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Endocrine Review—2017
Timothy C. Evans, MD PhD FACP
Department of Medicine
& MEDEX Northwest
University of Washington
NCCPA Disclaimer
• I am on the Board of Directors (BOD) of NCCPA.
• The BOD is involved with strategic direction and policy.
• The BOD does not develop or review the exams.
• I have never taken nor seen the PANCE, PANRE, or
individual test items.
• In this lecture I am not speaking on behalf of the
NCCPA, nor with any knowledge of specific exam test
items.
Scope
• Anterior and posterior pituitary
• Thyroid
• Parathyroid
• Adrenal cortex and medulla
• Metabolic bone disease (osteoporosis,
osteomalacia, Paget’s disease)
• Lipids
Anterior Pituitary
• Sella turcica
• Hypothalamus
• Six hormones—controlled by hypothalamic
releasing hormones except prolactin,
controlled by inhibiting factor
• Feedback control
• Disease—too much, too little, mass effect
Anterior Pituitary Hormones
• Growth hormone (GH)
• Adrenocorticotropic hormone (ACTH)
• Thyroid stimulating hormone (TSH)
• Luteinizing hormone (LH)
• Follicle stimulating hormone (FSH)
• Prolactin
Case #1
•
• What would you do next
– a) CXR
– b) Growth hormone
– c) Prolactin
– d) Pituitary MRI
– e) Visual field exam
Case #2
• 47 y/o man with headaches is found on MRI
to have a large pituitary tumor with
substantial suprasellar extension.
• What do you expect to find?
– a) Increased hat and glove size
– b) Hyperprolactinemia
– c) Hyperthyroidism
– d) Hypopituitarism
– e) Bitemporal hemianopsia
This is a normal sagittal FLAIR MRI scan demonstrating the midline with the
frontal lobe and parietal lobe and occipital lobe and cerebellum and genu of
corpus callosum and splenium of corpus callosum and mammillary body and
thalmus and midbrain and pons and medulla and cervical spinal cord and
tongue and nasal cavity.
The T1 weighted MRI scan in sagittal view here demonstrates a macroadenoma
of the pituitary that is bright with gadolinium enhancement. Such an enlarging
mass can produce the classic bitemporal hemianopsia by pressure effect on the
optic chiasm superiorly.
Case #3
• 24 y/o woman develops panhypopituitarism
following severe childbirth blood loss.
Symptoms include failure of lactation, fatigue,
abdominal pain, anorexia, hypotension.
• Which hormone should be replaced first?
– a) Growth hormone (GH)
– b) Cortisol
– c) Levothyroxine
– d) Estrogen/Progesterone
– e) Prolactin
Posterior Pituitary
• Arginine Vasopressin (or antidiuretic
hormone)—Results in production of
concentrated urine.
• Oxytocin—Stimulates uterine contraction
and breast milk ejection at parturition.
Case #4 • Following a severe head injury, a 43 y/o man
develops urine output of 10–15 L/d, low osmolal.
• Volume is replaced with iv fluid. Electrolytes are normal.
• Cosyntropin stimulation test and free thyroxine are normal.
• What is the probable necessary treatment?
– a) Cortisol
– b) Levothyroxine
– c) AVP in the form of desmopressin
– d) Pituitary surgery
– e) Insulin
Case 4a
• 72 y/o man admitted with pneumonia. Serum
Na 125, serum osmolality low, urine osmolality
high. BUN/creat, TSH, cosyntropin stim nl.
VS nl, no edema. You would:
– a) give hydrocortisone
– b) administer hypertonic saline
– c) give furosemide
– d) restrict water
– e) restrict sodium
Hypothyroidism
•
Hypothyroidism—Etiology
• Autoimmune thyroiditis
• Post thyroid ablation (surgery, 131I)
• Multinodular goiter
• Transient (postpartum thyroiditis, subacute
thyroiditis)
• Drugs—lithium, amiodarone
• Congenital
Hypothyroidism Rx
• Thyroid hormone is a cardiac stimulant.
• Treatment risk is precipitation of cardiac
ischemia.
• Go slow in fragile elderly patients, or even
wait until the ischemic heart disease is
stabilized before thyroid treatment.
• Monitor TSH, after 6 wks equilibration.
Case #5
• 25 y/o woman, fatigue, constipation, heavy
periods, cold intolerance, neg PMHx
• Thyroid gland twice normal size, firm,
symmetrical
• TSH—43 mU/L, free T4 0.2
• Dx? Rx?
Case #6
• 75 y/o woman, fatigue, constipation,
difficulty concentrating, weight loss
• LDL 192 mg/dL
• Thyroid twice normal size, nodular, no
dominant nodule
• TSH 55, free T4 0.4
• Dx? Rx? Why? How?
Case #7
• 29 y/o woman, 4 months postpartum,
fatigue, firm thyroid twice normal size,
euthyroid before/during pregnancy
• What is this?
• What would you do?
Hyperthyroidism
• Clinical Presentation—restlessness, tachycardia, heat intolerance, loose stools, eye changes, weight loss
• Thyroid may be diffusely enlarged, nodular, or nonpalpable.
• TSH low, T4 and T3 high
• RAIU and scan to distinguish causes.
• Rx because of cardiac and bone comp.
Hyperthyroidism Etiology
• Graves’ disease
• Multinodular goiter
• Autonomous nodule
• Exogenous thyroid hormone
• Transient—subacute thyroiditis, postpartum
thyroiditis
• Drugs—amiodarone
Hyperthyroidism
Treatment Options
• Antithyroid drugs —methimazole,
propylthiouracil
• 131I ablation
• Surgery
• Propranolol
• Thyroid storm—add SSKI, ipodate,
glucocorticoids
Case #8
• 27 y/o woman, tachycardia, agitation,
weight loss, heat intolerance, diffuse thyroid
enlargement, thyroid bruit, exophthalmos,
not pregnant
• TSH < 0.03, T4 15.2, T3 358
• What is the diagnosis?
• Treatment?
Case #8—Part 2
• After one month treatment, TSH < 0.03, T4
10.2, T3 180
• What is the interpretation of these lab
values?
• Now what?
Thyroid Nodules—Etiology
• Colloid nodule
– Single or multinodular goiter
• Cysts
• Thyroiditis
• Benign adenoma
• Malignancy
– Papillary (75–85%)
– Follicular (10–15%)
– Anaplastic
– Medullary—calcitonin
– Lymphoma
– Metastasis
Thyroid Nodule Evaluation
From Ross et al., UpToDate 2017
Thyroid and Drugs, 1
•
Thyroid and Drugs, 2
•
Amiodarone, 1
•
Amiodarone, 2
• Hypothyroidism—esp with high dietary I and + anti-TPO, transient or longer, Rx LT4
• Hyperthyroidism
– Type I—hyperfunction if baseline nodular and autonomous thy func, esp with low dietary I, Rx thionamide
– Type II—destructive thyroiditis, weeks to months with hypothyroid phase then recovery, Rx corticosteroid, LT4 during hypothy phase
Calcemic Control
• Parathyroid Hormone—Increases serum calcium by actions on bone and kidney and by activating vitamin D.
• Vitamin D—1,25-dihydroxy D increases serum calcium by stimulating increased absorption of dietary calcium.
• There is no active mechanism to lower serum calcium. (Calcitonin only minor physiologic role in humans.)
Case #9 • A 52 y/o woman is seen for routine exam and is
found to have a serum calcium of 11.0 mg/dL.
• She takes no medicines, has normal renal
function, smokes 1 ppd.
• What would you order next?
– a) Serum 25-hydroxy vitamin D
– b) Serum intact PTH
– c) CXR
– d) Serum TSH
– e) Serum PTHrP
Parathyroid hyperplasia is shown here. Three and one-half glands have been
removed (only half the gland at the lower left is present). Parathyroid hyperplasia
is the second most common form of primary hyperparathyroidism, with parathyroid
carcinoma the least common form.
Adrenal Cortex
• Produces cortisol, aldosterone, and androgens.
• Cortisol—stress response, intermediary metabolism, vascular tone, controlled by ACTH.
• Aldosterone—Sodium retention (exchange for potassium/hydrogen), controlled by renin/angiotensin II system and serum K.
A normal right adrenal gland is shown here positioned between the liver and the
kidney in the retroperitoneum. Note the amount of adipose tissue, some of which
has been reflected to reveal the upper pole of the kidney and the adrenal.
The pair of adrenals in the center are normal. Those at the top come from a patient
with adrenal atrophy (with either Addison's disease or long-term corticosteroid
therapy). The adrenals at the bottom represent bilateral cortical hyperplasia. This
could be due to a pituitary adenoma secreting ACTH (Cushing's disease), or
Cushing's syndrome from ectopic ACTH production, or idiopathic adrenal
hyperplasia.
Cushing’s Syndrome
• Excess glucocorticoid, cortisol
• Exogenous most common
• Also endogenous—ACTH-producing pit tumor, primary adrenal overproduction, ectopic ACTH
• Screening tests: 24 hr UFC (urine free cortisol), 1 mg overnight dexamethasone suppression test, nighttime salivary cortisol
Case #10 • 42 y/o male with diabetes, hypertension, obesity,
abdominal striae. He has both acute and chronic
alcoholism.
• Lab tests show glucose 174 mg/dL, AST/ALT 167/83
U/L. 24 hour UFC is 156 mcg/d (nl up to 100).
• What would you do next?
– a) Serum ACTH
– b) Pituitary MRI
– c) Wait until acute alcoholic hepatitis
resolves and recheck 24 hr UFC.
– d) Abdominal CT scan
– e) 1 mg overnight dex suppression test
Adrenocortical Insufficiency
• Low cortisol (aldo too if 1º adrenal
destruction)
• Most common is suppression after high
dose corticosteroid use. (No aldo ↓)
• Addison’s disease—autoimmune
• Also secondary to ACTH deficiency
• Screening test: cosyntropin stimulation test
Case #11 • 33 y/o woman with Addison’s disease, on
prednisone replacement 5 mg qam/2.5 mg
qpm, develops productive cough, fever,
CXR consistent with atypical pneumonia.
• She is started on a macrolide antibiotic.
• What else would you do?
– a) Check 24 hr UFC.
– b) Perform cosyntropin stimulation test.
– c) Increase prednisone to 40 mg per day.
– d) Add dexamethasone.
– e) Change to hydrocortisone 80 mg iv tid.
Aldosterone Excess
• One of the surgically correctable causes of
hypertension
• Suspect when K is low, esp if < 3 meq/L.
• Caused by adenoma or bilat hyperplasia.
• Screen with aldosterone/renin ratio.
• Spironolactone specifically inhibits aldo
receptor.
• Treat surgically if adenoma.
Here is a 1.3 cm left adrenal adenoma found in a patient with hypertension. She
had hypokalemia on a routine chemistry panel. Further workup revealed a high
serum aldosterone and a low serum renin, findings consistent with an aldosterone
secreting adrenal adenoma (Conn's syndrome). This lesion accounts for about
two-thirds of cases of primary hyperaldosteronism (PHA), while bilateral adrenal
hyperplasia accounts for about 30% of PHA. Such adenomas are typically less
than 2 cm in size and yellow on cut surface.
This abdominal CT scan demonstrates a small adrenal adenoma adjacent to the
liver on the right. There is an incidental simple cyst of the liver.
Pheochromocytoma
• Another surgically correctable cause of
hypertension
• Classic triad—HA, diaphoresis, palpitations
assoc with episodic HBP
• Screen—24 hr urine for catecholamines and
metanephrines
• Treat surgically after pretreatment. Alpha
blockade first, then beta blockade.
This large adrenal neoplasm has been sectioned in half. Note the grey-tan color of
the tumor compared to the yellow cortex stretched around it and a small remnant
of remaining adrenal at the lower right. This patient had episodic hypertension.
This is a tumor arising in the adrenal medulla--a pheochromocytoma. The
anesthesia record below gives an indication of the nature of this neoplasm. Note
the sudden rise in blood pressure midway through the operation as the tumor was
being manipulated during removal.
This abdominal CT scan demonstrates a right adrenal pheochromocytoma that
abuts the liver and the inferior vena cava.
Metabolic Bone Disease
• Osteoporosis—decreased bone mass,
mineral and protein matrix
• Osteomalacia—decreased bone
mineralization, normal matrix
• Paget’s disease—focal disordered bone
structure
Osteoporosis
• Type I—postmenopausal women, trabecular
bone, vertebral and wrist Fx
• Type II—elderly women and men, cortical
bone, hip Fx
• Many contributors to bone turnover—
Est/T, cortisol, thyroid, activity, Ca, vit D
• Asymptomatic until Fx
Bone Mineral Density (BMD)
• Current gold standard, DEXA
• T-score: # of standard deviations from peak
young normal BMD (age 25-35)
• [Z-score: # of standard dev from age and
sex matched BMD]
• Osteopenia = T-score -1 to -2.5
• Osteoporosis = T-score < -2.5
Case #12 • 73 y/o woman with recent acute back pain. CXR
shows T12 compression Fx.
• DEXA shows osteoporosis level BMD in lumbar spine and hip, (T-score -2.80).
• Dx = established osteoporosis
• She is started on 1000 IU vitamin D supplement, 1500 mg elemental Ca, and graded exercise.
• What else would you do?
– a) Start estrogen/progesterone.
– b) Avoid exercise.
– c) Start raloxifene.
– d) Start alendronate.
– e) Increase calcium intake.
Here is a "compressed" fracture of the vertebral column. The middle vertebral
body shown here is greatly reduced in size. Such fractures are common in
persons with osteoporosis in which there is accelerated bone loss, particularly
older women, and can occur with even minor trauma.
This MRI of the spine demonstrates marked
kyphosis with compressed fractures. Such
a finding can be seen as a consequence of
osteoporosis.
Estrogen
•
Dyslipidemia—ATP 4
• Four statin benefit groups
– Clinical ASCVD
– LDL > 190 mg/dL
– DM, 40-75 yrs, LDL 70-189 mg/dL
– 40-75 yrs, LDL 70-189 mg/dL, 10-yr risk 7.5%
or higher, no DM or ASCVD
New Risk Calculator
• 10-yr risk for ages 40-75 years
• Similar risk factors to Framingham
– Sex, age, race, total cholesterol, HDL-
cholesterol, systolic BP, Rx for HBP, diabetes,
smoking
• Diabetes not an automatic ASCVD risk
equivalent
• http://clincalc.com/Cardiology/ASCVD/Poo
ledCohort.aspx
Statin Intensity
• High—lowers LDL by > 50%
– atorv 40-80 mg, rosuv 20-40 mg
• Moderate—lowers LDL by 30 to < 50%
– atorv 10-20, rosuv 5-10, simva 20-40, similar
moderate doses for the other statins
• Low—lowers LDL by < 30%
– simva 10 mg, similar low doses other statins,
no atorv or rosuv