Endocrine Board
Review
Ria Dancel, MD
6/22/2009
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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.
• Prolactin causes amenorrhea by suppressing
GnRH
Hyperprolactinemia in pt
with secondary amenorrhea
Causes of hyperprolactinemia:
•
Physiologic:
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Pregnancy
Lactation
Pharmacologic:
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–
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Antipsychotics, MAOI, SSRI, antiemetics
Calcium channel blockers, estrogens, opiates, cocaine
Pathologic:
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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.
B.
C.
D.
Pregnancy
Cirrhosis
Primary hypothyroid
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.
B.
C.
D.
E.
Re-measure serum prolactin level
Start estrogen/progesterone cyclic therapy
Start dopamine agonist therapy
Measure TSH and free T4
Refer to neurosurgeon for pituitary surgery
The Adrenal Gland
Glucocorticoids – Cortisol
Mineralocorticoids – Aldosterone
Sex steroids – Testosterone,
Estrogen
Catecholamines – Norepi, epi, DA
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
Step 1: Draw plasma fractionated metanephrines,
sensitivity 97% but specificity 85%
Step 2: Confirm with 24 hour urine collection for
metanephrines, specificity > 94%
Step 3: Localize with abdominal CT, with special attention
to the adrenal glands
Cushing’s: Hypothalamicpituitary-adrenal axis
ACTH and
corisol highest
in the AM,
lowest in PM
and at night
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
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•
•
•
Caused by excess glucocorticoids
Cortisol is the 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 = Cushing’s syndrome. 10% of
cases of endogenous excess
4. Paraneoplastic syndrome. 10% of cases of endogenous excess
Cushing’s disease and
Cushing’s syndrome
Step 1: Confirm glucocorticoid excess
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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
Step 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
pg/ml (2 pmol/L)
Late PM ACTH < 5
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
Step 1: Assess hormonal activity
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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
Step 2: Assess malignant potential with CT
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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.
B.
C.
D.
MRI of the abdomen
Observation only
Repeat CT scan in 1-3 months
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.
B.
C.
D.
Selective adrenal venous sampling
Repeat biochemical testing and CT in 6 months
Iodocholesterol imaging of adrenals
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:
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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
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 thyroidstimulating 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.
B.
C.
D.
E.
Thyroid scan
FNA of dominant nodule
Serum thyroglobulin level
Serum antithyroid peroxidase and antithyroglobulin antibodies
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. Fineneedle 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.
B.
C.
D.
E.
Serum calcitonin level
Repeat biopsy with immunostaining with calcitonin
Serum PTH level
Urine metanephrines
Urine calcium, phosphate, and citrate
Key point: Screen all patients with suspected medullary thyroid cancer
for pheochromocytoma before sending them to surgery!
Confirm thyrotoxicosis
factitia
• Signs/Sx of thyrotoxicosis: 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:
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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
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•
•
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
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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.
B.
C.
D.
E.
Calcium and vit D supplementation
Alendronate
Parathyroidectomy
Nasal calcitonin
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.
Order the appropriate dx test
for a man with hypogonadism
• Testosterone < 100 ng/dL in a young man
is nearly always pathologic
• Image pituitary with MRI of sella