a left sided parathyroid
adenoma was removed. His iPTH decreased to 49pg/ml
and his serum calcium to 9.9mg/dl immediately after surgery. His postoperative course was complicated by hypocalcemia, with an ionized calcium nadir of 0.80mmol/l. He
– 68 –
ABSTRACTS – Obesity
ing waist circumference and blood pressure measurements
was obtained. Using the International Diabetes Federation
(IDF) 2005 definition, central obesity was defined as waist
circumference of > 90cm (men) or > 80cm (women).
Hypertension was considered to be present if blood pressure was >130/85 mmHg at two different visits or on antihypertensive medications.
Results: 90/120 subjects were male with a mean age
of 22 (21-24) years. None of the medical students had any
known history of hypertension nor were they taking any
antihypertensive medications. 14% (17/120) of the medical
students had systolic blood pressure >130 mmHg and diastolic blood pressure >85 mmHg. 22% (26/120) medical
students had central obesity.
Conclusions: Our study shows an alarmingly high
prevalence of obesity and hypertension amongst otherwise
healthy young adults. This study clearly highlights the
need for primary preventative measures to reduce development of obesity, hypertension and eventually metabolic
syndrome and diabetes among young adults in Pakistan.
The results are disturbing and warrant further comprehensive studies. LEAP COHORT KEMU is an ongoing study
and we plan to follow these medical students throughout
their undergraduate medical career till they graduate. We
plan to perform fasting blood glucose, HDL cholesterol
and Serum triglycerides levels to identify metabolic syndrome amongst them.
OBESITY
Abstract #600
PREVALENCE OF CENTRAL OBESITY AND
HYPERTENSION IN YOUNG MEDICAL
STUDENTS: PRELIMINARY RESULTS OF
LAHORE EPIDEMIOLOGICAL ADULT
POPULATION COHORT KING EDWARD
MEDICAL UNIVERSITY (LEAP COHORT KEMU)
STUDY
Ali Asghar Jawa, MD, MPH,
Jawad Zaheer Mumtaz Hasan (S.I.),
Muhammad Shahid Jamil,
Umair Javaid Chaudhary,
Syed Ali Imran, and Ghazanfar Ali Jawa
Objective: Obesity and hypertension is on the rise
especially in adolescents and young adults. Anecdotal evidence suggests that awareness amongst medical students
and young health professionals is lacking at best. We systematically screened medical students studying at King
Edward Medical University, Lahore for frequency of central obesity and hypertension.
Methods: 120 medical students were enrolled in the
study. Their willingness to participate in this study was
construed as a verbal consent. Anthropometric data includ-
– 69 –
ABSTRACTS – Other
wise) is associated with pachydermoperiostosis. Treatment
is usually conservative with NSAIDS, and treatment of
complications of arthritis.
OTHER
Abstract #700
Abstract #701
PACHYDERMOPERIOSTOSIS: AN UNUSUAL
CAUSE OF ACREMEGALOIDISM
MALE HYPOGONADISM
Svetlana Fomin, MD, and Sunil Asnani, MD, FACE
Adefunke Omosefe Lipede, MBBS, and
Anthonia Ogbera, MBBS, MPH, MWCP, FACE
Objective: To describe an unusual case of acromegaloidism secondary to pachydermoperiostosis.
Case presentation: A 32 year-old hispanic male was
admitted to the trauma service after a motor vehicle accident. Endocrinology consultation was requested for questionable acromegaloid appearance. Patient was essentially
asymptomatic prior to admission. On direct questioning,
he did state that his hands and feet had gotten bigger over
last 5 years requiring different shoe sizes. His forehead
had also become more prominent. The patient denied any
significant past medical or surgical history; his social and
family history was noncontributory. Physical examination
revealed a normotensive male with BMI 23 kg/m2; he had
coarse facial features with seborrheic dermatitis of his scalp
and face. He also had enlarged, protruding jaw, enlarged
hands and feet with skin thickening, and mild clubbing.
There was no evidence of congestive heart failure or valvular dysfunction, or joint abnormalities. Initial laboratory
workup including a comprehensive metabolic panel, IGF-1
(127 [106-255] ng/ml), prolactin, testosterone, LH, FSH,
TSH, free T4 was within normal limits. Repeat set of labs
specifically assessing growth hormone overproduction
were within reference range as well: IGF-1 122(106-255)
ng/ml, IGFPB-3 2710(2500-5806) ng/ml, GH 0.26(0.011.0) ng/ml and Insulin 4(3.5-30) µU/ml. MRI of the pituitary to rule out a ‘burnt-out’ tumor was negative for any
abnormality. X-rays of the hand and distal ulna revealed
hyperostotic bone dysplasia and cortical thickening.
Discussion: This typical radiographic abnormality
with acgromegaloid features is consistent with a rare condition called pachydermoperiostosis or primary hypertrophic
osteoarthropathy. This disease is a rare genetic disorder,
and can lead to significant disability with musculoskeletal
morbidity with advancing polyarthritis. It is more common
in African American males; our case is unusual given his
Hispanic origin.
Conclusion: We present a case of pachydermoperiostosis, one of the differential diagnoses of acromegaloidism,
and often confused with acromegaly. Diagnosis is based on
characteristic phenotypical and radiological abnormality
and ruling out other diseases. It is important to recognize
this condition as a differential in workup of acromegaly
since no hormonal abnormality (growth hormone or other-
Background: Male hypogonadism is a condition in
which the body fails to produce enough testosterone or a
deficiency in spermatozoa production or both. It may result
from a disorder of the testes (primary hypogonadism) or
of the hypothalamic-pituitary axis (secondary hypogonadism). It is oft encountered in clinical practice. This case
report serves to describe the clinical features and cause of
hypogonadism occurring in a young man.
Case Report: A 39-year-old man presenting with a 5year history of erectile dysfunction and infertility. Further
questioning revealed a history of reduced libido, increase
in breast size and reduced body hair. He also complained
of easy fatigability and weight gain. He admitted to loss
of early morning erections and a history of reduction in
penile and testicular size. He noticed these adverse bodily
changes progressively over a period of 5 years preceded by
a history of torsion of both testes. (He had torsion of his left
testis and refused surgical intervention. He subsequently
had torsion of the right testis a year later). He had no history suggestive of a thyroidal disorder. There is no family
history of delayed sexual maturation. He is the first male
in a family of six children and his younger brothers have
no history of sexual dysfunction. Examination revealed a
young man with a feminine body pattern (absence of beard,
and body hair, gynaecomastia–Tanner Stage 4). He had
eunuchoidal bodily proportions. Weight was 120Kg, height
1.62m and a BMI of 46Kg/m2. He also had centripetal obesity with a waist circumference of 115cm. The cardiovascular system examination was essentially normal. Genital
examination revealed bilateral pea sized testes. An assessment of the testicular size using an orchidometer was 2ml.
Investigation results showed normal thyroid function test,
low testosterone levels and elevated gonadotrophin levels.
Discussion: Hypogonadism can affect males at any
age and present with clinical features which differ according to the timing of disease onset in relation to puberty.
In post-pubertal onset, the established secondary
sexual characteristics regress slowly, and the effects can
occur at different rates. Energy and libido diminish within
days to weeks and the hematocrit decline within a few
months. Decreases in sexual hair, muscle mass, and bone
– 70 –
ABSTRACTS – Other
over decades. The condition is relatively common among
Finns, Sardinians, and Iranian Jews. This is the first study
of APECED in the Saudi population.
Conclusions: APCED manifested at an early life in
all, majority of cases were familial, & it was relatively common in females. The rank order distribution of the organ
system exhibited the following pattern: HP was most frequently present, followed by MC, alopecia, KCJ, AI, hepatitis. T1 DM, hypothyroidism & PA were least frequent.
Sequential involvement of different organ system did not
manifest a predictable pattern. Early age HP/MC should
trigger the possibility of APCED & longitudinal FU should
be undertaken at uncovering other organs involvement.
mineral density are usually not recognized until years later.
Testicular torsion causes permanent damage especially if
not treated promptly.
Conclusion: Testicular torsion, a surgical emergency
could lead to primary hypogonadism.
Abstract #702
AUTOIMMUNE POLYENDOCRINOPATHYCANDIDIASIS- ECTODERMAL DYSTROPHY
(APECED)
Mohammed Ahmed, MD, FACP, FACE,
Saud Al-Harthi, MD, and Bassam Bin-Abbas MD
Abstract #703
Objectives: To study the natural history of Autoimmune
Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy
(APECED) in the Saudi population, with a special emphasis regarding the variability of the syndrome. Specifically,
our objective was to explore the age of onset, the sequence
in which the clinical features unfold with advancing age,
constellation of the affected organ system, relative frequency of each affected organs,& the presence or absence
of malignancy.
Case Presentation: It was a retrospective study of
clinical, biochemical, & hormonal data for 13 pts. They
were first diagnosed with APCED at ages ranging 1 ½ 8 yrs; there were 8 females & 5 males. Familial cases
accounted for 10 cases. The frequency distribution of the
organ system involved were: Hypoparathyroidism (HP)
was the commonest endocrinopathy (12: 92%), followed
by mucocutaneous candidiasis (MC) (10:77%), alopecia
(7: 54%), keratoconjunctivitis (KCJ: 5:38%), adrenal insufficiency (AI: 4:31%), hepatitis 3 (23%). Type 1 diabetes
mellitus (DM) & primary hypothyroidism each was present in 2 pts.(15%). One pt. had Pernicious anemia (PA). HP
was the presenting feature in 6(46%) & MC in 4 (31%).
Pts. were followed for a median of 77 months. There was
no orderly sequence of the evolution of organ involvement.
For example HP was followed by either DM or hepatitis,
or dystrophic nail changes; alternatively HP followed MC.
Synchronous involvement of various organs consisting of
MC, HP, KCJ, hepatitis occurred in one, MC & alopecia
in another, & MC & AI in a third pt. Liver Cirrhosis complicated hepatitis in one pt. None had kidney involvement,
celiac disease nor cancer.
Discussion: APECED is a rare autosomal recessive
disorder with protean clinical manifestations. The cardinal features consist of classical triad of chronic MC,
HP, and AI. Two of these, the dyad, are required for the
diagnosis. However, the disorder is much more complex
and variable with several other clinical features unfolding
THE ENDOCRINOPATHIES OF END STAGE
ANOREXIA NERVOSA
Lisa S. Usdan, MD, Lalita Khaodhiar, MD, and
Caroline M. Apovian, MD
Objective: To discuss the endocrine abnormalities
which develop in end stage anorexia nervosa (AN).
Case Presentation: A 20 year old woman was admitted with malnutrition, dizziness, weakness, electrolyte
instability, profound bradycardia, and hypothermia. She
had struggled with AN for five years. Prior to admission
she consumed 200 calories a day. She weighed 68 pounds,
and her body mass index was 11.7. Physical exam revealed
an extremely cachexic, restless female with cool skin, bradycardia, and profound muscle atrophy. Admission labs
revealed thrombocytopenia, neutropenia, hypoglycemia,
and transaminitis. She had a complicated hospital course
involving resistance to refeeding, transient hepatic failure,
severe edema, and urgent neurosurgical intervention following a fall. Refeeding was initiated and maintained in
the postoperative period. A 10% weight gain was achieved
at discharge.
Discussion: AN is a life-threatening psychiatric illness
associated with significant morbidity and mortality. Severe
malnutrition precipitates hormonal aberrancies which help
preserve energy in times of inadequate nutrition. All hormonal axes appear to be affected by starvation.
Amenorrhea is a diagnostic criteria for AN, and is
noted early in the disease course. Although amenorrhea
impairs ovulation and fertility, the lack of estrogen also
leads to significant and sometimes irreversible bone loss. Growth hormone and glucocorticoid resistance are well
described findings in AN. The thyroid dysfunction seen
in AN is akin to sick euthyroid syndrome. Osteoporosis
is very common in patients with AN due to a variety of
hormonal and activity factors.
– 71 –
ABSTRACTS – Other
Treating the AN patient involves a multidisciplinary
approach to maximize caloric intake while preventing the
medical complications of refeeding syndrome. Behavioral
therapy and social support must also be available to address
the psychiatric needs of these patients. Maintaining a
healthy weight is crucial for resolving the hormonal aberrancies of AN, as well as for achieving a cure of this devastating illness.
Conclusion: AN is a severe psychiatric disorder
which can lead to extreme malnutrition and starvation. AN provides a model for the body’s hormonal response to
starvation. Alterations in the hormonal axes are initially
adaptive, mitigating the devastating consequences of starvation. Those who recover from AN face long term complications from prolonged malnutrition, such as osteoporosis and infertility. AN patients require close monitoring as
interventions geared toward achieving a healthy weight are
aggressively pursued.
Abstract #704
POST-OPERATIVE ADJUVANT RADIATION
THERAPY FOR PARATHYROID CARCINOMA
CAN BE ASSOCIATED WITH PROLONGED
DISEASE-FREE SURVIVAL
John T. Chow, MD, Robert L. Foote, MD,
Haitham S. Abu-Lebdeh, MD, and
Robert A. Wermers, MD
fractions (range, 30-35) over 50 days (range, 42-63). At
the time of last follow-up, none of the 5 patients who had
undergone adjuvant RT had evidence of recurrence (mean
follow-up duration, 95 months). Recurrence occurred in
9 of 22 patients (41%) who underwent surgery alone and
returned for follow-up at our institution.
Discussion: Parathyroid carcinoma is a rare cause
of hyperparathyroidism, and can have a variable clinical
course. En bloc surgical resection is the standard method
of treatment, but cure is often not possible due to tumor
burden or microscopic disease. In a previous retrospective review of patients at the Mayo Clinic, the 5-year rate
of locoregional disease progression was 44% in patients
treated with surgery alone. Although there is controversy
as to whether adjuvant RT changes the outcome of patients
with parathyroid carcinoma, there is evidence that the disease-free interval can be increased. Our study supports
this notion in a small subset of patients seen at a large referral center, at especially high risk for recurrence. Although
there are no clear guidelines for the use of adjuvant RT, it is
reasonable to consider this measure in patients at high risk
for post-operative locoregional progression. Data from
larger cohorts is needed to identify patients most suited for
adjuvant RT.
Conclusion: In patients with parathyroid carcinoma
at high risk for recurrence following en bloc resection,
adjuvant RT may provide prolonged disease-free survival.
Abstract #705
Objective: To assess long-term outcome in patients
with parathyroid carcinoma treated with post-operative
adjuvant radiation therapy (RT).
Methods: All cases of parathyroid carcinoma from
January 1, 1991 to December 31, 2006, were identified
through the diagnostic code index and tumor registry of the
Mayo Clinic (Rochester, MN) and reviewed through the
medical record. Patients included in the analysis required
confirmation of surgical pathology at our institution, if the
initial operation was performed elsewhere.
Result: Thirty-four confirmed diagnoses of parathyroid carcinoma were identified, of which 25 patients (74%)
had at least one operation performed at our institution. The
mean age at the time of surgery was 52 years, and the male:
female ratio was 1:1. The mean pre-operative serum calcium was 13.7 mg/dL. Adjuvant RT was administered to
5 patients due to concerns of residual microscopic disease
following surgery (including 3 with evidence of tumor
invasion into soft tissue). The mean pre-operative calcium
and post-radiation calcium levels in this subset were 14.1
mg/dL and 9.5 mg/dL, respectively. The median radiation dose was 70 Gy (range, 60-70), administered in 35
CHROMIUM INFUSION REVERSES
EXTREME INSULIN RESISTANCE IN THE
CARDIOTHORACIC ICU
Michael Via, MD, Jayashree Raikhelkar, MD,
Corey Scurlock, MD, Gabriele Di Luozzo, MD,
and Jeffrey I. Mechanick, MD, FACP, FACE, FACN
Objective: To report a case of a thoracic surgery patient
who developed extreme insulin resistance postoperatively.
The resistance to insulin was apparently attenuated by
intravenous chromium, a trace metal micronutrient.
Methods: We present a case report, including hourly
blood glucose, insulin and chromium infusion data in a
critically ill patient. A summary of the related literature is
also provided.
Result: Insulin resistance is common and often multifactorial in acutely critically ill patients. The patient presented required 2,110 units of insulin over 40 hours following surgical repair of a thoracic aorta aneurysm. After the
administration of intravenous chromium, the blood sugar
normalized and insulin therapy was discontinued.
– 72 –
ABSTRACTS – Other
Discussion: This case represents an example of
extreme insulin resistance, which poses a significant obstacle to successful intensive insulin therapy in the ICU. The
administration of intravenous chromium coincides with
this patients decline in insulin requirements and improved
glycemic control.
Conclusion: We utilized a unique approach toward
the achievement of glycemic control in acute critical illness. Therapeutic intravenous chromium reduced insulin
resistance.
calcium excretion. Our patient presented with hypocalcaemia secondary to vitamin D deficiency and decreased calcium consumption. As a 44-year-old adult, he should have
been consuming about 1000mg/day of dietary calcium and
200 IU of vitamin D. By following the Ital diet, our patient
believed that his healthy eating habits would protect him
from obesity, diabetes and dyslipidemia, which are common to the typical Western diet.
Conclusion: Approximately 2.5% of adults in the
United States follow vegan diet, and if well-balanced,
that diet can provide an adequate source of the necessary
vitamins and minerals. Clinicians should emphasize the
importance of a well-balanced diet to their vegan patients,
educate them about diet supplementation and vegetablebased sources of calcium and vitamin D, and provide early
screening for osteoporosis.
Abstract #706
UNHEALTHY OUTCOME FROM
A “HEALTHY” DIET
Kateryna Komarovskiy, MD, and
Nathaniel Winer, MD, FACP, FACE
Abstract #707
Objective: To describe hypocalcemia caused by
dietary modifications in patient from Grenada who was
following vegan diet.
Case presentations: A 44 year old male without significant past medical history presented with generalized
weakness and bone pain for 2 to 3 months. He was practicing Rastafarian culture, including strict vegan (Ital) diet (all
food was consumed unprocessed) and was working night
shifts. His laboratory tests were significant for calcium,
corrected by albumin of 6,6 mg/dl, phosphorus 2.8 mg/dl,
intact PTH (parathyroid hormone) 214 pg/ml, creatinine
0.4 mg/dl, magnesium 2.0 mg/dl, vitamin D 25 level less
than 4 (20-100) ng/ml, vitamin D1-25 8 (19-67) pg/ml, no
evidence of malabsorption. Due to bone pain X-Ray was
done and showed poorly healed old fractures of multiple
ribs and pelvic bones with evidence of severe osteopenia. The patient was diagnosed with secondary hyperparathyroidism, hypocalcaemia due to vitamin D deficiency caused
by combination of his diet, minimal exposure to sunlight
and race (hyperpigmented skin). After dietary counseling,
calcium and vitamin D supplementation, his calcium level
normalized, and his generalized weakness and bone pain
improved.
Discussion: In the United States dairy products are
major contributors of calcium in the typical diet. Boiling
vegetables reduces their calcium content by 25%. Most of
commonly accessible products consumed by Ital dieters are
poor source of calcium: most vegetables provide less than
5% daily calcium value. Vegetarians consume food rich in
oxalic (chives, parsley, spinach) and phytic acids (flaxseed,
whole grains, nuts), compounds which interfere with calcium absorption from vegetable sources. In addition, typical vegetarian diets contain less protein, which may reduce
– 73 –
VITAMIN D DEFICIENCY AND
INSULIN RESISTANCE
Marjan Vahedi, MD, Gail Nunlee-Bland, MD,
Wolali Odonkor, MD, Mariama Semega-Janneh, MD,
James T. Williams, MD, Kanwal Gambhir, PhD,
and Cynthia Abrams, PhD
Objective / Introduction: Vitamin D deficiency has a
negative effect on beta cell function and has been linked to
metabolic syndrome and insulin resistance. Recent studies
have shown that decreased vitamin D level is associated
with increased age, body mass index (BMI), systolic blood
pressure and decreased HDL-C. Vitamin D supplementation might be an element in the treatment and prevention of
diabetes mellitus (DM) type-2.We sought to compare the
25-hydroxyvitamin D (25OHD) levels in a group of obese
adolescents with lean controls, and examine its relationship with insulin resistance, body mass index (BMI) and
adiponectin. Adiponectin is a protein hormone produced
by adipose tissue and low level adiponectin is associated
with obesity, diabetes, and cardiovascular disease.
Methods: 19 obese African American adolescents
with BMI > 85% for age, with first or second degree relatives with DM, ages 10-21 years, were studied. The control
group consisted of 15 normal weight African American
adolescents with a family history of DM, of the same age.
Parameters compared between the two groups were 25OHD
levels, BMI, adiponectin, and insulin resistance measured
by Homeostatic Model Assessment (HOMA).
Results: The 25OHD level was 13.48 ng/ml +3.97 in
the study group vs 20.77 ng /ml +7.45 in the control group
(p <0.003). BMI (percentile) was 98.84+ 0.50 in the study
ABSTRACTS – Other
group, compared to 64.80 +19.25 in the control group (p =
0.000). HOMA was 3.96 +1.84 in the study group vs 2.34+
0.94 in the control group (p < 0.002). Adiponectin was
6.79 +4.55 in the study group vs 17.28+ 6.89 in the control
group (p = 0.000). Calcium intake was 46% of the recommended daily allowance in the obese group and 45% in the
control group. Vitamin D intake was 67% of the recommended daily allowance in the obese group and 52% in the
control group. The difference of the calcium and vitamin
D intake was not significantly different between the two
groups (p = 0.74 and p = 0.45 respectively). The 25OHD
level correlated negatively with HOMA and BMI (p <0.042
and p < 0.002, respectively) but correlated positively with
adiponectin level (p <0.001).
Conclusion: In these African American adolescent
patients, vitamin D levels appear to be related directly to
adiponectin and inversely to body mass index and insulin
resistance.
stopped on Day 5. After stopping levofloxacin the patient
did not experience any further hypoglycemic episodes.
However despite the continued normolycemia over the
next 36 hours there was no improvement in the neurological status. Medical efforts were withdrawn on Day 8 at the
request of the family and the patient went home were he
expired.
Discussion: At the time of the first episode of hypoglycemia the possibilities which were considered in this
patient were hypoglycemia due to renal failure and/or
because of systemic sepsis. However over the next 48
hours the continued hypoglycemia despite increasing infusions of Dextrose fluids and the elevated serum insulin levels despite low blood sugar values make the above etiologies unlikely. In addition to levofloxacin the patient was
receiving piperacillin/ tazobactum, clindamycin, pantoprazole, deltaparin, diclofenac sodium and tramadol. Among
the drugs the patient was receiving the most likely cause
of the adverse event was levofloxacin. A score of four was
obtained on the Naranjo probability scale with levofloxacin which denoted the possibility of hypoglycemia being a
levofloxacin related adverse event. Similar to other reports
with levofloxacin the hypoglycemia was documented
within 24 hours of starting levofloxacin. Our patient was
elderly, had underlying renal impairment as seen in other
reports. The mechanisms of development of hypoglycemia
are related to abnormalities in insulin secretion from the
beta cells. Flouroquinolones increase insulin release from
rat isolated beta cells. The molecular mechanism of insulin
release is similar to sulfonylurea drugs which are by inhibiting the K ATP channels.
Conclusion: Hypoglycemia with the use of levofloxacin is an uncommon occurrence but failure to recognize the
cause could lead to disastrous results.
Abstract #708
FATAL HYPOGLYCEMIA WITH LEVOFLOXACIN
USE IN AN ELDERLY PATIENT
Jubbin Jagan Jacob, MD, Madhurita Singh,
and Navjot Singh
Objective: To report a case of Fatal Hypoglycemia
with the use of Levofloxacin in an elderly surgical patient.
Case Presentation: A 65 year old non diabetic Asian
gentleman was admitted with complaints of acute onset
severe periumblical pain with a provisional diagnosis of a
duodenal ulcer perforation. On admission the patient’s renal
function determined by the creatinine clearance was 12ml/
min/1.73m2. After the patient was stabilized with intravenous fluids and dialysis he was taken up for an exploratory
laparotomy. Intraoperatively, over two litres of pus was
drained from the peritoneal cavity. In the immediate post
operative period he was empirically started on piperacillin- tazobactum 4.5 gm three times daily, clindamycin 600
mg three times daily and levofloxacin 200mg once a day.
Twenty four hours after the first dose of levofloxacin the
patient was noticed to have low blood sugar values with
autonomic and neuroglycopenic symptoms. For the next 72
hours patient received multiple infusions of 50% Dextrose
and Dextrose containing fluids but continued to have recurrent hypoglycemic episodes with progressively worsening
neuroglycopenic symptoms. In the later part of this period
the patient developed seizures and decerebrate posturing.
Serum insulin levels sent during an episode of hypoglycemia revealed unsuppressed values (57microIU/ml) suggesting hyperinsulinemic hypoglycemia. Levofloxacin was
Abstract #709
SURVEY OF THE USE OF LEVOFLOXACIN AND
GATIFLOXACIN AND AWARENESS ABOUT ITS
POTENTIAL HYPOGLYCEMIC SIDE EFFECTS
Jubbin Jagan Jacob, MD, and Navjot Singh MD
Objective: Hypoglycemia has been reported with all
flouroquinilone antibiotics. Dysglycemic episodes with
Gatifloxacin (GTX) are well reported in literature but
potential hypoglycemia with Levofloxacin (LFX) is less
well reported. This questionnaire survey attempts to quantify prescription practices with respect to LFX and GTX
and the awareness of these antibiotics to potentially cause
hypoglycemia.
– 74 –
ABSTRACTS – Other
Methods: Questionnaire survey was conducted
among doctors in the clinical services of a University affiliated teaching hospital regarding prescription practices with
LFX and GTX and about the awareness of its hypoglycemic side effects.
Results: About 64 completed questionnaires were
obtained out of a 134 doctors approached. Majority of them
were from internal medicine or its allied specialties (IMAS)
34 (53%). The rest were from surgery and allied specialties
(SAS); 14 (22%), Otolaryngology; 4 (6%), Orthopedics; 4
(6%), Ob/Gyn; 4 (6%) and Critical Care; 4 (6%). Eighteen
of 64 doctors (28%) and 19/64 (30%) prescribed LFX more
than 3 times a week among Outpatients (OP) & Inpatients
(IP) respectively. While 3/64(5%) & 4/64 (7%) prescribed
GTX >3/week in IP & OP respectively. 22% and 48% of
physicians were aware that LFX & GTX causes hypoglycemia respectively. Five (8%) of doctors recalled having
observed a hypoglycemic episode with LFX while 7 (11%)
recalled a hypoglycemic episode with GTX. The majority
of doctors prescribing LFX (52% &56%) & GTX (9% &
9%) > 3/week in OP & IP were from IMAS. Awareness
that LFX and GTX cause hypoglycemia was 9% and 30%
respectively among doctors in IMAS. In the SAS awareness was 21% and 2% about hypoglycemia and LFX &
GTX respectively. Specifically among those doctors prescribing LFX > 3/week in OP the awareness that it causes
hypoglycemia was only 5% and with GTX >3/week in OP
it was 50%.
Discussion: LFX is more widely prescribed flouroquinilone than GTX in our Hospital. While a little less than
half of doctors are aware of the hypoglycemic side effect of
GTX only a little over a fifth of the doctors were aware of
similar side effects with LFX. There was a higher awareness
of LFX induced hypoglycemia among doctors in surgical
specialties probably because of an unfortunate death of a
surgical patient with LFX induced hypoglycemia. Doctors
from Internal medicine and specialties, who were among
the most frequent prescribers of LFX, were least aware of
the hypoglycemic side effect of LFX. There seemed to be
similar number of recalled episodes of Hypoglycemia with
both drugs.
Conclusion: Despite widespread use of LFX and
GTX in medicine and Surgical specialties the awareness
about its hypoglycemic side effect is less than satisfactory.
There appears to be a prescription bias in favour of LFX as
fewer doctors are aware of its potential hypoglycemic side
effects though the recalled hypoglycemic episodes with
both agents appear to be similar.
Abstract #710
THE CHALLENGES OF ENDOCRINOLOGY
PRACTICE IN NIGERIA:
FOUR ILLUSTRATIVE CASES
Felicia Ohunene Anumah, MBBS, MWCP, FMCP
Objective: In Nigeria endocrine disorders are on the
increase and constitute a significant cause of morbidity and
mortality. They have not had much attention because of
the enormous burden posed by infectious diseases. This
presentation attempts to highlight a few management challenges in our setting using 4 case illustrations in our endocrine practice in Nigeria.
Case Presentation: Case 1: A 56year old male motor
mechanic who has had diabetes mellitus and hypertension for 20 years, He could not afford proper control of his
diabetes and developed bilateral amputation, diabetic retinopathy and nephropathy. He therefore lost the source of
income and was eventually dependent on goodwill for his
medicare. He died from acute complications of diabetes.
This is an illustration of the vicious cycle of poverty and
disease which led to fatality.
Case 2: A 17 year old female school student from
the low socio-economic class. She presented with florid
features of Graves disease and Graves ophthalmopathy.
She defaulted while on treatment and opted for alternative
medical therapy. She unfortunately reappeared a year later
to our center with bilateral blindness due to corneal opacity. This patient should have benefited from corneal graft
but the facility was not readily available. She has been lost
to follow up.
Case3: A 20 year old younger brother of a medical
doctor who was diagnosed diabetic for 5 years and was
placed on insulin therapy. He, however, despite adequate
counseling, preferred alternative medical care. He eventually presented in our center with short stature, pancreatic
diabetes and malabsorption syndrome. He has since been
lost to follow up.
Case 4: A 45 year old house wife who presented with
features of acromagly and congestive cardiac failure secondary to acromegalic cardiomyopthy. She could not have
a complete hormonal assessment because of poverty. She
could only afford bromocriptin erratically but was not able
to afford other treatment modalities such as surgery and
radiotherapy. She was eventually lost to follow up.
– 75 –
ABSTRACTS – Other
Conclusion: The four cases illustrated a few of
the challenges of endocrine practice such as ignorance,
poverty, the menace of untrained alternative caregivers,
affordabilty and availability of dequate treatment facilities
in our setting. The cases also illustrated the impact of disease on morbidity and mortality due to these challenges.
hip and spine BMD over time were independent of baseline CrCl (interaction P-values=0.10–0.63).
Discussion: Both subgroups showed highly significant relative risk reductions greater than 60%. However,
there was a marginally significant treatment-by-baseline
CrCl interaction for the reduction in morphometric vertebral fractures, with patients with renal impairment showing a lesser response (P=0.0504). For hip fractures, there
was no significant interaction with baseline CrCl (P=0.58),
with risk reduction of 34% in the <60 mL/min group and
46% in the ≥60 mL/min group.
Conclusion: In conclusion, the 30–40% increase in
bone exposure to ZOL in patients with mild-to-moderate renal failure has no significant impact on the skeletal
response to ZOL, as assessed by histomorphometry, biomarkers of bone turnover, BMD or antifracture efficacy.
Abstract #711
THE SKELETAL RESPONSE TO
ZOLEDRONIC ACID IS NOT AFFECTED
BY RENAL IMPAIRMENT
Paul D. Miller, MD, Steve Boonen, Dennis Black,
Deborah Sellmeyer, Henry Bone, Arne Skag, S Giannini,
K Lippuner, Peter Mesenbrink, and Erik Fink Eriksen
Objective: To test whether or not skeletal response
is affected by zoledronic acid in patients with renal
impairment.
Methods: In patients with mild-to-moderate renal
impairment [creatinine clearance (CrCl) >20 mL/min and
<60 mL/min], pharmacokinetic studies show a moderate
30–40% increase in serum levels of zoledronic acid (ZOL).
To test whether this difference had any impact on the tissue level response to ZOL infusion, we compared skeletal
responses to ZOL in patients with a baseline CrCl ≥60
mL/min (n=4222) to the responses observed in patients
with a baseline CrCl <60 mL/min (n=3514) in the 3-year
HORIZON-Pivotal Fracture Study (n=7736). Patients with
a baseline CrCl <30 mL/min were excluded from the study.
The analysis comprised bone histomorphometric parameters, bone mineral density (BMD), biomarkers of bone
turnover, and morphometric and clinical fractures in the
two groups.
Result: Comparison of histomorphometry results
showed that the reduction of bone turnover, as shown by
activation frequency and mineralizing surface, was similar
in the two groups (63% in patients with CrCl <60 mL/min
vs. 56% in patients with CrCl ≥60 mL/min, and 88% in
patients with CrCl <60 mL/min vs. 91% in patients with
CrCl ≥60 mL/min, respectively). Microcomputed tomography indices related to bone structure were also unaffected
by baseline CrCl. There was no association between treatment and baseline CrCl in the reduction of biochemical
markers of bone formation (serum bone-specific alkaline
phosphatase and serum procollagen type I intact N-terminal propeptide) and bone resorption (serum C-telopeptides) over time (6–36 months) after treatment with ZOL
(interaction P-values=0.09–0.67). Also, increases in total
Abstract #712
A FAMILY WITH MEN 2 DUE TO A
NOVEL MUTATION
Sumedha Ram Pathak, MD, and Ram D. Pathak, MD
Objective: To report a family with MEN 2 with rare
mutation where phenylalanine (TTC) replaced cystein
(TGC) at codon 618.
Case Presentation: A 53 year old male was noted
to have thyromegaly. Ultrasound of thyroid revealed a 5
cm nodule in the left lobe. Fine needle aspiration biopsy
revealed medullary thyroid cancer (MTC). Serum calcitonin was markedly elevated at 22000. He underwent total
thyroidectomy with modified neck dissection on left side.
Histopathology revealed invasive medullary carcinoma in
both lobes with extension to lymph nodes. There was no
family history of MTC. Genetic testing revealed a mutation
in RET proto-oncogene at codon 618 where cystein was
replaced with phenylalanine and patient was diagnosed
with MEN 2. Evaluation for pheochromocytoma was negative. Genetic screening done for this mutation is positive
for 6 out of 8 family members, all of whom except a 3
year old grandson underwent total thyroidectomies. All the
specimens were positive for medullary thyroid cancer on
histopathology. The patient and the affected family members are being serially monitored for pheochromocytoma.
Discussion: MTC is a rare calcitonin producing
tumor. Familial variety is seen in 3 distinct forms- MEN
2A where it is associated with pheochromocytoma and
parathyroid adenoma; MEN 2B where it is associated with
pheochromocytoma, marfanoid habitus, mucosal neuromas
– 76 –
ABSTRACTS – Other
and intestinal ganglioneuromas. In third form or familial
MTC (FMTC), it is not associated with other manifestations. All 3 forms are inherited as autosomal dominant.
Genetic defect involves mutation of RET proto-oncogene
on chromosome 10. The majority of mutations in MEN
2A and most in FMTC kindreds involve cystein residue
in RET protein’s extracellular domain encoded in exon 10
(codons 609,611, 618 and 620) or 11 (codons 630 or 634).
There is a clear genotype-phenotype correlation between
specific mutation, component of MEN 2 and course of
the disease. We hereby report a novel mutation on codon
618 where cystein residue was changed to phenylalanine.
Because FMTC is the most limited variant of MEN 2A,
making wrong diagnosis of FMTC could result in missing a pheochromocytoma in a patient with MEN 2. The
clinical distinction of FMTC from MEN 2A may be difficult, the designation of FMTC has been changed to MEN
2A in some families. Therefore FMTC kindreds should be
defined using more rigorous criteria.
Conclusion: Early diagnosis by screening of ‘at risk’
family members is essential because MTC is a life threatening disease that can be prevented by early thyroidectomies. Close monitoring for pheochromocytoma is also
mandatory.
with inappropriately raised proinsulin of 64.1 pmol/L, CPeptide 3.8ng/mL and beta-hydroxybutyric acid of 1.0 mg/
dL. An endoscopic ultrasound guided biopsy of the mass
confirmed insulinoma. This was subsequently removed
along with another satellite lesion on pancreatectomy and
splenectomy.
Discussion: This rare case has many interesting learning points. First, Insulinoma is a rare tumor affecting only
1 in 100,000 people in the general population, and less than
10% of the cases are malignant. Secondly, in contrast to
our patient’s presentation, islet cell tumors arise most frequently in the fifth to seventh decades. T he history is often
lengthy involving neuropsychiatric symptoms and weight
gain from increased food ingestion. Third, even though
far less is known about the pathogenesis of hypoglycemia
induced peripheral neuropathy; it is nearly always symmetrical, predominantly distal, and usually sensori-motor.
Conclusion: Juvenile onset Insulinoma with sensori-motor neuropathy is uncommon and rarely described.
Unusual manifestations such as those in our patient make
the diagnosis even more challenging. An early diagnosis
may lead to definitive cure, like surgery in our patient.
Abstract #713
METASTATIC GASTRINOMA WITHOUT
TYPICAL ZE IN THE STOMACH
– NORMALIZATION OF GASTRIN WITH
SANDOSTATIN THERAPY
Abstract #714
HYPOGLYCEMIC POLYNEUROPATHY IN A
JUVENILE: A RARE CASE OF INSULINOMA
Deepa Taneja, MBBS, Ralph Miller, Lisa Tannock,
and L.R. Reynolds
Silvia Velinova, MD, and Rasa Kazlauskaite, MD
Objective: To present a rare case of a young patient
with asymptomatic metastic gastrinoma.
Case Presentation: 27- years-old female was diagnosed with prolactinoma in 1997, after presenting with
amenorrhea and galactorrhea. The size of the prolactinoma remained stable at 14 mm for 10 years, while treated
with dopamine agonists. The patient was diagnosed with
multiple duodenal ulcers in 2003, when she presented
with gastric outlet obstruction. Her symptoms resolved
with proton pump inhibitor (PPI) treatment. Due to the
prolactinoma, fasting gastrin levels were measured (330
pg/ml). Secretin test was also positive, but CT scan, PET
and Octreotide scans remained negative. Genetic testing
confirmed the diagnosis of multiple endocrine neoplasia
(MEN) type 1. She has had mild hypercalcemia periodically. Prior to exploratory laparotomy in 2005, the CT scan
of the abdomen revealed 10 mm tumor of the pancreatic
head. Laparoscopic wedge resection of the duodenum and
lymph node excision, confirmed well-differentiated neuroendocrine tumor with positive gastrin stains (T1N1MX).
Background: Insulinoma in children and adolescents
is extremely rare. Peripheral neuropathy associated with
hypoglycemia is even rarer. We report an unusual case of
malignant insulinoma with peripheral neuropathy associated with hypoglycemia in a 16 year old male.
Case: A 16 year male was admitted to the ER following
motor vehicle collision. CT scan of the abdomen and pelvis
demonstrated a presumptive pancreatic tail hematoma that
was found to be a 2.5 cm mobile nodular mass on exploratory laparotomy. Resection of this pancreatic mass was
deferred due to multiple traumatic injuries. Approximately
one year later, the patient was found to be unresponsive at
home and his blood glucose was documented to be 25mg/
dL. His symptoms resolved after administration of intravenous glucose. In concurrence with several subsequent
hypoglycemic episodes, the patient developed paresthesias
in both upper extremities, that later progressed to proximal and distal arm muscle weakness. An overnight fasting test showed plasma glucose of 40 mg/dL associated
– 77 –
ABSTRACTS – Other
Case Report: A 78 year old woman was referred
for evaluation of hypercalcemia which was noted several
months prior to referral. She did not report any history of
anorexia, difficulty in swallowing, weight loss or history
of kidney stones. Blood investigation shown high serum
calcium, high PTH intact, with normal 24-hour urinary
calcium. Thyroid profile was unremarkable. Bone density study shown severe osteoporosis. Tc-99m Sestamibi
imaging revealed suggestive of parathyroid adenoma on
the lower pole of the right thyroid lobe. Primary hyperparathyroidism possibly due to parathyroid adenoma was
confirmed biochemically and radiologically. Based on the
above findings, our patient underwent exploratory neck
operation. The location of the adenoma at the inferior part
of right thyroid lobe was confirmed by using a navigator
probe prior to the procedure. Right thyroid lobectomy was
performed because it was believed that the parathyroids
are intrathyroidal. The specimen was sent for the histology study. After the operation, the complete disappearance of radioactive activity was confirmed with the probe.
Intraoperative parathyroid assay was not carried out due to
mechanical failure of machine on that day. Postoperative
serum calcium level shown high level raised the suspicious
of possible persistent hyperparathyroidism. Interestingly,
the microscopic examination revealed the thyroid lobe
containing the Hurthle cell neoplasm with encapsulated
angioinvasion with a focus of angioinvasion beyond the
level of tumor capsule. Our patient declined for further
work up and treatment providing her advanced age and
asymptotic for years. Both serum calcium level and PTH
intact level are found to be still high in postoperative interval follow up. Four months after surgery, repeat Tc-99m
Sestamibi scan also revealed an area of retained activity
on lower pole of right side of the neck compatible with a
parathyroid adenoma.
Discussion: While Tc-99 m Sestamibi scan is now the
imaging procedure of choice particularly for localization
of parathyroid tumors, the specificity of Sestamibi scans
has been questioned because some reports in the literature shown that uptake has been demonstrated in coexisting thyroid carcinoma, metastatic thyroid carcinoma and
adenoma. The presence of Hurthle cell carcinoma obscure
the presence of the parathyroid adenoma by first Sestamibi
scan in our patient. Our report illustrates the importance
of awareness of rare coexisting of HCC with primary
hyperparathyroidism and it is always prudent to confirm
the removal of adenoma by measuring serum PTH in the
operating room before withdrawal of anesthesia.
Whipple’s procedure was deferred at that time. The
abdominal scan in 2006 showed stable size of the pancreatic mass, identified as gastrinoma and a liver mass 15 x
14 mm, confirmed to be a liver metastasis with Octreotide
scan.The patient remained completely asymptomatic on
PPI with gastrin levels 300 - 500 pg/ml and refused surgical treatment. As Octreotide scan has been positive, she
has been treated with Somatostatin with normalization of
serum gastrin levels (24 pg/ ml).
Discussion: The patient had primary duodenal gastrinoma as part of MEN 1 with lymph node metastasis and
residual disease in the head of the pancreas with metastasis
to the liver. The size of the pancreatic tumor of less than
3 cm favored less aggressive course. However, a combination of other aggressive growth predictors was present:
age younger than 35 years at diagnosis, liver metastasis
and duodenal tumor equal or more than 1 cm. The literature suggests surgical debulking of the pancreatic mass
and cryoablation of the liver metastasis could potentially
improve symptoms and survival, when cure cannot be
ascertained. Octreotide, similarly to Lanreotide (known
to reduce gastrin level and tumor size) has high affinity
for Somatostatin receptor subtype 2 (sst2), but higher for
sst5. Sst2 predominance is found in more than 80% of the
pancreatic endocrine tumors. However, majority of them
express multiple receptor subtypes.
Conclusions: Even though we still suggest surgical
debulking, adjuvant therapy with PPI and Somatostatinanalog preparations makes plausible sense in this young
patient with asymptomatic metastatic gastrinoma.
Abstract #715
INCIDENTAL FINDING OF HURTHLE
CELL CARCINOMA BY Tc-99 M SESTAMIBI
IMAGING IN A PATIENT WITH PRIMARY
HYPERPARATHYROIDISM.
Hla Win, MD
Introduction: Hurthle cell carcinoma, considered as
a variant of follicular cell carcinoma of thyroid, accounts
< 5% of all differentiated thyroid malignancies. It may
represent as a low-grade tumor or as a more aggressive
type. The pathological association of thyroid and parathyroid diseases are not uncommon, but the presence of
both thyroid cancer and parathyroid adenoma is rare. We
report a case of incidental finding of Hurthle cell carcinoma by Tc-99m Sestamibi scan in a patient with primary
hyperparathyroidism.
– 78 –
ABSTRACTS – Other
tablets along with erythropoietin should be the mainstay
of therapy. Weight gain has been reported to alleviate this
condition.
Conclusion: Physicians should be aware about possible cardiovascular and neurological complications of rapid
weight loss after GBS.
Abstract #716
DYSAUTONOMIA, A SIDE EFFECT OF
GASTRIC BYPASS SURGERY?
Mikhail Signalov, DO, Pratik R. Shukla, DO,
and Bankim Bhatt, MD
Abstract #717
Objective: Gastric bypass surgery (GBS) has become
a common treatment modality in the management of morbid obesity. The relationship between hypertension, diabetes and obesity is well-established. In most cases, the
weight loss after GBS has been associated with significant
improvement in diabetes and blood pressure control, but in
some cases it can be associated with dysautonomia. Here,
we report a case of 34-year-old woman who developed
severe dysautonomia after rapid weight loss as a result of
GBS.
Case: A 34-year-old woman with past medical history of morbid obesity (BMI 44), status-post GBS thirteen
months ago, was admitted with near syncope and dizziness.
During recent hospitalization at another institution, an
echocardiogram and 24 hour Holter monitoring were normal, while an MRI showed an empty sella with compressed
pituitary. On admission to our institution, she complained
of severe dizziness, improving only with supine position,
as well as generalized fatigue that has been worsening over
the last 5 to 6 months. She had lost over 175 pounds since
her GBS (current BMI 18). On physical exam, she had
significant orthostasis without reflex tachycardia (supine
BP 102/64 and upright BP 70/52 with HR 50). The rest
of the physical exam was remarkable only for decreased
sensation in lower extremities, left more than right, and
absent patellar reflexes. The evaluation of adrenal function
showed low morning cortisol level (1.4 mcg/dl) and a brisk
response to an ACTH (250 mcg) stimulation test (ACTH
= 6 pg/ml, baseline cortisol 2.4mcg/dl, 30 min and 60 min
cortisol levels 14.0 and 17.3 respectively). The rest of the
work-up (TFT, LH, FSH, Estradiol, Free T4, TSH, T3, B12
CBC, CMP) was normal. Treatment with steroids did not
improve the orthostasis. Abdominal wall fat biopsy was
negative for amyloid, while SPEP and UPEP did not show
any monoclonal bands. She was placed on fludrocortisone,
salt tablets, and erythropoietin with slow improvement in
the dizziness and blood pressure.
Discussion: Orthostasis following rapid weight loss
after GBS has been reported. A possible explanation for the
orthostasis is a direct effect of the quick change in BMI on
the sympathetic nervous system. It is unlikely that adrenal insufficiency is the primary cause of the hypotension
in this case since the patient did not improve with steroid
therapy. Volume expansion with fludrocortisone and salt
AN UNUSUAL CASE OF GYNECOMASTIA
Jorge Ivan Martinez Osorio, MD, and Jack E. Lewi, MD
Objective: Describe an infrequent cause of gynecomastia and increase in level of estradiol and estrone in a
patient due to increase ingestion of soymilk.
Case Presentation: A 60 year-old Caucasian male
presented with bilateral gynecomastia of 6 months of duration, decreased libido and erectile dysfunction. LFT, TSH,
LH, FSH, beta HCG, testosterone, prolactin, PSA, androstenodione, and DHEAS levels were normal. However,
serum estradiol and estrone levels were four-times the
upper limit of normal. A testicular ultrasound, CT of the
chest, abdomen and pelvis and a PET scan were unremarkable. The patient later reported a daily intake of over three
quarts of soymilk due to lactose intolerance. After discontinuation of the soymilk, his estradiol and estrone levels
gradually returned to normal and his gynecomastia slowly
improved.
Discussion: Gynecomastia has been reported with
herbal supplements containing phytoestrogen. Soymilk
and soy protein have been extensively studied for the last
fifteen years for possible beneficial effects in human health
which include: decreased levels of cholesterol, decreased
incidence of prostate cancer and breast cancer, decreased
menopausal symptoms, and increased bone density. It is
very well documented that soymilk has phytoestrogens.
More specifically, the soymilk phytoestrogens are known
as the isoflavones genistein and daidzein which are structurally and functionally similar to 17 beta-estradiol but
with weaker bioactivity than estradiol. Ingested isoflavones undergo biotransformation by the intestinal microflora followed by absorption and enterohepatic recycling
which can result in high circulating concentrations. This is
one reason why the estradiol levels were delayed in returning to normal. There is much variability in absorption of
isoflavones from one individual to another. Soy isoflavones
likely interfere with the CYP enzymes that assist in the
metabolism of estrogen. It is possible that isoflavones in
large amounts could explain the increase in estradiol and
estrone levels and caused the gynecomastia in our patient.
The normal amount of phytoestrogen in a cup of soymilk
– 79 –
ABSTRACTS – Other
Discussion: Fortunately, symptomatic hypercalcemia
that presents during pregnancy is a very rare occurrence,
with fewer than 200 cases reported. Asymptomatic hypercalcemia is usually detected incidentally on laboratory tests
and can usually be watched, with instructions to increase
PO fluid intake. If symptomatic, hypercalcemia usually
causes nephrolithiasis, but pancreatitis and hyperemesis
gravidarum are known complications. Further investigation poses a problem as sestimibi scans are contraindicated
in pregnancy. Ultrasounds can be done in an attempt to
localize an adenoma. Surgical parathyroidectomy would
ideally be performed in the second trimester, when risks
to the mother and fetus are minimized. In the third trimester, options for treatment are surgery or fluid hydration and
close monitoring, until the patient is considered safe for
induction of delivery and a follow up parathyroidectomy.
The presence of 4 gland hyperplasia versus adenoma, as
expected in MEN 1 or 2, would not alter treatment in this
circumstance.
Conclusions: The standard treatments of primary
hyperparathyroidism with symptomatic hypercalcemia
include medications that are all unsafe in the pregnant
patient. In the third trimester of pregnancy, close consultation with the obstetrics team, induction and delivery,
and subsequent surgical parathyroidectomy is an effective
management for this rare presentation.
is 25 mg. Our patient was taking three quarts a day of soy
milk which is the equivalent of taking 361mg of isoflavones a day. His breast tenderness resolved and his estradiol and estrone levels normalized with discontinuation of
use of soy products.
Conclusion: Soymilk is not considered an herbal or a
supplemental medicine. With a myriad of dietary supplements and choices, it is important for health care providers
thoroughly review patient’s habits as the review can reveal
the etiology of unusual medical conditions.
Abstract #718
A CASE OF HYPERCALCEMIA IN
A PREGNANT PATIENT
Supna Bhagat Lowery, MD, Elizabeth Mason,
Donald Richardson, John O’Brian, and Ann Colle
Objective: This report demonstrates the therapeutic
challenge in the manage-ment of a patient in her third trimester of pregnancy with hypercalcemia and pancreatitis.
Case Presentation: We present the unusual case of a
33 week pregnant G2P0 26 year old female with a remote
history of prolactinoma, treated intermittently with bromocriptine, and hyperemesis gravidarum earlier in her
pregnancy, who now presented with symptoms of abdominal pain, nausea, and vomiting. Amylase and lipase were
elevated, and clinical signs were consistent with pancreatitis. In her evalauation, the patient was noted to be hypercalcemic with an ionized calcium of 6.9 mg/dL, elevated
PTHs of 60.2 and 90 pg/mL, and a 24 hour urinary calcium level of 767 mg/24 hours, all consistent with primary
hyperparathyroidism. The combination of a history of a
prolactin-secreting pituitary adenoma and primary hyperparathyroidism suggested MEN1 Syndrome.
The routine treatments for hypercalcemia (e.g., calcitonin, bisphosphonates, sensipar) could not be employed
as they are all pregnancy category C. As she was in her
third trimester, neck exploration surgery was not preferred.
The patient was maintained on intravenous hydration and
underwent induction at 34 weeks with a successful delivery.
She then received intravenous pamidronate as a temporizing measure. A subsequent neck exploration resulted in the
removal of a 417 mg adenomatous-appearing parathyroid
gland. Intraoperative PTH fell from 182 to 22 (consistent
with curative adenomectomy as opposed to a reduction of
hyperplastic parathyroid mass).
Her Prolactin was 167 at the time of presentation, consistent with physiologic hyperprolactinemia of pregnancy.
A MENIN gene test has been ordered.
Abstract #719
TURNER SYNDROME ASSOCIATED WITH
AORTIC INSUFFICIENCY AGGRAVATED
UNDER GROWTH HORMONE AND
ESTROPROGESTATIVE THERAPY
Cristina Iuliana Bejnariu, MD, and Pavel Suciu, MD
Objective: To estimate the evolution of cardiovascular
disorders, stature, secondary sexual characteristics, bone
density with adequate endocrinologic treatment.
Case presentation: We are presenting a 21 year old
female with Turner Syndrome (diagnosticated from the
age of three years old) associated with aortic insufficiency
(second degree), hypertension, polycystic left kidney,
youthful glaucoma, chronic lymphedema at the left shank.
In the last three years the patient received growth hormone
therapy and in the last year it was associated with estroprogestative therapy. Under this therapy the height range
was between 139-148 cm. The estroprogestative treatment
permitted the maturation of breasts and of genitals. We also
administered beta blockers, diuretic and venolymphatic
trophic treatment. Her physical examination was remarkable for turnerian fenotype. Systemic examination indi– 80 –
ABSTRACTS – Other
rhea. Physical examination revealed high blood pressure,
facial plethora, moon face, buffalo hump, truncal obesity,
branched reddish purple abdominal striae extending to
the chest and tights and bilateral lower extremity edema.
Laboratories revealed high cortisol levels after low and high
dose dexamethasone suppression tests, high ACTH levels,
metabolic alkalosis, and hypokalemia. That correlates with
ectopic ACTH secretion. Abdominopelvic CT scan and
Thorax CT scan revealed a right pericardial mass. Head
MRI suggested a pituitary microadenoma. Patient was
referred to cardiothoracic surgery for removal of mediastinal mass. Pathology reported a carcinoid tumor. Removal
of the tumor lead to marked clinical improvement. Four
years after tumor resection she presented with recurrence
of symptoms clinically and biochemically. No mediastinal
masses detected in thorax CT scan. Whole body PET/CT
scan showed hypermetabolic left mediastinal tumor. Mass
was resected and phenotype study was consistent with a
neuroendocrine carcinoma with cytoplasmic expression of
ACTH. Patient persisted with evidence of ectopic ACTH
secretion after second thoracic surgery. Imaging studies did
not reveal evidence of any mass. Octreotide scintigraphic
showed evidence of residual disease. The optimal therapy is
surgical excision. Patient is currently on an adrenal enzyme
inhibitor, pending radioguided surgery, using a hand-held
probe after IV administration of radiolabeled octetreotide.
This procedure has allowed detection and removal of residual multiple tumor foci and previous incomplete removal
of the tumor in previous case reports.
Discussion: Carcinoid Tumor consists of a neuroendocrine carcinoma that can have cytoplasmic expression
of ACTH. There is not a single endocrine test or imaging
procedure accurate enough to diagnose and localize occult
ectopic ACTH-secreting carcinoids, which make them a
formidable diagnostic challenge. Recurrences have been
previously demonstrated in medical literature years after
surgical treatment. These recurrent tumors can be difficult
to localize with modalities like CT or MRI. Some ectopic
ACTH-secreting tumors can be detected by scintigraphy
with 111-In-octreotide or an analog of octreotide because,
like other neuroendocrine tumors, their cells have cellsurface receptors for somatostatin, which illustrate the
relevance of octreotide scan as a diagnostic tool to detect
carcinoid tumors.
Conclusion: We can take advantage of the presence
of cell-surface receptors for somatostatin in recurrent carcinoid syndrome, when usual imaging modalities fail to
localize the tumor. In this case we identify the tumor using
scintigraphy with 111-In-octreotide. This can also help in
it’s intraoperative localization using radioguided surgery
with IV administration of radiolabeled octreotide.
cated aortic regurgitation spill IV/VI. Under this treatment
laboratory evaluation showed: subclinical hypotyroidism,
hypercholesterolemia, IGF 1 normal range. Radiology
exam: osteoporosis, the presence of growth cartilages. E
chocardiography: bicuspid aortic valve with severe aortic
insufficiency (third degree). Pelvic ultrasound: polycystic
left kidney.
Discussion: Hypotyroidism is often associated with
Turner Syndrome but it could appear during growth hormone therapy. So we started to administrate thyroid replacement therapy. It is known that thyroid hormone have a
permissible effect for growth hormone and this increases
the growth. It is important to evaluate bone density and
how much the estroprogestative treatment in association
with growth hormone therapy influences its recovery. We
observed that aortic insufficiency had an accelerating evolution in the last year, probably influenced by the highest
doses of growth hormone and estroprogestative therapy. At
the moment the patient needs surgical treatment.
Conclusions: Even if the treatment with growth
hormone is useful for increase of bone density it is possible that the high doses are aggresive for aortic insufficiency. For that reason the growth hormone therapy should
be stopped after the growth cartilages are closed and the
estroprogestative therapy remains as of long standing treatment for a good bone density. It is known that patients with
Turner syndrome appear to have a decreased life expectancy as a result of complications of heart disease. For a
good quality of life the patient needs a variety of follow-up
controls which can be obtained through a multidisciplinary
approach.
Abstract #720
RECURRENCE OF CUSHING’S SYNDROME
SECONDARY TO NEUROENDOCRINE TUMOR
DETECTED BY OCTREOTIDE SCINTIGRAPHY
AFTER A SECOND MEDIASTINAL MASS
RESECTION
Meliza Martinez, MD, Myriam Allende, MD,
Margarita Ramirez, MD, and Vilma Rabell, MD
Objective: To report a case of recurrent carcinoid syndrome and the diagnostic usefulness of octreotide scintigraphy for tumor localization.
Case presentation: This is a 29 y/o female referred
to endocrinology clinics with a two years history of 29
kg weight gain associated with abdominal and facial
obesity. She also presented increase in facial hair, easy
bruising, acne, proximal muscle weakness and amenor– 81 –
ABSTRACTS – Other
Discussion: Metabolic Clinic is ideal for Chronic
CAD management with excellent results. What is the
explanation of these important findings? First let us start
from our understanding of the pathogenesis of ischemia in
acute vs. chronic CAD. The Atheroma in Acute Coronary
Syndrome (ACS) is unstable, vulnerable, has thin surface, few smooth muscles, less supporting collagen fibers,
large lipid core, many inflammatory cells, ready to rupture
leading to acute MI or unstable angina, often with minor
obstructive feature which may not even be recognized on
catheterization, thus not treated by stenting until the acute
clot phase.
On the other hand; Atheroma in chronic Coronary
Artery Disease is stable, has thick surface, more smooth
muscle cells, more supporting collagen fibers, lesser lipid
core, less inflammatory cells, resistant to rupture but produce more obstruction, seen large often at catheterization,
and but associated with more symptoms in the pattern of
chronic stable Angina and less risk of rupture in acute
form. But which one today is treated more by stenting?
The numbers speak: 85% of stenting are done in chronic
stable disease. The reverse should be true.
Conclusion: Optimum medical therapy in
Metabolic Clinic is recommended to All patients with stable CAD. it is effective in 85% of cases. Stint is reserved to
15% with acute presentations. Optimum medical therapy
includes: Aspirin, Statin, B blocker, Ace or ARB, with
the intensive management of diabetes, hypertension, obesity, lifestyle changes (diet, exercise and smoking). This
is exactly what a good internist or an endocrinologist will
do. This is exactly why I believe it is important you stop
sending every CAD patients to cardiac catheterization laboratory. Treat in optimum fashion “The deadly quartet”:
diabetes, hypertension, obesity, hyperlipedemia, and help
your patients modify their lifestyle (smoking, exercise,
and diet). This is what our patients deserve because they
deserve the best evidence medicine. This is what we are
all about in our professional life. This is the future of CAD
management.
Abstract #721
EDOCRINOLOGISTS SHOULD TREAT
MAJOR RISK FACTORS, NOT INVASIVE
CARDIOLOGISTS
Saad Sakal, MD, FACE
Objective: Endocrinologists had a long interest
in Atherosclerosis as physicians who treat cardiovascular
risk factors (diabetes, obesity, hyperlipedemia, hypertension and lifestyles). The question is then who should deal
with CAD in their own patients: is the issue of atherosclerosis an issue of biologic vascular integrity for the endocrinologist or just an obstruction for the cardiologist? The
question should be asked today, not ignored.
Methods/Case series: We compared the medical
therapy given to our Metabolic clinic patients to Optimum
medical therapy (OMT) as we know it described in the
Courage Trial: 1) Antiplatelets aggregation with small
dose of Aspirin or clopidogrel 2) Antianginal therapy with
nitrates, Beta blocker or calcium channel blocker 3) Anti
lipids therapy: to lower cholesterol a Statin alone or with
ezitimib, To lower triglycerides a fibrate alone or with niacin to raise HDL. 4) Anti rennin/angiotensin system: an
ACE or an ARB.
Results: 1) In Courage Trial 70% had LDL cholesterol below 85 mg/dl. (67% in our clinic) 2)94% had
diastolic BP below 85, 65%had systolic BP below 130.
(ours: 90% and 77% respectively) 3)45% of diabetics had
HgA1C below 7%. (ours: 65%) 4)77% followed diet, 40%
exercise. (ours: 66% and 55% respectively) 5) Compliance
with therapy was very good: 85% received B blocker, 40%
nitrate or calcium channel blocker. (ours: 80%and 40%)
95%used Aspirin daily. (ours: 89%) 93%used a statin, 40%
used fibrate or ezitimib. (ours: 84%and 64%) 60% used
ACE inhibitor, 11% used ARB.( ours : 70% and 20% ) In
general a good compliance rate with a reasonable success
in therapy end points of similar or better than OMT in the
lttreture. At 5 years the CV events were equal.
– 82 –
ABSTRACTS – Pituitary Disorders
can be effective in treating approximately 50% of these
adenomas. Therefore, octreotide therapy was initiated in
our patient in order to facilitate a more optimal surgical
outcome. The nodule in the thyroid, and subsequent histological and Tc99m characteristics were concerning for a
concurrent follicular neoplasm.
Conclusion: This case demonstrates the importance
of complete evaluation of any thyroid abnormality, since,
in the setting of a TSH-secreting pituitary adenoma, a goiter or nodule might be attributed to hypertrophy of normal
gland, missing a thyroid malignancy.
PITUITARY DISORDERS
Abstract #800
A PAIN IN THE HEAD AND NECK: A CASE OF A
THYROTROPIN/SOMATOTROPIN-SECRETING
PITUITARY MACROADNEOMA PRESENTING AS
THYROID GOITER
Robert J Carpenter, DO, Christopher J. Warner, MD,
Nicole M. Dankert-Hsu, William L. Falls,
Jeffery S. LaRochelle, MD, and K.M. Shakir, MD
Abstract #801
Objective: There are fewer than 350 cases of TSHsecreting pituitary adenomas reported in the medical literature. In order to emphasize the importance of thorough
evaluation of any thyroid abnormality, we present a case
of a TSH/GH-secreting pituitary macroadenoma that presented with symptoms of hyperthyroidism and thyroid
nodule subsequently found to have characteristics of a follicular neoplasm.
Case presentation: A 55-year-old Caucasian female
with hypertension (treated with atenolol), macular degeneration, and migraines presented with 3-week history of
left neck mass. She noted a 20lb weight loss over 3-month
period coincident with diet and exercise, and new headache
over the prior 3 weeks associated with nausea, emesis, and
olfactory hypersensitivity. She reported mild palpitations
and denied insomnia, diarrhea, anxiety and heat intolerance.
PE was remarkable for blood pressure 197/118, pulse rate
77, fine postural tremor, a 5cm thyroid nodule and normal
DTRs. Serum free T4, total T3, and TSH concentrations
were all elevated prompting subsequent MRI examination
of the sella, which revealed a 2.6x1.5cm enhancing intrasellar mass. Thyroid ultrasound revealed a 5.6x4.1cm nodule in the left lobe. In addition to inappropriately elevated
TSH, complete evaluation of anterior pituitary hormone
metabolism revealed only elevated serum IGF-1. In addition, oral glucose tolerance testing failed to suppress GH
suggesting unregulated secretion of GH by the intrasellar
mass. In-111-Octreotide concentrated in both the intrasellar mass and the left thyroid nodule. A 5.0 mCi Tc99m
pertechnetate thyroid scan showed decreased activity in
the nodule and FNA revealed abundant follicular cells with
no definite colloid.
Discussion: TSH-secreting adenomas represent a
small percentage of pituitary adenomas. Those that also
secrete GH are even more rare and account for approximately 16% of TSH-secreting tumors (with fewer than 55
reported in the medical literature). While surgical resection remains the treatment of choice for pituitary adenomas, studies have demonstrated that somatostatin analogs
DETECTION OF PITUITARY ADENOMA
FOLLOWING USE OF LEUPROLIDE
Jasleen Kaur Duggal, MD, Poonam Beniwal,
Kanwal Mallhi, Sarabjeet Singh, Navneet Attri,
Eshraq Al-Jaghbeer, Paula Butler, and Earl Smith
Objective: To report a rare presentation of the pituitary adenoma.
Case presentation: A 60 year old African American
man was diagnosed with prostate adenocarcinoma via
an ultrasound guided transrectal biopsy in June of 2007. Pt had a Gleason score of 6(3+3).Shortly after diagnosis, patient began prostate cancer therapy consisting of
daily subcutaneous leuprolide (Gonadotropin Releasing
Hormone agonist-GnRH) injections. Approximately fourteen days after initiating this therapy, the patient experienced gradual onset of bilateral diplopia, dizziness, headache (8/10 intensity) and vomiting. Patient presented to
the hospital because of worsening of these symptoms.
Examination revealed left eye mydriasis, ptosis, absence
of direct and consensual pupil responses, restricted adduction, elevation, and depression motion, consistent with
left cranial nerve III and IV deficit. Fundus exam revealed
bilateral normal fundi. MRI of the brain revealed a 2x2
cm pituitary adenoma occupying an enlarged sella turcica
and extension into the left sphenoid sinus. No hemorrhage
observed. Endocrine evaluation were-TSH: 0.65 uIU/mL
(0.34-5.60), free T4: 0.85ng/mL (0.58-1.64), FSH: 8.2 mIU/
mL (1.3-19.3), prolactin: 4.0 ng/mL (<15), ACTH: 8.0 pg/
mL (7-50), IGF-1: 77 ng/mL (87-255), IGF BP3: 2.0mg/L
(3.4-6.9),Testosterone 0.2 ng/mL(1.75-7.81), urine osmolality: 357Osm (250-1200). This evidence supports the
diagnosis of a non-functioning pituitary macroadenoma.
A trans-sphenoidal surgical resection was performed.
Histopathological examination showed non-functioning
pituitary adenoma with hemorrhagic component.
– 83 –
octreotide(SandostatinTM )30 mg I.M.once monthly.MRI
scan obtained six months after initiation of this treatment
showed significant reduction of tumor size compared to the
pre-treatment images( from 14x12x11 mm to 11x8x7 mm
)as well as less mass effect on the optic chiasm. Thus, surgery involving craniotomy to remove the pituitary tumor
has been postponed due to the decrease in tumor size in
response to medical therapy.
Discussion: NFMA of the pituitary gland are generally treated surgically; however, the results are often disappointing. Most studies have found a very limited or no
effect of octreotide and/or cabergoline therapy on shrinking
the NFMA. Anderson et al demonstrated that combination
therapy with cabergoline and octreotide in 6 patients with
NFMA resulted in a reduction of tumor size. These investigators selected patients based on elevated levels of serum
alpha subunit; somatostatin receptor status of the tumors
were not evaluated. We are the first to evaluate the somatostatin receptor status of the pituitary tumor by scan and
to then assess the response to combination therapy with
cabergoline and octreotide. Although OctreoScan demonstrated somatostatin receptors in the pituitary gland, cabergoline was added based on the evidence of previous study
reported by Anderson et al.
Conclusion: In summary, this case demonstrates that
combination treatment with cabergoline and octreotide
may be effective in treating somatostatin receptor-positive NFMA. Additional prospective controlled studies are
needed to confirm this finding.
Discussion: Pituitary adenomas arise from epithelial pituitary cells and account for 10-15% of all intracranial tumors. GnRH agonist given for prostate cancer interacts with LH and FSH receptors and can lead to pituitary
tumor growth and apoplexy as in this patient. The symptom
complex produced is characterized by its endocrine effects
and mass effects. The mass effects manifest as headache,
nausea, vomiting, visual impairment and opthalmoplegia
which if present acutely denotes a pituitary apoplexy. Our
patient exhibited symptoms consistent with this. Of note
was normal hormonal work up indicating non functioning
tumor. There was no sequela of pituitary hypofunction that
can occur from the pressure effects by the mass. Incidental
detection of the adenoma subsequent to the use of GnRH
analogues as a rare presentation made this case worth
reporting.
Conclusion: GnRH analogs may occasionally
lead to rapid growth of a silent pituitary adenoma & present
acutely as pituitary apoplexy. Clinicians should be aware
of this rare complication of GnRH analog therapy.
Abstract #802
COMBINATION TREATMENT WITH
OCTREOTIDE AND CABERGOLINE REDUCES
TUMOR SIZE IN A PATIENT WITH NONFUNCTIONING PITUITARY MACROADENOMA
Thaslim Ahamed Kassim, MBBS, William M Yudt, MD,
Patrick W Clyde, MD, and K.M. Mohamed Shakir MD
Abstract #803
Objective: To demonstrate therapeutic effect of treating somatostatin receptor positive non functioning pituitary macroadenomas (NFMA) with combination therapy
of octreotide and cabergoline.
Case Presentation: A 42 year old male, 12 years
status post transsphenoidal surgery(TSS)of the pituitary
gland for NFMA, presented to our hospital for followup. Because of tumor recurrence, he underwent TSS four
additional times since his initial surgery 12 years ago. The
surgeries resulted in central hypogonadism and diabetes
insipidus, for which he takes testosterone gel and desmopressin, respectively. There were no symptoms or signs of
other hormonal imbalances. His visual fields were normal.
Serum TFT’s,prolactin,IGF-1and alpha subunit levels were
normal. A recent MRI of the pituitary revealed a macroadenoma abutting the optic chiasm and nerve. An OctreoScanR
(In-111 pentetreotide)spect imaging performed to evaluate
whether the patient may respond to somatostatin analogue
confirmed the presence of somatostatin receptors in the
tumor. After discussing the possible treatment options, he
began cabergoline 0.5 mg twice weekly and long-acting
PITUITARY APOPLEXY IN AN ELDERLY
ANTICOAGULATED GENTLEMAN
N
Teresa Allison Nimmo, MD, Jonathan Stringer, MD, and
Vitaly Kantorovich, MD
W
A
R
Objective: To describe a case of pituitary apoplexy in
an elderly gentleman on anticoagulation. His presentation
and management of this acute insult resulted in a variety of
challenging management issues.
Case Presentation: A 76 year old previously independent man with multiple chronic medical problems developed progressive lethary and confusion. He initially presented to his primary care provider with a severe headache
and was found to have pituitary apoplexy. Initial imaging
studies did not reveal a source for his confusion on chemistry and endocrine lab data indicated he may have an issue
with his pituitary function.
Discussion: Pituitary apoplexy is a rare cause of pituitary dysfunction. Its onset is described by a classic “thun-
W
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IT
D
H
derclap headache” that occurs with sudden onset. There are
many risk factors for pituitary apoplexy including trauma,
tumors and It is important to assess pituitary function with
a suspected pituitary apoplexy. Water and electrolyte balance may also pose a challenge with am acute insult to the
pituitary. A patient on antcoagulation may present a unique
management dilemma when determining whether on not
to discontinue anticoagulation or to proceed with surgical
intervention.
child with congenital HIV infection and precocious puberty
has been described. There is need to establish whether is
one of the HIV-related endocrinopathies
Abstract #805
ENDOCRINOLOGIC ABNORMALITIES IN
SELLAR MENINGIOMAS
Airani Sathananthan, MD, John Atkinson, MD,
Bernd Scheithauer, MD, and Dana Erickson MD
Abstract #804
Objective: Review of Endocrinologic Abnormalities
in a case series of sellar meningioma.
Case Series: Patients were selected from a Mayo
Clinic, Rochester MN neurosurgical registry with diagnosis of sellar meningioma between 1987 and 2003. Records
were retrospectively reviewed for initial presentation, preand post-operative endocrine status, operative results, and
pathology. The study group consisted of 7 patients (3 male
and 5 female), age 31-74 years.
Discussion: Initial Presentation: Five patients had
visual complaints, one had galactorrhea, and one presented
with confusion secondary to hyponatremia. Two additionally had headaches and one had vertigo. Preoperative
formal visual field testing was abnormal in 6 out of the 7
patients.
Pre-operative Endocrinopathies: Three patients were
on dopamine agonist treatment for hyperprolactinemia.
The patient with hyponatremia had secondary hypothyroidism and secondary adrenal insufficiency. One patient
had pre-existing primary hypothyroidism. 3 patients had
no endocrinopathies.
Surgical Treatment: Primary surgical approach with
goal of tumor debulking was done in 6 patients, and one
had primary external radiation followed by surgery. Four
had transsphenoidal surgery (3 transnasal endoscopic and
1 sublabial), 1 right orbitofrontal craniotomy, and 1 right
pterional craniotomy. One had transphenoidal biopsy only.
Post-operative Endocrinopathies: Three patients
developed new secondary hypothyroidism, 3 patients had
new secondary adrenal insufficiency, one patient had hypogonadism and one had low IGF-1. Two patients had normal pituitary function. No preoperative endocrinopathies
reversed.
Pathology: Various forms of meningioma were seen
including 2 with meningeal meningioma, 1 with psammomatous meningioma, and 1 transitional meningioma.
One patient had meningioma with bony infiltration, while
one had no further specification of their meningioma
Post-operative course: Six patients had residual tumor
following surgery. One patient underwent repeat surgery
PRECOCIOUS PUBERTY AND HIV INFECTION: A
POSSIBLE EMERGING ENDOCRINOPATHY?
Sandra Omozehio Iwuala, MBBS,
Adekunle Adeyemi – Doro, MBBS, Anas Sabir, MBBS,
Ife Odeniyi, MBBS, and Femi Fasanmade, MBBS
Objective: To report a case of precocious puberty associated with HIV infection and review the possible association between precocious puberty and HIV infection.
Case presentation: The patient presented at age six
years with an 11- month history of appearance of features
of puberty but denied history of ejaculations or sexual relationship. He had tested positive to HIV five months prior to
presentation after his mother was found to be seropositive.
There was no history of blood transfusion. Pregnancy and
early childhood were unremarkable. There was no family history of precocity. Physical examination revealed a
healthy looking, big for age boy, without café-au-lait spots,
visual field defects, or palpable organ enlargement intraabdominally. He was 1.48 m tall and weighed 39 kg. The
B.P. was 80/60 mmHg. He had pubic hair of Tanner stage
4.The testes and phallus were of adult size. Basal plasma
hormone assays showed testosterone of 0.8ng/ml, LH of
13mIU/ml, FSH of 10mIU/ml, Cortisol 170ng/ml(A.M),
DHEA-S of 550ng/ml. His bone age was between 9 to 14
years. Abdominal USS and skull X rays were normal. A
diagnosis of central precocious puberty(CPP) was made.
He was placed on medroxyprogesterone acetate. Pubertal
development has since not progressed.
Discussion: HIV infection and/or its treatment are
associated with a variety of endocrinopathies. However,
precocious puberty ascribable to HIV infection appears to
be very rare. The diagnosis of CPP is not in doubt in this
patient. He was unable to do further investigations required
or get the treatment of choice due to financial constraints as
patients still pay out of pocket in our country.
Conclusion: It is conjectural that the HIV could have
induced the precocious puberty in this boy but such association appears very rare. One case of an African American
– 85 –
tumors is meningioma and glioma. Only one previous
publication reports a patient with concurrent prolactinoma
and vestibular schwannoma. Although there was no histological confirmation of the prolactinoma, the high prolactin
level and the positive response to bromocriptine support
the diagnosis. Coexisting primary brain tumors occur in
those with a history of brain irradiation or hereditary neurocutaneous syndromes such as neurofibromatosis types 1
and 2, tuberous sclerosis, and Von Hippel-Lindau disease. This patient has no personal history of brain irradiation,
and no family history of brain, neurocutaneous, or neuroendocrine tumors. The prevalence of pituitary adenoma
has been reported to be 1 in 1000, and that of vestibular
schwannoma 1 in 100,000. Given these statistics, the likelihood of having both of these brain tumors concurrently
is very low.
Conclusion: The simultaneous presentation of primary
brain tumors of different histologies is rare. Prolactinomas
may coexist with other types of brain tumors and each may
need a separate therapeutic approach.
with near complete resection. Of the other 5 patients, 1
underwent external radiation, 3 were observed and the
biopsied patient was treated with external radiation. Five
patients had post-operative visual field testing and all had
improvement in their vision. Follow-up duration ranged
from 4 to 59 months (mean 34).
Conclusion: Patients with sellar meningiomas have
a heterogeneous presentation, in this series predominately
complaints of mass effect. Hyperprolactinemia is present
likely due to stalk effect as one of the initial endocrine
abnormalities. The majority of patients had residual disease after surgery and five of the seven (71 %) developed
partial hypopituitarism.
Abstract #806
SIMULTANEOUS PRESENTATION OF
PROLACTINOMA AND VESTIBULAR
SCHWANNOMA
Leo Tchong, MD, Colleen Veloski, MD,
and Elias Siraj, MD
Abstract #807
Objective: To report a case of prolactinoma presenting as one of two concurrent primary brain tumors with
different histologies.
Case Presentation: A 45-year-old man presented with
headaches, decreased libido, and erectile dysfunction of 5
years duration. A total testosterone level was low at 24
ng/dL. The prolactin level was elevated at 2179 ng/mL. An MRI showed a 3.2 x 2.7 x 2.6 cm sellar mass suggestive of pituitary macroadenoma, and a 3.1 x 4.2 x 3.4 cm
mass in the left cerebellopontine angle (CPA) consistent
with schwannoma. Surgical debulking of the latter mass
was performed, and the diagnosis of schwannoma was
confirmed. Postoperatively, the prolactin level continued
to be high. Since a pituitary prolactinoma was suspected,
bromocriptine therapy was started. Levothyroxine, hydrocortisone, and a testosterone patch were started for panhypopituitarism confirmed by biochemical testing. Six
weeks after the initiation of bromocriptine therapy, the
prolactin level decreased to 172 ng/mL, and was near normal after 9 months of therapy. Repeat MRI showed an
interval decrease in size of the CPA mass consistent with
resection, and an interval decrease in size of the sellar mass
by approximately 50% after 9 months of dopamine agonist
therapy.
Discussion: The coexistence of multiple primary
brain tumors of different histologies is rare, with the incidence reported to be 0.3% of all brain tumors. The most
common combination of histologically different brain
– 86 –
PITUITARY MACROADENOMA
PRESENTING AS PROGRESSIVE
REFRACTORY WEIGHT GAIN DUE TO
ADULT GROWTH HORMONE DEFICIENCY
Alla Khalfin, DO, and Harriette Mogul, MD
Objective: To describe two cases of pituitary macroadenoma presenting as a dramatic weight gain due to
occult adult Growth Hormone Deficiency (GHD).
Case Presentation: Case 1 is a 63 year old female presented with the complaint of not being able to loose weight
despite extensive physical exercise and diet. Her weight
was 166.5 lbs and height was 61 inches. She had abdominal girth with waist circumference of 35.5 inches. Glucose
tolerance test revealed insulin resistance and impaired glucose tolerance. The patient was started on Metformin, but
still remained in the same weight range one year later. IGF1, measured at that time, was 204, BP-1 was 52. Repeat
IGF-1 was 90. Growth hormone stimulation test with LDopa confirmed GHD. All other pituitary hormones were
normal. MRI of the brain showed pituitary tumor, with
an area of central necrosis, displacing infundibular stalk.
Case 2 is a 51 year old female, with past medical history
of polycystic ovarian syndrome and gestational diabetes
requiring insulin, presented for evaluation of obesity. The
patient gained 40 lbs in the last 2 years. On physical exam
her weight was 202 lbs, height 62 inches. She had truncal
obesity, waist measurement was 46 inches. The patient was
diagnosed with hyperlipidemia, impaired glucose tolerance
and insulin resistance and was also started on Metformin
and diet modifications. The patient’s total cholesterol
and triglycerides improved significantly from 232 to 187
and from 558 to 97 respectively. However, she achieved
minimal weight loss. The measurement of IGF-1 was 65,
BP-1 was <5.0. Growth Hormone failed to stimulate with
L-Dopa and GHD was confirmed. MRI of the brain was
performed demonstrating pituitary macroadenoma involving sell and suprasellar region extending into the sphenoidal sinus. Both patients underwent transphenoidal surgery
for the removal of pituitary mass without complications.
Discussion: Adult GHD is the most common hormone deficiency among patients with pituitary macroadenomas. It is associated with marked increase in total fat
mass, reduction in lean body mass, reduced exercise capacity, disturbed lipoprotein pattern, and reduced quality of
life. GHD has been linked to obesity and insulin resistance
in numerous investigations. One of the main clinical features of insulin resistance includes central obesity with an
increase in intraabdominal adiposity being also a frequent
characteristic seen in adults with GHD, including both of
our patients. The study by Iton, E etc. found that insulin
resistance values in patients with GHD were significantly
higher than in normal individuals. It has been proposed that
severe insulin resistance in GHD adults is mainly due to
inhibition of glucose storage pathway and glycogen synthase activity in peripheral tissues. These metabolic defects
seem to be related to the duration of GHD and are associated with alterations in triglyceride levels, abdominal obesity, and fasting insulin. Given that our patients were at
increased risk for prevalence of cardiovascular complications accompanying the illustrated metabolic defects and
insulin resistance we referred both of them for the removal
pituitary tumor. Both patients were able to loose weight
after the surgery and had negative glucose tolerance test.
Conclusion: The cases presented highlight the importance of testing for GHD in people with new onset of obesity and diagnosed insulin resistance failing the conventional therapy as GHD may be the only manifestation of
pituitary macroadenoma.
Abstract #808
RESULTS FROM A PHASE II STUDY OF
PASIREOTIDE (SOM230) IN PATIENTS WITH
ACROMEGALY: EFFECTS ON GLUCOSE
METABOLISM AND GROWTH HORMONE
NADIR DURING THE ORAL GLUCOSE
TOLERANCE TEST
Joan Glusman, MD, Nicole Unger, Klaus Mann,
Stephan Petersenn, MD, and
The Pasireotide Acromegaly Study Group
Objective: Pasireotide (SOM230), the novel multireceptor ligand somatostatin analogue, has high binding
affinity for four of the five somatostatin receptor subtypes
(sst1,2,3 and sst5). In a randomized Phase II study of 59
patients with de novo, persistent or recurrent acromegaly,
pasireotide effectively controlled GH and IGF-I levels and
reduced pituitary tumor volume. Here we report the impact
of pasireotide on glucose metabolism and GH levels during
glucose suppression in 12 patients enrolled in the Phase II
study.
Methods: Patients in this study had a GH level >5
µg/L, an elevated IGF-I level and a lack of suppression of
GH to <1 µg/L post-OGTT. After treatment with octreotide
100 µg sc tid for 28 days, patients received pasireotide 200,
400 and 600 µg sc bid in random order for 28 days each.
Glucose and GH levels were measured during the OGTT
in 12 patients prior to treatment, after octreotide treatment
and after each pasireotide treatment phase.
Results: During glucose suppression, four of the 12
patients had a similar GH nadir (<10% difference) after
pasireotide or octreotide treatment (-71.0% vs -72.3%),
and eight patients had a stronger GH suppression with
pasireotide than with octreotide (-75.1% vs -22.8%).
Under fasting conditions prior to therapy, seven patients
had normal glucose tolerance, two patients had impaired
glucose tolerance, and three patients had diabetes mellitus.
At the last assessment during treatment with pasireotide,
nine patients remained in the same category, one patient
improved, and two patients had increased glucose levels.
Similar results were seen for glucose metabolism 120 minutes post-OGTT; after treatment with pasireotide, eight
patients remained in the same category they were in prior
to therapy, two patients improved, and two patients had
increased glucose levels.
– 87 –
Conclusions: Compared with octreotide, pasireotide
suppressed GH levels during the OGTT to a similar extent
in four of 12 patients and to a significantly greater extent
in eight of 12 patients, indicating that pasireotide may be
effective in patients with octreotide-resistant acromegaly.
Furthermore, using stringent criteria for glucose tolerance, the majority of patients did not demonstrate relevant
changes in glucose metabolism by the end of the pasireotide treatment period.
patients had normal IGF-1 levels (56%). With the assumption that an arginine/GHRH test correctly identifies the
presence or absence of GHD, these results suggest that the
sensitivity of a normal IGF-1 test may be as low as 70%
for ruling out GHD in patients where GHD is highly suspected and that the specificity of a low IGF-1 test may be
as poor as 56% for correctly diagnosing GHD in this same
population.
Conclusions: We found that the IGF-1 test had 56%
specificity and 70% sensitivity for correctly identifying the
status of the GH axis in a population highly likely to have
GHD due to underling pituitary disease. We conclude that
although IGF-1 remains a valuable test to screen for GHD,
dynamic stimulation tests such as ITT or arginine/GHRH
test should still be done in the context of a normal IGF-1
when clinical suspicion for GHD is high.
Abstract #809
IGF-1 LEVEL MAYBE NORMAL IN SOME
PATIENTS WITH GROWTH HORMONE
DEFICIENCY
William Henry Ludlam, MD, Jaimie M. Augustine, and
Marc R. Mayberg
Abstract #810
Objective: To determine the sensitivity and specificity
of the IGF-1 level in correctly identifying the status of the
GH axis in patients with known pituitary pathology.
Case Presentation: Adult GHD is characterized by
fatigue, memory loss, central obesity, hyperlipidemia and
bone loss. It is typically seen in the context of pituitary
pathology caused by tumors, surgery, radiation or other
diseases. Although the arginine/GHRH stimulation test is
considered to be a very sensitive (95%) and specific (91%)
means of evaluating the GH axis, the measurement of IGF1 (with age specific normal range) is commonly used as a
screening test before this or other dynamic GH stimulation
tests are performed. Despite its common use as a screening
test, it is not clear how sensitive a normal IGF-1 is for ruling out GHD when the clinical suspicion for GHD is high.
We reviewed 286 patients evaluated for pituitary disorders
at Swedish Medical Center over a 1-year period (12/1/06 to
11/30/07). IGF-1 levels were measured in 194 patients and
57 were noted to be low. 22 of the patients with low IGF1 were further evaluated with arginine/GHRH testing. 22
additional patients with normal IGF-1 were also evaluated
with arginine/GHRH testing due to high clinical suspicion
of GHD.
Discussion: Of the 22 arginine/GHRH tests performed
in patients with low IGF-1, 7 had positive arginine/GHRH
tests confirming GHD (GH level < 4.1 ng/dl at five time
points over 2h after stimulation with arginine and GHRH)
and 15 had negative tests. Of the 22 arginine/GHRH tests
performed in patients with normal IGF-1, 3 had positive
tests confirming GHD and 19 had negative tests. Stated
otherwise, of the 10 patients with positive arginine/GHRH
tests, 7 patients had consistently low IGF-1 levels (70%).
Of the 34 patients with negative arginine/GHRH tests, 19
NEURODEGENERATIVE LANGERHANS CELL
HISTIOCYTOSIS AND PANHYPOPITUITARISM:
A CASE REPORT
Nicole Stephanie Nader, MD, Aida Lteif, MD, and
Marc Patterson, MD
Objective: We examine a case of neurodegenerative
Langerhans Cell Histiocytosis (LCH) that was diagnosed
years after the development of panhypopituitarism in order
to illustrate the importance of obtaining serial MRIs in
patients with diabetes insipidus.
Case Presentation: We present a 15 year old girl diagnosed at the age of 2 years with diabetes insipidus after she
presented with polyuria and polydipsia. Her MRI showed
absence of the posterior bright spot. At the age of 4.5, she
was also diagnosed with central hypothyroidism and ACTH
deficiency requiring replacement with thyroid hormone and
hydrocortisone. Growth hormone deficiency was diagnosed at the age of 7 and treatment with growth hormone
was initiated at the age of 7.5. At around age 6, the patient
began developing hand tremors and poor coordination. A
bone survey did not demonstrate any lytic lesions. Spinal
fluid analysis was negative. Tumor markers were normal. A series of MRIs demonstrated progressive enlargement of
an area of T2 signal abnormality involving the central and
medial cerebellar hemispheres bilaterally. T1 sequences
suggested central cavitation of these lesions. There was
also slight progression of an area of T1 hyperintensity in
the globus pallidus bilaterally. The small volume pituitary
demonstrated no focal lesions, although the infundibular
stalk was mildly deviated to the left. These findings were
consistent with the neurodegenerative form of LCH.
– 88 –
At age 15, the patient is intellectually delayed, with
severe dysarthria, ataxia, and spasticity. She is mobile only
in a wheelchair.
Discussion: LCH is caused by a clonal proliferation
of dendritic cells. Diabetes insipidus and anterior pituitary hormone deficiencies are the most common CNS
manifestations of LCH being seen in 10%-20% of LCH
patients. A neurodegenerative form of LCH has also been
described, but is much rarer. This form is characterized
by lesions seen on MRI located in the cerebellum or basal
ganglia which lack active LCH cells. Previous research
has shown that neurodegeneration is present after 15 years
in 10.8% of patients with LCH and pituitary dysfunction,
but seen in only 0.4% of LCH patients without pituitary
dysfunction. Therefore, LCH patients who develop endocrinopathies are at risk for neurodegeneration and require
long term follow up.
Conclusion: Since LCH is sometimes not found until
years after the diagnosis of diabetes insipidus or panhypopituitarism, serial MRIs are warranted in children with
a diagnosis of diabetes insipidus even in the absence of
neurologic symptoms and other features of LCH. Early
recognition of neurodegenerative LCH may lead to better
treatment options.
increased to only 136 nmol/L following synacthen administration. Serum ACTH: <1 ng/L (RR: 5-60), FT4 6.0 pmol/
L (RR:12-22), TSH 0.59 mU/L (RR: 0.27-4.2), testosterone <0.1 nmol/L (9.9-27.8), free androgen index <0.1%
(14.8-94.8), LH <0.1 IU (1.7-8.60, FSH 0.6 IU (1.5-12.4),
prolactin 17.1 ug/L (4.1-18.4), GH 0.8 mU/L (0-13), IGF1
<25 ug/l (116-358), serum osmolality 275 mosmol/kg,
(275-300), low urine osmolality (182), inappropriately low
urine Na+ (61 nmol/L).The Dx of hypopituitarism due to
pituitary metastases was entertained; MRI showed a large
38x36x34 mm complex solid, partially multicystic sellar
and suprasellar mass. Pt. received hormonal replacement
consisting of hydrocortisone followed by LT4 & testosterone replacement. As expected underlying central diabetes
requiring DDAVP administration got unmasked following
this replacement Rx. At transspenoidal surgery only limited
decompression could be achieved. Histopathology: metastatic adenocarcinoma compatible with intestinal origin. At
6 months following Dx of panhypoituitarism pt. is alive.
Discussion: Pituitary metastases are an unusual cause
of intrasellar/suprasellar mass. Autopsy series have reported
an incidence of 3.6% for pituitary metastases. Breast and
lung malignancy are the commonest ones to metastasize to
pituitary in accordance with the high prevalence of the two
cancers. Although colon cancer is a fairly common malignancy, it rarely metastasizes to the pituitary.
Conclusions: The clinical & MRI features of pituitary
metastasis can closely mimic pituitary adenoma. Although
relatively uncommon, pituitary metastasis should be considered in pts. with advanced cancer in whom hypopituitarism develops. With improved survival of cancer pts. the
recognition of pituitary metastases may increase; hormonal
Rx can improve their quality of life.
Abstract #811
DISTURBED CONCIOUSNESS RESULTING
FROM HYPONATREMIA AS A PRESENTING
FEATURE OF PANHYPOPITUITARISM DUE TO
METASTASIS FROM COLON CARCINOMA.
Shakir Bakkari, MD, Mohammed Al-Harathi, MD,
Imaduddin Kanaan, MD, and Hindi Al-hindi, MD
Abstract #812
Objective: To describe disturbed consciousness
resulting from hyponatremia as a presenting feature of
panhypopituitarism due to pituitary metastasis from colon
carcinoma.
Case Presentation: A 55 year-old man, a known case
of colon cancer with metastases to lungs, presented with
confusion, hallucination, hypotension (BP 84/52), hypothermia (oral temperature 35 Celsius, bradycardia (PR
52/min).His BMI was 24.He was pale, with pronounced
facial wrinkles, absence of axillary and pubic hair and had
atrophic testicles. Visual acuity had deteriorated to finger counting at 3 feet in both eyes. On admission he had
microcytic hypochromic anemia (Hb 114 g/L), hyponatremia (Na+ 120mmol/L).A clinical diagnosis of panhypopituitarism was made that was confirmed with the following
lab data: AM serum cortisol 12.7 nmol/L (RR: 171-536), it
DIABETES INSIPIDUS AND HYPOPITUITARISM
AS INITIAL PRESENTATIONS OF A
SUPRASELLAR ANEURYSM
Victor Richard Marlar, MD, Razvan F. Buciuc, MD,
Benjamin W. Seale, MD,
William C. Nicholas, MD, FACE, FACP, and
Christian A. Koch, MD, PhD, FACE, FACP
Objective: To report diabetes insipidus as a rare presentation of a suprasellar aneurysm causing panhypopituitarism and to speculate on the mechanism of pituitary
dysfunction.
Case Description: A 32-yo woman developed severe
headaches followed by decreased vision in her left eye. She
then was hospitalized for dehydration after presenting with
– 89 –
hypotension and intractable nausea and vomiting. Further
history was notable for fatigue, anorexia, hair loss, amenorrhea, polyuria and polydipsia. Physical exam revealed
pale skin, scant pubic hair and a left visual field deficit.
CT showed a 14 mm suprasellar lesion felt to represent a
pituitary adenoma, however MRI and subsequent angiography confirmed the presence of a paraophthalmic aneurysm causing compression anteriorly to the pituitary and
superiorly to the optic chiasm. Laboratory testing revealed
panhypopituitarism with the following values: cortisol 0.3,
ACTH < 10, free T4 0.47, TSH < 0.006, FSH < 0.4, LH
< 0.5, and prolactin <1.4. Also notable were serum Na
151, serum osmolality 335 and urine SG <1.005, suggesting diabetes insipidus. Visual field testing revealed a left
temporal hemianopsia. DDAVP was administered with
immediate resolution of polyuria and polydipsia, confirming the diagnosis of central diabetes insipidus. The patient
underwent endovascular coiling of the aneurysm without
complications and was discharged home two days later on
prednisone and levothyroxine. DDAVP was prescribed on
an as needed basis though she had only required one dose
at the time of her one week follow-up.
Discussion: Aneurysms projecting into the sellar
region account for 1% to 2% of all intracranial aneurysms
and mimic pituitary adenomas both clinically and radiologically. They are a rare cause of pituitary dysfunction
with less than 40 cases reported. Presentations may include
headaches, nausea, visual impairment or symptoms related
to hypopituitarism. Review of the literature shows that
the gonadal axis is deficient in 67.5% of patients, adrenal axis in 48.6% and thyroid axis in 40.5%. Diabetes
insipidus upon presentation is very rare, estimated at
<10%. Hyperprolactinemia is usually present, suggesting
hypothalamic or pituitary stalk compression rather than
intrinsic pituitary damage as the mechanism of hormone
deficiencies.
Conclusion: Suprasellar aneurysm should be considered in patients diagnosed with a pituitary tumor and
reliable imaging techniques are important in making the
distinction. While diabetes insipidus could be explained by
hypothalamic or stalk compression, low prolactin levels as
seen in this case suggest pituitary damage as the pathogenesis for endocrine dysfunction.
Abstract #813
A MYCOTIC PITUITARY ABCESS PRESENTING
AS PANHYPOPITUATARISM
Robert M. Lind, MD, and Mary Vouyiouklis, MD
Objective: To describe a case of a fungal pituitary
abscess presenting as panhypopituitarism.
Case Presentation: A 37 year old Hispanic female
with a past medical history of systemic lupus erythematosus presented with complaints of fatigue, dry skin, cold
intolerance, and amenorrhea of 8 months duration. She
also complained of extreme polyuria and polydipsia. She
denied any headaches, blurry vision, or fevers. TSH was
0.39mIU/L, free T4 0.2mcg/dL, total T4 1.6mcg/dL, and
total T3 0.9ng/mL. LH was <1mIU/L, FSH 3mIU/L, estradiol 7pg/mL. B-HCG was negative. Prolactin was 78.3ng/
mL. AM cortisol was 0.71mcg/dL, and IGF-1 was 40ng/
mL. Serum Na+ was 146meq/L, with plasma osmolality
of 306mOSm/kg, and urine osmolality of 215mOsm/Kg.
A diagnosis of hypopituitarism was made, and the patient
was started on glucocorticoids, thyroid hormone, oral contraceptives, and nasal DDAVP. Pituitary MRI revealed a 2
cm sellar mass without extension into the cavernous sinus
or optic chiasm. The patient was referred to neurosurgery,
but returned prior to surgical evaluation with complaints
of headaches, diplopia, and a new left sixth cranial nerve
palsy. The patient was admitted for emergent surgical
intervention. Transsphenoidal surgery revealed a grossly
necrotic pituitary mass. Pathology and cultures were consistent with a fungal infection (Candida). The headaches
and cranial nerve palsy resolved after surgery and antifungal therapy. The patient remains with panhypopituitarism.
Discussion: Pituitary abscesses are rare conditions,
with only a few hundred cases reported in the literature.
These may develop in the gland via hematogenous routes
or direct extension of infection in the sphenoid sinus or the
CSF. Risk factors include prior pituitary surgery, irradiation, or an immunocompromised state. Many patients present without any risk factors. The most common presenting
complaint is headache, and only a minority present with
fever and leukocytosis. The literature suggests that 3050% of patients present with anterior pituitary deficiencies,
and about 30% present with diabetes insipidus. Surgical
removal provides the most effective treatment. Most common organisms found in culture are staphylococcus, but up
to 1/3 of cultures isolate no organisms. Fungal infections
are an extremely rare form of pituitary abscesses. Recovery
of pituitary function has been shown to be very variable in
different cases.
– 90 –
Conclusion: Pituitary abscesses are rare conditions,
but should be included in the differential diagnosis of sellar
masses. In this case, the patient had a fungal abscess, which
is an even rarer condition. Diagnosis can be challenging in
absence of surgical pathology and culture. Pituitary function should be checked preoperatively and followed closely
in the postoperative period.
spite of lifestyle modifications and development of violaceous striae led to persistent biochemical testing and subsequent diagnosis of Cushing’s disease.
Conclusion: The diagnosis of early Cushing’s syndrome is a challenge, especially in an environment of
increasing obesity. Maintaining a high level of clinical
suspicion and repeating biochemical tests periodically is
important in such cases.
Abstract #814
Abstract #815
A CLINICAL CONUNDRUM IN DIAGNOSING
EARLY CUSHING’S SYNDROME IN AN
EPIDEMIC OF OBESITY
INCIDENTAL PITUITARY ABNORMALITIES IN
PREGNANT WOMEN
Ashwini Reddy, MD, and Uzma Khan
Deepa Sundararajan, MD, Maneet Kaur Narula, and
Harmeet Singh Narula, MD
Objective: To describe the challenge in diagnosing
early Cushing’s syndrome.
Clinical Presentation: A 22 year old active, previously
non obese woman was evaluated for a 30 lbs weight gain
and “stretch marks” developing over a 9 month period. No
other features of Cushing’s syndrome were noted. Family
history was negative for obesity. A 24 hours urinary free
cortisol (UFC) was 51.8 µg/d (normal < 60 µg/d). Thyroid
function, CBC and CMP were normal. The patient returned
to the clinic 3 months later with an additional 5 lbs weight
gain in spite of diet and lifestyle modifications. A repeat 24
hours UFC was 74 µg/d.
The patient was reevaluated at 6 months by which
time she had developed violaceous striae on the abdomen
with a 6 lbs weight gain. Another 24 hours UFC was 84.38
µg/d. She was then screened with additional tests including an overnight 1 mg dexamethasone suppression test
(DST) with the serum cortisol post test being elevated at
10 µg /dl. Two midnight salivary cortisol samples were
obtained, which were both elevated at 0.58 and 0.72 µg/dl
(0.05- 0.17). Serum ACTH at 8 am was 9 pg/ml. Serum
cortisol after a standard 0.5 mg q 6 hourly two day DST
was elevated at 3.7 µg /dl. An MRI of the pituitary and
CT of the adrenal glands was normal. The inferior petrosal
sinus to peripheral ACTH ratio revealed a three fold elevation on the right side. In the interim the patient also developed HTN and hyperglycemia. As the clinical testing was
consistent with Cushing’s disease, the patient underwent
a transsphenoidal removal of pituitary tissue which was
identified as an adenoma on the pathology report.
Discussion: Endogenous Cushing’s syndrome is a
relatively uncommon condition and resembles many of the
phenotypic features of obesity, PCOS and depression. One
of the major manifestations of the obesity epidemic is the
increase in the number of patients with Cushing’s phenotype. As seen in this case, the continued weight gain in
Objective: To describe two cases with pituitary abnormalities incidentally noted during pregnancy
Case 1: 26 year old woman, 6 months pregnant with
no significant past medical history presented to ER with
headache for 2 days and left facial weakness. On exam,
vitals were stable & visual fields intact. She had Left facial
weakness (lower motor neuron). CT head revealed a pituitary abnormality. A dedicated pituitary MRI revealed
enlarged pituitary, 2 cm x 1.2 cm slightly elevating optic
chiasm with T1 Hyper- & T2 hypo-intensity suggesting
a possible hemorrhage. Detailed pituitary function tests
were normal for a pregnant woman (AM Cortisol 25,free
T4 0.97,Prolactin 206,FSH & LH low). With pain meds,
patient felt well. The presentation was felt to be secondary
to Bell’s Palsy, unrelated headache & exuberant pituitary
hyperplasia related to pregnancy and decision was made to
observe the patient clinically. The patient’s pregnancy proceeded uneventfully and she delivered a healthy baby. She
breastfed postpartum & repeat hormonal testing & MRI of
pituitary were both normal (pituitary 8mm in size, no hemorrhage) 8 months postpartum
Case 2: 39 year old woman, 6 months pregnant, with
no significant past medical history, saw an ophthalmologist
for floaters. On exam she was found to have unusual hemorrhages in the eyes, and possible papilledema. She had a
MRI of the brain which incidentally revealed enlarged of
the pituitary, 1.3cm (H) x 1.2 cm (T), homogeneous with
elevation of optic chiasm. The patient denied headaches
or visual field defects and was asymptomatic apart from
floaters. Her pregnancy had been coming along well. On
Exam, vitals were stable & visual fields intact. She did
not appear acromegalic or cushingoid. Hormonal testing
was normal for a pregnant woman with Prolactin 235,
AM Cortisol 30, free T4: 1.1 & undetectable LH, FSH.
Her pituitary enlargement was felt to be due to exuber– 91 –
function. Involvement of the anterior pituitary can disrupt
secretion of gonadotropic and other hormones. Pituitary
MRI in these patients shows significant reduction of the
T2 signal intensity, which correlates with excess hepatic
intracellular iron and severity of pituitary dysfunction. Our
patient with hypogonadotropic hypogonadism had the classic MRI picture of iron deposition in the pituitary gland.
Conclusion: Hematogenic disorders that require frequent blood transfusions, especially when coupled with
ineffective erythropoiesis, can cause iron overload and
failure of multiple endocrine organs. We have reported
a unique case of myelodysplastic syndrome, secondary
hemochromatosis and anterior pituitary dysfunction. It is
important to be aware of this complication, with the potential for development of panhypopituitarism. Further follow
up of pituitary functions is critical in patient management.
ant pituitary hyperplasia related to pregnancy and she was
observed. Her pregnancy went uneventfully and she delivered a healthy baby girl. Patient breastfed postpartum, and
repeat hormonal testing and MRI of pituitary were both
normal (pituitary 8mm in size) 4 months postpartum
Discussion & Conclusion: In normal pregnancy,
pituitary enlargement (due to lactotroph hyperplasia) up to
10mm is considered normal. In some women, as in these
two cases more exuberant enlargement of pituitary may be
seen. In women presenting with neurological symptoms
during pregnancy, it is important to remember exuberant
pituitary hyperplasia as a cause of pituitary enlargement to
prevent unnecessary therapy including surgery
Abstract #816
SECONDARY HEMOCHROMATOSIS OF
THE PITUITARY
Abstract #817
Marina Strizhevsky, DO, Zinoviy Abelev, Prajesh Joshi,
Bianca Alfonso, and Adrienne M. Fleckman
PANHYPOPITUITARISM AND DIABETES
INSIPIDUS COEXISTING WITH EMPTY SELLA
SYNDROME STARTING IN CHILDHOOD
Objective: To report a case of hypogonadotropic
hypogonadism with transfusional hemochromatosis in a
patient with myelodysplastic syndrome (MDS).
Case Presentation: A 47 year old African American
woman with recently diagnosed diabetes mellitus presented with hyperglycemia. Her history includes systemic
lupus erythematosus, non-Hodgkin’s lymphoma and MDS
diagnosed 3 years ago, requiring multiple blood transfusions. She became menopausal 2 years ago. The patient
reported increased skin pigmentation and elevated blood
sugars about 3 months prior to admission. Physical exam
was significant for cachexia, non-uniform hyperpigmentation of the legs, abdomen and neck, and hepatosplenomegaly. On admission hemoglobin A1c was 10 % (6.4 %
three months ago), and hemoglobin was 5.7 g/dL. Further
work up showed ferritin of 6953 ng/mL, iron of 108 mcg/
dL, undetectable level of estradiol, FSH of 1.9 mU/mL, LH
of 0.5 mIU/mL, morning cortisol level of 17 mcg/dL, prolactin of 8.5 ng/mL and normal thyroid function tests. CT
of the abdomen and pelvis showed hepatosplenomegaly,
hyperdensity in the liver and normal pancreas and adrenal
glands. MRI of the brain showed diffuse abnormal low T2
signal of the pituitary gland parenchyma, consistent with
iron overload/hemochromatosis. Repeated treatments with
chelating agents did not improve ferritin levels.
Discussion: Secondary hemochromatosis, an acquired
form of parenchymal iron overload, results from increased
iron intake or multiple blood transfusions. Iron deposits in
the liver, heart and endocrine organs impair their normal
Esperanza Valentin, MD, Edgar Avendaño,
Ma. ��
Alejandra Ramos, Francisco J. Gómez Pérez, and
Juan Rull
Objective: To present a case of panhypopituitarism
and diabetes insipidus with empty sella that initiated in
childhood.
Case presentation: A 20 year old woman consulted
with a history of normal childhood development until age
8, when she developed polyuria, polydipsia, fatigue, asthenia, and stunted growth. She dropped out of school due
to poor performance and severe polyuria with increased
water ingestion, up to 8 liters/day. Two years later she was
diagnosed with diabetes insipidus and GH deficiency; no
imaging studies were performed. She received a GH analog for 6 months, grew about 16 cms, but discontinued it
and received no further treatment. At first consultation she
referred water ingestion of 10 lts/day, nicturia, asthenia,
dry skin and primary amenorrhea. At physical examination
her appearance was that of a 10 year old child with 143cm
in height, she weighed 83lbs, had a BP of 120/80 supine
position and 100/70 standing with a pulse of 82x´ that
increased by 15 at position change. Her skin was dry, she
had no axillary or pubic hair and her breasts were Tanner I.
Her lab findings included serum estrogen < 5, LH 0.3, FSH
0.6, GH 0.05, ACTH 17, cortisol 2, T3 2.2 (1.34-2.73),
T4 67.5 (78.38-157.4), TSH 3.93, glucose 90, Na 139, K
4.2 and urinary density 1.003. An MRI showed absence
– 92 –
of both, anterior and posterior pituitary tissue. Her bone
age is about 12 years. Cortisone 30 mg and fludrocortisone
0.25 mg/day were initiated. One week later her polyuria
and polydipsia increased and she was started on oral desmopressin 0.05mg QD and then BID; and levotiroxine first
25 and one week later 50 mcg/d.Estrogen replacement was
started. She isn’t on GH replacement due to economical
reasons.
Discussion: Although panhypopituarism in children
is rare, even more unusual is the coexistence of an empty
sella and the combination of panhypopituarism and diabetes insipidus. As is unusual for these children to remain
untreated until adulthood. It is believed that 50% of cases
with multiple hormonal deficiencies are due to mutations in
the PROP-1 gene; in fact these patients frequently develop
empty sella due disappearance of the hypophisis; nonetheless it’s coexistence with diabetes insipidus has not to our
knowledge been reported. Trauma another possible etiology was not reported by the patient.
Conclusion: We report a rare case of panhypopituitarism, diabetes insipidus and empty sella in a young woman
whose symptoms presented as a child.
PM cortisol 1397 (RR:64-340), abnormal 24h urine free
cotrisol 2000 nmol/D (RR:100-379), abnormal overnight
1mg& abnormal 8 mg dexa test (post 1 mg value 760
nmol/l: post 8 mg: 500 nmol/l), serum ACTH 151 ng/l (560 ng/l). Pituitary MRI: enhancing 2.3x1.3 cm mass in lt.
pituitary fossa invading parasellar/cavernous sinus w/ a lt.
dural tail. An inferior petrosal sinus sampling for ACTH
with CRH stimulation was done to determine the source
of abnormal ACTH. It confirmed the pituitary source of
abnormal ACTH secretion with lateralization to the left.
(basal ACTH left/right: 4095/764 ng/l: ratio 5.3: post CRH
left/right at +10 min: >20,000/1701: ratio11. 7). AT TSS
surgery/histopathology: left sided corticotroph adenoma
was removed with unexpected finding of purulent material
filling up the sphenoid sinus with 4+ pseudomonas aeruginosa & 3+ polymorphs. Adenoma showed atypical features consisting of increased mitosis, & Ki-67 proliferation
index. It was positive for bacterial culture. Postoperatively,
pt. developed bacteremia & was treated using appropriate
antibiotics with eventual recovery.
Discussion: ACTH-producing pituitary macroadenoma is unusual for CD in its size, in association with
severe signs/symptoms of hypercortisolemia & in mimicking ectopic ACTH-secreting tumor.
Conclusions: ACTH-secreting macroadenoma can
mimic ectopicACTH-producing tumors. It can manifest unusual radiological feature consisting of a dural tail
that was initially thought to be specific for meningiomas.
Tumoral proliferative activity can be determined by the
detection of Ki-67 antigen, a biological marker that is significantly higher in invasive adenomas, information that
can be useful in therapeutic postoperative management.
The case highlights the need to avoid inadequate surgery
and extreme care in avoiding inadvertent seeding of infection in pituitary bed in the context of severe immunocompromised state that is characteristic of CD.
Abstract #818
CUSHING’S DISEASE MIMICKING ECTOPIC
ACTH-SECRETING TUMOR BUT DUE TO
ACTH-PRODUCING PITUITARY
MACROADENOMA EXHIBITING ATYPICAL
FEATURES OF INCREASED MITOSIS &
ABNORMAL MIB-1(Ki-67)
PROLOFERATIVE INDEX
Saud Al-Harthi, MD, Shaheen Marwan, MD,
Ahmed Nazmi, MD, Imaduddin Kanaan, MD, and
M Dababo, MD
Abstract #819
Objective: We report a case of pituitary macroadenoma (PM) that mimicked ectopic ACTH-secreting tumor
in clinical presentation. The resected tumor demonstrated
atypical histopathological features. Additionally, an unexpected sphenoid sinus abscess was encountered at transphenoidal surgery (TSS).
Case presentation: A 62-yr.man w/Cushing’s disease (CD) was referred from outside hospital following a
minimal debulking of a PM. Pt. presented with myopathy
& classical signs of CD, BP was 230/110 despite the use
of maximal antihypertensive medications, uncontrolled
diabetes (FBS 11.5 mmol/l, HbA1C 10.9%), hypokalmic
alkalosis (K+ 2.4 mmol/l, CO2 of 32 mmol/l), loss of diurnal serum cortisol (AM value: 1314 nmol/l (RR:171-536),
SHEEHAN’S SYNDROME MASQUERADING AS
SYMPTOMATIC HYPONATREMIA
Hiba Al-Dabagh, MBBS, Wolali Odonkor, MD,
Gail Nunlee-Bland, MD, and
Mariama Semega-Janneh, MD
Objective: Recognize Sheehan’s syndrome (SS) as
one of the disorders to be considered in the differential
diagnosis of hyponatremia.
Case presentation: Four days after initiating appropriate antibiotic treatment for a urine tract infection, this
46 year-old Hispanic lady was admitted to the hospital
– 93 –
with persistent vomiting, abdominal and flank pain. On
examination she was afebrile, hypotensive (BP 98/56), and
dehydrated. She was alert and oriented but irritable and
agitated. The remainder of her examination was remarkable for absent axillary hair and sparse pubic hair; no
hyperpigmentation. Initial labs revealed Na108 meq/l, Cl
80 meq/l non-anion gap metabolic acidosis, K 3.9 meq/l,
BUN 8 mg/dl, Cr 0.8 mg/dl, and glucose 75 mg/dl; serum
osmolality was 223 mmol/kg. The review of systems was
significant for fatigue, nausea and dizziness for 2 wks prior
to presentation, amenorrhea since the age of 29, cold intolerance, hair loss and dry skin. Past medical history is significant for postpartum bleeding after her last delivery. She
was not on any regular medication and denied smoking,
drinking alcohol or using illicit drugs. Family history was
not contributory. Evaluation of the hyponatremia revealed
normal TSH, low T4 and T3; random cortisol level was
low at 1.66 μg/dl; ACTH stimulation test confirmed the
diagnosis of adrenal insufficiency. She was started on
hypertonic saline and decadron which resulted in gradual
correction of hyponatremia and resolution of symptoms.
Further investigations confirmed a pituitary cause of adrenal insufficiency: ACTH level was < 5 pg/ml; FSH, LH,
estradiol, IGF-1 and prolactin were low and an MRI of the
brain showed empty sella. A diagnosis of panhypopituitarism was made. The patient was discharged home on prednisone and levothyroxine
Discussion: SS is one of the causes of pituitary failure; classically it develops following severe post partum
hemorrhage. In pregnancy, pituitary gland enlarges due to
estrogen stimulation making it hypervascular and susceptible to acute changes in arterial pressure. Although SS is
less frequent in the era of current obstetric care it remains
an important cause of hypopituitarism that is often missed
for a long period of time. Hyponatremia is reported variably in SS (5-35%) however symptomatic hyponatremia as
the initial presentation of SS is uncommon.
Conclusion: Hyponatremia is a common problem
in general medical practice. A detailed history (including
reproductive history in childbearing women) and physical
examination is essential to make a timely diagnosis and
avoid further morbidity and mortality.
Abstract #820
HYPOPITUITARISM AND QUALITY OF LIFE
FOLLOWING TRAUMATIC BRAIN INJURY AND
SUBARACHNOID HEMORRHAGE
Lakshmi Srinivasan, MD, Brian Roberts, Gary Steinberg,
David A Spain, MD, Tamara Bushnik, PhD,
Zahraa Al-Lawati, Henry L Lew, MD, PhD, and
Laurence Katznelson, MD
Objective: To correlate pituitary function with quality
of life and overall performance-function in patients with a
recent history of TBI and SAH
Methods: 18 subjects with moderate (Glasgow Coma
Scale (GCS) 9-13) or severe (GCS <9) TBI including 6
female (F)/ 12 male (M) with mean age 31.9 yr (range
20 – 59) and 17 with SAH of any Hunt and Hess grade,
including 12 F / 5 M of mean age 50.3 yr (range 25 – 64)
were evaluated in a cross-sectional study 6-12 months following the event. Pituitary hormonal assessment included
prolactin, thyroid and gonadal testing; a low dose (1 mcg)
cortrosyn stimulation test (normal > 18 mcg/dL at 45
min) to assess adrenal reserve; and growth hormone (GH)
reserve via a GHRH-Arginine stimulation test (GH deficiency defined by peak GH < 10 ng/mL). The ‘Satisfaction
with Life (SWL)’ questionnaire was administered to assess
quality of life. Craig Handicap Assessment and Reporting
Technique (CHART), Disability Rating Scale (DRS), and
Functional Independence Measure (FIM) were administered to assess overall performance-function
Results: Hypopituitarism (at least one axis deficient)
was present in 22 (63%) subjects, including 17 (49%) with
adrenal insufficiency (AI). Hypothyroidism, GHD, and
hypogonadism were present in 7 (20%), 9 (26 %), and no
subjects, respectively. Ten subjects (29%) were deficient in
at least two axes. Subjects with hypopituitarism (= 1 axis
deficient) reported a non-significant trend towards lower
quality of life compared to subjects with normal pituitary
function (24.1 ± 7.2 vs. 27.9 ± 6.4; p = 0.13). The presence
of hypothyroidism correlated negatively with SWL (r=-.-4,
p=0.02. Overall performance-function scores did not correlate with presence of hypopituitarism, though there was
a trend towards impaired functional measurements compared to subjects with normal pituitary function (CHART:
533 ± 74.5 vs. 562 ± 82.6 p = 0.35; DRS: 1.3 ± 1.8 vs.
0.7 ± 1.7 p=0.34; FIM: 123 ± 3.2 vs. 124 ± 3.8 p=0.4).
There was no statistical difference in functional measures
between subjects with isolated AI and those with normal
pituitary function.
– 94 –
months postoperatively, he continues to be symptom-free
with normal urinary and midnight salivary cortisol values.
Discussion: Cyclic CS is a rare disorder with 65
cases reported in the literature since 1960. It is characterized by periodic fluctuation of adrenal cortisol secretion
with cycles of hypercortisolism lasting from 12 hours to
86 days alternating with inter-cyclic phases of normal or
low cortisol production lasting from days to years. The
cyclic nature of the disease often makes the diagnosis
challenging. Cyclic CS is associated most commonly with
pituitary corticotroph adenomas and less commonly with
ectopic ACTH-producing neoplasms or adrenal adenomas.
Ectopic pituitary adenomas are rare. These generally occur
in anatomic locations along the path of the embryologic
development of the anterior pituitary and may be a cause of
surgical failure in the treatment of Cushing disease.
Conclusion: To our knowledge, this is the first case of
cyclic CS due to an ectopic pituitary adenoma.
Conclusions: In our series, hypopituitarism was present in 63% of subjects with history of TBI or SAH. The
presence of hypothyroidism correlated with worse quality
of life. AI assessed with a low dose cortrosyn stimulation
test was more prevalent than previously reported using a
standard cortrosyn stimulation test, suggesting that a modest degree of AI may be highly prevalent following TBI
and SAH. Endocrine function, particularly thyroid and
adrenal, should be routinely tested in these subjects.
Abstract #821
CYCLIC CUSHING SYNDROME DUE TO AN
ECTOPIC PITUITARY ADENOMA: A CASE
REPORT
Rahfa Kurdi Zerikly, MD, Esin Eray, MD,
Charles Faiman, MD, Robert R. Lorenz, MD,
Robert J. Weil, MD, and Amir H. Hamrahian, MD
Abstract #822
Objective: To describe a case of an ectopic pituitary
adenoma as a rare cause of cyclic Cushing syndrome
(CS).
Case Presentation: A 39 year-old Caucasian male
presented with facial plethora, a 45-pound weight gain and
easy bruisability. The following lab results were consistent
with hypercortisolemia: urinary free cortisol (UFC) 120
µg/d (20-100), two consecutive midnight salivary cortisol 1500 and 384 ng/dL (<100), serum cortisol 13.3 µg/dL
at 15 minutes during a 2-day DEX/CRH test. The ACTH
level of 44 pg/mL (6-48) indicated ACTH-dependent CS.
Pituitary MRI was normal. At the time of inferior petrosal
sinus sampling (IPSS), he was found not to be hypercortisolemic, which triggered further investigation. Weekly 24hr UFC measurements ranged from 7.3 to 789 µg/d, consistent with cyclic CS. He underwent a second IPSS after
confirming a significantly elevated 24 hr UFC (692 µg) the
day before the procedure. Once again, he was found not
to be hypercortisolemic during the test (cortisol 5.6 µg/dL
at baseline) indicating a change in ACTH secretion in less
than 24 hours. The patient underwent trans-sphenoidal surgery, during which a 5 mm firm, round midline lesion was
encountered in the sphenoid sinus, pedicled to the posterior
wall by a thin bridge of mucosa. The pituitary gland exploration was normal. The sphenoid sinus lesion had been
preoperatively interpreted as a mucosal polyp on imaging.
Microscopically, it was found to be a pituitary adenoma
which stained diffusely for ACTH. Postoperatively, the
patient became hypocortisolemic and had resolution of
all his Cushingoid features. He was found to have normal adrenal function at 3 months following surgery. At 12
SILENT PITUITARY APOPLEXY AS A
COMPLICATION OF METASTATIC PROSTATE
CANCER THERAPY: MULTIPLE ENDOCRINE
IMBALANCES AT TWO POINTS IN THE
HYPOTHALAMIC-PITUITARY-ADRENAL AXIS
Sofronio Cruz Ramirez, Jr., MD, Simonette Soler, MD,
and Latha Dulipsingh, MD
Objectives: To describe & review the literature on
the atypical presentation of silent pituitary apoplexy as
a complication of GnRH agonist treatment for patients
with prostate cancer. To present the physiologic effects
of medications used in prostate cancer therapy on adrenal
steroidogenesis.
Case Presentation: An 82-year old male was admitted for altered mental status. He was discharged 3 days
prior with the diagnosis of metastatic prostate cancer, with
obstructive uropathy on presentation. He was sent to a
short-term rehab facility on bicalutamide, ketoconazole,
tamsulosin, & received an initial dose of intramuscular
leuprolide before discharge. Three days later, the patient
was found unarousable, and was brought to the ER. He was
found to be hypoglycemic. IV glucose was administered
with improvement in sensorium. ROS revealed anorexia,
constipation, & easy fatigability, without headache, visual
changes, nausea or vomiting. Exam revealed a weak-looking, cachectic, elderly male with pale mucous membranes
and dry oral mucosa. He had full extraocular movements
and no visual field cuts, proptosis, lid lag, or ptosis. Thyroid
– 95 –
was nonpalpable. Subsequent evaluation for hyponatremia
revealed suppressed TSH (0.34uIU/mL), and low FT4
(0.27ng/dL) & total T3 (0.67ng/mL). He had low ACTH
(5pg/mL) & low cortisol (0.4ug/mL). Serum FSH, LH, total
& free testosterone were decreased (0.5mIU/mL, 0.5mIU/
mL, 2ng/dL, & 0pg/dL, respectively). Prolactin was 6.0ng/
mL. On standard ACTH stimulation test, there was with
low baseline, 30-minute, & 60-minute cortisol (0.2ug/mL,
1.5ug/mL, & 3.4ug/mL, respectively). Brain MRI results
were consistent with pituitary apoplexy. He was started on
corticosteroids & levothyroxine. Ketoconazole was discontinued. Prednisone, levothyroxine, bicalutamide, tamsulosin, & leuprolide were continued on discharge.
Discussion: Pituitary apoplexy is an endocrine emergency classically presenting with headache, nausea, vomiting, visual impairment, and meningismus. Pituitary apoplexy after GnRH analog therapy for advanced prostate
cancer has been reported in the setting of an underlying
pituitary adenoma. GnRH analogs have become a promising treatment for prostate cancer. The few cases of pituitary apoplexy with GnRH analog use were associated with
symptomatic pituitary apoplexy. The presentation is peculiar in that typical signs & symptoms of apoplexy were
absent. In addition, impaired response to ACTH stimulation test in the setting of a relatively acute event cannot
be fully explained by secondary adrenal insufficiency.
Ketoconazole has been reported to cause primary adrenal
insufficiency by inhibiting the 11?-hydroxylase step in
steroidogenesis.
Conclusion: Silent pituitary apoplexy in the setting of
GnRH therapy for advanced prostate cancer is rarely recognized and likely underreported. The catastrophic sequelae
associated with pituitary apoplexy make recognition of
this clinical presentation crucial. The multiple influences
of pharmacotherapy for advanced prostate cancer on the
HPA axis make cautious interpretation of endocrinologic
tests equally important.
the disease confined in the brain and was characterized of
hydrocephalus and diabetes insipidus.
Case description: A 31-year-old female who had history of six months of worsening headache, blurred vision
and progressive polyuria, polydipsia and nocturia despite
well controlled diabetes mellitus. She also reported amenorrhea and weight gain over the past year. Initial investigation revealed hydrocephalus which was treated by mean
of a VP shunt. Physical examination revealed a morbidly
obese woman. Visual field exam revealed bitemporal
defects. Laboratory studies: prolactin 100 ng/dl, FSH and
LH <1mIU/ml, estradiol 23.5 pg/ml, progesterone 0.4
ng/ml and TSH 1.84 μIU/ml. Serum and urine osmolality
were 310 mOsm/kg and 74 mOsm/kg respectively. Serum
sodium was 152 mEq/L and urine volume was 8 L/day.
Serum ACE was 19 u/L. No hilar adenopathy was seen in
a CXR. CSF fluid revealed high protein, low glucose and
lymphocytic pleocytosis. VDRL, HIV Ab and ANA were
negative. AFB and fungal culture were also negative. A
CT of the brain showed hydrocephalus secondary to fourth
ventricle blockage.
A MRI of the brain revealed numerous patulous
areas of enhancement within the ventricular system which
obstructed the ventricular outlet. The evidence for central diabetes insipidus, hypogonadism and hyperprolactinemia raised the possibility of infiltrative lesion in the
hypothalamo-pituitary area. DDAVP was instituted with
an improvement of sodium level and urine output to 138
mmol/L and 4 L/day respectively.
A brain biopsy was performed to make a definitive
diagnosis. Pathologic examination demonstrated non-necrotizing granulomatous inflammation consistent with neurosarcoidosis. High dose intravenous methylprednisone
was started and subsequently changed to oral prednisone.
Discussion: CNS involvement occurs in only approximately 5 % of patients with sarcoidosis. In particular,
hydrocephalus and central diabetes insipidus due to infiltrative lesions in the hypothalamo-hypophyseal region
are relatively unusual manifestations of this disease. Our
patient illustrates a rare presentation of sarcoidosis because
she exhibited CNS involvement without other systemic
manifestations of the disease.
Abstract #823
DIABETES INSIPIDUS AND HYDROCEPHALUS:
ATYPICAL PRESENTATIONS OF SARCOIDOSIS
Tanyanan Tanawuttiwat, MD, Natasha Akhter, MD, and
Stanley Blumenthal, MD, FACE
Objective: Sarcoidosis is a chronic multisystem disorder of unknown cause characterized by the presence
of non-caseating epithelioid-cell granulomas. The organs
most commonly involved are the lungs, skin, eyes and
lymph nodes. We describe a case of sarcoidosis in which
– 96 –
Conclusion: This case highlighted delayed diagnosis and concormitant presence of hyperpituitarism and
hypopituitarism. In the short term patient can be controlled
medically but long term management poses challenges.
Abstract #824
GIGANTISM ASSOCIATED WITH
HYPOPITUITARISM
Ifedayo Adeola Odeniyi, MBBS,
Adekunle Adeyemi-Doro, MBBS, Chuks Ekpebegh,
Olufemi Fasanmade, MBBS, FWACP,
and Augustin Ohwovoriole, FMCP, FWACP
Abstract #825
SEPTO-OPTIC DYSPLASIA: A RARE CAUSE OF
CONGENITAL HYPOPITUITARISM
Objective: To present an unusual case of gigantism
due to pituitary tumour in a patient who was also having
features of hypopituitarism.
Case Report: A young Nigerian diagnosed as having
gigantism secondary to pituitary adenoma is reported in
this communication. He was referred from the orthopaedic clinic where he was being managed for pathological
fracture. He is 18 year old senior secondary school student.
He was very tall compared with his peers in the neighborhood and his siblings. Pregnancy and early childhood were
uneventful. He had excessive somnolence, sluggishness
and weight gain. His weight was 114 kg, height was 2.10m,
upper segment was 1.0m, lower segment was 1.10m and
arm span was 2.32m. He was dull, anemic, had thick lips,
bilateral gynaecomastia with milky nipple discharge, large
hands and feet. He had scanty axillary hair, and his pubic
hair distribution was Tanner stage 4. He had bitemporal
hemianopia, diminished reflexes globally, but no delayed
relaxation phase of the ankle reflex. His pulse rate was
86bpm; blood pressure was 90/60mmHg. Basal growth
hormone was markedly elevated. Basal Prolactin was also
elevated. Thyroid and testicular functions were impaired.
Basal cortisol and stimulated cortisol were equivocal.
OGTT with serial growth hormone measurement showed
no suppression of growth hormone. Imaging studies confirmed enlarged pituitary fossa due to pituitary tumour.
The problems with this patient are hyperpituitarism with
hyperprolactinaemia, hypothyroidism, hypogonadism
and borderline adrenocortical function. He is currently
responding to treatment with bromocriptine and hormonal
replacement.
Discussion: Gigantism is a rare disorder, a major
cause of which is hyperpituitarism. Even rarer is hyperpituitarism causing gigantism in the company of pituitary
failure. Our patient has a combination of hypopituitarism
and hyperpituitarism as shown by the presence of hypothyroidism, hypogonadism and borderline adrenal function
with hyperprolactinaemia and excessive growth hormone.
He is on hormonal replacement presently and doing well.
The challenge in his management is the refusal of the parents to accept surgical intervention as the better option for
the management of his case.
Deepa Sundararajan, MD, Maneet Kaur Narula, MD,
and Harmeet Singh Narula, MD, FACE
Case Presentation: A 27 y woman with Panhypopituitarism presented for refill of her meds. She had recently
moved from California; old records were unavailable. Her
prior endocrinologist also did not have her remote records,
and had been refilling her meds. Physical examination
revealed a short obese woman with severe visual impairment without any dysmorphic features. Her biochemical
testing at the time of presentation to us was consistent
with panhypopituitarism, with IGF-1 of 12 ng/mL (normal
114-492); repeat <25 ng/mL; Prolactin 16ng/mL, free T4
normal on T4 175mcg/d, Cortisol low, on hydrocortisone
replacement, gonadotropins undetectable on Estrogens (as
birth control pill). She had no evidence of DI. She was diagnosed with Growth hormone deficiency (GHD) & adrenal
insufficiency at age 9. Hypothyroidism was diagnosed at
age 15; she had primary amenorrhea and was started on
estrogen at age 19. She was legally blind in her Rt eye and
had very poor vision in her left eye and had been told of
optic nerve hypoplasia; she also had astigmatism, nystagmus & myopia. Because of the optic nerve abnormalities
and the panhypopituitarism, a diagnosis of septo-optic dysplasia was considered. An MRI of the pituitary confirmed
severe optic nerve hypoplasia, hypoplastic pituitary, ectopic posterior pituitary, but septum pellucidum was present,
likely a variant of septo-optic dyplasia. Further detailed
history from the patient revealed prolonged jaundice as
newborn, several hospitalizations as a child for febrile illnesses, frequent migraines, growth delay starting early in
life, consistent with congenital panhypopituitarism which
was not diagnosed until much later in life.
Discussion & Conclusion: Septo-Optic Dysplasia
(De Morsier syndrome), a rare developmental disorder, can
cause congenital hypopituitarism. It is most commonly sporadic, although rare familial forms, with HESX1 mutations
have been described. Patients typically have abnormalities
of septum pellucidum, severe optic nerve hypoplasia and
other midline abnormalities. Patients with septo-optic dysplasia may have hypopituitarism and may have morphological abnormalities of the pituitary. Adult endocrinolo– 97 –
Conclusions: Timely recognition, prompt glucocorticoid Rx & decompression of pituitary bleed results in
a satisfactory outcome. Pituitary apoplexy may produce
complete or partial tumor destruction of tumor, may result
in serious visual deficits, varying degrees of pituitary insufficiency requiring long term hormonal replacement therapy
& empty sella (ES).The presence of an enlarged eroded ES
in a patient with visual deficit is a reasonable presumptive
evidence of an infracted pre-existing pituitary tumor.
gists need to be aware of this syndrome as some cases may
not be accurately diagnosed earlier in life.
Abstract #826
CLASSICAL PITUITARY APOPLEXY:
PRESENTATION AND FOLLOW-UP OF
THIRTEEN PATIENTS.
Saleh Al-Ahmed, MD, Mohammed Al-Sheef, MD,
and Imaduddin Kanaan, MD
Abstract #827
LYMPHOCYTIC HYPOPHYSITIS: A RARE
CAUSE OF HYPOPITUITARISM
Objective: To report presenting features, FU data &
outline recommendations for management of patients with
classical pituitary apoplexy (CPA).
Case Presentation: Thirteen patients (8 males & 5
females, aged 19-60 yrs) with pituitary adenomas presented
with CPA. Apoplexy antedated the presentation by several
days to weeks in 4. Eight patients had visual disturbances
(bitemporal hemianopsia in 4, acute visual acuity decrease
in 2, bilateral blindness in one & optic atrophy in one. Four
had cranial nerve paralysis:3rd & 6th cranial nerves in 2 &
6th nerve palsy in 2. All had macroadenomas (suprasellar
with/without parasellar extension) on MRI imaging. All
had MRI findings consistent with recent pituitary bleed.
The tumors were nonfunctioning in 6,GH-producing in 3,
prolactinomas in 3 & ACTH-producing in one. All patients
had hormonal deficiencies at presentation. These consisted
of hypopituitarism in 5,central hypoadrenalism in 3,central
hypogonadism in 3, a combination of central hypothyroidism & hypoadrenalism in one & central hypothyroidism in
concepts. were treated with stress doses of glucocorticoids
after obtaining blood samples for baseline studies. Twelve
pts. had transsphenodial decompression & one had transfrontal surgery. They had FU for 3-164 months. External
beam therapy was given to 2 patients (with residual GHsecreting and ACTH-secreting tumors). Seven patients
developed empty sella (ES) with resolution of the tumors.
Tumor recurrence occurred in 2 patients. Aforementioned
hormonal deficiencies have persisted in all requiring
replacement therapy. Two patients were lost to follow up at
22 & 34 months. The rest were alive with persistent visual
deficits in all but one.
Discussion: CPA is a rare acute clinical syndrome
of an abrupt onset characterized by sudden headache, disturbed consciousness, & visual disturbance caused by the
enlargement of a pituitary tumor due to hemorrhage or an
extensive infarction. Little is known about the long term
outcome of pts. Most of the reported information relates
to a limited experience describing initial presentations of
isolated cases or small series.
Ana Lugaro-Gomez, MD, Margarita Ramirez, MD,
Myriam Allende, MD, and Vilma Rabel, MD
Objective: To describe the atypical presentation of a
rare cause of hypopituitarism reporting a case of lymphocytic hypophysitis.
Case Report: 43 y/o woman with past medical history
of fibromyalgia and HBP taking naproxen 500mg po bid
and enalapril 5mg po daily who came to our clinic referred
due to hyperprolactinemia and galactorrhea. Patient had
very strong right sided throbbing headaches, amenorrhea since 4 months previous to the evaluation, decreased
libido, 15 pounds weight gain, fatigue, cold intolerance,
constipation, dry skin, and axillary hair loss. Also refers
polyuria, polydypsia, dizziness, nausea, and vomits and
states that she noted the symptoms since about 3 months
prior to the evaluation one month after her last menstrual
period. Her last delivery was on 1989. Physical examination with stable vital signs and remarkable for dry oral
mucosa, decreased temporal vision bilaterally, decreased
relaxation phase of the DTR’s, and absence of axillary hair.
The brain MRI showed a T2 hyperintense mass expanding the sella and causing mass effect upon the optic chiasm and pituitary stalk. It also showed a right CP angle
mass of 1.9cm x 1.3cm. Was found to have hypogonadotropic hypogonadism(FSH-4.03MIU/ML), secondary
hypocortisolism(ACTH-less than 10.0pg/ml and cortisolless than 0.20ug/dl), secondary hypothyroidism (TSH0.46MIU/ML, free T4-0.77ng/dl), and hyperprolactinemia
(prolactin-55.2ng/ml). Diabetes insipidus was confirmed
with a water deprivation test. She was started in hormone
replacement therapy for cortisol and thyroid deficiencies as
well as DDAVP. She underwent a craniotomy with partial
resection of the tumor which pathology showed chronic
inflammation and lymphocytic infiltration as seen in lymphocytic hypophysitis. IGF-I levels and new prolactin
levels are pending to evaluate for GH deficiency and to
– 98 –
determine if the hypogonadism is secondary to elevated
prolactin levels or due to the infiltration itself.
Discussion: Lymphocytic hypophysitis is a rare disorder initially characterized by lymphocytic infiltration
and enlargement of the pituitary; followed by destruction
of the pituitary cells. Most often occurs in late pregnancy
or postpartum period. Female:Male ratio is 8:1 and usually coexists with other autoimmune disorders. About 100
cases has been described since the original report in 1962.
Final diagnosis is done based on histological examination due to the lack of markers for the disease as antipituitary antibodies have been detected in only a minority of
patients. Affected patients typically present with headaches
of intensity out of proportion to the size of the lesion and
hypopituitarism. Preferential hypofunction of ACTH and
TSH secreting cells has been described. However, diabetes
insipidus, hyperprolactinemia, growth hormone excess can
be present.
Conclusion: This case comprises an atypical presentation for this already uncommon disease which made it difficult to diagnose it on clinical bases only. The patient was
not in the peripartum period nor had any associated autoimmune disease. The importance of developing new markers would be helpful in order to diagnose and treat patients
like this without the need for a surgical intervention.
patient admitted to no medication or follow up for over 10
years. Other causes for pericardial tamponade, including
tuberculosis, neoplasia, uremia, bacterial, cardiomyopathy and myocardial infarction were ruled out. Following
hemodynamic stabilization, he was given hydrocortisone
100mcg TID and later levothyroxine 50 mcg IV daily. He
was discharged on hydrocortisone 20mg in AM and 10mg
PM, and levothyroxine 100mg daily. Two months later,
TSH normalized; MRI showed a small pituitary gland with
no masses and testosterone replacement was begun.
Discussion: We will discuss the association of CT
with untreated hypothyroidism and hypocortisolism.
Cardiac symptoms in hypothyroidism include rhythm disturbances, failure, and ischemic disease. Pericardial effusion is the most common cardiac manifestation of primary
hypothyroidism; however, due to the decreased metabolic
state, florid tamponade with cardiovascular compromise
(as in this case) rarely occurs. The low incidence of CT
in hypothyroidism is likely due to slow accumulation
of fluid in the pericardium and increased distensibility.
Hypocortisolism has also been rarely associated with CT.
One case of isolated ACTH deficiency with CT and several
cases with Addison’s disease and an autoimmune process
linked to serositis have been described.
Conclusion: Clinicians should be aware of the association of hypothyroidism and hypocortisolism with CT.
A diagnosis of exclusion, this rare and life threatening
complication may be the presenting manifestation of these
endocrine disorders.
Abstract #828
HYPOTHYROIDISM AND HYPOCORTISOLISM
PRESENTING WITH CARDIAC TAMPONADE
Abstract #829
Evana Valenzuela, MD, Paulina Kunecka, MD,
Regina Dodis, MD, and Nancy J. Rennert, MD, FACE
TSH-SECRETING PITUITARY MICROADENOMA:
DIAGNOSIS BY DYNAMIC CONTRAST
ENHANCED MR SCAN AND OCTREOSCAN
Objective: To report a case of cardiac tamponade (CT)
associated with hypothyroidism and hypocortisolism.
Case presentation: A 48 year-old male with a history
of pituitary adenoma resection (using a cranial approach) 20
years prior presented with chest pain. Initially, the patient
had stable vital signs but decompensated with hypotension
(BP 40/negligible) and mental status changes. Physical
exam was remarkable for tachycardia and faint pulses. EKG
had low voltage and CXR was negative. Echocardiogram
showed large pericardial effusion, with evidence of
increased pressures (right ventricular diastolic collapse
and marked respiratory variation in mitral inflow velocities) consistent with CT. Pressor support was initiated and
a pericardial window was performed. Laboratory values on
admission showed primary hypothyroidism (TSH 75uIU/
mL, total T4 3.1mcg/dL) and hypocortisolism (random
cortisol 3mcg/dL). ACTH was not measured. Testosterone
and gonadotropins were low. Upon later questioning, the
Mae Sheikh-Ali, MD, Lina Aguirre, MD,
Robert Wharen, MD, Leo Czervionke, MD,
and Robert C. Smallridge, MD
Objective: to demonstrate the advantage of using
Dynamic MR Scan for detecting pituitary microadenoma.
Case Presentation: A 55-year-old woman presented
with irritability, fatigue, nervousness, tremulousness and
palpitations. Her mother had a history of hyperthyroidism. On physical exam, her pulse = 60/min (on atenolol), and
there was no proptosis or visual field defect. She had a
small, firm, diffuse goiter, mild tremor and brisk reflexes. She had no symptoms or physical evidence of galactorrhea,
acromegaly or Cushing’s syndrome. Serum free T4 = 3.0
ng/dL (normal < 2.8); free T3 = 558 pg/dL (< 420), and
TSH = 1.7 mIU/L (increasing to 7 mIU/L after TRH). – 99 –
Alpha-subunit = 1.3 ng/mL. Thyroid stimulating and binding inhibitory immunoglobulins were normal. Thyroid
ultrasound showed a goiter and pituitary MR showed sellar
asymmetry but no discrete lesion.
Discussion: The mild increase in alpha-subunit and
sellar asymmetry suggested a pituitary tumor, but the
family history of hyperthyroidism and TSH response to
TRH suggested thyroid hormone resistance syndrome. Conventional MR revealed enlargement of the pituitary
gland on the left with deviation of pituitary stalk to the
right of the midline. A dynamic contrast enhanced MR
scan of the pituitary revealed a discrete ovoid 6 mm in
diameter relatively hypointense mass within the pituitary
gland which became visible at 90 seconds post injection.
An Octreoscan showed intense uptake in the pituitary
region. Transphenoidal surgery confirmed a TSH tumor
(cells positive for TSH, alpha- subunit and rarely for GH
and PRL). Three years latter, thyroid tests were normal
while taking 25 mcg L- T4, and dynamic MR scan showed
no tumor recurrence.
Conclusion: This case illustrates the value of multimodality neuroimaging in detecting small pituitary
tumors.
– 100 –
ABSTRACTS – Reproductive Endocrinology
Conclusion: Idiopathic hypogonadotrophic hypogonadism is more common than hypergonadotrophic hypogonadism. Testosterone replacement offers men the opportunity to regain some of the vigor of their youth. Done while
closely monitored, it is a relatively low-risk proposition
that has many benefits, including boosting cognition, muscle mass, and bone density while decreasing abdominal fat.
Restoration of a eugonadal state can restore well-being and
in crease compliance with other aspects of health care.
REPRODUCTIVE
ENDOCRINOLOGY
Abstract #900
MALE HYPOGONADISM IN TERTIARY
CARE CLINIC
Saeed Ahmed Mahar, MD, FCPS, Abdul Jabbar,
and Najumul Islam
Abstract #901
Introduction: Male hypogonadism is one of the most
common endocrinologic syndromes. The diagnosis is
based on clinical signs and symptoms plus laboratory confirmation via the measurement of low morning testosterone
levels on two different occasions. Serum luteinizing (LH)
hormone and follicle-stimulating hormone (FSH) levels
distinguish between primary (hypergonadotropic) and
secondary (hypogonadotropic) hypogonadism. Androgen
replacement therapy in hypogonadal men has many potential benefits: improved sexual function, an enhanced sense
of well-being, increased lean body mass, decreased body
fat, and increased bone density.
Objective: To study the presentation and type of
hypogonadism.
Methods: Medical records were reviewed of all
the patients who attended the endocrine clinic at Aga
Khan University Hospital Karachi, from January 2000 to
December 2006 and were found to have low testosterone
levels, were included in the study. The patients with diabetes mellitus were excluded from the study.
Results: Sixty one (mean age 24 years) with
Hypogonadotropic hypogonadism, and thirteen males
(mean age 25 years) with Hypergonadotropic hypogonadism were enrolled in the study. In Hypogonadotropic
hypogonadism, common presentations were lack of facial
hairs (23%), decreased libido (21.3%), and small penis
(19.7%). In Hypergonadotropic hypogonadism, most common presentations were small penis (30.8%), decreased
Libido (23.1%), and infertility (23.1%). All patients with
Hypogonadotropic hypogonadism had low pretreatment
Testosterone levels as compared to Hypergonadotropic
hypogonadism (46.13 ± 34.1 vs. 106.92 ± 76.6). Serum FSH
and LH level were low in Hypogonadotropic hypogonadism patients. After treatment Axilary hair were increased
in all groups of patients. Hypogonadotropic hypogonadism patients were more likely to be young (p=0.03), less
likely to have over weight, more liely to have small penis
size (p=0.05), sparse axillary hair (p=0.01), less pubic hair
(p=0.02), low serum LH (p=0.002), and less likely to have
Testosterone level (p=0.001).
COMPLETE ANDROGEN
INSENSITIVITY SYNDROME
Sachin Kumar Jain, MBBS, MD, DM, FACE,
Pramila Diwaker, and Ajay Ajamani
Objective: To present a case of Complete Androgen
Insensitivity Syndrome ( CAIS ).
Case Presentation: 37 yr. old reared as a female,
presented with primary amenorrhoea Patient had a normal female phenotype and had not ever pursued serious
evaluation, was a known case of schizophrenia and was
on treatment (Resperidone and Clonazepam) for last 13
yrs. There is history of some problem of sexual development in maternal grandmother’s sister, details of which
are not available. Pt’s height-160.9 cms (mother’s ht150 cms, father’s ht-163 cms),which was close to target
male height / BMI-25.7 kg/m2 / female habitus / normal
breast development / scanty axillary and pubic hairs / illdefined swellings in both inguinal regions (gonads) / vaginal orifice admitted only little finger / rest of the systemic
examination was normal. Investigations revealed- normal
hemogram and serum chemistry; testosterone 2.08 ng/ml
(female<0.81); normal LH 7.55mIU /ml & FSH 7.32mIU/
ml; serum Prolactin 51.9 ng/ml(up to 25 ng/ml increased
levels? due to Antipsychotics use); Estradiol 37.4 pg/ml;
Androstenedione 3.5 ng/ml(0.3-3.5); DHEAS 197 µg/dl
(35-430); TSH 4.37 µIU/ml; HCG stimulation test by 2000
IU of HCG intramuscularly for 3 days -S. Testesterone
rose from 2.08 to 11.57 ng/ml; USG of abdomen -uterus,
cervix, ovary not visualized, thin vaginal strip; MRI abdomen revealed – bilateral undescended testes in inguinal
region with left ependidymal cyst with thin strip of vaginal
canal, however uterus, ovaries not visualized; karyotype
was 46XY.
Discussion: Patient had primary amenorrhoea with
female phenotype, very few axillary & pubic hair, significant family history, height close to target male height, elevated basals Testosterone and marked rise in testosterone
on HCG stimulation test and, bilateral undescended testes,
– 101 –
no ovary, uterus and male genotype. Based on these, patient
was diagnosed as having- Complete Androgen Insensitivity
Syndrome. Patient underwent bilateral gonad excision,
which revealed testicular tissues on both specimen with
atrophic seminiferous tubules, leydig cell hyperplasia, no
spermatogenesis; left gonad revealed sertoli cell adenoma.
Bilteral inguinal hernia repair was done. Vaginal dilatation
/ reconstruction were not performed, as pt was not sexually active. Post-op testosterone was 0.47 ng/ml with no
rise in testosterone after HCG stimulation test; Estradiol
19.71 pg/ml; FSH 39.02 mIU/ml; LH(20.41 mIU/ml;
Prolactin 34.02 ng/ml. Patient developed postmenopausal
symptoms relieved after premarin 0.625mg/day. CAIS is an
X-linked recessive disorder with prevalence between 1 in
20,000 to 1 in 60,000 male live births. 1-2% of phenotypic
female with bilateral inguinal hernia have CAIS. It is the
most common identifiable cause of male pseudohermaphroditism with karyotype XY and mutation in AR gene. At
puberty, female habitus with primary amenorrhoea,scanty
pubic & axillary hairs, height close to target male height,
with testes usually undescended, vestigial mullerian structures; testicular histology reveals there are sertoli cell only
seminiferous tubules with sparse spermatogonia & absent
spermatogenesis. Elevated LH, testosterone & estradiol
with normal/mildly increased FSH seen upon hormonal
evaluation along with positive HCG stimulation test. There
is an increased risk of gonadal tumours in Defective Sexual
Differentiation especially in presence of Y–chromosome.
Conclusion: Our patient had CAIS with left sertoli
cell adenoma. Unique feature being that patient presented
at the age of 37 years with primary amenorrhoea.
Abstract #902
GONADOTROPIN-INDEPENDENT PRECOCIOUS
PUBERTY DUE TO TESTOTOXICOSIS
and penile length was 8x3cm. Testes were prepubertal and
measured 2 cm in greatest diameter. Laboratory studies
showed suppressed LH at 0.3 IU/L and FSH at 0.5 IU/L
with an elevated testosterone at 125 ng/dL. Thyroid function studies, 17-hydroxyprogesterone, androstenedione
and DHEAS were normal. Testicular ultrasound was normal and bone survey was negative for bony dysplasia. His
bone age was read between 9 and 10 years. Lupron stimulation showed no LH or FSH response. Genetic testing for
familial-male limited precocious puberty (testotoxicosis)
was positive. He was started on anastrazole 1mg daily. At
4 months, bone age is unchanged, LH and FSH are suppressed, testosterone is 38 ng/dL and growth rate is 3.6
cm/year.
Discussion: Testotoxicosis is a rare cause of GIPP. It
is secondary to an activating mutation of the LH receptor. This is a sex-limited autosomal dominant disorder but
sporadic cases can occur as may be the case in our patient.
Other more common causes for GIPP such as congenital
adrenal hyperplasia, McCune-Albright syndrome or malignancy were excluded in this patient. Our patient started
with secondary sexual maturation at the age of 4 years and
a very advanced bone age, as is the typical presentation
for testotoxicosis. Treatments for this disorder are usually
limited by poor final adult height and toxicity. Our patient
was started on anastrozole, and bicalutamide may be added
in the future depending on his response since this combination has been reported effective. Genetic testing is important especially for counseling.
Conclusion: Testotoxicosis should be considered
after other more common causes of GIPP are ruled out. The
rarity of this disorder limits the amount of patients enrolled
in clinical trials to test different treatment options. So far
aromatase inhibitors and anti-androgens seem to be efficacious in decreasing skeletal maturation and virilization.
Long-term data on final adult height are lacking and ongoing trials will provide more information in the future.
Naim Mitre Calderon, MD, Aida Lteif, MD
Objective: To report a 5 year old boy with gonadotropin-independent precocious puberty (GIPP) secondary to
testotoxicosis and to underline the importance of genetic
testing.
Case Presentation: A 5 year 9 month old boy presented with a history of increased penile and testicular size
since the age of 4 years. He also had significant growth
acceleration where his height increased from the 30th to
greater than the 95th percentile. He developed pubic hair
and was reported to be aggressive. There was no family
history of early puberty. Physical exam showed a height
z score of 2.2. There was one 0.5cm café-au lait spot on
the anterior abdomen. Pubic hair was in Tanner stage II
Abstract #903
SERTOLI-LEYDIG CELL TUMOR AS CAUSE OF
SECONDARY AMENORRHEA
Catalina I Poiana, MD, PhD, FACE, Mara Carsote, MD,
Gabriel Banceanu MD, PhD, Maria Sajin, MD, PhD,
Bogdan Stanescu, MD, PhD, and
Mihail Coculescu, MD, PhD, FACE
Objective: Sertoli-Leydig cell tumor is a type of sex
cord stromal (SCS) tumor, often associated with androgens
secretion, which sometimes can mimic menopause.
– 102 –
Case Presentation: We present the case of a 46 years
old female, with secondary amenorrhea since age of 40.
At that time, she was considered as premature menopause and no investigation was further performed. With
time, hirsutism developed with marked frontal alopecia.
On admission in our hospital, laboratory findings showed
mild polyglobulia and a total cholesterol of 225 mg/dL.
Testosterone values were 10 times above normal: 8.01 ng/
mL (range 0.14 to 0.76 ng/mL). The computed tomography
scan revealed a tumor of 3.5 by 2.8 cm on the right ovary.
Resection of the tumor was performed. There was no evidence of secondary dissemination. The pathology report
revealed a Sertoli-Leydig cell tumor with intermediate
grade of differentiation. The immunohistochemistry profile showed: inhibin and calretin highly positive, pancytokeratin intensely reactive, CD99 moderately positive, epithelial membrane antibody weakly reactive. Postsurgery,
left leg thrombophlebitis complicated the evolution. The
patient was well 3 months later, with decreasing levels
of testosterone and slowly reducing hirsutism. However,
the clinical exam showed a left thyroid nodule. The fine
needle aspiration biopsy suggested a papillary carcinoma.
Thyroidectomy with total neck lymphadenectomy was performed and the diagnosis of sclerosing type of papillary
carcinoma (T2N0M0) was sustained.
Discussion: The term of Sertoli-Leydig cell tumor
usually refers to SCS tumors of testicular type and it is
synonymous to arrhenoblastoma and androblastoma. They
account for 3-10% of gonadal tumors. The main incidence
is between 20 and 30 years, but it may occur at any age
(from 2 to 80 years). Clinical manifestations do not correlate with the histological subtypes or clinical stage. In our
case even if the cells from the tumor had intermediate grading, the clinical progression was slow. The most important immunohistochemical marker for the SCS tumors is
inhibin, which is positive in almost 100% of cases. Calretin
is considered as more sensitive, but less specific. In our
case they were both intensely positive.
Conclusions: Ovarian tumors are rare causes of
amenorrhea and hirsutism. Nevertheless, they should be
suspected if serum androgens are extremely high. We recommend increased awareness of endocrinologists to the
possibility of misdiagnosis with premature menopause.
The association with thyroid carcinoma is probable due to
an epidemiological overlap, because papillary carcinoma is
one of the most frequent forms of endocrine cancer.
Abstract #904
COMPLETE ANDROGEN INSENSITIVITY
CLINICAL PRESENTATION
Pushpa A Viswanathan, MD, and Selma F Witchel
Objective: To describe the variations in the clinical
presentation of complete androgen insensitivity(CAIS).
Case Presentation: A 17 1/2 year old female presented with primary amenorrhea. Following lack of withdrawal bleeding with medroxyprogesterone, additional
evaluation included a karyotype, which showed 46XY,
total testosterone 1161ng/dl and, free testosterone 129.2pg/
ml. A diagnosis of CAIS was made and patient referred
for gonadectomy. Of significance was her past medical history. She had bilateral inguinal hernias at birth, which were
repaired at birth and the “misplaced ovaries” were placed
into the abdominal cavity. Family history was not available since the patient was adopted and androgen receptor
(AR) mutation analysis not performed. This case illustrates
the importance of careful evaluation of inguinal hernia and
masses in infants and adults with female external genital
development.
A 4 day old baby girl was referred for evaluation of
labial masses. Her genitalia were otherwise consistent with
normal female external genital development. Testosterone
level was 74.9ng/dl, FSH<0.3mIU/ml, LH<0.4mIU/ml,
estradiol of 30pg/ml. Her repeat testosterone levels a week
later was not high-40.3ng/dland remained low at 20.2ng/
dl. Karyotype was 46XY and absent uterus by ultrasound.
Additional history revealed a maternal aunt diagnosed with
CAIS at age 30 years. The aunt’s karyotype was 46XY. No
mutations in her AR were identified by DNA sequence
analysis, which included the promoter, coding exons, and
all exon/intron boundaries. Patient underwent gonadectomy at the age of 6 months. Pathology revealed testicular
tissue with sertoli cell predominant tubules. PLAP stain
was negative indicating absence of neoplasia.
Discussion: Androgen Insensitivity is a common
cause of undermasculinization of a 46XY fetus.AR signaling is the key determinant of virilization of the male external genitalia. This is highlighted in the AIS, which presents with a wide ranging phenotype from normal female
in CAIS to lesser degrees of genital ambiguity in PAIS.
Here we describe two patients with CAIS who presented at
different chronologic ages. Recently heterozygous mutations in genes other than in AR have been reported in PAIS,
Coutant et al. JCEM 2007. Among a large cohort of patients
with presumed AIS, AR mutations were not identified in 13
CAIS patients out of 57 patients; presentation was mainly
with inguinal hernia. This raises the question of karyotyp-
– 103 –
ing in females with inguinal hernia, Ahmed et al, JCEM
2000.These two cases emphasize the index of suspicion
needed for the accurate diagnosis of patients presenting
with inguinal hernia. Although elevated testosterone levels
are usually found in CAIS, absence in the newborn period
does not exclude the diagnosis, Ahmed et al Arch Dis Child
1999.
Conclusions: AR mutations can be identified in many
patients with androgen insensitivity, but genetic abnormalities have not been identified in all. Testosterone levels may
be within normal limits after birth in CAIS. All females
with inguinal hernia especially with history of primary
amenorrhea may benefit from karyotype analysis.
Abstract #905
EFFECTS OF INTRATHECAL OPIOIDS ON
THE HYPOTHALAMIC-PITUITARY- GONADAL
AXIS IN A WOMAN WITH POLYCYSTIC OVARY
SYNDROME
sible advantage in efficacy of pain control compared to
oral opioids. The effects of oral and intrathecal opioids
on the hypothalamic-pituitary-gonadal axis have been
described in the literature as adverse effects. However,
here we describe a case of a woman with polycystic ovary
syndrome and chronic nonmalignant pain that required
the intermittent intrathecal administration of opioids and
demonstrate suppression of her hypothalamic-pituitarygonadal axis and improvement in her symptoms of hyperandrogenism during therapy that returned to baseline with
discontinuation of therapy.
Conclusion: This case illustrates the interesting effects
of intrathecal opioids, but also may provide insight into the
pathophysiology of polycystic ovary syndrome. This raises
intriguing questions about the role of the opioid system in
polycystic ovary syndrome, and demonstrates changes in
laboratory and clinical abnormalities with central disruption of the hypothalamic-pituitary-gonadal axis.
Abstract #906
Marideli Colón Scanlan, MD, and Alan Burshell, MD
Objective: Presentation of clinical and laboratory
data that demonstrate the suppressive effects of intrathecal opioids on the hypothalamic-pituitary-gonadal axis in a
woman with polycystic ovary syndrome.
Case Presentation: A 35 year-old woman with a history of vitiligo, Hashimoto’s thyroiditis, Stiff-person syndrome, and polycystic ovary syndrome had a testosterone
level of 100 ng/dL (treated with metformin) prior to requiring intrathecal opioids for her chronic pain. In 2001, she
began receiving intrathecal opioids, and her testosterone
level, as well as her estradiol, LH, and FSH levels became
undetectable (total testosterone <10 ng/dL, estradiol <10
pg/mL, LH <0.1mIU/mL, FSH <0.3 mIU/mL). Over the
next year, her levels became detectable, but remained low
(total testosterone 21.4 ng/dL, estradiol 27 pg/mL, LH was
not measured, FSH 1.4 mIU/mL). Later, as the dosage of
her intrathecal opioids decreased dramatically, the levels of
testosterone, estradiol, LH, and FSH increased (total testosterone 49 ng/dL, estradiol 61 pg/mL, LH 12 mIU/mL,
FSH 5.7 mIU/mL). When she discontinued the intrathecal
opioids, her levels returned to near baseline (testosterone
75 ng/dL, estradiol 86 pg/mL). The patient experienced
changes in her clinical symptoms of hyperandrogenism of
hirsutism and acne that accompanied these biochemical
changes.
Discussion: Opioids have long been used to treat
chronic nonmalignant pain, and the intrathecal route of
administration is being used as an alternative more often
due to the smaller dose needed, less expense, and a pos-
GIGANTOMASTIA: BENIGN CONDITION
IMPOSING RADICAL TREATMENT; CASE
REPORT
Simona Vasilica Fica, MD, PhD, Carmen Barbu,
Madalina Constantin, Dana Terzea, and Ioan Lascar
Objective: to report a case of gigantomastia, a rare
benign disorder of the breast, marked by an extremely sudden and homogeneous increase of breast volume with the
onset of puberty, leading to severe physical and psychological complications.
Case Presentation: a 13-year-old premenarchal girl,
with no previous medical history, was referred to our clinic
in July 2007 for excessive breast enlargement up to 100
cm in thoracic circumference, developed in less than 5
months, associated with inflammatory and necrotic skin
lesions. Juvenile bilateral gigantomastia was diagnosed
after extensive endocrine, immune and imagistic studies,
and treatment (progestin and non steroidal anti-inflammatory) was started.
After 3 months of follow up with continuous enlargement of breasts and extension of epithelial necrosis with
ulceration, the entire breast tissue was surgically removed;
subcutaneous mastectomy was done considering the high
rate of recurrence of gigantomastia reported after conservative surgery such as reduction mammaplasty.
The histological pattern (extensive stromal fibrosis,
ductal epithelium with moderate hyperplasia, and no acinus) is specific for gigantomastia and ruled out a malignant
disorder.
– 104 –
Immunohistochemical study showed positive reaction
for both estrogen and progesterone receptors in almost 90%
of epithelial cells and the presence of nuclear proliferation
factor Ki67 in both stromal and epithelial tissue.
Discussion: There was no particular hormone overproduction in our case. However, taking into account the
moment of the onset in our case, the role of the hormonal
milieu as the promoting event remains highly probable, as
well as the steroid receptor hypersensitivity suggested by
the immunohistochemical investigation.
There are some reported cases of inflammatory gigantomastia in a context of immune mediated diseases, outlining the relationship between the immunological factors
and the hormonal factors. In our case there were no clinical
signs of autoimmune disease or immune mediated condition, as well as no perilobular lymphocytic infiltrate.
Conclusion: Although the pathogenesis of this condition is still unknown, our case highlights the steroid
receptor hypersensitivity as an important mechanism in a
particular paracrine regulation between stromal and epithelial breast tissue, both of them Ki67 positive. Moreover, in
spite of the benign character of the disease, it needs radical
surgical treatment due to rapid and severe complications
and ineffectiveness of the antiestrogen therapy, as well as
the frequent recurrence reported after a simple reduction
mammaplasty.
– 105 –
ABSTRACTS – Thyroid Disease
The observed decline in LDL-C induced by levothyroxine, although a modest 5.75%, is significant in terms
of reduction for CAD (33). Furthermore, the increased
levels of LDL-C in non-treated SCH patients were mild
3% but reached statistical significance. The Helsinki
Heart Study has shown that only a 7% decrease in LDL-C
levels is associated with a 15% reduction in the incidence
of CAD(34). Physiological, TSH guided, levothyroxine
treatment should be initiated in SCH as it may reduce
morbidity and mortality in patients with this common
syndrome.
Conclusion: SCH has a negative impact on the lipoprotein profile in premenopausal women and may translate into a sizeable cardiovascular risk if untreated.
THYROID DISEASE
Abstract #1000
ATHEROGENIC LDL-C RISES IN UNTREATED
SUBCLINICAL HYPOTHYROIDISM
George Samir Mikhail, MBBCh, MSc,
Sameer Alshammari, MD, FRCPC,
Mohammed Alenezi, MD, FRCPC,
Maged Mansour, MD, PhD, and Nesreen Khalil, MSc
Objective: To evaluate the effects of physiological
doses of Levothyroxine replacement on the lipoprotein
profile in patients with SCH.
Methods: We used a prospective double blind, placebo controlled study design. We enrolled one hundred
and twenty patients with SCH mostly but not exclusively
premenopausal women. Patients were randomly assigned
to either a Levothyroxine treatment group (59 females
and one male age ranged 15-53yrs) or a placebo group
(59 females and one male age ranged 14-57). Total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDL-C) and
triglycerides (TG) were measured before and 52 weeks
after assignment to either group.
Results: In the Levothyroxine treatment group, TC
was 5.04±0.98 mmol/L before and 4.74±0.87 after treatment (P<0.0001), LDL-C was 3.30±0.90 mmol/L before
and 3.11±0.77 after treatment (P<0.01), TG was 1.18±0.71
mmol/L before and 0.95±0.53 after treatment (P<0.002)
and HDL-C was 1.20±0.33 and 1.19±0.32 (P=0.29) after
treatment. In the placebo group, TC values before and
after 52 weeks remained unchanged 4.99±0.72, 5.04±0.67
(P=0.16), HDL-C 1.15±0.23, 1.10±0.25 (P=0.88), TG
1.01±0.66, 1.06±0.59 (P=0.77) but LDL-C values rose
from 2.79±0.60 mmol/L to 2.89±0.59 reaching statistical
difference (P<0.016).
After 52 weeks we compared the mean values of TC,
LDL-C, HDL-C and TG in both groups of patients those
who received Thyroxine and of the control group. Total
cholesterol showed a significant difference (p<0.029 at
95% C.I.) while LDL-C showed a high significant difference (p<0.0001 at 95% C.I.) in thyroxine receiving group
to the control. The difference did not reach statistical significance in TG and HDL-C.
Discussion: We used a prospective double-blind,
placebo-controlled study design. Our patient selection
was those with no prior known thyroid disease, previous surgery or radiation therapy of thyroid gland which
indeed reflect the subset of patients that we address the
question of whether to treat or not.
Abstract #1001
IS THE SUGGESTED CHANGE OF THE
UPPER LIMIT OF THE TSH REFERENCE
RANGE FEASIBLE?
Rashid O. Al Jawair, MD,
Merill Edmonds, MD, FRCPC, FACP,
Irene Hramiak, MD, FRCPC, and
Sonya Tokmakejian, PhD, FCACB
Objectives: It has been proposed to lower the upper
limit of TSH from the conventional (presently 5.00 mIU/
L LHSC). We looked at the feasibility of the suggested
change.
Methods: We have looked at the distribution of TSH
in 190 students tested under well defined conditions.
Anti TPOAb were also measured when aliquots frozen at
-800C were available.
Results: There were 190 students age group 21-40
years old included in the study, 119 (62.6%) were males
and 71 (37.4%) were females. In individuals without a
history of thyroid disease the median TSH was 2.40mIU/
L and the percentile distribution from 2.5%-97.5% is
0.4-6.87mIU/L. We have excluded three students with
known thyroid disease in addition to two students who
were diagnosed to have thyroid disease based on the laboratory finding. Anti TPOAb was measured in 57(30%)
students. The anti TPOAb was positive (> 40U/ml) in
three students, The first subject has been on Thyroxine
supplement and the second unfortunately was measured
four years later and there was no follow up. The result of
the third subject was moderately increased which could
have been explained by gross hemolysis.
Conclusions: We concluded that changing TSH
upper limit reference cutoff to 2.5 or 3.5mIU/L is not feasible since about 50% or about 28% respectively of TSH
– 106 –
that a more aggressive approach to her management was
required. A thyroidectomy was performed and radioiodine ablation therapy was given to ablate the peritoneal
strumosis. Thyroid hormone suppressive therapy was
also initiated.
Conclusions: This is a report on a rare case of struma
ovarii with peritoneal strumosis. Aggressive management
with surgical excision of the lesions, radioiodine ablation
therapy, and thyroid hormone suppression therapy was
employed in spite of the benign pathology because of the
risk of an unrecognized low-grade malignancy and the
potential of malignant transformation.
levels will be classified as above normal. There is no evidence that starting these people on thyroid hormone will
have any benefit.
Abstract #1002
PERITONEAL STRUMOSIS: A CASE REPORT
Judith M Castillo-Perez, MD, Francisco Correa, MD,
Emmanuel Javier, MD
Objective: To report a striking case of peritoneal
strumosis.
Case Presentation: A 37 year-old female presented
with a two-month history of lower abdominal pain. MRI
study showed a left adnexal mass measuring 4.8x5.1x3.0
cm and a 12x6x6 cm mass in the mid pelvis. The TSH
was suppressed at 0.11uIU/mL with a normal free T4 of
1.33 ng/dl. She had no prior signs or symptoms of thyroid disease. On physical examination the thyroid was not
enlarged, with no palpable nodules. The remainder of her
examination was within normal limits. At age 28 y, she
had a left ovarian cystectomy for a benign serous cystadenoma. At age 32 y, she had a right ovarian teratoma
removed.
A TAH-BSO was performed and several peritoneal
implants were also excised. Pathology of the right ovary
showed mature cystic teratoma composed exclusively
of benign thyroid tissue consistent with struma ovarii.
Peritoneal and recto-sigmoid implants were compatible
with strumosis. The left ovary showed multiple cysts
with no thyroid tissue present. Post-surgery, a wholebody iodine scan demonstrated focal areas of increased
uptake in the abdomen and pelvis. An FDG-PET/CT
performed showed non-FDG-avid, multiple abdominal
subcutaneous and intraperitoneal nodules. Total thyroidectomy was done and pathology revealed focal chronic
lymphocytic thyroiditis without evidence of malignancy.
She later received 148 mCi of I131 to ablate the remaining strumosis. She is now on thyroid hormone suppressive therapy.
Discussion: Struma ovarii occurs in about 2% of
mature cystic teratomas. Peritoneal strumosis denotes
presence of thyroid tissue in the peritoneal cavity, and is
rare. Patients usually present with signs and symptoms
related to a pelvic tumor and rarely present with hyperthyroidism. This patient has a benign struma ovarii with
benign peritoneal strumosis. However, the presence of a
well-differentiated follicular carcinoma with metastatic
peritoneal lesions cannot be completely ruled out. The
risk of malignant transformation of benign struma ovarii
has also been reported. With this possibility, we decided
Abstract #1003
MULTIDISCIPLINARY MANAGEMENT
OF METASTATIC PAPILLARY THYROID
CARCINOMA ARISING FROM MALIGNANT
STRUMA OVARII
Maeve Elizabeth Hutchinson, MBBCh, BAO,
Ian D. Hay, MD, PhD, FACE, FACP, FRCP,
Keith C. Bible, MD, PhD, Clive S Grant, MD,
Geoffrey B Thompson, MD, and William F Young Jr, MD
Objective: To describe 3 patients with malignant
struma ovarii (MSO) managed via a multidisciplinary
approach and followed for a combined period of 48 postoperative years.
Case 1: A 46 year old woman in 1983 underwent
ovarian resection for MSO. Five years later, diffuse lung
metastases were noted and biopsy confirmed papillary
thyroid cancer (PTC). Total thyroidectomy on her normal gland was performed, followed by radioactive iodine
(RAI) treatment—cumulative I-131 dosage to date is 1200
mCi. The lungs remain the only metastatic site. Chest
X-ray and serum thyroglobulin (Tg) levels are stable on
levothyroxine (T4) treatment. Suppressed Tg in 1996 was
74.7ng/mL and 94ng/mL in 2007; TSH-stimulated Tg
was 618ng/mL in 1996 and 549ng/mL in 2007. Despite
persistent lung metastases at 24 postoperative years, she
remains asymptomatic and desires no more RAI therapy.
Case 2: A 28 year old woman in 1995 had, at salpingo-oophorectomy (SPO), a 13-cm ovarian mass;
pathology showed PTC arising from MSO. In 2001 she
developed abdominal fullness and a right ovarian tumor.
Total abdominal hysterectomy, right SPO, appendectomy
and omentectomy were performed, showing MSO with
PTC involving all biopsied organs and 13 lymph nodes.
Rapidly recurrent disease postoperatively prompted thyroidectomy. Post-thyroidectomy, TSH-stimulated Tg was
42,000ng/mL. She was treated with a cumulative dose of
– 107 –
950mCi I-131 and aggressive interposed abdominal debulking surgery. The patient is now 13 years postoperative,
with negative whole body I-131 scintigraphy, FDG-PET
and abdominal CT scans. Tg on a suppressive dose of T4
is 1.2ng/mL.
Case 3: A 46 year old woman presented with thyrotoxicosis; I-131 uptake occurred in her goiter, mediastinum, and bilateral chest. CT suggested widespread
metastases. Subsequent evaluation verified metastatic
PTC originating in MSO with peritoneal carcinomatosis
plus pleural space and mediastinal disease. Seven years
before, she was treated for an ovarian tumor; re-evaluation of pathology revealed PTC in MSO. Thyroidectomy
was performed—confirming Graves’ disease without
intra-thyroidal PTC. Following surgical debulking of
intra-abdominal and thoracic deposits her Tg was 249ng/
mL. Subsequently, she was treated with a total of 450mCi
I-131 and T4 replacement. Eleven years following her
first surgery there is no clinical evidence of PTC and her
FDG-PET-CT scan is negative. Tg on a suppressive dose
of T4 is 0.2ng/ml.
Conclusion: MSO is both rare and challenging.
Patients with MSO can receive sustained benefit from
a considered and multidisciplinary approach. The coexistence of MSO and Graves’ disease is unique to our
knowledge and further complicated the management.
IU/L (30-235), TPO antibodies > 1000.0 IU/ml (0.0-3.9),
Thyroid Stimulating Immunoglobulins (TSI) 54% (positive if >16%). Electrocardiogram showed atrial flutter
with a rate of 117 beats/ minute.
She was diagnosed with TPP based on her clinical
presentation and laboratory findings of thyrotoxicosis.
She was treated with intravenous potassium and intravenous then oral propranolol. Her symptoms improved
within four hours and she was able to walk eight hours
after admission. Thyroid uptake and scan showed a
homogenously enlarged thyroid gland with elevated I123 uptake of 78.2% and 79.3 % at 5 and 24 hours respectively. She was then treated with 19.1 mCi of I-131 and
was discharged on oral propranolol. On follow-up visit
two weeks later, she had no further episodes of weakness.
TSH was 0.02 uIU/ml (0.35-5.5), free T4 was 1.43ng/dl
(0.58-1.64), serum potassium was normal at 4.1 mEq/ml
and we continued her propranolol.
Discussion: TPP is a well-known complication
of thyrotoxicosis in Asian populations, predominantly
affecting males. Only sporadic cases of TPP have been
reported in other non-Asian populations, and it is rarely
reported in Hispanic females. Paralysis is caused by severe
hypokalemia that is a result of sudden intracellular shifting of potassium and is not due to potassium deficiency.
Propranolol blocks the intracellular shifting of potassium
and thus is important in treating and preventing the recurrence of TPP. However, treating the underlying cause for
hyperthyroidism is the definitive treatment for TPP.
Conclusion: TPP should be considered in the differential diagnosis of weakness in female and male patients
of all races. Our case represents a rare occurrence of TPP
diagnosed in a Hispanic female.
Abstract #1004
THYROTOXIC PERIODIC PARALYSIS
Hussam H. Alhawari, MD, Debra L. Simmons, MD,
Fred H. Faas, MD, and Antoine Makdissi, MD
Objective: To present a case of young Hispanic
female who presented with generalized weakness and
severe hypokalemia. She was later diagnosed with thyrotoxic periodic paralysis (TPP) in the setting of Graves’
disease.
Case: A 21-year-old previously healthy Hispanic
woman presented with a two-day history of recurrent
transient episodes of generalized weakness lasting few
hours. Her weakness was so profound such that she was
unable to walk. The patient also complained of nausea,
palpitations, and excessive sweating. On examination,
she appeared anxious, had diffuse thyroid enlargement,
tachycardia, motor strength of one out of five in both
upper and lower extremities and absent deep tendon
reflexes. Serum potassium was less than 1.0 mEq/ml,
phosphorus 2.2mg/dl (2.5-4.5), magnesium 1.7mg/dl
(1.8-2.9), TSH 0.01 uIU/ml (0.35-5.5), T4 total 18.3
mcg/dl (4.5-10.9), T3 total 3.4ng/ml (0.6-1.8), CK 139
Abstract #1005
THYROGLOSSAL DUCT REMNANT:
EXPERIENCES AT A TERTIARY CARE CENTRE
Rafif Farhat, MD, Fatima Al-Zidjali,
and Asma Tulbah, MD
Objective: To define the clinical features, the natural
history & the management of thyroglossal duct remnant
(TGDR) during a 28-year period at a tertiary care center.
Case presentation: 16 pts.were treated for TGDR
between 1979 to 2006. Their case records, diagnostic
procedures undertaken, the histopathological & followup (FU) data were reviewed. Results: There were 10
males & 6 females, aged 2-43 yrs (mean 12.2). All pts.
– 108 –
presented with non-tender midline upper neck swelling, 5
had draining sinuses. All cases were diagnosed clinically;
however, ultrasound was needed to confirm the diagnosis
in 3 cases. I 123 thyroid scan was done in 7 pts. MRI/CT
were done in 3 pts. None of imaging procedures helped
differentiate simple cysts versus those harboring malignancy. All pts. underwent Sistrunk procedure. TG sinuses
were associated with recurrence in 3 pts. that required
repeated excision.5 pts. (31%: 4 females/1 male, aged 830 years) had papillary thyroid carcinoma (PTC) of the
TG duct that was diagnosed after Sistrunk surgery. Pts.
were followed up to 10 years. TT (total thyroidectomy)/
bilateral neck dissection (BND) was done in 4 pts. followed by I 131 Rx for ablation of postop remnant. Three
of these pts. are in remission, & the oldest pt. aged 30
years had recurrence requiring a 2nd surgery. The latter
had 1.5 cm PTC in the cyst, had invasion of the neck
muscles & the thyroid gland was free of cancer at the
initial TT & BND. At re-exploration, lymph nodes were
positive for carcinoma. Pt. received I 131. At 20 months
FU, she is in remission.
Discussion: TGDRs manifesting as midline cystic
neck swellings represent a developmental anomaly of
thyroid. TGDR carcinoma is found in about 1% of the
lesions. The Dx of carcinoma is seldom made preoperatively. The cysts are usually asymptomatic & the presentation of pts. with carcinoma is indistinguishable from the
simple cyst. Sistrunk surgery is the treatment of choice. It
consists of removal of the cyst, middle part of hyoid bone
& the TG duct. Following appropriate Rx long term survival of pts. with TGDR carcinoma is excellent in majority cases.
Conclusion: The possibility of TGD carcinoma
should be entertained in pts. with TGDR Thyroid US,
radioiodine scan, CT/MR imaging cannot reliably
exclude the presence of carcinoma. PTC is the commonest malignancy in TGDR. The frequency of PTC was
very high (31%) in our series. An occasional pt. operated
at a later age may have an aggressive course with recurrence. Excision of the cyst at an early age is therefore recommended to facilitate the Dx of underlying malignancy
in the cyst, & also to prevent other complications such as
infection, & sinus formation.
Abstract #1006
RETROSPECTIVE STUDY OF RADIOACTIVE
IODINE TREATMENT OF HYPERTHYROIDISM
Jennifer Carter Wheaton, DO, Abid Yaqub, MD,
Imran Choudhry, MD, and Bina Jain, MD
Objective: To determine the incidence of hypothyroidism following radioactive iodine (RAI) treatment for
hyperthyroidism and to study the relationship between
pretreatment RAI uptake and treatment dose and the subsequent development of hypothyroidism.
Methods: Retrospective chart review of patients
treated with RAI for hyperthyroidism between 1995 and
2000. 180 charts were reviewed but 41 met the inclusion
criteria. Data was collected regarding the cause of hyperthyroidism, initial RAI uptake, initial dose of RAI, number of RAI treatments, and post treatment thyroid status.
Results: 70% of patients with Graves’ disease
became hypothyroid after their first RAI treatment, 22%
had recurrent or persistent hyperthyroidism, and 7%
remained euthyroid. 45% of patients with toxic multinodular goiter developed hypothyroidism, 18% had
recurrent or persistent hyperthyroidism, 27% remained
euthyroid, and 9% had transient hypothyroidism. None
of the patients with toxic adenoma became hypothyroid.
There was no relationship between the dose of RAI or
pretreatment RAI uptake and the likelihood of developing hypothyroidism.
Discussion: A recognized consequence of RAI ablation is possible permanent hypothyroidism. Our study
showed a relatively higher incidence of hypothyroidism
following RAI treatment for hyperthyroidism as compared to previously published studies. However, consistent with other reported studies, we also found a relatively greater proportion of patients with Graves’ disease
developing post-ablative hypothyroidism in comparison
to those with toxic nodular goiters.
Conclusion: Within this study, post-ablative hypothyroidism was more prevalent in Graves’ disease than
in toxic nodular goiters. Neither the magnitude of the
administered dose nor the pretreatment RAI uptake predicted the development of hypothyroidism.
– 109 –
of age. Simultaneous occurrence of MTC and PTC in the
same thyroid is rare. Somatic mutations in tumor suppressor genes and oncogenes were described in PTC, which
include RET. The inherited RET mutation may predispose to other malignancies.
Conclusion: Simultaneous occurrence of MTC and
PTC is a rare phenomenon; only two cases have been
reported in MEN 2A patients. However, MTC and microPTC association may be more frequent as originally
thought.
Abstract #1007
RECURRENT MEDULLARY AND
SIMULTANEOUS MICRO-PAPILLARY
THYROID CARCINOMA
Suzette Adele Robinson, MBBS,
Nandalal Bagchi, MD, PhD, and
Abdul Abou-Samra, MD, PhD
Objective: To report a MEN2A case of recurrent
medullary thyroid carcinoma (MTC) and a simultaneous
micro- papillary thyroid carcinoma (PTC).
Case Presentation: This is a 47 y old African
American female with elevated parathyroid hormone
(PTH), a history of hemithyroidectomy for thyroid cancer at age 13 and left adrenalectomy at age 31 (details of
surgeries unavailable). No family history for parathyroid,
thyroid and adrenal diseases. Examination was significant for a 2cm left thyroid nodule. PTH was 109 pg/ml
(7-53); Ca 11.7 mg/dl (8.2-10.6); Alb 3.5 g/dl (3.5-5.3);
Mg 1.9 mg/dl (1.6-3.0); Phos 3.2 mg/dl (2.3-5.0); 25-OH
vitamin D 7 ng/ml (20-47); Calcitonin 529 pg/ml (0.04.6); Plasma free Metanephrine 1.65 and 2.73 nmol/L
(0.0-0.49); Normetanephrine 4.22 and 4.66 nmol/L
(< 0.90) and CEA 33.1 ng/ml (0.0-3.0). Ultrasound
revealed a left thyroid lobe with two nodules; the largest
was 2.5 x 1.8 cm with calcifications, hypo and hyperechogenecity. FNA cytology: single and cluster cells; most
were plasmacytoid with granular cytoplasm, multinucleated with salt and pepper nuclear chromatin appearance,
and reactive with calcitonin antiserum. Abdominal MRI
showed a right 3.8 x 2.4 cm adrenal mass consistent with
a pheochromocytoma; no local or distant metastases. The
patient was prepared with a and b blockers and had right
adrenalectomy followed by thyroidectomy on the next
day. Pathology confirmed the right pheochromocytoma
and the medullary thyroid carcinoma. In addition, a 0.5 cm
PTC, follicular variant was present in the thyroid specimen. Central node biopsy was significant for a 0.3 cm
focus of medullary carcinoma seen within an involuted
thymus tissue; it was not possible to distinguish extra thyroid extension from metastasis. Patient was discharged on
prednisone, florinef and synthroid. RET proto- oncogene
Cys634Arg mutation at exon 11 was identified.
Discussion: MTC is rare accounting for 3-10%
of thyroid cancer. Hereditary forms, such as MEN2A,
accounts for only 15% of all MTC, occurs at younger
age, and is caused by an activating mutation in the retinoblastoma proto-oncogene (RET). Somatic RET mutations are also found in 50% of sporadic MTC. MEN2A
carriers usually develop bilateral MTC before 10 years
Abstract #1008
SIGNIFICANCE OF CRP LEVEL RISE IN
PATIENTS WITH SUB-ACUTE THYROIDITIS
AND ITS ROLE IN PREDICTING THE NEED
FOR GLUCOCORTICOID THERAPY
Manash Pratim Baruah, MD, and
Sonali Barman Bhuyan
Objective: This study was aimed to find the significance of C-reactive protein (CRP) level rise in patients
with sub-acute thyroiditis (SAT) and examine what level
(of CRP) warrants the need for initiating Glucocorticoid
therapy.
Methods: CRP levels were measured in twenty-nine
study subjects (12 Male, 17 Female, mean age 38.1 ± 8.6
year) with SAT and 19 patients with Graves’ disease (2
Male, 17 Female, mean age 36.8 ± 16.5 year) as controls at
initial presentation. Erythrocyte sedimentation rate (ESR)
was measured in all thirty patients with SAT by Westergren
method. High resolution ultrasonography(HRUSG) was
performed in 14 patients with SAT whereas thyroid scan
was performed in 15 patients. Thyroid FNAC was performed in 11 patients. Sixteen patients with SAT received
glucocorticoid therapy.
Results: Elevated CRP level (cut off 5mg/dL) was
seen in 18(62%) patients with SAT with a mean CRP
level of 32.95 ± 4.17 mg/dL. However, all patients had
normal CRP level in the control group with a mean CRP
level of 4.09 ± 0.56 mg/dL. Median CRP level amongst
the patients with SAT was 10.2 mg/dL. ESR was high
amongst SAT patients (68.3 ± 4.11) mm after first hour
(Westergren) and significantly correlated to that of CRP
level (p<0.02). Glucocorticoid had to be initiated in
16(55%) patients of SAT, as they were showing no relief
even after adequate usage of non-steroidal anti-inflammatory drugs (NSAID) at least for one week. Mean CRP levels amongst patients requiring glucocorticoid was 50.62
± 4.82 mg/dL (median value 47.15 mg/dL) compared to
11.2 ± 1.54 mg/dL amongst those not requiring glucocor– 110 –
A women and this effect was manifested in the first 3
months after delivery. These data suggested that clinically significant numbers of women with HT have further exacerbation of their hypothyroidism after childbirth
compared to nulliparous women. The mechanism of this
decreased thyroid reserve requires further delineation
but is likely to be similar to the enhanced thyroid cell
apoptosis observed with transient post partum thyroiditis
which in itself is a transient form of Hashimoto’s thyroiditis. However, in this category of patients the thyroid cell
damage is usually permanent.
ticoid (p<0.02) in patients with SAT. Discussion: CRP,
which is a marker of inflammation, has not been widely
studied in inflammatory thyroid disorders particularly
in SAT. Glucocorticoid therapy is widely used to alleviate symptoms in patients with SAT. Our study is first of
its kind comparing CRP levels in two major etiological
groups of thyrotoxicosis. Moreover no previous study has
prospectively tried to ascertain at what level of CRP steroid may be considered mandatory.
Conclusion: The rise of CRP level in patients with
SAT is statistically significant (p<0.02) compared to controls and correlates well with the rise in ESR. Moreover,
it can guide in instituting glucocorticoid therapy who fails
to respond after NSAID therapy.
Abstract #1010
SKULL BASE METASTASIS:
PRESENTING FEATURE OF
DIFFERENTIATED THYROID CANCER
Abstract #1009
PREGNANCY ACCELERATES THYROID
FAILURE IN HASHIMOTO’S THYROIDITIS
Ahmed Nazmi, MD, Mohammed Al-Harthy, MD,
Imaduddin Kanaan, MD, and Hindi Al-Hindi, MD
Terry F. Davies, MD, FRCP, FACE, Richard Haber,
and Juan C. Galofre
Objectives: To characterize salient features of skull
base metastasis(SBM) from papillary thyroid cancer
(PTC),outline the diagnostic strategies,& propose rational Rx guidelines.
Case Presentation: A 47-yr man presented to
Neurosurgical service with 5 mos. hx of headache, and
diplopia due to 6th cranial nerve paralysis. CT Skull
revealed a large expansile osteolytic lesion at rt. skull
base that had eroded the central clivus, middle cranial
fossa, rt. pertous apex, extended into the intracranial
cavity centrally into the prepontine cistern & rt. cerebropontine angle. A dx of clival chordoma was made & pt.
underwent transsphenoidal debulking; histopathological
Dx: metastatic papillary thyroid carcinoma (PTC), immunostains were positive for thyroglobulin (TG), & thyroid
transcription factor1.At our examination a lt. thyroid
nodule was detected. FNA Dx: PTC. Seven yrs. ago pt.
had undergone thyroid surgery at an outside hospital; no
information could be tracked down. Neck/Chest CT:7mm
hypodense lesion lt. thyroid lobe/multiple bilateral pulmonary nodules, right. mediastinal lesion, a 4x4x4.5 cm
large right. posterior apical paravertebral pleural mass
causing 3rd rib destruction & lytic lesions of the rt. 7th
rib & T2 vertebra were detected. I123 whole body scan:
intense uptake (15%) left thyroid bed, skull base, lungs,
mediastinum multiple skeletal foci (right ribs, 4th lumbar
vertebra, left. femur iliac bone), TG >5000 ug/l, TSH 4.8
mU/l, TG antibodies 64 u/ml.Pt. underwent completion
thyroidectomty. Histopath: PTC lt. thyroid lobe, multiple soft tissue & lymph nodes deposits of PTC. Postop
Objective: Clinical manifestations of autoimmune
thyroid disease are common in the postpartum period
and are considered secondary to the immune suppression
which occurs in pregnancy. We hypothesized that patients
with established Hashimoto’s thyroiditis (HT) should also
experience an exacerbation in the post partum with further impairment of thyroid function. Such clinical exacerbations would be revealed by a long term increase in
the need for LT4 supplementation in the postpartum when
compared with the pre-pregnancy dose.
Methods: We performed a retrospective study
review of 38 unselected pregnant women with HT, aged
20-45 years. Of these women, 26 were euthyroid (TSH
<4.5uU/ml) prior to pregnancy with a mean ± SD initial
TSH of 2.1±1.0 uU/ml (Group A). We also reviewed 32
age-matched non-pregnant women with HT as controls
and a mean initial TSH of 1.8±1.0 uU/ml (Group B). In
Group A we measured the total LT4 supplementation
(mg) taken during the 9 months before pregnancy (TS-1)
and then the 9 months after pregnancy (TS-2). Similarly,
in Group B we measured the total LT4 supplementation
(mg) consumed during two 9 month periods (TS-1 and
TS-2) separated by an intermediate 9 months. The mean
LT4 amounts (TS-1 and TS-2) were compared in the two
groups using Student-t testing: Group A: TS-1: 23.5 ±
13.2; TS-2: 26.6 ±12.9 (p<0.01). Group B: TS-1: 25.2 ±
11.4; TS-2: 26.3 ±11.8 (p=ns).
Results: Pregnancy induced a long-term 15%
increase in LT4 requirements in the postpartum of Group
– 111 –
pt. received I 131 x 2 using thyrogen (cumulative dose
510 mCi) under cover of steroids (because of intracranial
mets.) for persistent uptake of I131 in skull base, bones &
lungs. External beam radiation (XBR) to brain & mediastinum was given. Follow-up TG 889/TSH 119. Pt. is
alive & fully functional at 15 months FU.
Discussion: Skull base metastasis from differentiated
thyroid cancer (DTC) is rare; only 20 cases are reported
till 7/2007. There is no clear consensus on management
strategy for SBM from DTC. The reported overall survival ranged from < a yr. to > 10 yrs. from the detection
of metastasis. Our case is unique because of extensive
erosion of the skull base & the surrounding structures.
It represented part of disseminated metastases involving
lungs, mediastinum & skeletal system.
Conclusions: Metastasis from DTC needs to be
considered in the differential Dx of destructive skull base
lesions. Histopatholigical confirmation is mandatory followed by debulking of skull base metastasis, total thyroidectomy, radioiodine, external beam radiation & longterm TSH suppression.
Discussion: Painless thyroiditis is a self-limited disease typically associated with an abrupt onset of hyperthyroidism. The thyrotoxicosis is usually mild and is due
to inflammatory mediated damage of thyroid follicles
with subsequent release of preformed thyroid hormone. It is associated with low radioactive iodine uptake, and
the diagnosis can be confirmed by biopsy revealing diffuse lymphocytic infiltration. The ESR and WBC count
are elevated in approximately half of affected patients. The etiology is thought to involve an autoimmune process, but the precise mechanism remains unclear. There
is developing interest in the possibility that painless thyroiditis is mediated by cytokines released in response
to infection or subclinical injury. The temporal relation
between symptom onset and immunization, coupled with
the absence of antecedent infection leads us to believe
that the influenza vaccine was the inciting factor in our
patient’s thyroiditis. There is a case report in Taiwan
attributing subacute thyroiditis in a 25-year-old female
to the influenza vaccine she received two days prior to
symptom onset, but this is the first report in the United
States postulating that the influenza vaccine appears to be
responsible for a case of thyroiditis.
Conclusion: We bring this case to the attention of
medical practitioners because it is the first reported case
in the U.S. speculating a link between the influenza vaccine and thyroiditis. Certainly, even a strong temporal
relationship does not equate to an absolute cause and
effect, and more research is needed to elucidate the exact
mechanism of painless thyroiditis.
Abstract #1011
WORSE THAN THE FLU? THE INFLUENZA
VACCINE AS A POSSIBLE CAUSE OF
PAINLESS THYROIDITIS
Rob Ennis, MD, and
Hossein Gharib, MD, MACP, MACE
Objective: To report a case of painless thyroiditis
presumably caused by the influenza vaccine.
Case Presentation: A previously healthy 51-yearold male presented to our institution with a 3 week history of fatigue, subjective fever, and sweats. He dated
the onset of symptoms to 1-2 days after receiving his first
ever influenza vaccine. The initial evaluation suggested
primary hyperthyroidism with suppressed TSH (0.01
mIU/L; normal 0.3- 5.0 mIU/L), elevated FT4 (3.3 ng/
dL; nl. 0.8-1.8 ng/dL) and T3 (228 ng/dL; nl. 80-190 ng/
dL). The ESR was also elevated (60 mm/hr; normal 0-22
mm/hr). He was subsequently referred to Endocrinology. He denied upper respiratory symptoms and neck pain. On exam, his thyroid was not tender or nodular but
was slightly enlarged and diffusely firm. A four hour
RAIU scan revealed suppressed uptake at 0.2%. These
findings were consistent with painless thyroiditis, and the
temporal relation between symptom onset and vaccination strongly support the notion that the influenza vaccine
was responsible for his thyroiditis.
Abstract #1012
INTERFERON-β INDUCED GRAVES’ DISEASE
IN A PATIENT WITH MULTIPLE SCLEROSIS
Harpreet Singh Bajaj, MD, and
Robert Zimmerman, MD, FACE
Objective: We report a case of a patient with
Multiple Sclerosis (MS) who developed Graves’ disease
after Interferon-β (IFN-β) treatment. This case supports
the theory that IFN-β can induce Thyroid Stimulating
Immunoglobulins (TSIs) in high-risk patients and depicts
a clear transformation of a normal Radioactive Iodine
(RAI) study prior to therapy to one of classic Graves’
after initiation of IFN-β treatment.
Case presentation: An 18 year old female with
relapsing-remitting MS was referred to Endocrinology
clinic for evaluation of abnormal thyroid function tests
(TFTs) and fatigue before initiation of IFN-β therapy. She
– 112 –
denied other hyperthyroid symptoms. Her TSH was low
at 0.15 uU/mL (normal 0.4-5.5 uU/ml) with a normal free
T4 and free T3 at 1.2 ng/dl (0.7-1.8 ng/dl) and 3.5 pg/ml
(1.8-4.6 pg/ml) respectively. Her TSIs were just above
normal at 158% (normal 70-150 %). A RAI study demonstrated normal, homogeneous 24-hour uptake of 18.4%
(normal 5-25%) in her thyroid gland. She was cleared for
IFN-β treatment with close follow-up. Three weeks after
the initiation of IFN-β, the patient was still clinically and
biochemically euthyroid. By three months of therapy, she
had lost 7 pounds and was complaining of palpitations,
sweating and dizziness. Her repeat TFTs were clearly in
the thyrotoxic range (TSH 0.008, Free T4 3.1 and Free
T3 15.1) and TSIs had increased significantly to 5156 %.
A repeat RAI study demonstrated an increased, homogenous 24 hour uptake of 47.3%. Hence, a diagnosis of
IFN-β induced Graves’ disease was made and anti-thyroid treatment was started.
Discussion: Thyroid dysfunction has been reported
in about one-fourth of MS patients treated with IFN-β,
most often occurring within the first year of treatment.
Hypothyroidism is the most common manifestation followed by IFN-β induced thyroiditis. Graves’ is a rare
cause of hyperthyroidism in this population and can be
differentiated from thyroiditis by measuring TSIs or RAI
uptake, as done in this case. Multiple studies substantiate
the usefulness of baseline anti-thyroid antibody levels as
the strongest predictive factor for future thyroid dysfunction development in IFN-β treated patients.
Conclusion: This case demonstrates the benefits of
screening for anti-thyroid antibodies before initiation of
IFN-β therapy and of rigorous monitoring of high-risk
patients during this treatment. With increasing usage of
IFN-β and other such biologic agents, there is a greater
need for endocrinologists to be aware of hormonal
complications associated with these medications and to
understand the pathophysiology, investigation and treatment options for such complications.
Case Presentation: This case presentation identifies a 62 year-old black female with a history of hypothyroidism who presented to an ophthalmologist with
left unilateral proptosis. Subsequent MRI demonstrated
a 5x5 cm lesion in the left frontal lobe extending into
the left orbit. She was admitted for planned resection of
suspected meningioma. After mass resection via craniotomy, initial pathology was most consistent with metastatic disease, and a primary malignancy was sought. Hypodensities of the thyroid gland were noted during CT
scan, and subsequent thyroid ultrasound revealed a mass
lesion in the left thyroid bed. Final pathology of the intracranial lesion identified a well-differentiated follicular
thyroid carcinoma. This patient interestingly reported a
left hemithyroidectomy twelve years prior secondary to a
symptomatic goiter. Pathology at that time was negative
for malignancy. Additionally, this patient had labwork
that was consistent with primary hyperparathyroidism. As there have been some reported cases of parathyroidhormone-secreting papillary thyroid cancers, tissue from
the meatstatic lesion was stained for parathyroid hormone. Stain for parathyroid hormone, however, was negative. This patient had completion thyroidectomy with concominant parathyroidectomy, yielding appropriate resolution
of hypercalcemia. She is currently awaiting radioactive
iodine ablative therapy.
Discussion: Follicular thyroid carcinoma is the second most common type of thyroid cancer after papillary
thyroid cancer. This well-differentiated tumor of the thyroid epithelium may represent up to thirteen percent of
all thyroid cancers. These typically present as nodules
within the thyroid. Metastatic disease at presentation
uncommon, representing only seven percent of cases of
follicular thyroid carcinoma. The large retro-orbital mass
seen in this case represented a solitary metastatic focus. Such presentation is rare, though there have been a few
reports of similar. This particular cancer may spread
through hematogenous dissemination and has a predilection for metastasis to bone and lung. The skull is often
among bony sites to which this disease can spread, and
such appears to be the case with this patient.
Conclusion: This presentation should serve as evidence to consider spread of malignancy such as follicular
thyroid carcinoma in the differential diagnosis of a patient
presenting with findings suggestive of retro-orbital mass
effect.
Abstract #1013
FOLLICULAR THYROID CARCINOMA
PRESENTING AS UNILATERAL PROPTOSIS
Ben Williamson Seale, MD, and William Nicholas, MD
Objective: To demonstrate an atypical presentation of follicular thyroid carcinoma, such that this diagnosis may be considered in future patients with similar
presentation.
– 113 –
EUTHYROID GRAVE’S OPTHALMOPATHY: A
CASE REPORT
cedes the hyperthyroidism in 20 % of cases, patients with
apparent euthyroid graves opthalmopathy should be followed over a period of time to detect hyperthyroidism at
an early stage and to prevent complications.
Anne Marie Van Hoven, MD, and Saima Khan, MD
Abstract #1015
Abstract #1014
Objective: To discuss a case of Grave’s Ophthalmopathy
in a euthyroid patient.
Case Presentation: A 63 year old female with past
medical history of hypertension presented with complaints of periorbital swelling and blurring of vision for
2weeks. It was associated with excessive tearing, redness
and discomfort but no pain. It was not associated with
double vision. On examination she had periorbital and
conjunctival edema and injection, normal extra ocular
movements, no nystagmus, no diplopia on extremes of
gaze, no lid lag, stare or proptosis, normal fundi and thyroid examination. Labs showed normal kidney and liver
function, TSH 0.812, free T4 0.9, total T4 5.8, total T3
113. TSI was checked and it was found to be positive.
MRI head showed changes consistent with graves orbitopathy. Diagnosis of euthyroid graves orbitopathy was
made and patient was started on steroids and significant
improvement was seen within a month. At 6 months follow up, patient remained asymptomatic and thyroid functions remained normal.
Discussion: Graves’s ophthalmopathy occurs in
25% - 50% of patients with Graves Hyperthyroidism.
Euthyroid Graves ophthalmopathy is much less common,
occurring in approximately 10% of patients with Graves
ophthalmopathy (1).The initial activation of T cells in
Graves’ ophthalmopathy is thought to be initiated by thyrotropin (TSH) receptor antigen. TSH receptor antibodies,
and not just T cells, may play an important role in the eye
disease by activating fibroblast and adipocyte TSH receptors. The volume of both the extra ocular muscles and
retro orbital connective and adipose tissue is increased,
due to inflammation and the accumulation of hydrophilic
glycosaminoglycans. GAG secretion by fibroblasts is
increased by activated T-cell cytokines. Risk factors for
the development of Graves’ ophthalmopathy include
genetics, female sex, smoking, and possibly radioiodine
therapy. Ophthalmopathy appears before the onset of
hyperthyroidism in approximately 20 percent of patients,
concurrently in about 40 percent, in the six months after
diagnosis in about 20 percent, and after treatment for
Graves’ hyperthyroidism in the remainder (most commonly after radioiodine therapy).
Conclusion: Grave’s Opthalmopathy may occur
even in the absence of hyperthyroidism and therefore
may be difficult to diagnose. Since ophthalmopathy pre-
RECURRENT SILENT THYROIDITIS
Monica Agarwal, MD, Debra L. Simmons, MD,
and Antonie Makdissi
Objective: Recurrent silent thyroiditis is an unusual
event in an uncommon disease. We present a rare case of
silent thyroiditis with recurrence after 12 years.
Case: 42 year-old Caucasian man presented in 1995
with fatigue and palpitations. He had a family history of
hypothyroidism. The thyroid was not tender. TSH was
0.00 mIU/dL (0.4 – 6) with total T4 of 17.2 ug/dL (4.5 11.5). The 24-hour radioactive iodine uptake (RAIU) was
2%. He was diagnosed with silent thyroiditis. The RAIU
three months later was 16%. Patient did not require thyroxine. In 2002, patient was admitted with atrial fibrillation. His TSH was 2.72 mIU/dL and total T4 was 10.7 ug/
dL. In 2007, he presented with fatigue. The thyroid was
nonpalpable. TSH was 0.01 mIU/dL, total T4 17.6 ug/dL
and thyroid peroxidase antibodies (TPO) were 103 IU/mL
(0-60). The thyroid uptake and scan showed normal size
thyroid with uptake of 1.7% (5-15%) at 24 hours. Thyroid
ultrasound showed hypoechogenic thyroid gland. The 24
hour urine iodine was 227 ug/L (42-350) and whole body
scan was negative for ectopic thyroid tissue. Two months
later the patient became clinically hypothyroid. The TSH
was 41 mIU/dL (0.4 -5.5). Hormone replacement was
initiated, but tapered off by four months. The TSH was
3.7 mIU/dL and 4.4mIU/dL at two and three months after
discontinuation of synthroid.
Discussion: Silent thyroiditis (or painless subacute
lymphocytic) is one of the variants of painless thyroiditis.
Others include Hashimoto’s (or chronic lymphocytic),
drug-induced and postpartum thyroiditis. It is characterized by thyrotoxicosis associated with depressed values
of the RAIU in the absence of excess body iodide stores.
There is lack of a viral prodrome and tenderness in the
thyroid bed. About 50% of patients have TPO antibodies.
Following the thyrotoxic phase, there is a transient euthyroid phase then a hypothyroid phase before a long-term
return to euthyroidism. Patients can be treated symptomatically with beta-blockers in the thyrotoxic phase. The literature discussing recurrence has been scarce and limited
to case reports and series. To our knowledge, there have
been only three cases where the recurrence has occurred
– 114 –
over a span longer than 12 years. Repeated recurrences
may need a more definitive treatment such as treatment
with I131 or thyroidectomy. The constellation of clinical,
biochemical and imaging data in our patient support at
least two episodes of silent thyroiditis 12 years apart.
Conclusion: Silent thyroiditis is normally a selflimited and nonrecurring disease. This is a rare case of
recurrent silent thyroiditis with at least two episodes 12
years apart.
ter size and low iodine uptake. On the other hand, age,
presence of multiple chronic diseases, polypharmacy,
and poor medication compliance underscores the limitations encountered with surgery and long-term use of
anti-thyroid medications. Theoretically, favorable results
with 131I therapy could be expected, if thyroidal uptake
of iodine is increased by a compound such as rh-TSH.
Combined rh-TSH and radioiodine has been utilized for
the management of euthyroid, multinodular goiter. To the
best of our knowledge, this approach has not been tested
for the treatment of toxic, multinodular goiter with low
radioiodine uptake.
Conclusion: The present case illustrates the beneficial effect of adjunct therapy with rh-TSH and radioactive iodine in decreasing the goiter size, and treatment
of hyperthyroidism in elderly patients with toxic multinodular goiter and low iodine uptake. Close clinical monitoring of these patients is absolutely necessary, due to
transient exacerbation of hyperthyroidism, and therefore
potential risk of cardiovascular decompensation.
Abstract #1016
ADJUNCT USE OF RECOMBINANT TSH
(rh-TSH) WITH 131I IN THE TREATMENT OF
TOXIC MULTINODULAR GOITER WITH LOW
RADIOACTIVE IODINE UPTAKE
Hema Padmanabhan, MBBS, MD,
Rathnakara Sherigar, MD, and Ali Iranmanesh, MD
Objective: To describe the effectiveness of adjunctive use of recombinant TSH (rh-TSH) with 131I radioiodine for treatment of toxic multinodular goiter with low
iodine uptake in an elderly man
Case presentation: A 94 year old male with toxic
multinodular goiter and low radioactive iodine uptake,
was treated with 15.4 mCu of 131I after thyroid gland
was primed with rh-TSH. As a result, radioactive iodine
uptake increased from a baseline of 2% (2 hr) and 6%
(6 hr) to 14% (2 hr) on day 1, maximized at 61% (2 hr)
and 79% (6 hr) on day 28, and returned to values of
3.6% (2 hr) and 3.9% (6 hr) by day 70. Concomitantly,
serum FT4 concentration (normal range: 0.65-1.75 ng/
dL) increased from a pre-treatment of value of 2.11 to
a maximum of 12 on day 3, with marked decrease to 4.9
on day 5 and a gradual decline to normal value of 1.67
by day 140. Circulating FT3 concentrations (normal: 2.34.5 pg/mL) followed a similar pattern at respective values
of 4.9 and 10.5 for pre-treatment and day 5 post-treatment, but an earlier recovery to normality (4.5) by day
70. Pretreatment serum TSH concentration was less than
0.03 uIU/mL. The patient continued to be euthyroid without thyroid replacement at his last clinic visit (555 days
post-treatment) with serum FT4, and TSH (normal: 0.483.94 uIU/mL) concentrations of 1 ng/dL and 1.9 uIU/mL,
respectively. Recovery from hyperthyroidism was associated with a 71% reduction in the size of thyroid gland, as
determined by ultrasound.
Discussion: Management of toxic multinodular
goiter in elderly could be challenging at times. Although
preferred in most hyperthyroid states, treatment with
131I may not produce the best outcome due to the goi-
Abstract #1017
FREE THYROXINE INDEX VERSUS FREE T4 IN
THE ASSESSMENT OF THYROID FUNCTION
Hema Padmanabhan, MBBS, MD, John Badlissi, MD,
and Ali Iranmanesh, MD
Objective: To compare free thyroxine index
(FTI: Total T4 x T3uptake/100) and Free T4 in the evaluation of thyroid function.
Methods: In this retrospective survey, the results of
FT4 and concomitant FTI were reviewed in 417 subjects
who had normal serum concentrations of TSH. Thyroid
tests were performed in the Endocrine Laboratory as
requested by primary care providers for various clinical
indications. FT4, total T4, T3 uptake, and TSH were measured by chemiluminescent methodology, using 2 different fully automatic analysers, namely ACS-180 (Bayer
Diagnostics Corp, MN), and Immulite 2000 (Siemens
Diagnostics, CA). Free T4 was analyzed by analog
method.
Results: Of the 417 cases with normal TSH, FT4
was elevated in 26, while abnormally high FTI was
observed in only one. The results differed with the type
of autoanalyser used. Of a total of 269 assays performed
by Immulite 2000, FT4 was increased in 18 (specificity:
93%), as opposed to one subject with documented high
FTI (specificity: 99.6%). On the other hand, specificity
with ACS-180 was 95% (8 of 147) for FT4, and 100% for
FTI (0 of 147).
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Discussion: The validity of FT4 results has been
questioned in euthyroid patients with nonthyroidal illness, hereditary dysalbuminic hyperthyroxinemia, and
the presence of thyroid antibodies. In healthy subjects,
measurement of circulating free thyroxine (FT4) correlates well with thyroid status and with results obtained by
equilibrium dialysis.
Analog assays for FT4 produce inaccurate results
because the T4 analog is sequestered by albumin. This
is not overcome even by chemically blocking analogalbumin, because the chemically blocked FT4 assay
appears to be “thyroxin-binding globulin” (TBG) dependent, producing inappropriately low FT4 results with low
TBG concentrations and high values with high TBG.
Equilibrium dialysis using chemical blockers, displace
T4 analog from albumin, but in high concentrations, also
displace it from TBG.
Our data showed that FTI has a higher specificity
than FT4. Of the 26 patients with high FT4, 12 were on
drugs which are known to decrease the peripheral conversion of T4 to T3.
Conclusion: FT4 by analog methods has a higher
false-positive rate compared to FTI. This is possibly due
to the prevalence of non thyroidal illnesses and use of
drugs( such as beta-blockers, amiodarone and corticosteroids), which are known to decrease peripheral conversion of T4 to T3, at the expense of increased circulating
concentrations of reverse T3 and FT4. We, therefore,
conclude that FTI is a more specific test for evaluating
thyroid functions.
dL (0.7-1.7), free T3 - 6.9 pg/mL (2.3-4.2), thyrotropinbinding inhibiting immunoglobulin (TBII) showed 30 %
inhibition (<16), glucose was 492 mg/dL and hemoglobin
A1c was 15%. Anti thyroid peroxidase antibodies (TPO)
was less than 10 IU/mL (<34.9) and thyroid stimulating immunoglobulins (TSI) was less than 75% (<125).
Thyroid ultrasound showed multiple hypoechoic nodules;
the largest was 1.2 cm in the left mid to lower lobe with
prominent vascularity. The 123I thyroid scan showed heterogeneous 55% uptake (normal 10-30%), with an area of
increased uptake in the left lobe. The patient was treated
with 10.9 mCi of 131I. Two weeks later a post-treatment
thyroid scan with oblique views confirmed Graves’ disease with a superimposed hot nodule in the left mid to
lower pole corresponding to the largest nodule seen on
ultrasound.
Discussion: The clinical and biochemical presentation of hyperthyroidism in this patient (exophthalmos;
smooth, bilaterally enlarged thyroid gland; elevated
uptake; diffuse enhancement on scan; and elevated TBII)
is consistent with Graves’ disease. In addition, the nuclear
scan showed a “hot” nodule in the precise location of
the dominant nodule on thyroid ultrasound. Marine and
Lenhart described “cold” and “cool” adenomatous nodules in Graves’ disease. Although other authors have used
the term Marine-Lenhart syndrome to describe AFTN in
euthyroid Graves’, there are only a few documented cases
such as ours, with confirmed “hot” nodules in the presence of thyrotoxic Graves’ disease.
Conclusion: The co-existence of Graves’ disease
and autonomously functioning nodules is rare. Although
overwhelmingly adenomas, carcinoma has been reported
in this setting. Re-evaluation of the nodule, including
consideration of biopsy, should occur following initial
therapy.
Abstract #1018
HYPERTHYROID GRAVES’ DISEASE AND A
SIMULTANEOUS HOT NODULE
Marina Strizhevsky, DO, Yun Feng, Katherine Groh,
and Adrienne M. Fleckman, AACE
Abstract #1019
PAPILLARY THYROID MICROCARCINOMA
PRESENTING AS SOLITARY LATERAL CYSTIC
NECK MASS: A RARE PHENOMENON
Objective: To report and review the literature on the
coexistence of Graves’ disease and autonomously functioning thyroid nodules (AFTN).
Case Presentation: A 43-year-old deaf Hispanic
woman with a history of diabetes mellitus and hyperthyroidism was admitted for uncontrolled diabetes. The
patient was diagnosed with hyperthyroidism one year
ago but did not follow up. Her only complaint referable
to the thyroid was increasing fatigue for several months.
Physical exam was remarkable for left-sided exophthalmos and stare, without lid lag. The thyroid was enlarged
(50-60g), smooth and firm, without bruit or distinct nodules. TSH was <0.03 mU/L (0.38-5.5), free T4 - 2.8 ng/
Maria Paulina Santos Parong, MD,
Jennifer Wheaton, DO, Abid Yaqub, MD,
Thomas Dougherty, MD, and Paul Durst, MD
Objective: To describe an unusual presentation of
Papillary Thyroid Microcarcinoma and subsequently
reaffirm the need for careful and meticulous diagnostic evaluation of such cases.
Case Presentation: A 32 year old male patient presented with a 6 year history of solitary, cystic, nontender,
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Case Presentation: A 47-year-old woman presented
with anterior neck discomfort and a palpable thyroid
mass. Thyroid ultrasound revealed a 1.2 x 0.8 x 1 cm heterogeneously hypoechoic right thyroid nodule. TSH was
normal at 0.639 mIU/l. FNA biopsy showed scant cellularity. A hemorrhage into the thyroid was suspected. At
follow-up in four weeks the patient complained of rightsided neck pain. The thyroid gland was tender. Ultrasound
demonstrated an enlarging hypoechoic area in the right
thyroid lobe. Neck CT was negative for abscess, ESR
was elevated at 56 mm/hr, TSH was mildly suppressed at
0.18 mIU/L. Diagnosis of subacute thyroiditis was made.
Subsequently the patient developed left-sided neck pain
and an extension of the hypoechoic areas into the left lobe. Two weeks of prednisone resulted in marked symptomatic
improvement, and a decrease in hypoechoic areas. After
discontinuation of prednisone the symptoms recurred but
the patient refused a repeat course of steroids.
Discussion: Diagnosis of subacute thyroiditis is
usually based on the presence of typical findings of neck
pain, diffuse tender goiter, elevated ESR, characteristic
phases of thyroid function change from hyperthyroidism
to hypothyroidism with subsequent normalization, low
radioactive iodine uptake on scintigraphy. Diagnosis is
more difficult in atypical cases with absence of significant pain or tenderness or only with focal thyroid gland
involvement. FNA biopsy can help to rule out a neoplasm.
Thyroid ultrasound can be very useful in differentiating
subacute thyroiditis from other disorders. It typically
shows heterogeneously hypoechoic areas with ill-defined
borders and no flow on color Doppler. The ultrasound
picture is not pathognomonic of subacute thyroiditis, but
the changing findings on ultrasonography with a decrease
in hypoechoic areas after administration of steroids and
eventual complete disappearance of lesions help to confirm the diagnosis.
Conclusion: Subacute thyroiditis should be considered in the differential diagnosis of a thyroid nodule.
The typical features of subacute thyroiditis such as neck
pain, elevated ESR, suppressed TSH, hypoechoic areas
on ultrasound, response to steroids and a clinical course
help to establish the diagnosis. Serial ultrasound can be
very useful in diagnosis and monitoring of disease progression, especially in atypical cases.
4 x 5 cm left sided neck mass. CT of the neck showed
a large cystic structure in the lateral neck suspicious for
cystic hygroma versus branchial cleft cyst. The mass
was excised and the final pathologic report revealed a
focus of papillary thyroid carcinoma arising in the wall
of a branchial cyst. Repeat review of the same pathology specimen and use of special stains revealed lymph
nodal architecture consistent with cystic degeneration of
a metastatic lymph node thus proving a metastatic spread
from an undetected primary thyroid lesion. The patient
underwent total thyroidectomy with left modified radical
neck dissection and was found to have a 4mm papillary
thyroid carcinoma in the left lobe of the thyroid.
Discussion: Papillary Thyroid Microcarcinoma
(PTMC), defined as being less than 10mm in size, is
generally considered to be slow growing with relatively
good prognosis. Some reports however indicate that with
delay of diagnosis, there maybe increased risk of recurrence and mortality. Mazzaferri and Jhiang in their analysis of 1355 patients with thyroid cancer reported that
mortality rate was increased 2-3 fold with a year delay
in diagnosis. Although PTMC could be associated with
cervical lymphadenopathy, the affected nodes are usually solid and multiple. A presentation of PTMC with
a solitary cystic lateral neck mass is uncommon. About
35 cases have been reported in literature so far. When
PTMC presents this way, it is often challenging to differentiate between the occurence of malignant degeneration
of an aberrant lateral thyroid tissue versus a metastatic
lesion from an undetected primary thyroid cancer.
Conclusion: Our case report describes an uncommon presentation of PTMC. It is important for physicians to be aware that PTMC can also present initially
as a solitary cystic neck mass as appropriate and timely
diagnosis would clearly affect further management and
care of such patients.
Abstract #1020
SERIAL ULTRASONOGRAPHY IN THE
DIAGNOSIS OF SUBACUTE THYROIDITIS
PRESENTING AS A THYROID NODULE
Anna Leonidovna Marina, MD, and
Jann M. Johnston, MD, FACE
Objective: We report an unusual case of subacute
thyroiditis presenting as a thyroid nodule in a patient followed by serial ultrasonography to demonstrate the role
of serial ultrasound in the diagnosis of this disorder.
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progression from symptomatic hyperthyroidism to overt
hypothyroidism in just six weeks.
Conclusion: This is the first described case of a
patient with serologic autoimmunity, abnormal thyroid
function, and lymphocytic infiltration in the thyroid elements of a large cystic teratoma. Patients with ovarian
tumors or other foci of ectopic thyroid tissue should
be monitored closely for the development of thyroid
dysfunction.
Abstract #1021
BENIGN CYSTIC TERATOMA CONTAINING
THYROID TISSUE WITH LYMPHOCYTIC
THYROIDITIS IN A PATIENT WITH
THYROTOXICOSIS PROGRESSING TO
HYPOTHYROIDISM
Susan Jane Adamcik, MD, Manfred Blum, MD,
and Priya Kundra, MD
Abstract #1022
Objective: To present a case of a woman with thyrotoxicosis preceding removal of a benign cystic teratoma
containing thyroid tissue with lymphocytic thyroiditis.
Case Presentation: A 55 year old Russian woman
presented on May 30, 2007 for evaluation of a pelvic
mass. She described multiple courses of iodine treatment
in Russia for unknown reason, the last one year previously. There was no family history of thyroid disease. She lived thirty miles from Chernobyl in 1986. She
denied recent viral illness or neck trauma. Examination
was notable for an irregular tachycardia at 130, a non-tender thyroid, and a palpable abdominal mass. Laboratory
evaluation revealed a TSH of 0.009uIU, Ft4 of 8.92, TPO
Ab>1000, TG Ab of 370 with nonelevated ESR and TSI. Abdominal ultrasound revealed an 11x9x10cm mass in
the pelvic midline. I131 whole body scan on July 5, 2007
revealed <1% uptake in the neck and an area of uptake
posterior to the bladder within the region of the pelvic
mass. Repeat Ft4 level was 1.01 and 24hr urinary iodine
was 170u/L. On July 17, 2007, TSH was 48.17, Ft4 was
0.57 and the patient started levothyroxine. Thyroid ultrasound revealed a heterogeneous thyroid without focal
nodule. She underwent bilateral salpino-oophorectomy
on August 8, 2007 with removal of a benign 14.5x8x8cm
cystic teratoma of the left ovary containing 1cm2 of thyroid tissue with lymphocytic infiltration. Three months
later, the patient still requires levothyroxine.
Discussion: Mature cystic teratomas account for
10-20% of all ovarian neoplasms and contain components of all three germ layers, including thyroid tissue. They have been associated with certain autoimmune diseases including autoimmune hemolytic anemia and rare
encephalitides via production of antibodies against teratoma neoplastic cells. Thyroid hyperfunction with thyroid autoantibodies and lymphocytic thyroiditis has been
described in patients with struma ovarii, but there are
only five reported cases of histologic thyroiditis within
a benign cystic ovarian teratoma. Antithyroid antibodies were detected in two cases and none demonstrated
abnormalities in thyroid function. Our patient not only
had high titers of anti-thyroid antibodies, but a dramatic
METASTATIC PAPILLARY THYROID CANCER
PRESENTING AS A PARASELLAR MASS
Adalberto D. Gonzalez-Pantaleon, MD,
Elias Siraj, MD, FACE, and Colleen Veloski, MD
Objective: To report a case of papillary thyroid carcinoma presenting with brain metastasis.
Case Presentation: A 55-year-old male presented
with headaches and diplopia of 6 months duration. Brain
MRI revealed a 4.5 x 2.7 cm parasellar mass extending
into the sphenoid, cavernous sinus, and prepontine cistern. Further evaluation revealed a thyroid mass, which
on fine needle aspiration was indeterminate. Since the
location of the mass was atypical for pituitary adenoma,
a transphenoidal biopsy was performed. Initial pathology was suggestive of pituitary adenoma. Subsequent
immunostainings were positive for thyroglobulin and
TTF-1, strongly suggesting a metastatic thyroid carcinoma. Serum thyroglobulin (TG) level was >3000 ng/dL.
There was no evidence of significant hypopituitarism.
Total thyroidectomy was performed and final pathology
showed follicular variant of papillary thyroid carcinoma
(PTC) with vascular invasion. Transphenoidal debulking
was performed but was limited by significant intraoperative bleeding. Whole brain radiation therapy (WBRT)
was administered due to worsening of cranial nerves palsies. Radioactive iodine (RAI) therapy (200 mCi I 131)
was given and post treatment scan showed foci of iodine
avid metastases in the cranial vault, thyroid bed, chest,
and abdomen. After initial improvement of neurological
deficits, the patient is now showing evidence of progression, and the TG level remained high despite suppressive
levothyroxine therapy. He is being evaluated for possible
repeat RAI therapy, WBRT and/or chemotherapy as part
of a study protocol.
Discussion: PTC is the most common thyroid malignancy, and is usually discovered as a thyroid nodule. The
incidence of distant metastatic disease at presentation is
rare. Brain metastases occur in 1% of all cases and are
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necessaries to evaluate the impact of different treatments
kinds over cardiovascular system in patients with GD.
associated with poor prognosis. There is no consensus
regarding the management of PTC metastatic to the brain.
Surgical resection of metastatic lesions has been shown
in some studies to increase survival. The role of postoperative adjuvant WBRT is not clearly defined, but may
be effective in reducing recurrence. If the metastases are
iodine avid, RAI therapy may improve prognosis, but can
cause rare side effects such as acute cerebral edema.
Conclusions: PTC presenting with brain metastasis
is rare but is associated with poor prognosis. Although
no guidelines are available, surgical resection seems
to be the best therapeutic option to improve outcomes.
Postoperative WBRT and RAI therapy are reasonable
additional treatment options.
Abstract #1024
COCAINE USE AS A PRECIPITATING FACTOR
FOR THYROTOXIC PERIODIC PARALYSIS
Angel Rodolfo Alejandro, MD, and
Anup Sabharwal, MD
Objective: To report a case of Thyrotoxic Periodic
Paralysis (TPP) in a 37 year old woman precipitated by
cocaine use on two isolated occasions.
Case Presentation: A 37 year-old African American
woman presented with bilateral lower extremity paralysis
and upper extremity weakness. She had required hospitalization one month prior for a similar episode. At that
time, she was found to have a serum potassium of 1.6
mmol/l, and her muscle weakness resolved following
potassium replacement. She was discharged home with
only potassium supplementation. After discharge, labs
revealed a TSH of <0.004 µIU/ml, a free T-4 of 3.50 ng/
dl (normal 0.93-1.70 ng/dl), and a urine screen was positive for cocaine. On the recent hospitalization, she complained of palpitations and heat intolerance, and admitted
to cocaine use the night before. Positive physical findings
included tachycardia, absent deep tendon reflexes, and
decreased motor strength in all extremities. EKG revealed
prominent U-waves and a prolonged QT interval. Serum
potassium was found to be 1.8 mmol/l. Her muscle weakness resolved following potassium replacement. She was
discharged home with methimazole 10mg daily. In follow
up, she is both clinically and biochemically euthyroid and
has had no further episodes of paralysis reported.
Discussion: TPP is a reversible electrolyte and
motor disorder which is characterized by hypokalemia
and acute muscle weakness in the setting of hyperthyroidism. This patients experience leads us to believe that
cocaine use may have precipitated the attacks of TPP. The
pathophysiology of TPP involves over activation of the
Na+-K+ATPase pump with resultant hypokalemia and
paralysis. Hyperthyroidism results in a hyperandrenergic state with ß-adrenergic stimulation directly activating the Na+-K+ATPase pump. Excess thyroid hormone
increases the sensitivity of the ß-adrenergic receptors,
further increasing the catecholamine induced activation
of the Na+-K+ATPase pump. Additively, cocaine use
also induces an adrenergic surge which may have further
precipitated this patient’s TPP by over activation of the
Na+-K+ATPase pump.
Abstract #1023
CARDIAC EFFECTS OF SUBCLINICAL
HYPERTHYROIDISM (SH) IN PATIENTS
WITH GRAVE’S DISEASE
Hernando Vargas Uricoechea, MD
Objective: To evaluate some cardiac effects of SH in
patients with GD.
Methods: 40 women with SH (main group) due
to GD, demonstrated by TSH levels <0,4 mUI/ml and
normal levels of FT3 and FT4, with radiologic criterias
established by thyroid ultrasonography and nuclear imaging with radioiodine uptake (131I), were matched with 40
healthy women (adjusted by age) who had normal levels
of thyroid hormone; all they for make cardiac tests (doppler echocardiography, 24-h holter ECG and 24-h ambulatory blood pressure monitoring). Patients with active
treatment for GD and patients intaking drugs that injure
the cardiac rhythm/function were precluded.
Results: The diurnal Systolic Blood Pressure (SBP)
average was 140 mmHg in main group, and 128 mmHg
in control group (P=0.03). The nocturnal SBP average in
main group was 144 mmHg, and 127 mmHg in control
group (P=0.04). Differences in Diastolic Blood pressure
levels, were not found. The heart rate average in main
group was 90 bpm and 73 bpm in control group (P=0.02).
Echocardiography showed diastolic dysfunction, defined
like reduction in E/A in main group, compared with control group: 0.91 [0.85;0.96] vs. 1.24 [1.18;1.3] (P=0.03).
8 women in main group (20%) revealed criterias for ventricular hypertrophy; nobody revealed these criterias in
control group (P=0,002).
Conclusion: SH in patients with GD is related with
relevants and importants cardiac effects. Clinical trials are
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levels < 1 ng/ml; no visible uptake in the thyroid bed was
observed in 20/21 patients (95.2%) from Group A and
17/19 patients (89.5%) from Group B. No statistical differences between the two groups were observed for both
ablation criteria (Fisher exact test).
Discussion and Conclusion: The use of rhTSH for
preparation of low risk DTC patients to ablation therapy
with low doses of 131I (50 mCi) is safe and effective,
exposes the patients to lower radiation doses and avoids
the discomfort due to hypothyroidism. It might be the
optimal ablation procedure in this group of patients.
Conclusions: Cocaine’s catecholamine effect on
the Na+-K+ATPase pump may be a precipitating factor
of TPP in this patient. It is important to recognize that
treatment of hyperthyroidism remains the primary goal
in the management of TPP. This is illustrated by the fact
that despite continued cocaine abuse, this patient, who
remains euthyroid on anti-thyroid medication, has not
had any further episodes of paralysis.
Abstract #1025
LOW DOSE RADIOIODINE POSTSURGICAL
REMNANT ABLATION IN THYROID CANCER:
COMPARISON BETWEEN HORMONE
WITHDRAWAL AND USE OF rhTSH IN
PATIENTS AT LOW RISK
Abstract #1026
IVIG THERAPY IN THE TREATMENT OF
GUILLAIN-BARRE SYNDROME, RESULTING
IN IMPROVEMENT OF COEXISTING GRAVES’
DISEASE
Enrico Papini, MD, FACE, Chianelli M., MD,
Papini Laura Todino V., MD, Graziano F., MD,
Guglielmi R., MD, and Signore A., MD
Javeria Ahmed, MBBS, and Thomas Hughes, MD
Objective: To present a case of Guillain-Barre syndrome (GBS) with concomitant Graves’ disease. Therapy
with intravenous immunoglobulin (IVIG) resulted in
decline of thyroid stimulating immunoglobulin (TSI) and
resolution of the hyperthyroid state.
Case Presentation: A 46 yo white female was admitted with a one week history of progressive numbness,
tingling and weakness of her bilateral lower extremities
(BLE), which was rapidly progressive. She denied any
other focal weakness (diplopia, dysarthria, dysphagia).
The only recent infection was a left otitis media about
2 months prior. Exam was significant for a palpable thyroid gland with fullness at the isthmus, sinus tachycardia, resting tremor, and 4/5 BLE strength, absent deep
tendon reflexes and distal BLE hypoesthesia. Work up
for secondary causes of neuropathy was negative. TSH
was reported to be 0.02 mIU/mL, FT4 2.5 ng/dL (0.581.64) and TT3 245 ng/dL (87-178). TSI was elevated at
246%. She was started on a beta-blocker with return to
normal sinus rhythm. Plasmapheresis was initiated for
treatment of GBS, but was changed to IVIG after lack of
improvement in neurological symptoms. RAIU & scan
was consistent with Graves’ disease, and showed a 24
hour uptake of 75%. RAI ablation was planned, but this
was delayed due to the extended hospital course to treat
GBS. Repeat TFTs subsequent to IVIG therapy showed
resolution of her hyperthyroid state, with TSH 0.11 mIU/
L, FT4 0.8 ng/dL. TSI decreased to within normal range
(97%).
Discussion: Guillain-Barre syndrome and Graves’
disease both have underlying autoimmune etiologies.
Objective: To compare the efficacy of low dose (50
mCi) 131I ablation in low risk patients with differentiated
thyroid cancer (TNM stage pT1-T2, pN0, M0) randomized to using L-T4 withdrawal vs rhTSH stimulation.
Methods: All patients, on the day of treatment,
underwent 131I neck scintigraphy and radioiodine uptake;
post-therapy whole body scan (WBS) was also acquired
4-6 days after the therapeutic dose of 131I. Neck ultrasound
examination (US) was performed at time of treatment to
assess the completeness of thyroidectomy. Efficacy of
ablation therapy was assessed after 6-12 months by WBS,
Tg and TgAb measurement following L-T4 withdrawal.
Patients positive to Tg autoantibodies were excluded from
the study. Patients were raned in two groups: Group A,
preparation with L-T4 withdrawal; 24 patients received
131
I (54.6+/-5.9 mCi) after 37 days of L-T4 withdrawal
and 20 days of T3 replacement. On the day of treatment
TSH, Tg, TgAb were measured; Group B, stimulation
by rhTSH; 21 patients received 131I (53.2+/-4.9 mCi) 24
hours after the 2nd injection of rhTSH (0.9 mg). TSH, Tg
and TgAb were measured on the day of treatment and
after two days.
Result: All patients showed visible uptake in the thyroid bed at the post-therapy WBS. In Group B, however,
six patients did not show any visible uptake in the thyroid
bed at the pre-therapy scan and, on average, lower neck
uptake was observed (4.7+/-4.5% vs 1.4+/-1.41%, Group
A vs Group B, p=0.004). High ablation rates have been
observed in both groups of patients. At follow up, after
L-T4 withdrawal, 18/20 patients (90.0%) from Group A
and 14/18 patients (77.7%) from Group B had serum Tg
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Although GBS may be associated with other endocrinopathies, the coexistence with Graves’ disease has only
rarely been reported. IVIG is now the standard of care in
the treatment of GBS. There are reports of IVIG use in
severe cases of Graves’ associated ophthalmopathy. Our
patient represents a rare instance of resolution of hyperthyroid symptoms and reduction of TSI as a result of
IVIG therapy for her GBS.
Conclusion: In selected and rare cases, IVIG may
be considered as an alternative therapeutic option in the
management of severe hyperthyroid patients.
and 16 of the RET proto-oncogene. However, tumor cells
were not tested for RET proto-oncogene rearrangements
or mutations.
Work up for hyperparathyroidism and pheochromocytoma was negative.
Discussion: Simultaneous occurrence of papillary
and medullary carcinoma as two distinct tumors is very
rare. While some case reports argue against any embryological or genetic association between these tumors, others suggest a common origin.
Obtaining serum calcitonin levels prior to surgery
would have been a useful approach. Levels >100 pg/ml
would strongly suggest presence of medullary thyroid
carcinoma.In addition, recent evidence indicates that
measurement of calcitonin in FNA biopsy specimens
maybe helpful in diagnosing MTC.
Conclusion: It is likely that two carcinomas in our
case do not share common genetic or embryological
background. Increased vigilance for medullary thyroid
carcinoma is needed in a person with thyroid nodules and
elevated levels of carcinoembryonic antigen.
Abstract #1027
SIMULTANEOUS OCCURENCE OF PAPILLARY
AND MEDULLARY THYROID CARCINOMA
Yuriy Gurevich, DO, and Alina Gouller, MD
Objective: To describe a case of simultaneous occurrence of papillary and medullary thyroid carcinoma and
review pertinent literature.
Case Report: A 54-year-old woman presented
for evaluation of multinodular goiter incidentally discovered on whole body PET scan, which revealed two
hypermetabolic foci in the thyroid gland. PET scan was
performed for assessment of elevated carcinoembryonic
antigen. The patient was asymptomatic. There was no
history of radiation exposure or family history of thyroid
cancer. She was clinically and biochemically euthyroid. Ultrasound examination of the thyroid revealed a 16 x 12
x 7 mm hypoechoic nodule with punctuate calcifications
at the junction of the isthmus and left lobe. There were
two hypoechoic nodules measuring 24 x 19 x 21 mm and
18 x 16 x 18 mm in the superior and inferior poles of the
left thyroid lobe, respectively.
Fine needle aspiration of the nodule in the left superior pole was interpreted as epithelial neoplasia with
Hurthle cell changes and atypical features. The isthmus
nodule biopsy results were consistent with papillary thyroid carcinoma.
Patient underwent total thyroidectomy. Surgical
pathology of the nodule in the superior pole of the left
lobe was consistent with medullary thyroid carcinoma
with focal capsular invasion. Diagnosis was confirmed
by immunoreactivity to chromogranin, cacitonin, CEA,
synaptophysin and lack of reactivity to thyroglobulin.
Pathology of the second nodule revealed papillary thyroid carcinoma with extrathyroidal invasion. This tumor
was immunoreactive to thyroglobulin only.
DNA analysis of the peripheral leukocytes indicated
that there were no mutations in exons 10, 11, 13, 14, 15,
Abstract #1028
A CASE OF PROPYLTHIOURACIL INDUCED
HEPATIC FAILURE
Alvin Ng, MBBS, and Kwang-Wei Tham. MB, BCh
Objective: To report a case of propythiouracil
induced hepatic failure. We highlight the pitfalls of diagnosis and discuss the non-thionamide strategies for controlling thyrotoxicosis.
Case Presentation: A 38 year old female with
Graves’ disease presented with progressive painless jaundice over a few days. She had developed pruritus after
taking carbimazole and was switched to propylthiouracil
6 weeks ago. Clinically, she was mildly thyrotoxic with a
Burch and Wartofsky score of 20. Investigations showed
hyperbilirubinemia, elevated alkaline phosphatase and
transaminases and coagulopathy. Her Thyroid Stimulating
Hormone (TSH) was <0.006 mU/L and free Thyroxine
(fT4) was 26.6 pmol/L. Liver biopsy showed submassive necrosis of hepatocytes. Her thyrotoxicosis was controlled with propranolol 20 mg qid, lithium carbonate 250
mg bid, cholestyramine 4mg tid, IV hydrocortisone 100
mg 6 hourly and IV sodium iodide 1g over 24 hours. On
the 7th day of admission she received a living donor graft
from her husband in a 12 hour surgery uneventfully. On
the 23rd day after the last iodide dose, 30 mCi of radioiodine was given to render her hypothyroid.
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after delivery she developed symptoms of thyrotoxicosis. At this time TSH was <0.01 and free T4 was 10.44. RAI
uptake and scan revealed a homogenous 24-hour uptake
of 73%. Levothyroxine was discontinued and the patient
was started on methimazole. When symptoms persisted,
the patient sought treatment at our hospital. Upon admission, TSH was <0.01, free T4 was 2.02, and TSI was
357%. Methimazole was discontinued due to marked
transaminase elevation and the patient received 10mCi of
I-131 for definitive treatment.
Discussion: Hyperthyroidism is known to occur
early in the course of Hashimoto’s thyroiditis and is commonly termed “Hashitoxicosis.” Following this phase,
during which the inflamed thyroid leaks preformed hormone, the injured gland loses synthetic ability and hypothyroidism ensues. Patients who have already entered
the hypothyroid phase of Hashimoto’s thyroiditis are
not expected to subsequently develop thyrotoxicosis. A
handful of case reports in the literature, however, describe
patients that have transitioned from one form of autoimmune thyroid disease to another. These studies show that
the same patient may express one or more of the different
TSH receptor antibodies in addition to anti-TPO or antithyroglobulin antibodies. We suggest that our patient’s
relatively low level of anti-TPO antibodies was insufficient to completely destroy her thyroid. During the
postpartum period, her immune state likely altered such
that TSI became the predominant antibody in circulation. This allowed her clinical expression of disease to shift
toward thyrotoxicosis.
Conclusion: Transformation of Hashimoto’s hypothyroidism to Grave’s hyperthyroidism is extremely rare
but can occur. When hypothyroid patients have unexpected symptoms or changes in thyroid function tests,
especially during pregnancy or the postpartum state,
this unlikely diagnosis should be entertained and treated
accordingly.
Discussion: It is crucial to recognize that liver dysfunction may be a consequence of thyrotoxicosis. Cardiac
failure with hepatic congestion can cause hyperbilirubinemia while autoimmune hepatitis and hemolytic anemia
have been associated with Graves’ disease. Up to 60%
of hyperthyroid patients have at least one abnormal liver
biochemistry. However, it was unlikely that an uncontrolled state of thyrotoxicosis was the cause in this case as
the history and temporal sequence strongly favoured PTU
induced hepatic injury. Beta–blocker can ameliorate the
adrenergic effects and block conversion of T4 to T3 while
high dose corticosteroids inhibit hormone secretion and
also block conversion of T4 to T3. Its immunosuppressive effects may be beneficial considering the purported
mechanism of immune-mediated damage by PTU. Iodide
acutely inhibits organic binding but this is transient. Its
main action is to inhibit hormone release. Lithium also
inhibits hormone secretion but unlike iodide, it enhances
the retention of RAI in the gland and increases its efficacy. In thyrotoxicosis, there is increased entero-hepatic
circulation of thyroid hormones and cholestyramine
sequesters these hormones in the gut.
Conclusion: PTU induced hepatic injury must be
distinguished from hepatocellular dysfunction resulting
from thyrotoxicosis itself as the management in both
situations are very different. When thionamide is contraindicated, there are other medical modalities which can
be used in a synergistic manner to control thyrotoxicosis
with success.
Abstract #1029
DEVELOPMENT OF GRAVE’S
HYPERTHYROIDISM IN A WOMAN WITH
HASHIMOTO’S HYPOTHYROIDISM
Diane E. Fresca, MD, and Xiangbing Wang, MD, PhD
Objective: To report a case of Grave’s hyperthyroidism in a postpartum woman previously treated with thyroid
hormone replacement for Hashimoto’s hypothyroidism.
Case Presentation: A 32-year-old female was
diagnosed with Hashimoto’s thyroiditis three months
after a miscarriage. At the time of diagnosis TSH was
32, free T4 was 0.8, anti-TPO antibodies were 67.7, and
24-hour RAI uptake was 13%. Four months after initiation of treatment with levothyroxine the patient became
euthyroid and remained stable until becoming pregnant
in August 2006. During her first trimester, TSH rose to
98 and her levothyroxine dose was increased. Thyroid
function tests normalized and the patient remained euthyroid through her uncomplicated delivery. Six months
Abstract #1030
IODINE DEFICIENY IN CENTRAL NEW JERSEY:
A CASE REPORT
Alexander Kulczycki, MD, and
Xiangbing Wang, MD, PhD
Objective: To recognize iodine deficiency (ID) as a
reemerging cause of goiter in central New Jersey (CNJ).
Case presentation: A 29 year-old Hispanic female
living in CNJ presented to Endocrinology clinic for evaluation of possible hyperthyroidism. She complained of
weight gain, dysphagia, hand tremors, polydipsia, breast
– 122 –
tenderness, hot flushes, and amenorrhea with inducible
menses. On physical exam a diffusely enlarged thyroid
gland and galactorrhea were noted. All other examinations were all within normal limits (WNL). CBC, metabolic panel, prolactin, FSH, LH, testosterone, insulin
levels were WNL. Thyroid chemistries were WNL: TSH
2.05miU/L, free T4 1.2ng/dL, total T3 158ng/dL. The
TPO antibody level was elevated at 213.3iU/mL. Pituitary
MRI demonstrated no micro- or macroadenomas or any
other intracranial pathology. An iodine-123 uptake and
scan demonstrated a 24-hour uptake of 72% (hyperthyroid range) and a diffusely enlarged gland with no focal
nodules. A 24-hour collected urinary iodide level showed
no detectable urinary iodide. Further discussion with the
patient revealed that she actively avoided consumption
of iodized salt and seafood. Based on these findings, the
patient was diagnosed with ID.
Discussion: In the early 1900s ID was identified as
the leading cause of widespread endemic goiter in the
United States. Since the introduction of iodine supplementation of salt and other foods (bread, meat, milk,
etc) starting in the 1920s, though, ID has been virtually
unheard of in this country. ID can still be observed in
remote developing nations and some developed nations
like Denmark that only initiated iodine replacement programs within the past ten years. Among certain ethnic
subgroups, where there is over-dependence on foods high
in groitrogens (cassava/yucca, millet, sweet potatoes, cabbage) ID can also be observed. Consequently, the mechanism of ID in this case included 1) avoidance of iodized
salt and seafood and 2) consumption of goitrogenic foods
which might inhibit iodine absorption. Further investigation, such as screening the patient’s family members for
ID, remains to be done.
Conclusion: We report a case of goiter caused by ID
in CNJ. Given that iodine levels in processed foods have
been decreased in recent years and the use of goitrogenic
foods in certain increasingly prevalent ethnic subgroups,
iodine deficiency should again be included in the differential diagnosis of goiter in the United States. A full diet
history and 24-hour iodine level are necessary to confirm
the diagnosis. Fortunately, the treatment is as simple as
adding iodized salt to the diet.
Abstract #1031
PREDICTIVE VALUE AND DISCRIMINANT
CALCULATION IN DIAGNOSE
THYROTOXICOSIS IN HYDATIDIFORM
MOLE PATIENTS
Nanny Natalia Mulyani Soetedjo, MD, Sri Hartini,
and K.S. Kariadi
Objective: Tyrotoxicosis in hydatidiform mole
patients is not uncommon and may create a severe problem. It was progress rapidly but silently and may emerge
suddenly as an alarming situation. There are no specific
thyroxic signs and symptoms which lead to prompt recognition and treatment. Thus to able to establish the diagnosis of thyrotoxicosis the determination of high fT4, fT3
and TSH <0,1 mIU/ml is crucial but it requires some time
to get the results.
Methods: The inability to get the result in time will
cause the diagnosis is established too late and makes the
critical condition unavoidable especially after the mole
evacuated. A study with the purpose to create a simple
procedure to enable the clinicians to diagnose thyrotoxicosis more instantly concluded that prediction. Factors
were pulse rate > 100/mt or uterine size is > 20 weeks,
and discriminant calculation, with high accuracy. To
reevaluate the accuracy of the predictive factors and the
discriminant calculation, we analyzed hydatidiform mole
patients from January 2002 until December 2005.
Result: There were 105 patients, aged range between
16-50 years old. Thyrotoxicosis was found in 76 (72,4%)
patients. Using predictive factors criteria, 36 patients who
had pulse rate ³ 100/mt, 32 (88,9%) of them had thyrotoxicosis and among 55 patients who had uterine size >
20 week, 40 (72,7%) patients was found thyrotoxicosis.
Discussion: In patients who had combination of predictor factors, calculation with Discriminant formula
there was no thyrotoxicosis. Among 69 patients who had
pulse rate < 100/mt, 44 (63,8%) patients had thyrotoxicosis (p=0,006), with discriminant calculation there was 32
(46,4%) patients D<0 (p=0,724). Among 50 patients who
had uterine size < 20 weeks, 36 (72%) patients had thyrotoxicosis (P=0,934), whom with discriminant calculation
was found 47 (94%) patients D<0 (<0,001). Among 11
patients who had pulse rate < 100/mt and had uterine size
< 20 week, with discriminant calculation there was found
all patients D<0 (p<0,001).
– 123 –
Conclusion: Predictive values seem capable to
diagnose thyrotoxicosis. If there was no predictive values, discriminant calculation could be used to diagnose
thyrotoxicosis in hydatidiform mole.
goiter in the absence of clinical symptoms, as seen in our
case, is distinctly unusual.
Conclusion: Primary thyroid lymphoma, though
rare, should be considered in all patients with Hashimoto’s
thyroiditis who present with unusually large goiters or
acute onset of rapid enlargement of thyroid gland.
Abstract #1032
AN UNUSUAL PRESENTATION OF
THYROID LYMPHOMA
Abstract #1033
AUTO-INFARCTION OF A HURTHLE CELL
NODULE AFTER FNA
Anjali Bhagra, MBBS, and Vahab Fatourechi, MD
Objective: To discuss an unusual presentation of primary thyroid lymphoma.
Case presentation: A 51 year old man presented
with an asymptomatic neck mass that had gradually
increased in size over 5 years. Clinical examination
revealed an asymmetrically enlarged, non-tender thyroid
gland, with the right lobe measuring 9 cm. Symptoms
of thyroid dysfunction or mechanical compression were
absent. Fine-needle aspiration demonstrated extensive
lymphocytic infiltration and cytologic features consistent with Hashimoto’s thyroiditis. Computed tomography (CT) of the neck showed massively enlarged right
thyroid lobe (9 cm) causing marked tracheal deviation to
the left. Thyroid function tests were within normal range.
Given the significant cosmetic disfigurement related to
the thyroid mass, the patient elected to proceed with surgical excision. Right lobectomy and isthmectomy were
performed by standard cervical exploration. Pathology
confirmed severe Hashimoto’s thyroiditis with atypical
lymphoid follicles, suspicious for thyroid lymphoma. The
lymphoid follicles stained positive for CD20, CD10 and
bcl-6 and showed kappa light chain restriction, confirming a diagnosis of follicular lymphoma (Grade IIIA).
Discussion: Primary thyroid lymphoma should be
considered in the differential diagnosis of patients with
thyroid nodules, because the prognosis and treatment differ from other diagnostic entities. Thyroid lymphoma is
rare, with an estimated annual incidence of 2 per million
and a 4:1 female predominance. Autoimmune thyroiditis
confers a relative risk of 67. Half of all cases of thyroid
lymphoma arise in the background of autoimmune thyroiditis. Thyroid lymphoma usually presents acutely as a
rapidly enlarging goiter, often larger than 5 cm with substernal extension and mechanical compressive symptoms.
“B symptoms” (fever, night sweats, weight loss) may be
rarely present. When lymphoma is suspected, immunohistochemical staining / flow cytometry of thyroid core
biopsy are necessary for diagnosis. The diagnosis of primary thyroid lymphoma in the setting of a long standing
Deepa Sundararajan, MD, Maneet Kaur Narula, MD,
and Harmeet Singh Narula, MD, FACE
Case Presentation: A 44 year old woman was seen
in Endocrine clinic for an incidentally discovered thyroid
nodule found on routine physical exam. A 3 cm nodule
was easily palpable in Left mid-thyroid. On sonogram
the nodule was solid & another nonpalpable 1.5 cm solid
nodule was seen in Rt mid-thyroid. FNA of the dominant Left thyroid nodule was performed in the office and
was consistent with a Hurthle cell lesion. One week after
the FNA, the patient complained of pain and increasing
swelling in the nodule; examination in the office confirmed
a mild increase in the nodule which was tender; thyroid
sonogram confirmed the nodule to have increased in size
from 3.2x2.4 cm to 3.4x3.2 cm, solid with cystic areas.
Her discomfort improved significantly with Ibuprofen;
Thyroid function studies, ESR and White count remained
normal, ruling out infection & subacute thyroiditis.
On repeat examination 1 month later, the dominant Lt
Thyroid nodule was much smaller, 1cm on palpation. On
repeat thyroid sonogram, the nodule was 1.9x1.2cm, cystic. Three months later, the nodule was nonpalpable and
measured 1.3cm on sonogram, again cystic. It measured
9mm on sonogram 6 months later. The right sided nodule
was benign on FNA and remained stable at 1.5 cm (solid)
during follow-up. The sudden enlargement of the nodule
after the FNA and its subsequent dramatic decrease in its
size and change in characteristics from solid to cystic all
point to the auto-infarction in the Hurthle cell nodule post
FNA
Discussion & Conclusion: Thyroid nodules may
occasionally infarct post FNA. Hurthle cell nodules
may have an increased predilection for auto-infarction
post FNA as the nodule may outgrow its blood supply.
Endocrinologists need to be aware of this presentation,
as patients may present with acute pain & enlargement
of the nodule post FNA, raising concern for bleeding or
infection of the nodule.
– 124 –
thyroidism also improved off of antithyroid medication,
suggesting that treating celiac disease might also help
thyroid abnormalities.
Conclusion: Routine screening for celiac disease
should be highly considered for patients with both hyperthyroidism and iron-deficiency anemia. Treating celiac
disease may reduce morbidity and improve quality of life
in patients with hyperthyroidism and celiac disease.
Abstract #1034
HYPERTHYROIDISM, IRON-DEFICIENCY
ANEMIA AND CELIAC DISEASE.
Cindy Huang, MD, Amy Toscano-Zokor, DO, and
Xiangbing Wang, MD, PhD
Objective: To report a case of Graves’ hyperthyroidism associated with iron-deficiency anemia and celiac
disease.
Case Presentation: A 37 year old woman with no significant past medical history presented to Endocrinology
clinic with one year history of palpitations, tachycardia, anxiety, diarrhea and weight loss. Clinical and biochemical findings were consistent with overt hyperthyroidism. TSH 0.02 mIU/L (0.4-5.5), free T4 2.9 ng/dL
(0.8-1.8), T3 388 ng/dL (60-181), and thyroid uptake
showed increased 24 hour uptake at 65%. Thyroid ultrasound showed diffusely enlarged thyroid with no focal
lesion. Patient was started on Methimazole 10mg bid and
Propranolol 40mg bid for symptom control. She developed facial rash after starting Methimazole, so it was
discontinued. Blood tests showed H/H 10.9/33.3%, and
iron studies revealed iron-deficiency anemia. Patient was
referred to Gastroenterology for workup of anemia and
chronic diarrhea. She was found to have positive antigliadin antibody and positive tissue transglutaminase
IgG antibody consistent with celiac disease. Endoscopic
small bowel biopsies were suggestive of celiac disease.
Patient was then placed on gluten-free diet, with gradual
improvement of diarrhea and anemia. Two months after
gluten-free diet, patient was no longer anemic with H/H
14.4/41.4%, and her symptoms improved. She remained
clinically euthyroid, and blood test showed TSH 0.04
mIU/L, free T4 1.1 ng/dL, T3 115 ng/dL.
Discussion: The prevalence of celiac disease in
patients with Graves’ hyperthyroidism was 4.5% as compared with 0.9% in age and sex matched healthy controls,
and previous studies recommended routine screening for
celiac disease in patients with Graves’ hyperthyroidism.
A substantial number of patients with iron deficiency anemia were found, on small bowel biopsy, to have mucosal abnormalities compatible with the diagnosis of celiac
disease. The association of hyperthyroidism, celiac disease and iron deficiency anemia is clinically important
because early treatment of celiac disease may prevent or
reverse extraintestinal manifestations, including osteoporosis, anemia, fatigue, and may reverse some thyroid
abnormalities. In this case, patient’s anemia significantly
improved on gluten-free diet. Her symptoms of hyper-
Abstract #1035
THYROTOXIC PERIODIC PARALYSIS IN A
PATIENT OF RECURRENT HYPERTHYROIDISM
50 YEARS AFTER RADIOIODINE THERAPY
Sheng-Fong Kuo, MD, and Jen-Der Lin, MD
Objective: Thyrotoxic periodic paralysis (TPP) is
uncommon associated disorder of hyperthyroidism characterized by muscle paralysis and hypokalemia due to a
massive intracellular shift of potassium. This condition
mainly affects Asian young adult male of 20 to 40 years
old.
Case presentation: This study reports a TPP case
occurring 50 years after radioiodine therapy for hyperthyroidism. The 82-year-old male patient presented to our
emergency department with slurred speech and muscle
weakness (especially bilateral lower limbs) in August,
2006. His potassium level was 1.56 meq/L (Normal: 3.04.8), then. Serum creatine phosphokinase level was 243
U/L (Normal: 15-130) and serum phosphate level was 2.0
mg/dL (Normal: 2.4-4.7). The serum cortisol level was
normal and arterial blood gas revealed mild metabolic
alkalosis combined with mild respiratory alkalosis. After
potassium chloride infusion totally about 200 meq in two
days, the serum potassium returned to normal and he
regained his muscle power. The serum free T4 level was
1.99 ng/dL (Normal: 0.89-1.76), TSH was 0.043 uIU/mL
(Normal: 0.35 - 5.50) and thyroid auto-antibody (TBII)
was positive. The patient had diabetes and was treated
with oral anti-diabetes agents and insulin. He had hyperthyroidism 50 years ago and was treated with radioiodine
therapy. He was well thereafter without symptoms and
sign of hyperthyroidism. However, prior to this acute
paralysis, he had suffered from insomnia, anxiety, and
weight loss for half a year, and he visited Psychiatry
clinic and take medications for treatment. Finally, he was
treated with methimazole for hyperthyroidism and had no
more TPP attack since then.
Discussion: Recurrent hyperthyroidism in an elderly
patient long time after radioiodine therapy with the initial
presentation of TPP is rare. Although TPP usually affects
– 125 –
middle-aged male patients, it can affect elderly patients
as well. The symptoms and sign of hyperthyroidism are
usually not apparent in elderly patients as the present
case. Effective control of hyperthyroidism is indicated to
prevent the recurrence of paralysis.
Conclusion: TPP is a curable disorder that resolves
when a euthyroid status is achieved, and it can affect
elderly patient as well as young adult. Prompt diagnosis
and immediate treatment is important for such a patient.
Conclusions: PPT appears to be rare among
Nigerian women. The cause of this apparent rarity could
not be due to the study design. It is recommended that a
longer ‘span’ of follow up in the post partum period and
studies in other centres using a larger sample size should
be undertaken so as to determine the prevalence rates in
other parts of the country.
Abstract #1036
REVERSAL OF MENSTRUAL ABNORMALITIES
BY TREATING SUBCLINICAL
HYPOTHYROIDISM
Abstract #1037
PREVALENCE OF POSTPARTUM THYROIDITIS
AMONG NIGERIAN WOMEN
Lee Pletts Goscin, MD, PhD
Bilkisu Mohammed Mubi, MBBS, and
Prof Augustine E. Ohwovoriole
Objective: To report objective improvements including reversal of menstrual abnormalities and infertility by
treating subclinical hypothyroidism.
Case Presentation: The NHANES III and Colorado
Health Studies showed normal TSH for women is 0.5 to
2.5. In our clinical practice 40 women and 3 men with
TSH from 3.0 to 7.5 and symptoms of hypothyroidism
were treated with appropriate doses of Levothyroxine. The Levothyroxine was adjusted on a case by case basis
to decrease the symptoms. Four women with Amenorrhea
and Oligomenorrhea returned to normal menstrual cycles. One man with NIDDM showed a marked improvement in
Erectile Dysfunction (ED). Another young 47-year-old
married man was able to restore his marital relationship
and start on a second job. The third man had increased
energy and improved cholesterol.
Discussion: After the NHANES III and Colorado
Health Studies suggested a smaller normal range for
TSH in white women, patients with typical hypothyroid
symptoms had both TSH and free T4 measured. Of 46
women who were identified over three years 44 chose to
take Synthroid. The difference between these 44 women
and previous studies that showed no improvement on
Levothyroxine is that each woman was titrated to her
optimal dose for her.
Conclusion: This study shows that significant morbidity from premature menopause, increased cholesterol,
decreased ability to function at work, obesity and marital relationships can be improved by treating subclinical
hypothyroidism.
Objective: Post partum thyroiditis (PPT) is an
autoimmune disorder that presents in women with transient thyroid dysfunction, elevated thyroid peroxidase
antibodies (TPOab) and thyroid ultrasound abnormalities during the first year after parturition. Several epidemiological studies from different parts of the world
have reported a prevalence of PPT ranging from 1.1 to
16.7%. However, the prevalence of PPT among Nigerian
women has not been reported. This study set to determine
the prevalence of PPT among post partum women in
Northern Nigeria.
Methods: This was a cross sectional case control
study in which 85 women who were six weeks to nine
months post partum and an equal number of age matched
controls were studied for PPT. Relevant medical history
and physical examination for thyroid dysfunction were
carried out in the two groups of women. Blood samples
for serum assays of total T3 (TT3), total T4 (TT4) and
TSH and TPOab were taken and analysed using ELISA
method.
Data were analysed using the statistical software SPSS.
Results: PPT was found in only one case, presenting with thyrotoxicosis and high titres of TPOab (1.2
%). All the control subjects had normal thyroid function
test. The Mean ±SD of serum TT3, TT4 and TSH in the
study and control subjects were similar and comparable,
1.33 ±0.37 and 1.07 ±0.36 ng/ml; 102.13±11.29 and
93.33 ±19.34 nmol/l; and 1.77 ±1.08 and 1.57 ±1.08
mIU/L, p> 0.05 respectively. High titres of TPOab was
found in 1 (1.2%) of study subjects and 3 (3.5%) of control subjects, p > 0.05.
– 126 –
oil), nitric oxide (Mona Vie and nitroglycerin), and carbonic anhydrase inhibition (acetazolamide) all similarly
stimulate cerebral perfusion.
Conclusion: Hyperthyroidism causes a pseudoAlzheimer’s pattern of abnormal cerebral metabolism
which resolves with either natural or pharmacologic
cerebral perfusion stimulants, independent of their mechanism of action.
Abstract #1038
MILD HYPERTHYROIDISM CAUSES A
PSEUDO-ALZHEIMER’S PATTERN OF
CEREBRAL METABOLISM WHICH IS
REVERSIBLE WITH CEREBRAL
PERFUSION STIMULANTS
Harold Thomas Pretorius, MD, PhD,
and Nichole Richards
Abstract #1039
Objective: Compare cerebral metabolism in hyperthyroidism and Alzheimer’s disease.
Methods: Brain SPECT used 12 to 25 mCi Tc-99mHMPAO intravenous (IV) in a dark, quiet room. Basal
perfusion served as a marker of metabolism. Cortical
metabolic and perfusion indices (CMi and CPi) compared
patients before and 1 hr after Mona Vie (acai fruit juice)
or known cerebral perfusion stimulants: 500 mg acetazolamide IV or 0.6 mg nitroglycerin sl in 15 min or 10
g fish oil (Lovaza) oral in 3 hrs. Normal CMi (61+-10)%
and CPi (65+-9)% were from 20 patients with minor
complaints and low likelihood of disease.
Results: Decreased memory was noted in 3 hyperthyroid patients, 1 with toxic nodular goiter and 2
with Graves’ disease, without evidence of coexisting
Hashimoto’s thyroiditis, who had borderline low CMi
(50+-5)% but significant regional parieto-occipital and
mesial temporal defects, defined by regional CMi (40+8)%, calculated as the product of regional activity and the
ratio of active global (in a 60% isocontour) to regional
cortical areas, divided by total cerebral activity (in a
30% isocontour). The similar Alzheimer’s pattern in 2
cases was more pronounced, with much lower CMi and
regional CMi of (30+-10)%. In early Alzheimer’s and in
hyperthyroidism the regional perfusion defects resolved
with Mona Vie or any of the other perfusion stimulants,
resulting in normal CPi (58+-5)%. There was no consistent effect on patient symptoms within several months of
therapy with Lovaza; however, symptoms tended to remit
after successful therapy of hyperthyroidism.
Discussion: Multiple reports from the prospective
Rotterdam study show a > 300% increased incidence of
Alzheimer’s disease in hyperthyroidism, the mechanism of
which is unknown, but from the results here likely involves
specific cerebral metabolism defects. Epidemiological
studies suggest lower rates of Alzheimer’s disease with
increased fish consumption, although more recent reports
question if the beneficial effects of natural fish may be
compromised by increasing levels of neurotoxic pollutants, such as mercury. It is intriguing that multiple mechanisms, including dependence on prostaglandins (fish
ASSOCIATION OF SINGLE NUCLEOTIDE A/G
POLYMORPHISM IN CYTOTOXIC
T- LYMPHOCYTE ANTIGEN 4 (CTLA 4)
GENE (49 EXON 1) IN PATIENTS WITH
AUTOIMMUNE THYROID DISEASE
Rakesh Kumar Sahay, MBBS, P.L. Rekha, PhD,
M. Ishaq, PhD, P. Srinivas Rao, MD,
and G.C. Reddy, MD, DM
Objective: To investigate for a possible allelic association of the single nucleotide polymorphism (CTLA4A/
G) in exon 1 of the cytotoxic T lymphocyte antigen-4
(CTLA4) gene with autoimmune thyroiditis.
Back ground: CTLA-4 is a co stimulatory molecule
expressed on activated T (TH) cells, and functions as a
negative regulator of T cell activation. We investigated
the distribution of the CTLA4 exon 1 polymorphic types
(49 A/G at codon 17) in Graves’ disease and Hashimotos
thyroiditis. This dimorphism results in an amino acid
exchange (Thr/Ala) in the leader peptide of the expressed
protein and reduces the inhibitory function of CTLA4 and contributes to the pathogenesis of auto immune
diseases.
Method: A total of 383 subjects comprising of 128
patients with hypothyroidism, 60 with hyperthyroidism, 150 age and sex matched healthy controls and 45
first degree relatives participated in the present study.
Genotyping was done by PCR using a set of sequence
specific primers (PCR-SSP)
Results: Table 1 depicts the distribution of CTLA 4
genotypes among the patients and the controls. Analysis
of the results indicated highest risk associated with GG
genotypes in patient groups when compared to the control population (χ2 17.341, Pc 0.000. Odd’s Ratio 3.923
with 95% CI 2.057-7.472). Frequency of genotype GG
was observed to be higher in both the groups of patients
(Hashimoto’s thyroditis as well as GD) compared to other
genotypes. However Chi square analysis indicated that
the risk associated with GG genotype is higher towards
developing Grave’s disease (χ2 24.508, Pc 0.000. Odd’s
– 127 –
Ratio 6.551 with 95% CI 3.057-14.027) when compared
to Hashimotos (χ2 8.561, Pc 0.003. Odd’s Ratio 2.951
with 95% CI 1.469-5. 919). Further, the results were
analysed to study if there exists a negative correlation
between any of the genotypes and thyroid dysfunctions.
For this, statistical analyses were done for genotypes AA
and AG against other genotypes in patients in general as
well as hypothyroid cases and hyperthyroid cases separately. Analysis of the results indicated a negative correlation between genotype AA among patients in general
(χ2 12.725, Pc 0.000. Odd’s Ratio 0.287 with 95% CI
0.147-0.565).The association was analysed to be stronger in patients with GD (χ2 17.12, Pc 0.000. Odd’s Ratio
0.179 with 95% CI 0.08-0.4) compared to those with
Hashimotos (χ2 6.15, Pc 0.013. Odd’s Ratio 0.376 with
95% CI 0.82-0.779). When analysis was done for genotype AG, a strong negative association was observed with
patients in general (χ2 6.09, Pc 0.014, Odd’s Ratio 0.544
with 95% CI 0.0.342-0.864,) as well as with Grave’s
Disease (χ2 5.906, Pc 0.015. Odd’s Ratio 0.397 with 95%
CI 0.196-0.802,) compared to the control population. Such
an association was not statistically significant in patients
with hypothyroidism. Further, the distribution of CTLA 4
genotypes among the patients’ group were compared with
that among the unaffected first degree relatives of patients
with Hashimotos and Grave’s Disease (Table 1). In both
the groups of FDRs frequency of susceptible genotype
GG was observed to be nil. Statistical analysis revealed
a significant difference in the distribution of GG genotype in patients with Hashimotos thyrodidits (χ2 5.311,
Pc0.021, Odd’s Ratio Inf.) as well as Grave’s disease (χ2
8.97, Pc0.003, Odd’s Ratio Inf.) compared to the respective FDRs control group.
Conclusion: Genotype as well as allele frequency
studies indicate polymorphism at position 49 of CTLA4
gene as a candidate locus involved in the predisposition
of thyroid dysfunctions. Though reports are available on
this line from various other populations, to our knowledge reports from Indian series of patients are lacking.
Case presentation: An elderly female patient with
advanced metastatic follicular thyroid cancer received
Thyrogen (Genzyme Corp) to stimulate RAI uptake
using the compassionate use protocol. Within 24 hours,
the patient developed respiratory failure requiring intubation and ICU admission. To our knowledge, this is the
first report of Thyrogen-associated respiratory failure in
follicular thyroid cancer. The patient had longstanding
multinodular goiter, which enlarged despite suppressive
levothyroxine therapy. FNA results were suggestive of
a follicular carcinoma. The patient had subtotal thyroidectomy and postoperative RAI ablation with 75 mCi.
Pathology revealed low-grade follicular carcinoma with
vascular capsular invasion. Whole body scan showed
uptake only in the neck. Over the next few years, she
had debulking surgeries for local recurrences with spread
into the mediastinum and surrounding the internal jugular
vein. Despite this, she again developed a new mass in the
thyroid bed and had pulmonary metastates. Whole body I
131 scan and a PET scan were negative. Two years later,
she had additional local recurrence with tracheal compression and left vocal cord paralysis; she refused further surgery. When Thyrogen became available, palliative use (two consecutive doses of Thyrogen, followed by
RAI administration) was planned. The patient received
the first dose of 0.9 mg Thyrogen IM and 24 hours later,
she experienced severe shortness of breath and required
endotracheal intubation. CT scan showed a bulky neck
mass encasing the trachea, and pulmonary metastases.
CXR had a nonspecific pulmonary edema pattern. After
negative evaluation for other causes of respiratory failure,
she received 120 mg Solumedrol IV and was successfully
extubated two days later. She lived for a year after the
hospitalization.
Discussion: Respiratory failure associated with
Thyrogen administration has been reported in metastatic
papillary cancers and in large goiter. Possible mechanisms are low-grade inflammation and oxidative stress
linked to TSH increase. Alternative treatment options
in this case include: pretreatment with glucocorticoids
and the use of lower doses of Thyrogen to stimulate RAI
uptake. Clinicians should be aware of respiratory failure
as a potentially life threatening complication of Thyrogen
use in patients with large thyroid tumors, including follicular cancers.
Abstract #1040
THYROGEN-ASSOCIATED
RESPIRATORY FAILURE
Catalina Norman, MD, Anna C. Freitag, MD,
and Nancy J. Rennert
Objective: To report a case of Thyrogen-associated
respiratory failure in advanced follicular thyroid cancer and to review the mechanisms and treatment of this
potentially life threatening complication.
– 128 –
ABSTRACTS – Index
Adrenal Disorders
Author
AlAssad, Hani
AlAssad, Hani
Albarrán, Alfredo Reza
Alsoutary, Khalil M
Alsoutary, Khalil M
Amin, Alpesh
Añel, Marguerite
Ángeles, Arturo
Armas, Laura A. G.
Avendaño, Edgar
Avendaño, Edgar
Bhatt, Surya Prakash
Bravo, Emmanuel
Brietzke, Stephen
Bulchandani, Deepti
Cardenas, Elva
Clemente, Javier
Dale, Thompson H.
Diab, Dima L.
Doshi, Krupa
Drake III, Almond
Dube, Simmi
Dubey, T. N.
Espinet, Rafael
Farrokhi, Farnoosh
Gajula, Sonia
Gardner, David
Gardner, Michael
Gomez-Perez, Francisco
Gómez-Pérez, Francisco J.
Green, Kim
Guifarro, Maria Alejandra Ramos
Hamrahian, Amir H.
Hanna-Moussa, Abdullah
Harindhanavudhi, Tasma
Harper, Rene J.
Harrell, Michael
Ilahi, Marium
Isales, Carlos
Karounos, Dennis
– 129 –
Abstract No
Page
102
103
108
102
103
105
115
108
120
108
122
121
101
110
105
122
111
121
101
101
118
107
107
116
111
109
112
112
122
108
114
108
101
110
115
119
117
120
119
114
2
2
5
2
2
4
9
5
12
5
13
13
1
7
4
13
7
13
1
1
11
5
5
10
7
6
8
8
13
5
9
5
1
7
9
11
10
12
11
9
ABSTRACTS – Index
Adrenal Disorders (Cont.)
Author
Kelly, Rebecca
Khan, Asma Sohail
Khan, Khurshid
Khan, Uzma
Khaya, Saba
Kurukulasuriya, Lilamani Romayne G.
Llerena, Luis A.
Longo, Santo
Lugar, Richard
May, John
Meyer, Claudine G.
Mezitis, Spyros
Mihailescu, Dan
Nachnani, Jagdish S.
Nanda, Sudip
Odeke, Sylvester
Pamula, John
Panunti, Brandy
Pretorius, Harold Thomas
Ramos, Ma Alejandra
Reyes, Edgardo
Reynolds, L. R.
Richards, Nichole
Rios, Juan Manuel
Rivera, Luis Raul Ruiz
Rull, Juan
Rull, Juan
Shad, Fariha
Sharma, V. K.
Sulaimani, Riad
Sulaimani, Riyadh
Tanawuttiwat, Tanyanan
Taneja, Deepa
Tannock, Lisa
Valentin, Esperanza
Valentín, Esperanza
VanHoven, Anne Marie
Vedula, Ramya Smita
Velasco, German
– 130 –
Abstract No
Page
112
113
110
113
104
109
111
121
112
105
118
100
115
105
121
118
121
104
117
122
108
114
117
108
116
122
108
111
107
102
103
115
114
114
122
108
106
106
100
8
8
7
8
3
6
7
13
8
4
11
1
9
4
13
11
13
3
10
13
5
9
10
5
10
13
5
7
5
2
2
9
9
9
13
5
4
4
1
ABSTRACTS – Index
Adrenal Disorders (Continued)
Author
Weinberg, Andrew
Yasmeen, Tahira
Zalzaleh, Ghassan
Diabetes Mellitus
Author
Abbassy, Aly Abdel Latif
Aboderin, A. O.
Adamu, Abdullah Ndaman
Adeyemi-Doro, Adekunle
Adhiarta, I. G. N.
Aguilar-Salinas, Carlos
Aguirre, Lina
Ahmad, Imteyaz
Akinlade, Akinyele Taofiq
Alejandro, Rodolfo
Alejandro, Rodolfo
Alejandro, Rodolfo
Aljohani, Naji Jameel
Anumah, Felicia Ohunene
Arbab, Tarig Sayed Mustafa
Arbab, Tarig Sayed Mustafa
Attallah, Hamdee
Baddor, Nahed
Baidal, David A.
Baidal, David A.
Baidal, David A.
Bakari, Adamu Girei
Bakari, Adamu Girei
Bakhru, Nitasha
Bamiro, S. B.
Bamiro, S. B.
Bansal, Alka
Bays, Harold
Beel, Ruth
Behnke, Andrew John
Behnke, Andrew John
Bello-Sani, Fatima
– 131 –
Abstract No
Page
100
115
115
1
9
9
Abstract No
Page
206
211
205
254
253
247
213
255
215
232
225
231
227
218
203
256
207
221
206
227
231
225
200
219
216
253
254
212
230
245
245
246
203
18
20
17
45
45
41
21
46
22
32
28
32
29
24
16
46
18
26
18
29
32
28
15
24
23
45
45
21
31
40
40
41
16
ABSTRACTS – Index
Diabetes Mellitus (Cont.)
Author
Benzon, Melissa
Bernetti, Karina
Bulchandani, Deepti
Burke, Brian
Bushati, Besa
Button, Eric
Ceriello, Antonio
Chaudhary, Umair Javaid
Cheang, Mary
Chertow, Bruce
Chinenye, Sunday
Coker, Adekemi Olabisi
Cuevas-Ramos, Daniel
Cure, Pablo
Cure, Pablo
Curry, Andrea
Daru, Patrick
Drake III, A. J.
Eaton, Crystal
Emanuele, Mary Ann
Emanuele, Nicholas
Faradji, Raquel N.
Faradji, Raquel N.
Faradji, Raquel Noemí
Farrokhi, Farnoosh
Fasanmade, Olufemi Adetola
Fonseca, Vivian Andrew
Foster, Scott
Fox, Kathleen M.
Froud, Tatiana
Froud, Tatiana
Froud, Tatiana
Gavin III, James R.
Ghetany, Mohamed Kamal
Goldberg, Ronal
Goldfine, Allison B.
Gomez-Perez, Francisco
– 132 –
Abstract No
Page
245
231
240
239
244
226
226
220
218
233
234
204
213
227
231
227
235
228
240
224
224
225
231
227
214
254
204
253
222
226
223
231
227
225
223
206
237
222
213
40
32
37
37
40
29
29
25
24
33
34
17
21
29
32
29
35
30
37
27
27
28
32
29
22
45
17
45
26
29
27
32
29
28
27
18
36
26
21
ABSTRACTS – Index
Author
Gorn, Lisa
Goscin, Lee Pletts
Grandy, Susan
Gress, Todd W.
Guevara, Ximena
Guevara, Ximena
Guevara, Ximena
Hamburg, Mitchell
Hasan, Mumtaz
Hasan, Mumtaz
Hasan, Mumtaz
Herrada, Eva
Hudson, Sandra G.
Ikem, Innocent
Ikem, Innocent
Ikem, Rosemary Temidayo
Imran, Syed Ali
Imran, Syed Ali
Imran, Syed Ali
Inankur, Aysha Emily
Ishibashi, Hirotaka
Ismail-Beigi, Faramarz
Iwuala, Sandra
Iwuala, Sandra
Jamil, Muhammad Shahid
Jawa, Ali Asghar
Jawa, Ali Asghar
Jawa, Ali Asghar
Jawa, Ghazanfar
Jawa, Ghazanfar
Jing, Ming
Johnston, Jann
Jones, Michael
Jones, Michael R.
Karches, Kelli
Keaveny, Andrew
– 133 –
Abstract No
Page
225
249
223
233
242
241
243
240
220
236
215
231
251
210
209
211
209
210
220
236
215
239
226
229
253
254
220
215
236
220
215
236
220
229
244
230
222
216
255
28
42
27
33
38
38
39
37
25
35
22
32
43
20
19
20
19
20
25
35
22
37
29
30
45
45
25
22
35
25
22
35
25
30
40
31
26
23
46
ABSTRACTS – Index
Author
Khan, Alina
Khan, Zaffer Yab
Khoo, Teck-Kim
Kolawole, Babatope
Kummer, Mark A.
Kupin, Warren
Leitao, Cristiane Bauermann
Lenz, Oliver
Lohano, Suresh
Lohano, Vasdev
Lopez, Norma
Lubitz, Sara Elisabeth
Ludwig, Sora
Martin, Kimberly
Mathur, Sandeep Kumar
McBride, Nancy
McCallum, James
McCallum, James
Mcgarvey, Megan Elizabeth
McNeil, Rebecca
McQuillen, Kelly
Meek, Shon
Messinger, Shari
Messinger, Shari
Messinger, Shari
Mineo, Davide
Mineo, Davide
Mokshagundam, Sri Prakash L.
Monroy, Kathy
Monroy, Kathy
Morris, Margaret
Murray, Robert
Nabhan, Fadi Adel
Nachnani, Jagdish S.
Naidu, M.U.R.
Narasimhan, Kanakasabai
Newton, Christopher Alan
Odetoyinbo, Babatunde
– 134 –
Abstract No
Page
237
212
202
211
251
231
227
231
231
217
217
224
248
218
229
212
214
216
238
238
255
218
255
227
231
225
231
227
217
227
225
218
218
224
240
250
208
228
211
36
21
16
20
43
32
29
32
32
23
23
27
42
24
30
21
22
23
36
36
46
24
46
29
32
28
32
29
23
29
28
24
24
27
37
43
19
30
20
ABSTRACTS – Index
Author
Ogbera, Anthonia Okeoghene
Ohwovoriole, Efedaye
Ola, Bola
Ola, Bola
Olaogun, Matthew
Onyemelukwe, Geoffrey C.
Onyemelukwe, Geoffrey C.
Paturi, Bhanu Teja
Pileggi, Antonello
Pileggi, Antonello
Pinto, Miguel E.
Pinto, Miguel E.
Pinto, Miguel E.
Probst-Riordan, Julie
Puepet, Fabian
Rahman, Ibrahim Abdel
Rao, P.V.
Rasool, Tahir
Rasool, Tahir
Reddem, Sreekanth Reddy
Reiher, Alexandra
Rempel, Brenda
Ricordi, Camillo
Ricordi, Camillo
Ricordi, Camillo
Rizvi, Ali
Rodbard, Helena Wachslicht
Rull-Rodrigo, Juan
Saenz, Aleida
Sakal, Saad
Santhanam, Prasanna
Selvaggi, Gennaro
Selvaggi, Gennaro
Shah, Vipul
Sheikh-Ali, Mae
– 135 –
Abstract No
Page
254
253
234
232
201
204
210
209
209
200
219
250
231
227
243
242
241
248
235
206
250
236
215
250
224
218
227
225
231
208
223
213
227
252
233
231
227
244
255
45
45
34
32
15
17
20
19
19
15
24
43
32
29
39
38
38
42
35
18
43
35
22
43
27
24
29
28
32
19
27
21
29
44
33
32
29
40
46
ABSTRACTS – Index
Author
Shen, Garry
Shokry, Hazem
Sincaroe, James
Smith, Steven
Soetedjo, Nanny Natalia Mulyani
Soghikian, Maida
Sonny, Chinenye
Tanenberg, Robert Jay
Tarigan, Helen C.
Tharavanij, Thipaporn
Truitt, Kenneth
Truitt, Kenneth E.
Uchenna, Doris
Ukoli, Christiana
Uloko, Andrew Enemako
Unachukwu, Chioma
Usharani, P.
Valdes, Paloma Almeda
Varon, Juan Carlos
Villena, Jaime E.
Villena, Jaime E.
Villena, Jaime E.
Watwe, Veena
Wittlin, Steven
Yamanouchi, Toshikazu
Yashmaina, Sridhar
Zafar, Muhammad Abu
Zafar, Muhammad Abu
Zaheer, Jawad
Zaheer, Jawad
Zaheer, Jawad
Hypoglycemia
Author
Agarwal, Monica
Agosto, Agosto
Ahmad, Khraisat
Alejandro, Rodolfo
– 136 –
Abstract No
Page
218
206
224
202
247
238
201
228
247
227
231
230
222
234
235
235
234
250
213
237
243
241
242
221
226
226
250
215
236
215
220
236
24
18
27
16
41
36
15
30
41
29
32
31
26
34
35
35
34
43
21
36
39
38
38
26
29
29
43
22
35
22
25
35
Abstract No
Page
301
306
300
303
48
51
48
49
ABSTRACTS – Index
Hypoglycemia (Cont.)
Author
Aljaghbeer, Eshraq Nazir
Allende, Myriam
Almeda-Valdés, Paloma
Almeda-Valdés, Paloma
Baidal, David A.
Bernetti, Karina
Cruz, Sidney
Cure, Pablo
Elbein, Steven
Faradji, Raquel N.
Froud, Tatiana
Gabriel, Barnard San
Kowalczyk, Joseph
Mateo, Jose Garcia
Mihailescu, Dan
Mineo, Davide
Pileggi, Antonello
Rabell, Vilma
Ramirez, Margarita
Ricordi, Camillo
Rull, Juan
Rull, Juan
Saenz, Aleida
Santiago, Monica
Singh, Sant P.
Thomas, Tarita
Uribe-Uribe, Norma
Uribe-Uribe, Norma
Ventura-Gallegos, Jose Luis
Yasmeen, Tahira
Zarate-Diaz, Xeily
– 137 –
Abstract No
Page
300
306
305
302
303
303
300
302
305
303
301
303
303
304
302
305
304
304
303
306
304
303
303
306
306
303
305
302
303
306
300
304
303
304
305
302
302
304
305
48
51
50
49
49
49
48
49
50
49
48
49
49
50
49
50
50
50
49
51
50
49
49
51
51
49
50
49
49
51
48
50
49
50
50
49
49
50
50
ABSTRACTS – Index
Hypoglycemia (Cont.)
Author
Zarate-Diaz, Xeily
Zentella-Dehesa, Alejandro
Lipid Disorders
Author
Attallah, Hamdee
Baker, Mary
Bakry, Elsayed
Bhatt, Surya Prakash
Crisostomo, Analyn
Eledrisi, Mohsen
Handa, Rohini
Haq, Seema
Joosub, Omran
Nanda, Sudip
Saghier, Sadaf
Scofield, Hal
Sultan, Mohammed
Zambare, Suchitra V.
Metabolic Bone Disease
Author
Adachi, Jonathan D.
Agarwal, Niti
Ajamani, Ajay
Bodenner, Donald
Boonen, Steven
Borretta, Giorgio
Brown, J.
Castro-Magana, Mariano
Cesario, Flora
Clarke, Bart L.
Dedrick, Rebecca
Delmas, P. D.
Dube, Simmi
Dubey, T. N.
Fatourechi, Vahab
Flores, Mauricio Ernesto
García, Franklin
– 138 –
Abstract No
Page
302
302
49
49
Abstract No
Page
400
402
401
403
401
401
403
402
401
403
402
402
401
400
52
53
52
53
52
52
53
53
52
53
53
53
52
52
Abstract No
Page
517
502
502
505
518
519
511
516
519
515
504
511
510
510
522
516
501
64
56
56
57
64
65
61
63
65
63
57
61
60
60
66
63
55
ABSTRACTS – Index
Metabolic Bone Disease (Cont.)
Author
Gianotti, Laura
Grant, Kenneth
Grauer, Andreas
Grauer, Andreas
Grauer, Andreas
Greenspan, Susan L.
Hughes, Thomas A.
Jain, Sachin Kumar
Jasson, Lavi
Karmegan, Satish
Kline, G.
LaCroix, Andrea
Laura, Monsalve
Levin, Robert
Lindsay, Robert
Lindsay, Robert
Magro, Giampaolo
Manandhi, Aswatharayan
Mazhari, Alaleh
McClung, Michael R.
Mendoza, Ana
Miller, Paul D.
Moraghan, Thomas
Morales, Pedro E.
Moses, Arnold M.
Moses, Arnold M.
Movva, Arun Kumar
Mukherjee, Akta Patel
Nabhan, Fadi Adel
Paulo, Jr, Remberto Cuenca
Placzkowski, Kimberly Ann
Rao, Ambika
Ratti, Jyothi
Redman, Carolyn
Rieke, Suzanne
Roux, Christian
Roux, Christian
Rubin, Daniel
Saag, Kenneth
– 139 –
Abstract No
Page
519
520
518
517
513
504
506
502
501
520
511
504
501
509
517
504
519
520
512
518
523
518
521
501
503
514
503
500
512
508
515
520
520
505
500
517
513
509
504
65
65
64
64
62
57
58
56
55
65
61
57
55
59
64
57
65
65
61
64
67
64
66
55
56
62
56
55
61
59
63
65
65
57
55
64
62
59
57
ABSTRACTS – Index
Metabolic Bone Disease (Cont.)
Author
Sabharwal, Anup
Sarabu, Brijmohan
Schiefer, Amanda Reagan
Sharma, V. K.
Silverman, Stuart
Singh, Harinder
Siris, Ethel
Subbarayan, Sreevidya Kannoorpatti
Tassone, Francesco
Tebben, Peter J.
Torres, Mira S.
Venkatesh, Swamy
Watts, Nelson B.
Watts, Nelson B.
Watts, Nelson B.
Watts, Nelson B.
Yeh, James
Young, Lisa
Young, Lisa
Zaidi, Syeda Sadia
Zhou, Xiaojie
Zhou, Xiaojie
Zhou, Xiaojie
Obesity
Author
Chaudhary, Umair Javaid
Hasan, Mumtaz
Imran, Syed Ali
Jawa, Ali Asghar
Jawa, Ghazanfar Ali
Zaheer, Jawad
Other
Author
Abrams, Cynthia
Abu-Lebdeh, Haitham S.
Ahmed, Mohammed
Al-Harthi, Saud
– 140 –
Abstract No
Page
524
514
522
510
504
520
504
521
519
508
523
520
513
517
504
511
516
507
524
506
517
518
513
67
62
66
60
57
65
57
66
65
59
67
65
62
64
57
61
63
58
67
58
64
64
62
Abstract No
Page
600
600
600
600
600
600
600
69
69
69
69
69
69
69
Abstract No
Page
707
704
702
702
73
72
71
71
ABSTRACTS – Index
Other (Cont.)
Author
Allende, Myriam
Anumah, Felicia Ohunene
Apovian, Caroline M.
Asnani, Sunil
Bejnariu, Cristina Iuliana
Bhatt, Bankim
Bin-Abbas, Bassam
Black, Dennis
Bone, Henry
Boonen, Steve
Chow, John T.
Colle, Ann
Di Luozzo, Gabriele
Eriksen, Erik Fink
Fomin, Svetlana
Foote, Robert L.
Gambhir, Kanwal
Giannini, S.
Jacob, Jubbin Jagan
Jacob, Jubbin Jagan
Kazlauskaite, Rasa
Khaodhiar, Lalita
Komarovskiy, Kateryna
Lewi, Jack E.
Lipede, Adefunke Omosefe
Lippuner, K.
Lowery, Supna Bhagat
Martinez, Meliza
Mason, Elizabeth
Mechanick, Jeffrey I.
Mesenbrink, Peter
Miller, Paul D.
Miller, Ralph
Nunlee-Bland, Gail
O’Brian, John
Odonkor, Wolali
Ogbera, Anthonia
Osorio, Jorge Ivan Martinez
Pathak, Ram D.
– 141 –
Abstract No
Page
720
710
703
700
719
716
702
711
711
711
704
718
705
711
700
704
707
711
709
708
714
703
706
717
701
711
718
720
718
705
711
711
713
707
718
707
701
717
712
81
75
71
70
80
79
71
76
76
76
72
80
72
76
70
72
73
76
74
74
77
71
73
79
70
76
80
81
80
72
76
76
77
73
80
73
70
79
76
ABSTRACTS – Index
Other (Cont.)
Author
Pathak, Sumedha Ram
Rabell, Vilma
Raikhelkar, Jayashree
Ramirez, Margarita
Reynolds, L. R.
Richardson, Donald
Sakal, Saad
Scurlock, Corey
Sellmeyer, Deborah
Semega-Janneh, Mariama
Shukla, Pratik R.
Signalov, Mikhail
Singh, Madhurita
Singh, Navjot
Singh, Navjot
Skag, Arne
Suciu, Pavel
Taneja, Deepa
Tannock, Lisa
Usdan, Lisa S.
Vahedi, Marjan
Velinova, Silvia
Via, Michael
Wermers, Robert A.
Williams, James T.
Win, Hla
Winer, Nathaniel
Pituitary Disorders
Author
Abelev, Zinoviy
Aguirre, Lina
Ahmed, Mohammed
Ahmed, Mohammed
Ahmed, Mohammed
Akhter, Natasha
Al-Ahmed, Saleh
– 142 –
Abstract No
Page
712
720
705
720
713
718
721
705
711
707
716
716
708
709
708
711
719
713
713
703
707
714
705
704
707
715
706
76
81
72
81
77
80
82
72
76
73
79
79
74
74
74
76
80
77
77
71
73
77
72
72
73
78
73
Abstract No
Page
816
824
804
829
818
811
826
823
826
92
97
85
99
93
89
98
96
98
ABSTRACTS – Index
Pituitary Disorders (Cont.)
Author
Al-Dabagh, Hiba
Al-Harathi, Mohammed
Al-Harthi, Saud
Al-Hindi, Hindi
Al-Jaghbeer, Eshraq
Al-Lawati, Zahraa
Al-Sheef, Mohammed
Alfonso, Bianca
Allende, Myriam
Atkinson, John
Attri, Navneet
Augustine, Jaimie M.
Avendaño, Edgar
Bakkari, Shakir
Beniwal, Poonam
Blumenthal, Stanley
Buciuc, Razvan F.
Bushnik, Tamara
Butler, Paula
Carpenter, Robert J.
Clyde, Patrick W.
Czervionke, Leo
Dababo, M.
Dankert-Hsu, Nicole M.
Dodis, Regina
Duggal, Jasleen Kaur
Dulipsingh, Latha
Ekpebegh, Chuks
Eray, Esin
Erickson, Dana
Faiman, Charles
Falls, William L.
Fasanmade, Olufemi
Fasanmade, Olufemi
Fleckman, Adrienne M.
Glusman, Joan
Group, The Pasireotide Acromegaly Study
Hamrahian, Amir H.
– 143 –
Abstract No
Page
819
811
818
811
801
820
826
816
827
805
801
809
817
811
801
823
812
820
801
800
802
829
818
800
828
801
822
824
821
805
821
800
804
824
816
808
808
821
823
93
89
93
89
83
94
98
92
98
85
83
88
92
89
83
96
89
94
83
83
84
99
93
83
99
83
95
97
95
85
95
83
85
97
92
87
87
95
96
ABSTRACTS – Index
Author
Iwuala, Sandra Omozehio
Joshi, Prajesh
Kanaan, Imaduddin
Kanaan, Imaduddin
Kanaan, Imaduddin
Kantorovich, Vitaly
Kassim, Thaslim Ahamed
Katznelson, Laurence
Khalfin, Alla
Khan, Uzma
Koch, Christian A.
Kunecka, Paulina
LaRochelle, Jeffery S.
Lewi, Henry L.
Lindsay, Robert M.
Lorenz, Robert R.
Lteif, Aida
Ludlam, William Henry
Lugaro-Gomez, Ana
Mallhi, Kanwal
Mann, Klaus
Marlar, Victor Richard
Marwan, Shaheen
Mayberg, Marc R.
Mogul, Harriette
Nader, Nicole Stephanie
Narula, Harmeet Singh
Narula, Maneet Kaur
Narula, Maneet Kaur
Nazmi, Ahmed
Nicholas, William C.
Nimmo, Teresa Allison
Nunlee-Bland, Gail
Odeniyi, Ifedayo Adeola
Odeniyi, Ifedayo Adeola
Odonkor, Wolali
Ohwovoriole, Augustin
Patterson, Marc
– 144 –
Abstract No
Page
804
816
818
826
811
803
802
820
807
814
812
828
800
820
813
821
810
809
827
801
808
812
818
809
807
810
815
825
815
825
818
812
803
819
804
824
819
824
810
85
92
93
98
89
84
84
94
86
91
89
99
83
94
90
95
88
88
98
83
87
89
93
88
86
88
91
97
91
97
93
89
84
93
85
97
93
97
88
ABSTRACTS – Index
Author
Pérez, Francisco J. Gómez
Petersenn, Stephan
Rabel, Vilma
Ramirez, Margarita
Ramirez, Jr., Sofronio Cruz
Ramos, Ma. Alejandra
Reddy, Ashwini
Rennert, Nancy J.
Roberts, Brian
Rull, Juan
Sabir, Anas
Sathananthan, Airani
Scheithauer, Bernd
Seale, Benjamin W.
Semega-Janneh, Mariama
Shakir, K.M. Mohamed
Shakir, K.M. Mohamed
Sheikh-Ali, Mae
Singh, Sarabjeet
Siraj, Elias
Smallridge, Robert C.
Smith, Earl
Soler, Simonette
Spain, David A.
Srinivasan, Lakshmi
Steinberg, Gary
Stringer, Jonathan
Strizhevsky, Marina
Sundararajan, Deepa
Sundararajan, Deepa
Tchong, Leo
Unger, Nicole
Valentin, Esperanza
Valenzuela, Evana
Veloski, Colleen
Vouyiouklis, Mary
Warner, Christopher J.
Weil, Robert J.
– 145 –
Abstract No
Page
817
808
827
827
822
817
814
828
820
817
804
805
805
812
819
802
800
829
801
806
829
801
822
820
820
820
803
816
825
815
823
806
808
817
828
806
813
800
821
92
87
98
98
95
92
91
99
94
92
85
85
85
89
93
84
83
99
83
86
99
83
95
94
94
94
84
92
97
91
96
86
87
92
99
86
90
83
95
ABSTRACTS – Index
Author
Wharen, Robert
Yudt, William M.
Zerikly, Rahfa Kurdi
Reproductive Endocrinology
Author
Ajamani, Ajay
Banceanu, Gabriel
Barbu, Carmen
Burshell, Alan
Calderon, Naim Mitre
Carsote, Mara
Coculescu, Mihail
Constantin, Madalina
Diwaker, Pramila
Fica, Simona Vasilica
Islam, Najumul
Jabbar, Abdul
Jain, Sachin Kumar
Lascar, Ioan
Lteif, Aida
Mahar, Saeed Ahmed
Poiana, Catalina I.
Sajin, Maria
Scanlan, Marideli Colón
Stanescu, Bogdan
Terzea, Dana
Viswanathan, Pushpa A.
Witchel, Selma F.
Thyroid Disease
Author
Abou-Samra, Abdul
Adamcik, Susan Jane
Agarwal, Monica
Ahmed, Javeria
Ahmed, Mohammed
Ahmed, Mohammed
Al Jawair, Rashid O.
– 146 –
Abstract No
Page
829
802
821
99
84
95
Abstract No
Page
901
903
906
905
902
903
903
906
901
906
900
900
901
906
902
900
903
903
905
903
906
904
904
101
102
104
104
102
102
102
104
101
104
101
101
101
104
102
101
102
102
104
102
104
103
103
Abstract No
Page
1007
1021
1015
1026
1010
1005
1001
110
118
114
120
111
108
106
ABSTRACTS – Index
Thyroid Disease (Cont.)
Author
Al-Harthy, Mohammed
Al-hindi, Hindi
Al-Zidjali, Fatima
Alejandro, Angel Rodolfo
Alenezi, Mohammed
Alhawari, Hussam H.
Alshammari, Sameer
Badlissi, John
Bagchi, Nandalal
Bajaj, Harpreet Singh
Baruah, Manash Pratim
Bhagra, Anjali
Bhuyan, Sonali Barman
Bible, Keith C.
Blumenthal, Manfred
Castillo-Perez, Judith M.
Chianelli, M.
Choudhry, Imran
Correa, Francisco
Davies, Terry F.
Dougherty, Thomas
Durst, Paul
Edmonds, Merill
Ennis, Rob
Faas, Fred H.
Farhat, Rafif
Fatourechi, Vahab
Feng, Yun
Fleckman, Adrienne M.
Freitag, Anna C.
Fresca, Diane E.
Galofre, Juan C.
Gharib, Hossein
Gonzalez-Pantaleon, Adalberto D.
Goscin, Lee Pletts
Gouller, Alina
Grant, Clive S.
Graziano, F.
Groh, Katherine
– 147 –
Abstract No
Page
1010
1010
1005
1024
1000
1004
1000
1017
1007
1012
1008
1032
1008
1003
1021
1002
1025
1006
1002
1009
1019
1019
1001
1011
1004
1005
1032
1018
1018
1040
1029
1009
1011
1022
1037
1027
1003
1025
1018
111
111
108
119
106
108
106
115
110
112
110
124
110
107
118
107
120
109
107
111
116
116
106
112
108
108
124
116
116
128
122
111
112
118
126
121
107
120
116
ABSTRACTS – Index
Author
Guglielmi, R.
Gurevich, Yuriy
Haber, Richard
Hartini, Sri
Hay, Ian D.
Hramiak, Irene
Huang, Cindy
Hughes, Thomas
Hutchinson, Maeve Elizabeth
Iranmanesh, Ali
Iranmanesh, Ali
Ishaq, M.
Jain, Bina
Javier, Emmanuel
Johnston, Jann M.
Kanaan, Imaduddin
Kariadi, K. S.
Khalil, Nesreen
Khan, Saima
Kulczycki, Alexander
Kundra, Priya
Kuo, Sheng-Fong
Lin, Jen-Der
Makdissi, Antoine
Makdissi, Antonie
Mansour, Maged
Marina, Anna Leonidovna
Mikhail, George Samir
Mubi, Bilkisu Mohammed
Narula, Maneet Kaur
Nazmi, Ahmed
Ng, Alvin
Nicholas, William
Norman, Catalina
Ohwovoriole, Augustine E.
Padmanabhan, Hema
Padmanabhan, Hema
Papini, Laura Todino V.
– 148 –
Abstract No
Page
1025
1027
1009
1031
1003
1001
1034
1026
1003
1016
1017
1039
1006
1002
1020
1010
1031
1000
1014
1030
1021
1035
1035
1004
1015
1000
1020
1000
1036
1033
1033
1010
1028
1013
1040
1036
1016
1017
1025
120
121
111
123
107
106
125
120
107
115
115
127
109
107
117
111
123
106
114
122
118
125
125
108
114
106
117
106
126
124
124
111
121
113
128
126
115
115
120
ABSTRACTS – Index
Author
Papini, Enrico
Parong, Maria Paulina Santos
Pretorius, Harold Thomas
Rao, P. Srinivas
Reddy, G. C.
Rekha, P. L.
Rennert, Nancy J.
Richards, Nichole
Robinson, Suzette Adele
Sabharwal, Anup
Sahay, Rakesh Kumar
Seale, Ben Williamson
Sherigar, Rathnakara
Signore, A.
Simmons, Debra L.
Simmons, Debra L.
Siraj, Elias
Soetedjo, Nanny Natalia Mulyani
Strizhevsky, Marina
Sundararajan, Deepa
Tham, Kwang-Wei
Thompson, Geoffrey B.
Tokmakejian, Sonya
Toscano-Zokor, Amy
Tulbah, Asma
Uricoechea, Hernando Vargas
Van Hoven, Anne Marie
Veloski, Colleen
Wang, Xiangbing
Wang, Xiangbing
Wang, Xiangbing
Wheaton, Jennifer
Wheaton, Jennifer Carter
Yaqub, Abid
Yaqub, Abid
Young, Jr, William F.
Zimmerman, Robert
– 149 –
Abstract No
Page
1025
1019
1038
1039
1039
1039
1040
1038
1007
1024
1039
1013
1016
1025
1004
1015
1022
1031
1018
1033
1028
1003
1001
1034
1005
1023
1014
1022
1029
1030
1034
1019
1006
1006
1019
1003
1012
120
116
127
127
127
127
128
127
110
119
127
113
115
120
108
114
118
123
116
124
121
107
106
125
108
119
114
118
122
122
125
116
109
109
116
107
112

Document 6427306

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