Endocrine Board

Review
Ria Dancel, MD
6/23/2008
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 Hyperprolactinemia in pt
with secondary amenorrhea
• Secondary amenorrhea = Absence of menses
for 3 or more consecutive months in a woman
who has menstruated previously
• First test is always pregnancy test!
• PCOS is the most common cause of secondary
amenorrhea but hyperprolactinemia must be
excluded to make the Dx of PCOS
• Prolactin is unique in that it is under chronic
dopaminergic inhibition by the hypothalamus. It
causes amenorrhea by suppressing GnRH
 Hyperprolactinemia in pt
with secondary amenorrhea
Causes of hyperprolactinemia:
• Physiologic:
– Pregnancy
– Lactation
• Pharmacologic:
– Antipsychotics, MAOI, SSRI, antiemetics
– Calcium channel blockers, estrogens, opiates, cocaine
• Pathologic:
– Primary hypothyroidism (Low thyroid hormones  increased
thyrotropin releasing hormone  increase in TSH and
secondary increase in prolactin)
– Prolactinoma (Most common pituitary tumor)
– Tumor disrupting stalk
– Hepatic failure (Decreased secretion of prolactin)
– Renal failure (Decreased secretion of prolactin)
 Hyperprolactinemia in pt
with secondary amenorrhea
Causes of
hyperprolactinemia

Serri, O. et al. CMAJ 2003;169:575-581

Copyright ©2003 Canadian Medical Association or its licensors
 Hyperprolactinemia in pt
with secondary amenorrhea
History: Classic s/sx are amenorrhea, galactorrhea,
infertility
– Headaches prolactinoma or tumor disrupting stalk
– Fatigue, weakness, weight gain, cold intolerance 
hypothyroidism
Physical exam:
– Galactorrhea
– Bitemporal hemianopsia  tumor
Labs:
– Prolactin > 200, think TUMOR
– TSH, T4 if hypothyroidism is suspected
Treatment:
– Dopamine agonists: bromocriptine and cabergoline
– Surgery reserved for refractory cases, invasive disease,
persistent visual field deficits
 MKSAP Question
A 26-year-old woman is evaluated for amenorrhea. Her last menstrual
period was 3 months ago, and three home pregnancy tests have
been negative. She states that she has no other symptoms and
takes no medications. Menarche occurred at age 12 years, and her
menstrual cycle has been regular until 3 months ago. Upon further
questioning, she recounts weekly headaches and occasional
galactorrhea on breast palpation. Physical examination, including
neurological examination, is normal. Deep tendon reflexes are
normal. Serum prolactin level is 1665 ng/mL (1665 mg/L)

Which of the following is the most likely cause of this patient's

hyperprolactinemia?

A. Pregnancy
B. Cirrhosis
C. Primary hypothyroid
D. Prolactin-producing pituitary tumor
 MKSAP Question
A 34-year-old woman is evaluated for fatigue, weight gain, irregular
menstrual cycles, and milky discharge from both breasts for 6
months. She has had no change in vision and is not taking any
medications.
Physical examination reveals a small goiter, dry skin, bilateral
expressible galactorrhea, and normal visual fields. Laboratory results
include a negative pregnancy test and a serum prolactin level of 55
ng/mL (55 mg/L). MRI of the head shows an enlarged pituitary gland
that extends to within 1 mm of the optic chiasm.

Which of the following is the most appropriate next step in the

management of this patient?

A. Re-measure serum prolactin level

B. Start estrogen/progesterone cyclic therapy
C. Start dopamine agonist therapy
D. Measure TSH and free T4
E. Refer to neurosurgeon for pituitary surgery
 The Adrenal Gland

Glucocorticoids – Cortisol
Mineralocorticoids – Aldosterone
Catecholamines – Norepi, epi, DA
Sex steroids – Testosterone,
Estrogen
Confirm pheochromocytoma
• Adrenal medullary tumor of neural crest origin;
secretes norepi, epi, and dopamine
• Rule of 10’s: 10% extramedullary, 10% familial, 10%
malignant, 10% asymptomatic
• In hypertensive patients, the triad of sudden severe
headaches, diaphoresis, and palpitations has 94%
specificity and 91% sensitivity for pheo

1. Draw plasma fractionated metanephrines, sensitivity

97% but specificity 85%
2. Confirm with 24 hour urine collection for
metanephrines, specificity > 94%
3. Localize with abdominal CT, with special attention to
the adrenal glands
 Cushing’s: Hypothalamic-
pituitary-adrenal axis

Kirk LF, Hash RB, Katner HP, Jones T. Cushing’s disease: Clinical manifestations and diagnostic evaluation. Am Fam Physician.
2000 Sep 1;62(5):1119-27, 1133-4
 Cushing’s disease and
Cushing’s syndrome
• Caused by excess glucocorticoids
• Cortisol is major natural glucocorticoid
• Signs/Sx: central adiposity, moon facies, buffalo hump,
violaceous striae, hyperglycemia, hypertension,
hirsutism, amenorrhea, acne, proximal muscle
weakness, osteoporosis
• Causes – most to least common
1. Exogenous glucocorticoids
2. ACTH-secreting corticotroph adenoma of the pituitary =
Cushing’s disease. 80% of cases of endogenous excess
3. Unilateral adrenal adenoma. 10% of cases of endogenous
excess
4. Paraneoplastic syndrome. 10% of cases of endogenous excess
 Cushing’s disease and
Cushing’s syndrome
1. Confirm glucocorticoid excess
– Salivary cortisol concentration
– Overnight dexamethasone suppression test. Give
1 mg dexamethasone at 23:00, measure cortisol at
08:00. Should be < 5 μg/dL. (98% sensitivity, 80%
specificity)
– 24 hour urine cortisol (>95% specificity and
sensitivity)
– False positives caused by depression, chronic
EtOH, obesity = pseudo-Cushings
2. Determine if excess glucocorticoid is ACTH
dependent or ACTH independent by drawing
a late PM level of ACTH.
 Cushing’s disease and
Cushing’s syndrome
Late PM ACTH > 10 Late PM ACTH < 5
pg/ml (2 pmol/L) pg/ml (1 pmol/L)

ACTH DEPENDENT ACTH INDEPENDENT

•Cushing’s disease •Adrenal adenoma

•Ectopic ACTH (tumor) •Iatrogenic

(-)
High dose
dexamethasone

No effect TUMOR

Further testing: CRH stimulation test, inferior petrosal sinus sampling

 MKSAP Question
A 38-year-old woman is evaluated for an elevated salivary
cortisol concentration collected at 2300 hrs (9.3 nmol/L
[256.59 nmol/L]) on two separate occasions. The patient has
poorly controlled diabetes mellitus and signs of cortisol
excess. The serum ACTH is 29 pg/mL (6.39 pmol/L)
Which of the following is the most appropriate next diagnostic
test in this patient?
A. Dexamethasone 8 mg overnight suppression test
B. MRI of the head
C. Somatostatin receptor scintigraphy
D. Inferior petrosal sinus sampling
Cushing’s and osteoporosis
• Exogenous corticosteroid use is the most
common cause of secondary osteoporosis
• DEXA scan prior to starting steroids
• 1500 mg/day of Ca, 800 IU/day of vit D
• Start bisphosphonate therapy if pt will be
exposed to > 5 mg prednisone (or its
equivalent) daily x 3 months
• Repeat DEXA scan 6-12 months into steroid
therapy
 Manage incidental adrenal
tumor
• Most incidentalomas are hormonally silent and
have no malignant potential BUT up to 30%
secrete cortisol, aldosterone, androgens, or
catecholamines
1. Assess hormonal activity
– Rule out Cushing’s syndrome
– Rule out pheochromocytoma
– Rule out aldosterone secreting tumor in hypertensive pts with plasma
aldosterone : plasma renin activity ratios. PA:PRA > 20:1 suggests
primary aldosteronism with > 90% sensitivity and specificity
2. Assess malignant potential with CT
– Benign lesions: < 6cm, smooth borders, < 10 Hounsfield units, no
enhancement with contrast
– Malignant lesions: 25% of tumors > 6cm are carcinomas, ragged
borders, > 10 Hounsfield units, enhance with contrast
 Manage incidental adrenal
tumor
• Hypersecreting adenomas,
pheochromocytomas, and tumors 6 cm or
greater in diameter should be surgically
resected
• FNA lesions only when pt is known to
have primary malignancy elsewhere
• Repeat radiographic imaging and lab
work in 6-12 months for lesions < 6 cm
unless worrisome radiographic findings
present
 MKSAP Question
A 26-year-old woman is evaluated in the emergency department for lower
abdominal/pelvic discomfort. The blood pressure during the episode is
160/90 mm Hg, but she has no history of hypertension. She has been in
good health until her present episode, which started several hours before
the visit.
Her BMI is 26, and she has no hirsutism, striae, or central adiposity.
Hematologic findings and plasma glucose and serum electrolytes are
normal. During her evaluation, the discomfort lessens and resolves
spontaneously and she is released. CT scan of the abdomen done during
the evaluation shows a 1.8-cm irregularity in the right adrenal gland.

Which of the following would be the most appropriate follow-up of this

finding?

A. MRI of the abdomen

B. Observation only
C. Repeat CT scan in 1-3 months
D. Screen for pheochromocytoma, Cushing’s syndrome, and primary aldosteronism
 MKSAP Question
A 56-year-old man is evaluated for anorexia and a 5-kg (11-lb) unintentional
weight loss over the preceding 4 months. He has vague abdominal discomfort
and occasional flank pain.
On physical examination, the BMI is 27 and the blood pressure is 108/72 mm Hg.
Examination is unremarkable.
CT scan of the abdomen shows a 6-cm left adrenal mass. Attenuation value of
the mass is 32 Hounsfield units. The margins of the lesion are irregular and
the consistency is heterogeneous. Radiographic evaluation of the lungs and
kidneys reveals no other abnormality.
Plasma fractionated metanephrines are normal. Plasma aldosterone/plasma
renin activity (ARR) is 6 (normal <12). Serum cortisol at 0800 hrs after
dexamethasone 1 mg the preceding evening is 1.4 µg/dL (38.63 nmol/L).

Which of the following is the most appropriate next step in the management of
this patient?

A. Selective adrenal venous sampling

B. Repeat biochemical testing and CT in 6 months
C. Iodocholesterol imaging of adrenals
D. Referral for surgical resection of mass
 Solitary thyroid nodule
• 5% of thyroid nodules are malignant
• Poor prognostic factors: male, middle-age,
tumor size > 4-5 cm, local invasion, distant
mets
• Types of thyroid cancer
– Papillary: 75%
– Follicular: 15-20%
– Medullary: <5%, derived from calcitonin-producing
C-cells. 75% sporadic, remainder are inherited
– Anaplastic: <5%, 10-year survival ~15%
 Solitary thyroid nodule
• Multiple endocrine neoplasia
– Autosomal dominant inheritance
– RET proto-oncogene mutations
• MEN type 2A:
– Medullary thyroid carcinoma: 95-100% penetrance
– Unilateral or bilateral pheochromocytomas: 40-50%
penetrance
– Hyperparathyroidism: 10-20% penetrance
• MEN type 2B:
– Medullary thyroid carcinoma: 95-100% penetrance
– Pheochromocytomas: 50% penetrance
– Mucosal neuromas (tongue, under eyelids, intestinal)
– Marfanoid body habitus
 Solitary thyroid nodule -
diagnosis
1. Measure TSH
– Normal TSH  “cold”, nonfunctioning nodule
– Low TSH  “hot”, hyperfunctioning nodule
2. Ultrasound
– Distinguish solitary nodule from multinodular goiter
– Establish baseline size
– Eval for suspicious features; eg. stippled
calcifications
3. FNA all cold nodules
4. In multinodular goiter, nodules > 1.5 cm or fast
growing nodules are typically aspirated
 Solitary thyroid nodule -
management
• Papillary and follicular thyroid cancer  total
thyroidectomy and 131I at high doses. 10 year survival >
90%
• Medullary thyroid cancer  total thyroidectomy/neck
dissection.
– Since these are derived from C-cells and secrete calcitonin,
radioactive iodine has no effect
– Follow with calcitonin and CEA levels
– Key point: Screen all patients with suspected medullary thyroid
cancer for pheochromocytoma! Why? Sending a pt with
undiagnosed pheo for thyroidectomy can result in catastrophic
hypertensive crisis and fatal arrhythmia
 MKSAP question
A 45-year-old woman is evaluated for a sensation of fullness in her neck
and occasional difficulty swallowing. She feels well otherwise. She has
no history of head and neck radiation therapy. Her mother developed a
goiter in her 40s.
On physical examination, the thyroid gland is enlarged to approximately
twice the normal size and there is a dominant 2-cm nodule in the left
lobe. No cervical lymph nodes are palpable. The serum thyroid-
stimulating hormone (TSH) level is 1.8 µU/mL (1.8 mU/L). Thyroid
ultrasound reveals multiple small nodules in both lobes and a 2.2-cm
dominant nodule in the left lobe.

Which of the following is the most appropriate next step in the evaluation
of this patient?

A. Thyroid scan
B. FNA of dominant nodule
C. Serum thyroglobulin level
D. Serum antithyroid peroxidase and antithyroglobulin antibodies
E. Serial US measurements
 MKSAP question
A 42-year-old man is evaluated for an anterior neck mass. He has a family
history of thyroid cancer and hyperparathyroidism. On physical
examination, the blood pressure is 147/85 mm Hg and the pulse rate is
88/min; he has a 3-cm right thyroid nodule and bilateral anterior cervical
lymphadenopathy. Lungs are clear and cardiac examination reveals a 2/6
systolic ejection murmur; there is no pedal edema. Laboratory testing
shows a serum thyroid-stimulating hormone of 1.4 µU/mL (1.4 mU/L) and
calcium of 10.6 mg/dL (2.64 mmol/L), and microscopic hematuria. Fine-
needle aspiration biopsy of the nodule suggests medullary thyroid
cancer.

Which of the following tests is the most appropriate next test in the
evaluation of this patient?

A. Serum calcitonin level

B. Repeat biopsy with immunostaining with calcitonin
C. Serum PTH level
D. Urine metanephrines
E. Urine calcium, phosphate, and citrate
 Confirm thyrotoxicosis
factitia
• Signs/Sx of thyrotoxicosis: In order of diagnostic
importance: lid retraction, lid lag, fine finger tremor,
moist/warm skin, tachycardia.
– Other signs/sx: heat intolerance, weight loss,
arrhythmia/palpitations, brisk DTR, anxiety, diarrhea, hair loss,
bone loss
• When to suspect factitious disease:
– Absence of exophthalmos, pretibial myxedema
– Unpalpable thyroid
• Exams:
– Low TSH
– Low TRH
– High T4 or T3 (depending on levothyroxine or liothyronine)
– Normal ESR
– Low radio-iodine uptake
 Confirm acute thyroiditis
• AKA acute suppurative thyroiditis
• Staphylococcus aureus, Streptococcus
hemolyticus, and pneumococcus
• Sx: fever, chills, neck pain and erythema (may
be unilateral), sore throat, hoarseness, and
dysphagia
• Labs: Leukocytosis with left shift, increased
ESR, NORMAL thyroid function tests
• Studies: Radioactive iodine scanning
unnecessary, needle aspiration and culture
helpful if abscess suspected
 Diagnose iodine-induced
hyperthyroidism
• Exposure to betadine, amiodarone,
radiographic contrast dye in pt with pre-existing
nodular goiter
• Nodular goiters can be autonomous – lacking
autoregulatory mechanisms against excess
iodine
• High index of suspicion in middle-aged/elderly
pts with enlarged thyroid or nodule in the
correct setting
• Measure TSH, T4, and urine and serum iodine
• Tx: Remove source of iodine. May need
methimazole or PTU
 Manage primary
hyperparathyroidism
• Primary hyperparathyroidism is the most common cause of hypercalcemia
in the outpatient setting
• Single parathyroid adenoma is the cause in 85% of cases
• Double adenoma or multi-gland hyperplasia in 15% of cases. Usually
associated with MEN type 1 or MEN type 2 syndromes

2002 National Institutes of Health consensus conference guidelines for the

management of asymptomatic primary hyperparathyroidism
Indications for surgery
– Serum calcium level >1 mg/d above upper limit of normal
– 24-Hour urine calcium excretion > 400 mg
– Creatinine clearance reduced by ≥ 30%
– Bone mineral density: T-score <−2.5 at any site
– Age younger than 50 years
Recommended follow-up measurements for patients not undergoing
surgery
– Biannual serum calcium
– Annual serum creatinine
– Annual bone mineral density (lumbar spine, proximal femur, distal forearm)
 MKSAP question
A 51-year-old man is undergoing a routine physical examination. He has
no significant personal or family medical history. He still exercises
regularly, running 2 to 3 miles at least three times a week. He does not
smoke, drink alcohol, or use recreational drugs. Physical examination
is normal. Laboratory tests are normal other than a calcium level of
11.0 mg/dL (2.74 mmol/L). A subsequent serum parathyroid level is
120 pg/mL (120 ng/L). A 24-hour urine calcium excretion is 250 mg
(6.3 mmol). The creatinine clearance is normal. A DEXA scan shows a
T score of 0.99 at the left femoral neck, 0.68 at the lumbar spine, and
−2.5 at the distal third of the forearm.

Which of the following is the most appropriate management for this

patient?

A. Calcium and vit D supplementation

B. Alendronate
C. Parathyroidectomy
D. Nasal calcitonin
E. Ibandronate
 Confirm diabetes mellitus
ADA criteria:
1. Fasting glucose level > 126. Fasting = no caloric
intake for 8 hours.
2. Casual glucose level > 200 + symptoms of
hyperglycemia (polydipsia, polyuria, weight loss,
blurred vision).
3. 2-h plasma glucose >200 mg/dL (11.1 mmol/L)
during an oral glucose tolerance test (OGTT).
Confirm with repeat level
Use of the HgbA1C for the diagnosis of diabetes
is not recommended at this time.
American Diabetes Association (ADA). Standards of medical care in diabetes. I. Classification
and diagnosis. Diabetes Care 2008 Jan;31(Suppl 1):S12-3.