MEHLMANMEDICAL

HY ENDOCRINE
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HY Endocrine

- Na/K role of aldosterone à upregulates Na/K-ATPase pump on basolateral membrane of cortical

collecting duct + late-DCT à reabsorbs 3Na into blood for secretion of every 2K into tubular cell

(goes to urine)

- Acid-base role of aldosterone à causes direct proton secretion at apical membrane of cortical

collecting duct

- How does aldosterone relate to ENac? à increased reabsorption of Na at basolateral membrane

means decreased intracellular Na à favorable high-low gradient of Na from urine into tubular cell à

ENac upregulates on apical membrane to increase movement of Na into tubular cell

- Acid-base / biochemical disturbance in Addison à low Na, high K, low bicarb, low pH (metabolic

acidosis)

- Fatigued patient + hyperpigmentation + low BP à Addison disease (primary hypoadrenalism; low

aldosterone + low cortisol)

- Infective cause of Addison à Waterhouse-Friderichsen syndrome (WFS)

- What is WFS à hemorrhagic (not ischemic) necrosis of adrenal glands

- Cause of WFS à meningococcal septicemia (non-blanching rash)

- Low BP in WFS + fluids are given; next best step? à give dexamethasone to compensate for low

cortisol

- If WFS is hemorrhagic necrosis, what HY scenario contrasts à Sheehan syndrome is ischemic necrosis

of anterior pituitary following labor

- Cause of Sheehan à anterior pituitary doubles in size during pregnancy to increase prolactin

secretion; blood loss during labor à ischemic infarction

- USMLE arrow Q for Sheehan à down ACTH, down TSH, down prolactin, up aldosterone (NBME exam)

- How do you Dx Addison disease à ACTH stimulation test (if cortisol doesn’t go up appreciably, Dx

confirmed)

- Weird hematologic finding in Addison à eosinophilia (don’t go chasing ova, stool, parasites)

- Why fatigue in Addison à low cortisol causes chronic fatigue syndrome

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- Why hyperpigmentation in Addison à low cortisol, so less negative feedback at hypothalamus +

anterior pituitary à increase in CRH à increase in POMC (precursor to ACTH and alpha-MSH)

- Tx for Addison à fludrocortisone

- Important point about fludrocortisone à corticosteroid with high mineralocorticoid effect (acts like

aldosterone) à can be used to overcome low aldosterone + low cortisol caused by Addison

- Important point about prednisone + hydrocortisone + dexamethasone à glucocorticoids with very

low mineralocorticoid effect (do not act like aldosterone) à hydrocortisone classically used to treat

secondary hypoadrenalism (only decreased cortisol)

- Cause of Addison à autoimmune, typically part of polyglandular syndrome

- Cause of secondary hypoadrenalism à decreased ACTH production à usually due to impingement

by pituitary tumor (e.g, prolactinoma); can also be caused by Sheehan syndrome

- ACTH levels in Addison vs secondary hypoadrenalism à high in Addison; low in secondary

- Renin levels in Addison? à high

- Potassium levels in secondary hypoadrenalism? à normal because aldosterone intact through RAAS;

cause is merely decreased ACTH

- Primary hyperaldosteronism à Conn syndrome (tumor) or diffuse hyperplasia (autoimmune)

- Renin level in Conn syndrome à low

- High BP + high renin/aldosterone ratio in young woman à fibromuscular dysplasia (FMD)

- Dx of fibromuscular dysplasia? à MR angiography of renal arteries

- High BP + high renin/aldosterone ratio in older patient with cardiovascular disease à renal artery

stenosis

- Cause of renal artery stenosis à atherosclerosis

- Patient with high BP + given ACEi + now creatinine increases; Dx? à renal artery stenosis or FMD

- Acid-base / biochemical disturbance in RAS or FMD à high Na, low K, high bicarb, high pH (metabolic

alkalosis)

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- How does RAAS work? à Low blood volume à JGC secrete renin à renin cleaves angiotensinogen

(produced by the liver) in the plasma into angiotensin I à AT-I goes to lungs and is cleaved by ACE

into AT-II à AT-II goes to zona glomerulosa of adrenal cortex à upregulates aldosterone synthase

à converts 11-deoxycorticosterone into aldosterone

- Important functions of AT-II unrelated to aldosterone? à potent vasoconstrictor on systemic

arterioles (increases afterload) + renal efferent arterioles (increases filtration fraction [GFR/RPF] in

setting of low blood volume, meaning that GFR is maintained despite low renal plasma flow) +

increases PCT reabsorption of Na

- Why is AT-II-mediated PCT reabsorption of Na important? à water follows Na; mechanism to

increase fluid retention in setting of low blood volume

- Effect of giving ACEi on efferent arteriolar diameter à increases diameter

- ACEi (e.g., enalapril) effect on RAAS à increases renin, increases AT-I, decreases AT-II, decreases

aldosterone

- ARB (e.g., valsartan) effect on RAAS à increases renin, increases AT-I, increases AT-II, decreases

aldosterone

- Spironolactone effect on RAAS à increases renin, increases AT-I, increases AT-II, increases

aldosterone

- Eplerenone vs spironolactone à eplerenone way less likely to cause gynecomastia

- If suspected Dx of Conn syndrome à CT abdomen

- If CT abdomen negative (hyperplasia not tumor) à adrenal venous sampling to confirm

- What is pheochromocytoma à catecholamine-secreting tumor of adrenal medulla

- Paroxysmal headaches/palpitations (high BP) + normal electrolytes à pheochromocytoma (PCC)

- Paroxysmal headaches/palpitations (high BP) + high glucose à PCC (catecholamines cause liver to

make glucose)

- Tx for PCC à phenoxybenzamine first (irreversible alpha-1 blocker); never beta-blocker first

- Why phenoxybenzamine first to treat PCC à if you give beta-blocker first, you get “unopposed

alpha,” meaning all of the NE + E (catecholamines) floating around bind to alpha-1, causing massive

arteriolar vasoconstriction, shooting BP through the roof

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- Dx of PCC à urinary or serum metanephrines

- Who gets PCC à NF1, MEN2A/2B (ret gene)

- PCC adults or kids? à adults

- PCC-like presentation in kids? à neuroblastoma (n-myc gene)

- Dancing eyes + high BP + midline mass in kid à neuroblastoma

- Dancing eyes? Wtf? à opsoclonus-myoclonus syndrome (seen in neuroblastoma; yes, weird)

- Dx of neuroblastoma à abdominal ultrasound

- Kid with painless flank mass that doesn’t cross midline à Wilms tumor

- Dx of Wilms tumor à renal ultrasound

- Neonatal boy with midline suprapubic mass à posterior urethral valves

- Dx of posterior urethral valves à voiding cystourethrogram

- Cushing syndrome vs Cushing disease à syndrome = what you look like + refers to any cause of

Cushingoid appearance; Cushing disease only = anterior pituitary ACTH-secreting tumor; in other

words, Cushing disease is a cause of Cushing syndrome

- Most common cause of Cushing syndrome à exogenous glucocorticoids (e.g., prednisone)

- Pt not on exogenous steroids + Cushingoid; most common cause? à Cushing disease most common

cause of endogenous Cushing syndrome

- Main causes of Cushing syndrome à exogenous steroids (most common overall), Cushing disease

(most common endogenous), small cell bronchogenic carcinoma (ectopic ACTH), cortisol-secreting

tumor (or diffuse hyperplasia) of zona fasciculata of adrenal cortex; CRH tumor rare as fuck

- Patient with chronic disease (i.e., IBD, SLE, RA) + Cushingoid; what are the ACTH + cortisol levels à

need to know this means patient is taking prednisone à low ACTH + low cortisol (prednisone is NOT

the same thing as cortisol) à prednisone suppresses CRH and ACTH secretion at hypothalamus and

anterior pituitary à decreased endogenous cortisol production

- Patient with Cushing disease; ACTH + cortisol levels? à high ACTH + high cortisol

- Smoker + Cushingoid à small cell bronchogenic carcinoma

- Smoker + Cushingoid; ACTH + cortisol levels? à high ACTH (ectopic) + high cortisol

- When to do dexamethasone suppression test à Cushingoid patient not on exogenous glucocorticoids

and has high serum cortisol

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- Low-dose dexamethasone suppression test à tells us yes or no, patient has pathologic cause of

Cushing syndrome (i.e., Cushing disease, or SCC of lung, or cortisol-secreting tumor), but we can’t

establish the causation from this; if cortisol doesn’t suppress à yes, patient has true Cushing

syndrome (proceed to high-dose test); if cortisol suppresses à no, patient does not have Cushing

syndrome (do not proceed to high-dose test)

- High-dose dex à only cause of Cushing syndrome that will suppress in response is Cushing disease

- Pt has no suppression to low-dose dex + suppresses to high-dose à Dx = Cushing disease (ACTH

secreting tumor of anterior pituitary)

- Pt has no suppression to low- or high-dose dex à ACTH high? à Yes, answer = SCC of lung; No à

answer = cortisol-secreting tumor (or diffuse hyperplasia) of adrenal cortex

- Cushingoid + low ACTH + low cortisol à exogenous steroids

- Cushingoid + low ACTH + high cortisol à cortisol-secreting tumor (or diffuse hyperplasia) of adrenal

cortex

- Cushingoid + high ACTH + high cortisol à Cushing disease

- Most accurate test for Dx Cushing syndrome à 24-hour urine cortisol

- Why dex test not most accurate? à false-positives in e.g., depression, alcoholism

- Acanthosis nigricans + low K + hyperpigmentation à Cushing syndrome

- Why acanthosis nigricans à caused by insulin resistance (unrelated: also can be caused by visceral

malignancies)

- Why low K in Cushing syndrome à chronic elevation of glucocorticoid effect at kidney can push out

potassium similar to aldosterone

- Why hyperpigmentation à high ACTH secretion means POMC is high à high alpha-MSH as well

- Purple striae in obese patient à Cushing syndrome

- Why purple striae à glucocorticoids weaken collagen à micro bleeding into skin

- Why hypertension in Cushing syndrome à cortisol upregulates alpha-1 receptors on arterioles,

thereby allowing NE and E to do their job

- Graph shows you two scenarios: 1) NE given alone, then BP increases a little; 2) NE + cortisol given

together, then BP increases a lot; why the difference? à cortisol is permissive of the effects of

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catecholamines (don’t choose synergistic or additive); once again, cortisol merely allows NE and E to

do their job; cortisol isn’t directly increasing BP

- Why normally ratio of E to NE in the blood is 80/20? à NE draining venously out of the adrenal

medulla passes through the adrenal cortex à cortisol upregulates PNMT (converts NE to E)

- What does low cortisol cause? à chronic fatigue syndrome (as mentioned earlier but super

important)

- Function of PTH à increases blood Ca + decreases blood PO4

- Function of PTH at bone à increases bone resorption

- Cell PTH binds to at bone à osteoblast, not -clast

- If PTH causes bone resorption, why the fuck would it bind to osteoblasts (which build bone) à

because PTH causes osteoblasts to express RANK-Ligand on their cell surface à binds to RANK

receptor on osteoclasts à bone resorption

- How do osteoclasts resorb bone à intracellular carbonic anhydrase II (CAH-II) à creates H2CO3 from

H2O and CO2; then the H2CO3 à bicarb + proton à protons accumulate at bone-osteoclast interface

à surface for resorption

- What is teriparatide à N-terminus PTH analogue that binds to osteoblasts, and then rather than

causing bone resorption, actually stimulates bone growth (difference in mechanism not well

elucidated) à used in advanced osteoporosis

- Avoid teriparatide in whom? à Paget disease of bone patients; Hx of osteosarcoma

- Three effects of PTH at the kidney? à 1) it upregulates 1-alpha hydroxylase activity in the PCT

(converts inactive 25-OH-D3 into active 1,25-(OH)2-D3; 2) decreases PO4 reabsorption in PCT by

downregulating three types of apical membrane brush-border sodium-phosphate symporters; 3)

increases Ca reabsorption in the late-DCT by upregulating the apical TRPV5 transporter à reabsorbs

calcium.

- What does secretion in kidney terms mean à excretion through the tubular wall (excretion is

umbrella term à filtration = excretion through Bowman capsule; secretion = through tubular wall)

- Primary hyperparathyroidism biochemical disturbance? à high Ca, low PO4, high ALP, high PTH

- Why is ALP high à ALP reflects osteoblast activity; if PTH high, then ALP also high (but annoyingly, if

PTH is low, ALP will be normal, not low)

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- Who gets primary hyperPTH à usually parathyroid adenoma (e.g., 22 yr old girl with nodule)

- Who else gets primaryPTH à MEN1 + MEN2A (can be diffuse 4-gland hyperplasia in MEN patients)

- Fuck, what are the MEN syndromes again? à Relax. MEN1 = parathyroid, pituitary, pancreas; MEN2A

= parathyroid, PCC, medullary thyroid carcinoma; MEN2B = PCC, medullary thyroid carcinoma,

mucosal neuromas, and Marfanoid body habitus (“oid” means looks like but ain’t)

- Question says girl has high Ca + low PO4 + nodule of left, superior parathyroid gland; what’s the

embryo derivative? à 4th pharyngeal pouch

- 3rd pouch = thymus + two inferior parathyroids

- 4th pouch = two superior parathyroids

- USMLE classically likes DiGeorge syndrome for agenesis of 3rd + 4th pouches, but will see if you can

distinguish by asking parathyroid adenoma Qs

- Other weird info I need to know for primaryPTH? à Yeah, firstly, urinary Ca is high, not low.

- Wtf, how is that possible if PTH reabsorbs Ca from urine à because serum Ca is high, so the net

amount in the urine is still high (this is a HY arrow Q that everyone gets wrong); in other words, on

the USMLE, in primaryPTH à serum Ca up; serum PO4 down; serum ALP up; urinary Ca up (oh wow)

- Second weird factoid about primaryPTH à urinary cAMP is elevated (USMLE likes this for some

magical reason)

- What is the biochemical disturbance in secondary hyperparathyroidism? à Ca and PO4 opposite of

primary à low Ca; high PO4, high ALP + high PTH

- Who gets secondaryPTH à chronic renal failure

- Why does chronic renal failure cause secondaryPTH à inability to activate vitamin D3 in PCT à

decreased Ca absorption through small bowel à low serum Ca à stimulates PTH release (this

mechanism is on 2CK NBME interestingly); kidney also simply cannot reabsorb Ca as well, further

decreasing serum Ca and stimulating PTH release

- What about low Ca in acute renal failure; doesn’t it take a while for vitamin D effects to occur à if

low Ca in acute, due to mere inability to reabsorb from urine

- Why high PO4 in renal disease à kidney can’t filter it out; even though there’s less activated D3 and

PO4 absorption through small bowel is also decreased, the inability of the kidney to excrete it “wins”

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- Biochemical disturbance of vitamin D deficiency à low Ca, low PO4, normal/high PTH, normal/high

ALP

- Function of vitamin D à increases Ca + PO4 absorption in the bowel (don’t worry about minimal role

in bone)

- I don’t get it though; if in chronic renal failure there’s vitamin D deficiency due to less activation, why

is there low Ca and high PO4? Isn’t vitamin D deficiency always low Ca and low PO4? à chronic renal

failure “wins” in terms of phosphate always à so although low vitamin D, there’s still high PO4.

- Any changes to the bones in a patient with chronic renal disease à renal osteodystrophy

- Hip fracture in renal failure + x-ray shows “pseudofractures” à vitamin D deficiency

- Osteitis fibrosa cystica à high PTH can cause “brown tumors” of bone + cholesterol accumulation in

bone

- Kid with bowing of tibias + chostochondritis + craniotabes à rickets (vitamin D deficiency)

- Adult with pseudofractures à osteomalacia (vitamin D deficiency)

- Where does vitamin D deficiency start à stratum basale of skin (asked on USMLE)

- What is the sequence for production? à 7-dehydrocholsterol in skin goes to cholecalciferol via UV-B

à then cholecalciferol goes to liver where it takes on a hydroxylation to make 25-hydroxy-D3

(calcidiol) à then this goes to the kidney where, via PTH activing 1-alpha-hydroxylase, it gets

converted to active 1,25-(OH)2-D3 à then this goes to small bowel to cause Ca + PO4 absorption

- If person doesn’t get sunlight, what can he/she not make à cholecalciferol (7-dehydro is wrong

answer; this is on NBME)

- What about 7-dehydrocholesterol in relation to sunlight à we make this on our own, then UV-B

converts it into cholecalciferol

- Alcoholic who eats plenty of dairy + gets sunlight + has vitamin D deficiency à answer = decreased

hepatic hydroxylation

- Inject person with Ca; what happens to their vitamin D notably à answer = increased 24,25-(OH)2-

D3.

- Wtf is 24,25? à 25-OH-D3 is immediately converted to 24,25 as a storage form (think of them as the

same)

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- Inject with Ca à Ca binds to Ca-sensing receptor at parathyroid gland à negative feedback à causes

reduction in PTH release à decreased 1-alpha-hydroxylase activity at kidney à buildup of 25 form à

shunted to 24,25 form.

- Low calcium or potassium in a patient + he/she not responsive to supplementation à answer =

hypomagnesemia à Mg needed for basal levels of PTH release (so low PTH à low Ca) + renal

retention of K

- Alcoholic + low Ca or low K not responsive to supplementation à check serum magnesium

- Why low Mg in alcoholic à dietary deficiency

- Who gets high vitamin D (hypervitaminosis D) à granulomatous disease (sarcoidosis) à don’t be the

fool who says “girl tried to commit suicide by ODing on vitamin D pills?”

- Why high vitamin D in sarcoidosis à epithelioid (activated) macrophages secrete 1-alpha hydroxylase

à activate vitamin D à increased small bowel absorption

- Ca and PTH levels in sarcoidosis à high Ca, low PTH (negative feedback)

- Sarcoidosis, any weird fact they ask about Ca? à Answer = “decreased Ca in feces” (makes sense)

- Biochemical disturbance in high vit D à high Ca, normal or high PO4, normal or low PTH, normal or

low ALP (USMLE will only give you one correct answer, don’t worry, but I write the possibilities here

so you don’t get a Q where you see normal PTH or PO4 and are wondering wtf, but Ca always up)

- Sarcoidosis other weird info à increased serum ACE (correct, angiotensin-converting enzyme; weird)

- Sarcoidosis, what happens first, high urinary Ca or high serum Ca à high urinary Ca (kidney will

compensate before serum levels go up)

- 20s-30s African American woman with dry cough; CXR shows nodularity; Dx? à sarcoidosis;

nodularity just means “bihilar lymphadenopathy”

- 20s-30s African American woman with dry cough; CXR shows nodularity; Dx? à “noncaseating

granulomas” (sarcoidosis)

- 20s-30s African American woman with dry cough; CXR is normal Dx? à asthma (1/3 of asthma

patients only have dry cough; this is called cough-variant asthma)

- 20s-30s African American woman with dry cough; CXR is normal Dx? à “increased activation of mast

cells” (asthma)

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- Mutation in calcium-sensing receptor on parathyroid gland à loss of negative feedback à PTH goes

up, serum Ca up

- Mutation in calcium-sensing receptor on parathyroid gland à cause of familial hypocalciuric

hypercalcemia (FHH)

- High PTH + high serum Ca + low urinary Ca à FHH

- High PTH + high serum Ca + high urinary Ca à primary PTH

- Mechanism for low urinary Ca in FHH? à not fully elucidated, but literature suggests increased

tubular reabsorption, possibly paracellular, as serum Mg in FHH elevated relative to primaryPTH

- What is cinacalcet à calcimimetic à activates Ca-sensing receptor at PTH gland

- When to use cinacalcet à tertiary hyperPTH

- What is tertiary hyperparathyroidism? à classically seen in renal transplant patients; autonomous

four-gland hypersecretion of PTH following long-term secondary hyperparathyroidism and

hypocalcemia à parathyroid chief cell hyperplasia that does not resolve with renal transplant à

result is high Ca, variable PO4 (high if still renal impaired), high ALP, high PTH

- What is pseudohypoparathyroidism? à insensitivity to PTH à high PTH but low Ca + high PO4

- Anything special about pseudohypoparathyroidism? à Yes. This is one of the highest yield yet

underemphasized conditions on the USMLE Step 1. In other words, my students get these Qs on the

exam regularly but the resources don’t emphasize the different types of this condition

- What is presentation of pseudohypoparathyroidism? à need to know Types 1a, 1b, 2

- Type 1a = Albright Hereditary Osteodystrophy = is simply the name of the phenotype à AHO has

shortened 4th + 5th metacarpals, short stature + intellectual disability + urinary cAMP does not

increase with exogenous PTH administration (normally should go up in response to PTH)

- Type 1b à high PTH + low Ca + high PO4 + no AHO phenotype (just biochemical disturbance)

- Type 2 à same as Type 1b but urinary cAMP increases in response to exogenous PTH

- Mike, this sounds pedantic though. The USMLE really asks about pseudohypoparathyroidism like

that? à Yeah. They ask it as arrow questions. And I personally had two pseudohypoPTH Qs on my

Step 1 + my students do.

- What is pseudopseudohypoparathyroidism? à AHO phenotype but no biochemical disturbance

- Graves disease parameters à low TSH, high T3, high T4, increased iodine uptake

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- Mechanism of Graves à activating TSH-receptor antibody, called TSI – thyroid stimulating

immunoglobulin)

- Tx for Graves à propylthiouracil (PTU) or methimazole to address thyroid derangement

- PTU and methimazole MOAs à both inhibit thyroperoxidase, but PTU also inhibits peripheral

conversion by inhibiting 5-deiodinase à propylthiouracil is a longer word than methimazole, so it’s

the one that does both

- Tx for tachycardia in Graves à propranolol (because beta-blockade also decreases peripheral

conversion of T4 to T3)

- Important point about Graves? à proptosis/exophthalmos + pretibial myxedema are specific; in

other words, there are numerous causes of hyperthyroidism (e.g., toxic multinodular goiter, toxic

adenoma, etc.), but only Graves will cause the eye findings

- Tx for ophthalmopathy in Graves à steroids

- Why do the eye findings occur in Graves? à glycosaminoglycan deposition in/around extra-ocular

muscles

- High BP + fever + increased CK à thyroid storm (Tx with PTU + propranolol)

- What is the role of potassium iodide (KI) in hyperthyroid Tx? à shuts off gland production (Wolff-

Chaikoff effect) à answer in person exposed to nuclear fallout or radioiodine vapors in laboratory

- Hashimoto parameters à high TSH, low T3, low T4, decreased iodine uptake

- Mechanism for Hashimoto à antibodies against thyroperoxidase + thyroglobulin; anti-microsomal

- Histo of Hashimoto à lymphocytic infiltrate (easy to remember bc the non-eponymous name for

Hashimoto is chronic lymphocytic thyroiditis)

- Tx for Hashimoto = levothyroxine (synthetic T4)

- 50M + low mood + BMI 26 à Hashimoto

- Proximal muscle weakness in Hashimoto + increased serum CK à hypothyroid myopathy

- 45M + decreased ability to get up from chair unassisted + HR of 60 à Hashimoto

- 45M + high cholesterol + high hepatic AST + HR of 55 à Hashimoto (hypothyroidism can cause

bradycardia, high cholesterol, and high AST [the latter is weird, correct])

- Thyroid cancer in Hashimoto à thyroid lymphoma (autoimmune diseases à increased risk of

lymphoma)

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- 22M + viral infection + very tender thyroid à subacute granulomatous thyroiditis (de Quervain)

- De Quervain parameters à triphasic à causes hyper-, then hypo-, then rebounds to euthyroid state

à most important point is that iodine uptake is DECREASED in de Quervain + drug-induced

thyroiditis, even if patient is in a hyper-phase.

- Tx for de Quervain thyroiditis? à answer = NSAIDs

- 22M + very tender thyroid + HR of 88 + tremulousness + heat intolerance à low TSH, high T3, high

T4, decreased iodine uptake (in contrast to Graves, which is painless and uptake is high)

- 27F + gave birth to healthy boy 6 months ago following uncomplicated labor + no weight change or

mood disturbance + on no meds + vitals WNL + dry skin + thyroid gland enlarged and non-tender +

TSH high + T4 low; most likely explanation for these findings? à answer = “thyroiditis” à Dx =

postpartum thyroiditis (a type of silent thyroiditis) à characterized by thyrotoxicosis followed by

hypothyroidism (1/3 of women experience both phases; 1/3 experience just hyperthyroid phase; 1/3

only hypothyroid phase); affects 5-10% of women postpartum; hyperthyroid phase usually occurs 1-4

months postpartum; hypothyroid phase occurs about 4-8 months postpartum; thought to be caused

by postpartum immunologic rebound (immune system normally suppressed during pregnancy); Dx w/

Hx + ordering serum TSH; increased risk of progression to Hashimoto; Tx w/ short course of

propranolol if hyperthyroid; give short course of levothyroxine if hypothyroid

- Tx for subacute thyroiditis à aspirin first, not steroids; steroids may be used later

- Drugs causing thyroiditis à lithium + amiodarone

- Surreptitious thyrotoxicosis àself- injection of thyroxine à low TSH, high T3, high T4, small thyroid

gland with decreased uptake

- Injection of triiodothyroinine (T3) à TSH will go down, T3 goes up (clearly), T4 does not go up

because T3 isn’t converted to T4; only T4 is converted to T3

- Injection of thyroxine à TSH will go down (negative feedback), T4 goes up (clearly), T3 goes up (due

to peripheral conversion), reverse T3 also goes up

- What is reverse T3? à an inactive form of T3; T4 is converted peripherally into T3 (active) and reverse

T3 (inactive)

- Anything else I need to know about reverse T3? à it’s increased in euthyroid sick syndrome à times

of stress/surgery/illness à cortisol increases à cortisol decreases conversion of T4 to active T3, so

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more T4 is converted to reverse T3 à parameters in euthyroid sick syndrome: normal TSH, normal

T4, low T3, high reverse T3

- What is sublinical hypothyroidism à high TSH but normal T3 + T4 (don’t confuse with ESS)

- Subclinical hypothyroidism Tx à don’t treat unless TSH >10 (normal is 0.5-5), Hashimoto Abs are

present, or patient is pregnant à they ask this info on 2CK + Step 3

- Want to check thyroid function, what’s the first thing to order à TSH

- Want to check thyroid function in pregnancy, what’s the first thing to order à free T4

- What is free T4 à most thyroid hormone is protein-bound and inactive; free T4 tells you definitively

whether the patient has thyroid derangement or not

- Pregnancy and thyroid à estrogen causes increased thyroid-binding globulin production by the liver

à mops of T4 à less free T4 à less negative feedback at hypothalamus + anterior pituitary à TSH

goes up transiently to compensate à more T4 made à free T4 rebounds to normal but now total T4

is high à parameters you need to know for pregnancy: normal TSH + high total T4 + normal free T4 +

normal free T3 + high thyroid-binding globulin

- Hyperthyroidism in pregnancy à LH, FSH, TSH, hCG all share same alpha-subunit; their beta-subunits

differ; some women have increases sensitivity of TSH receptor to alpha-subunit, so high hCG in early

pregnancy can stimulate thyroid gland and cause transient hyperthyroidism

- Hashimoto in pregnancy à increase pregnant woman’s dose of levothyroxine by 50%

- Graves in pregnancy à avoid methimazole in first trimester (teratogenic; causes aplasia cutis

congenita) à give PTU in first-trimester à in second + third trimesters, switch from PTU to

methimazole (methimazole no longer teratogenic later in pregnancy + PTU is heavily hepatotoxic)

- Pt being treated for Graves + mouth ulcers à agranulocytosis (neutropenia) caused by methimazole

or PTU.

- Young child with normal free T4 and low total T4 à thyroid-binding globulin deficiency (opposite of

pregnancy)

- Young child + large belly + large tongue + hypotonia à cretinism (congenital hypothyroidism)

- Most common cause of cretinism à iodine deficiency

- Most common cause of hyperthyroidism in elderly à toxic multinodular goiter

- Evaluation of thyroid cancer, first step? à palpation of thyroid gland (on FM 2CK form as answer)

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- If thyroid nodule present, then check TSH; if TSH normal or high à answer = ultrasound first, then

FNA; if TSH low, do radioiodine uptake scan; thyroid cancer is cold, not hot, which is why no ultimate

FNA with low TSH

- Struma ovarii à thyroid hormone secreting ovarian germ cell tumor

- Diabetic ketoacidosis parameters à low serum Na, high serum K (hyperkalemia), low total body K,

low bicarb, low pH, low CO2 (all exceedingly HY)

- Why low serum Na in DKA à osmotic effect of high glucose in blood à dilutional hyponatremia; in

addition, there’s believed to be a contributory renal mechanism related to increased absorption of

water in the PCT due to increased SGLT2 reabsorption of glucose in PCT

- Why high serum K in DKA à three main reasons: 1) insulin normally drives K into cells, so if insulin

isn’t there, K is higher in blood; 2) less glucose driven into cells by GLUT4 (bc normally upregulated by

insulin) means less ATP production à normally 1 ATP drives 2K into cell and 3Na out; so if less ATP-

ase activation, less K enters cell à higher in blood; 3) potassium-proton exchange; if acidosis ensues,

more H driven into cells means K moves out to balance charge à hyperkalemia

- Then what does low total body potassium mean à just to be clear, the patient is hyperkalemic (high

K in the blood) yet has low K overall in the body à kidney senses high K in urine and therefore

increases excretion of it (kaliuresis) à body is now losing K à but three above mechanisms leading to

hyperkalemia continue unabated, so K stays high in serum even though body is now urinating it out.

- Why does the potassium stuff matter so much with DKA à because when you Tx DKA and start giving

insulin (fluids first btw; giving insulin immediately is the wrong answer; give insulin after first

administering a bolus of normal saline), K will now be driven into the cells, which will bring K down to

normal in the serum, but bear in mind it was low in the cells à so now risk of normal in cells but low

in blood à need to supplement K to patient when K falls below 5.2 (normal is 3.5-5 mEq/L). Stop all

insulin if K falls below 3.3.

- Overweight, middle-age patient with polydipsia + polyuria à type II DM

- High in serum in type II DM à insulin is high initially; ketones absent (only ketones in DKA; DKA is

type I only)

- Type II diabetic crisis? à hyperosmolar hyperglycemic non-ketotic syndrome (HHNS) à still give

fluids first

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- Glucose numbers in DKA vs HHNS à low-hundreds for DKA (i.e., 2-300s); can be 600-1000 for HHNS

- Acid-base disturbance in aspirin toxicity first 20 mins à resp. alkalosis (low CO2, high pH, normal O2,

normal bicarb [too acute to change])

- Acid-base disturbance in aspirin toxicity after 20 mins à mixed metabolic acidosis-respiratory

alkalosis (low CO2, low pH, normal O2, low bicarb)

- Tx for aspirin toxicity à bicarb (increased excretion through urinary alkalinization)

- Acid-base disturbance in PE à resp. alkalosis (low CO2, high pH, low O2, normal bicarb [too acute to

change])

- Acid-base disturbance in asthma à resp. alkalosis (low CO2, high pH, low O2, normal bicarb [too

acute to change])

- Electrolyte abnormality in anorexia à hypokalemia

- Most common cause of death in anorexia à arrhythmia from hypokalemia

- Refeeding syndrome (even if normal BMI) à hypophosphatemia

- Amenorrhea in anorexia à low FSH + low estrogen (hypogonadotropic)

- Premature ovarian failure + Turner syndrome + menopause à high FSH (low inhibin) + low estrogen

- High BMI female + irregular menstrual cycles à anovulation

- Anovulation + hirsutism à PCOS

- Anovulation. Cause USMLE wants? à insulin resistance à causes abnormal GnRH pulsation

- Why hirsutism in anovulation à abnormal GnRH pulsation causes high LH/FSH ratio

- Why high LH/FSH ratio important in anovulation/PCOS à ovulation stimulated when follicle not

ready à no ovulation (anovulation) à follicle retained as cyst

- What’s LH do? à Stimulates theca interna cells (females) and Leydig cells (males) to make androgens

- What’s FSH do? à Stimulates granulosa cells (females) and Sertoli cells (males) to make aromatase;

also primes follicles

- Tx for PCOS à if high BMI, weight loss first always on USMLE

- Tx for PCOS if they ask for meds and/or weight loss already tried à OCPs (if not wanting pregnancy);

clomiphene (if wanting pregnancy)

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- PCOS increases risk of what à endometrial cancer (unopposed estrogen)

- Where does ADH (vasopressin) act à medullary collecting duct à causes aquaporin insertion on

apical membrane à enables free H2O reabsorption

- Where is ADH made? à supraoptic nucleus of hypothalamus à merely stored in posterior pituitary

- Where is oxytocin made à paraventricular nucleus of hypothalamus à merely stored in p. pituitary.

- Neurophysins I’ve heard about. What are those à Showed up in UWorld à carrier proteins needed

to transport oxytocin + ADH from hypothalamus to posterior pituitary

- When does ADH go up à when serum sodium too high à brings sodium back down; ADH will also be

secreted in response to lower blood volume, although aldosterone is major volume regulator; ADH is

main tonicity regulator

- When considering SIADH vs diabetes insipidus (DI) vs psychogenic polydipsia (PP) à what’s the next

best step in evaluation/management à fluid restriction

- SIADH important causes à small cell bronchogenic carcinoma ectopic ACTH, or head trauma (can

actually cause SIADH or DI)

- SIADH parameters à high urine osmolality (concentrated) + low serum sodium (normal is 135-145)

- Tx for SIADH à if small cell lung cancer, chemotherapy (HY to know you can’t do surgery for small

cell); if insufficient, give -vaptans (conivaptan, tolvaptan), which are ADH receptor antagonists, or

demeclocycline (a tetracycline antibiotic that causes nephrogenic DI, but is a Tx for SIADH).

- Central diabetes insipidus à lack of production by hypothalamus or storage problem of posterior

pituitary à low ADH + low urine osmolality (dilute urine) + high serum sodium (concentrated serum)

- Cause of CDI à idiopathic, local malignancy, or head trauma

- Nephrogenic DI à lack of sensitivity of kidney V2 receptors to ADH à high ADH, low urine osmolality

(dilute urine) + high serum sodium (concentrated serum)

- Cause of NDI à lithium, demeclocycline

- Patient with bipolar disorder + tremors + polyuria + polydipsia à answer = NDI

- Diabetes insipidus urine parameters relative to serum: PCT is isotonic (same; always unchanged),

medullary collecting duct is hypotonic (dilute compared to serum), juxtaglomerular apparatus (JGA) is

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hypotonic (always hypotonic no matter what the patient’s condition bc value measured at the top of

thick ascending loop of Henle after ions have been absorbed out of urine)

- SIADH urine parameters relative to serum: PCT is isotonic (same; always unchanged), medullary

collecting duct is hypertonic (reabsorbing lots of free H2O), JGA is hypotonic (as discussed above)

- Dude jumps into cold lake; what happens to central blood volume + atrial natriuretic peptide (ANP) +

ADH levels? à CBV up (cold à sympathetic activation à alpha-1 agonism peripherally to decrease

surface area of blood vessels to conserve heat à blood forced to core) + ANP up (if CBV up, then right

atrial stretch up; ANP is body’s natural diuretic à causes PCT to decrease Na reabsorption) + ADH

down (baroreceptor at carotid sinus senses greater stretch à has a role not just on HR but also ADH

release)

- Psychogenic polydipsia (PP)? à person drinks too much à low serum sodium + low urine osmolality

- Prolactin does what à milk production à acts through JAK/STAT tyrosine kinase

- Oxytocin does what à milk letdown/secretion

- Growth hormone in young à giantism; in adults à acromegaly

- Important points about acromegaly à causes diabetes mellitus (GH causes insulin resistance),

hypertension, carpal tunnel syndrome, arthritis, cardiomyopathy; and yes, prognathism (lantern jaw)

- Growth hormone acts directly at tissues? à USMLE wants you to know it causes liver to increase

insulin-like growth factor 1 (IGF-1), which acts peripherally

- Which hormone counteracts GH à somatostatin à generally acts to shut off other hormone

secretions, and antagonizes the effects of GH (can be Tx for acromegaly)

- What is pegvisomant? à GH receptor antagonist

- Congenital adrenal hyperplasia (CAH) à caused by 21, 11, or 17 hydroxylase deficiency in adrenal

cortex (21 is 90-95% of cases) à autosomal recessive conditions

- 21 hydroxylase deficiency à severe lack of mineralocorticoid and glucocorticoid production by

adrenal à low BP + high K + high DHEA-S (adrenal androgen)

- 11 hydroxylase deficiency à adrenal can still make 11-deoxycorticosterone in zona glomerulosa + 11-

deoxycortisol in zona fasciculata à BP not low (sometimes high) + K not high; DHEA-S still high

- 17 hydroxylase deficiency à can’t convert pregnenolone + progesterone to 17-OH forms à adrenal

gland makes aldosterone in excess but not cortisol or DHEA-S

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- What does ACTH do at adrenal gland à upregulates desmolase, which converts cholesterol into

pregnenolone to start adrenal hormone synthesis

- What does angiotensin II do at the adrenal gland à upregulates aldosterone synthase, converting 11-

deoxycorticosterone into aldosterone

- What is metyrapone testing? à 11-beta hydroxylase inhibitor à can be used in the diagnosis of

adrenal insufficiency or Cushing à re the former, if you give metyrapone, cortisol should go down

normally and ACTH + 11-deoxycorticosterone should go up; if ACTH goes up but 11-

deoxycorticosterone doesn’t à adrenal dysfunction (Addison); if ACTH doesn’t go up, then it’s

secondary hypoadrenalism)

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