Week 1 Block 2: EGR

Question 1

(1) General Dx: increased fatigability, trouble sleeping, heart palpitations, weight loss, increased sweating (2) Specific Dx: lower-leg skin thickening and induration (3) Specific sx/disease mechanism

Answer 1

(1) Hyperthyroidism (2) GRAVES DISEASE - infiltrative dermopathy (i.e., pretibial myxedema) & exophthalmos are sx specific for hyperthyroidism due to Graves’ disease (3) Autoimmune response directed against the thyrotropin receptor, resulting in accumulation of glycosaminoglycans within affected tissues

Question 2

Acarbose: (1) Drug class (2) Cellular target (3) Mechanism (4) Another example of drug in this class used in US

Answer 2

(1) ALPHA-GLUCOSIDASE INHIBITORS decrease the activity of (2) MEMBRANE-BOUND DISACCHARIDASES on intestinal brush border (3) Carbohydrates are absorbed as monosaccharides; therefore, action of alpha-glucosidase inhibitors in preventing disaccharide breakdown allows delay in carbohydrate absorption. (4) Miglitol

Question 3

(1) DDx: maculopapular rash begins on head and neck and spread downward (2) Most likely Dx: also generalized LAD, particularly postauricular and occipital (3) Maternal sx of most likely dx (4) Congenital sx of most likely dx

Answer 3

(1) Measles (rubeola) or German measles (rubella) (2) RUBELLA (3) low grade fever, maculopapular rash with cephalocaudal progression, & posterior auricular and suboccipital LAD, most women develop polyarthritis and POLYARTHRALGIA as sequelae (4) sensorineural DEAFNESS, cataracts, and cardiac malformations (PDA)

Question 4

(1) Most common congenital breast anomaly (2) Often confused with (3) Presentation (4) Clinical approach. (5) What are ephelides?

Answer 4

(1) Accessory nipples (2) Nevi (3) Can be bilateral, usually asymptomatic, (4) not require excision (5) Freckles

Question 5

(1) Primary amenorrhea in patient with fully developed secondary sexual characteristics suggests (give general disorder & most common dx’s) (2) Presentation of most common dx

Answer 5

(1) Presence of anatomical defect, most commonly imperforate hymen or mullerian duct anomaly (2) Adolescent girls with undiagnosed imperforate hymen commonly present with cyclic abdominal or pelvic pain and PE findings suggestive of hematocolpos

Question 6

Leuprolide: (1) mechanism (2) causes what changes in testosterone and/or DHT levels; Finasteride: (3) mechanism (4) effects on testosterone and/or DHT levels

Answer 6

(1) GnRH agonist (2) First TRANSIENT INCREASE, THEN DECREASE IN BOTH testosterone and DHT levels (3) 5alpha-reductase inhibitor (4) discordant decrease in DHT levels

Question 7

Give type of osmolarity/volume change in each of the following instances: (1) Diabetes insipidus (2) Acute gastrointestinal hemorrhage (3) Sweating (4) Psychogenic polydipsia (5) Diarrhea (6) Adrenal insufficiency (7) SIADH (8) Infusion hypertonic saline

Answer 7

(1) Hyperosmolaric volume contraction (i.e., loss of free water exceeds loss of electrolytes) (2) Isoosmotic volume contraction (i.e., Loss of isotonic fluid) (3) Hyperosmolaric volume contraction (4) Hypoosmotic volume expansion (i.e., Ingestion of hypotonic fluid) (5) Isoosmotic volume contraction (6) Hypoosmotic volume contraction (i.e., sodium wasting and possibly some volume loss, low osmolarity of ECF would result in shifting of free water into ICF space) (7) Hypoosmotic volume expansion (8) Hypertonic volume expansion (both volume and osmolarity of ECF are increased; high osmolarity of ECF leads to shifting of water from ECF, further increasing extracellular volume)

Question 8

Results of administration of vasopressin during water deprivation test: (1) suggesting central DI (2) strongly suggesting complete central DI

Answer 8

(1) more than 10% increase in urine osmolality (2) urine osmolality increase above 50%

Question 9

(1) Most likely Dx: Subperiosteal erosions in medial sides of second and third phalanges of hand; granular, “salt and pepper” appearance of calvarium (2) Supporting labs

Answer 9

(1) Subperiosteal thinning seen in HYPERPARATHYROIDISM (2) High serum Ca, Low serum phosphorus

Question 10

Tamoxifen: (1) Mechanism (like - give other e.g. in drug class) (2) used as Tx for (3) increased risk/incidence of

Answer 10

(1) Selective estrogen receptor modulators (SERMs) because of their tissue-selective estrogen agonist and antagonist properties (e.g., Raloxifene) (2) Tx for osteoporosis and breast cancer (3) increased incidence of ENDOMETRIAL CANCER and thromboembolic disease

Question 11

DKA: (1) presentation (2) common patient population (3) preferred tx

Answer 11

(1) volume depletion (hypotension and tachycardia) with ketones and glucose in urine (2) most commonly in type 1 diabetics (3) REGULAR INSULIN (short acting insulin)

Question 12

Risperidone: (1) mechanism (2) clinical use (3) Explain reproductive toxicity

Answer 12

(1) Antidopaminergic action (2) Schizophrenia (3) Secretion of prolactin controlled by inhibitory effect of hypothalamic dopamine; Hyperprolactinemia causes hypogonadism by inhibiting release of gonadotropin-releasing hormone form the hypothalamus

Question 13

Neuromuscular hyperexcitability: (1) e.g. of clincal sign (2) electrolyte & critical level (3) common cause

Answer 13

(1) Chvostek sign (facial muscle contraction elicited by tapping on facial nerve just anterior to ear) (2) hypocalcemia - serum calcium levels are < or = 7.0 mg/dL (3) common cause of hypocalcemia is primary hypoparathyroidism, which is often due to loss of parathyroid during thyroidectomy

Question 14

Effect of estrogen on thyroid hormones and function: (1) in short/ultimate effect (2) mechanism

Answer 14

(1) increases total T4, but thyroid function remains normal (2) thyroid binding globulin (TBG) levels increase with estrogen use because the catabolism of TBG decreases when estrogen is present. An increase in TBG levels leads to an increase in total T4 (bound T4 plus free T4) and total T3. However, level of free thyroid hormones remains normal, so patients remain euthyroid and have normal TSH levels

Question 15

(1) Most common cause of adrenal insufficiency (2) Important clinical advisory note regarding management of patients with this cause

Answer 15

(1) Depression of entire hypothalamus-pituitary-adrenal axis by glucocorticoid therapy (2) Adrenal crisis can be precipitated in these patients under stressful situations (i.e., infections or surgery) if their glucocorticoid dose is not appropriate increased

Question 16

(1) Dx: easy fatigability, recent weight gain, constipation (2) Most common cause of that dx (3) Histology of that most common cause

Answer 16

(1) Hypothyroidism (2) In areas where iodine is sufficient, Hashimoto’s thyroiditis (3) Mononuclear, parenchymal infiltration (consisting of lymphocytes and plasma cells) with well-developed germinal centers; thyroid follicular epithelial cells undergo a metaplastic change, leading to formation of large, oxyphilic cells with granular cytoplasm, called Hurthle cells

Question 17

(1) Most common form of congenital adrenal hyperplasia (2) Female presentation (3) Male presentation (4) Diagnostic serum level

Answer 17

(1) 21-hydroxylase deficiency (2) Affected female infants present at birth with ambiguous (virilized) genitalia (3) Male infants have normal genitalia and present later with salt-wasting or precocious puberty (3) High serum level of 17-hydroxyprogesterone

Question 18

Benefits/Limitations of beta blocker therapy in Thyrotoxicosis

Answer 18

Treat acute sx of thyrotoxicosis in preparation for thyroid surgery. Beta blockers can relieve those symptoms related to sympathetic nervous system (tahycardia, hypertension, and tremor). Mood lability and fatigue may resolve as well, after symptoms stemming from sympathetic overactivation have subsided. Thyroid ophthalmia, however, is not affected by beta-adrenergic blockade. Ocular manifestations of Graves thyrotoxicosis (Exophthalmos - due to increased soft tissue mass within bony orbit) sometimes respond to corticosteroid therapy.

Question 19

(1) Pathophysiology of biliary stones in patients with somatostatinoma (2) Definition & other sx of somatostatinoma

Answer 19

Somatostatin (secreted by hypothalamus) inhibits production of GH from anterior pituitary gland & secreted from pancreatic “delta cells” to decrease secretion of secretin, cholecystokinin, glucagon, insulin, & gastrin. Gallbladder stones due to poor gallbladder contractility, secondary to inhibition of cholecystokinin release. (2) Somatostatinomas are rare pancreatic islet cell tumors that arise from delta cells. Patients present w/ hyperglycemia or hypoglycemia, steatorrhea (excessive fat in feces), & gallbladder stones

Question 20

(1) Dx: small flesh-colored nodules on lips and tongue, tall and slender, with disproportionately long arms and legs, fingers are also long and thin, underwent total thyroidectomy 5 years ago after discovery of palpable thyroid mass (2) Distinguishing this Dx from related dx’s

Answer 20

(1) Multiple endocrine neoplasia type 2 (MEN type 2 B) (2) MEN Type 2B - medullary carcinoma of thyroid, pheochromocytoma, & oral and intestinal mucosal neuromas vs. MEN Type 2A - also assoc. w/ parathyroid hyperplasia (unlike MEN 2B)

Question 21

(1) Pathophysiology behind progressive vision impairment and bilateral clouding of lens in patient with diabetes mellitus, hypertension, and gout (2) Other clinical implication(s) of this mechanism (3) Other related mechanisms

Answer 21

(1) During hyperglycemia, excess plasma glucose converted to sorbitol by aldolase reductase. Sorbitol accumulates within some cells and attracts water into these tissues leading to osmotic cellular injury. (2) This mechanism is implicated in pathophysiology of cataracts (osmotic injury to lens fiber cells) and peripheral neuropathy (osmotic injury to schwann cells) in diabetes. (3) Advanced glycosylation end products (i.e., attachment of glucose to amino acid residues in various proteins forming reversible glycosylation products that slowly stabilize the irreversible products, accumulate & cross link collagen in blood vessel walsl and interstitial tissues [microangiopathy and nephropathy] and proteins [atherosclerosis]) & Polyol pathway (i.e., hyperglycemia, glucose => sorbitol)

Question 22

Dx: 39 yo Caucasian female, palpable nodularity in right brest, lesion is composed of ducts distented by pleomorphic cells with prominent central necrosis, lesion does not extend beyond ductal basal membrane

Answer 22

Comedocarcinoma (DCIS) - solid sheets of pleomorphic, high grade cells with central necrosis

Question 23

(1) Dx: 2-4 yo boy with early virilization, increased linear growth, and elevated levels of 17-hydroxyprogesterone and androgens (2) Presentation of this dx in a female

Answer 23

(1) non-salt-wasting 21-hydroxylase deficiency (an adrenal cortical hyperplasia) (2) Females w/ classic 21-hydroxylase deficiency (with or without salt wasting) present w/ ambiguous genitalia at birht

Question 24

Tx of congenital adrenal hyperplasia (e.g., non-salt wasting 21 hydroxylase deficiency) & its mechanism

Answer 24

Defective conversion of 17-hydroxyprogesterone to deoxycortisol, which impairs cortisol synthesis. Decreased cortisol levels sense by hypothalamus & ACTH secretion by anterior pituitary increased, resulting in stimulation of adrenal cortex and androgen overpoduction. Tx: low (ie, physiologic) doses of exogenous corticosteroids to suppress ACTH secretion. By removing excessive ACTH stimulation, exogenous corticosteroids can decrease androgen production by the adrenal cortex.