Click any card to flip · 32 cards organized by LO 1–7In-House + In-House Anki + BnB / FA / Bootcamp / Physeo
LO 1 · Signaling Modes In House
Contrast endocrine · paracrine · autocrine · neural signaling. Give one canonical example of each.
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Answer
Endocrine — hormone travels through blood to a distant target (e.g., insulin → liver, muscle). Paracrine — signal acts on nearby cells without entering blood (e.g., somatostatin → α/β islet cells). Autocrine — cell signals itself (e.g., IGF-1 on growth-plate chondrocytes). Neural — neurotransmitter at synaptic cleft (e.g., NE at adrenergic synapse, milliseconds). Also:juxtacrine (direct contact; growth factors/cytokines) and neurocrine (neuron → blood, e.g., ADH from SON).
LO 1 · Target Specificity In House
If hormones reach nearly every cell, what determines which cell responds?
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Answer
Receptors create the specificity (in-house slide verbatim). A "target cell" is defined by expressing the receptor for a given hormone. Cells lacking the receptor are effectively deaf even though the hormone physically reaches them via the bloodstream.
LO 1 · Historical Firsts In House
Name two landmark experiments that established the concept of hormones.
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Answer
Berthold (1849): reimplanted rooster testes restored secondary sex characteristics without nervous reconnection → proved blood-borne signal. Horsley & Murray (1890s): sheep thyroid extract / implant reversed myxedema & cretinism in humans → first hormone replacement therapy.
LO 2 · Three Classes In House · FA 3.14
The three chemical classes of hormones — structure, solubility, and one example of each?
What four properties can you predict from a hormone's solubility alone?
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Answer
Hydrophilic → stored in vesicles · free in plasma · short t½ · membrane receptor · indirect signaling (2nd messengers). Hydrophobic → not stored (made on demand) · carrier-bound · long t½ · intracellular/nuclear receptor · direct signaling (transcription). Bioavailability corollary: hydrophobic = oral OK (levothyroxine, steroids); hydrophilic peptides must inject (insulin, GH).
LO 2 · Glycoprotein Hormones In House · FA 3.14
Which four hormones share the α-subunit, and what does the β-subunit do?
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Answer
TSH, LH, FSH, hCG — identical α-subunit; the β-subunit confers receptor specificity. Differential glycosylation fine-tunes specificity. The α-subunit is required for the conformational change that activates the receptor. Clinical: extreme hCG (molar pregnancy, choriocarcinoma) cross-reacts at the TSH receptor → hyperthyroidism.
LO 2 · Storability In House · FA 3.14
Match each hormone class to where (if anywhere) it is stored.
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Answer
Peptide → secretory granules/vesicles (regulated exocytosis on stimulus). Catecholamines → chromaffin granules (DβH acts inside vesicle). Thyroid hormone → iodinated thyroglobulin in colloid (extracellular — unique!). Steroid → NOT stored; synthesized de novo from cholesterol on demand. Eicosanoid → NOT stored; made locally from membrane arachidonic acid.
LO 2 · Eicosanoids In House · FA
What's the precursor? List the four subclasses and the enzymes that make them.
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Answer
All derived from arachidonic acid (released from membrane phospholipids by phospholipase A2). COX pathway: prostaglandins (PGE, PGD, PGF), thromboxanes (TXA₂), prostacyclin (PGI₂). LOX pathway: leukotrienes (LTB₄, LTC₄/D₄/E₄). Drugs: NSAIDs → COX; glucocorticoids → PLA2 (block both arms); zileuton → LOX; montelukast → LTD₄-R.
LO 3 · Synthesis Pathway In House · BnB 3.02
Write the catecholamine pathway from tyrosine to epinephrine, naming every enzyme.
Why do post-ganglionic sympathetic neurons release NE while the adrenal medulla releases ~80% Epi?
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Answer
PNMT (phenylethanolamine-N-methyltransferase) is the enzyme that converts NE → Epi. PNMT is cortisol-inducible, and only the adrenal medulla is bathed in very high local cortisol (via intra-adrenal portal system from cortex). Sympathetic post-ganglionic neurons lack this cortisol exposure → no PNMT → stay on NE.
LO 3 · Pheochromocytoma BnB 3.02 · Bootcamp 10.04
Cell of origin, classic symptoms, and best screening test?
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Answer
Origin: chromaffin cells of adrenal medulla (modified postganglionic sympathetic neurons). 5 P's:pressure (HTN), pain (headache), palpitations, perspiration, pallor — episodic. Best screen: plasma free metanephrines (or 24-h urine metanephrines/VMA). More reliable than catecholamines (pulsatile). Rule of 10s (bilateral / extra-adrenal / malignant / familial — MEN 2A/2B, NF1, VHL). Pre-op: α-blockade (phenoxybenzamine) FIRST, then β-blocker. Never β-block first.
LO 3 · L-DOPA / Carbidopa BnB 3.02 · FA
Why is L-DOPA given with carbidopa in Parkinson's?
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Answer
L-DOPA crosses BBB (dopamine does NOT) → converted to DA centrally by DOPA decarboxylase. Without adjunct: peripheral DOPA decarboxylase converts most L-DOPA to DA before it crosses BBB → side effects + less drug reaches brain. Carbidopa inhibits peripheral DOPA decarboxylase (does NOT cross BBB) → more L-DOPA reaches brain, fewer peripheral GI/cardiovascular side effects.
LO 4 · Initial Step In House · FA 3.15
What is the initial step of steroid biosynthesis? Which enzyme? What regulates it?
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Answer
Cholesterol → Pregnenolone Enzyme: Desmolase (CYP11A1 / P450scc) — inner mitochondrial membrane side-chain cleavage. Rate-limiting actually = StAR protein — transports cholesterol from outer → inner mitochondrial membrane (without it, desmolase has no substrate). Stimulated by ACTH (adrenal) and LH (gonads) via cAMP → PKA.
LO 4 · C21/C19/C18 In House · FA 3.15
How are steroids classified by carbon count?
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Answer
C21 — progestins + corticoids (cortisol, aldosterone). Retain cholesterol side chain. C19 — androgens (DHEA, androstenedione, testosterone). Side chain removed. C18 — estrogens (estradiol, estrone). Aromatase removes one more carbon (A-ring aromatization). Secosteroid: vitamin D/calcitriol — cholesterol-derived with broken B-ring.
LO 4 · Congenital Adrenal Hyperplasia BnB · FA · Anki
Three CAH enzyme defects — cortisol, aldo, androgens, clinical?
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Answer
21-OH deficiency (90%) — ↓cortisol, ↓aldo, ↑↑androgens → salt-wasting, hypotension, hyperkalemia, virilization. ↑17-OH-progesterone. 11β-OH deficiency — ↓cortisol, ↓aldo, but 11-deoxycorticosterone (weak MC) accumulates → HTN + hypokalemia + virilization. 17α-OH deficiency — ↑MC precursors → HTN, hypokalemia; ↓sex steroids → ambiguous genitalia / sexual infantilism. Mnemonic: 21 low BP · 11 high BP + virile · 17 high BP, no sex steroids.
LO 4 · Vitamin D Activation In House · BnB
Trace 7-dehydrocholesterol to active calcitriol. What regulates the rate-limiting step?
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Answer
Skin: 7-dehydrocholesterol + UVB → cholecalciferol (D₃). Liver: 25-hydroxylase → 25-OH-D (calcidiol, storage form). Kidney PCT:1α-hydroxylase → 1,25-(OH)₂-D (calcitriol, active). 1α-hydroxylase is RATE-LIMITING: ↑ by PTH, ↓ Pi, ↓ Ca²⁺; ↓ by FGF23 and high 1,25-D (feedback).
LO 5 · Carrier Roster In House · FA
Match each carrier protein to its hormone: CBG, TBG, SHBG, DBP, albumin.
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Answer
CBG (transcortin): cortisol (+ progesterone). TBG: T3 + T4. SHBG: testosterone, DHT, estradiol. DBP: vitamin D / 25-OH-D. Albumin: non-specific — low affinity, high capacity (all hydrophobic hormones).
LO 5 · Free Hormone Hypothesis In House
State the free hormone hypothesis. Give a clinical example where it matters.
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Answer
Only the FREE (unbound) fraction is biologically active; carrier-bound hormone is an inactive reservoir. The free fraction is governed by Kd of the carrier. Pregnancy: estrogen ↑ hepatic TBG → total T4 rises but free T4 unchanged → patient is euthyroid. OCPs: estrogen ↑ CBG → ↑ total cortisol, free cortisol unchanged. → Always order FREE T4, FREE cortisol — not total.
LO 5 · Half-Life In House · FA
Why do peptides have minute half-lives and thyroid hormone days?
LO 6 · Nuclear Receptor Superfamily In House · FA 3.15
Four ligand classes that use nuclear receptors. RXR partners?
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Answer
Four ligand classes: (1) steroid hormones (GR, MR, ER, PR, AR); (2) thyroid hormone (TR); (3) vitamin D (VDR); (4) retinoic acid (RAR). RXR heterodimerizes with RAR, VDR, TR, PPAR, LXR. Steroid receptors are usually cytoplasmic with HSP90, homodimerize after ligand binding. TR/VDR/RAR sit pre-bound to DNA and often REPRESS transcription until hormone binds.
LO 6 · Kd & Scatchard In House · FA
What does Kd measure? What does a Scatchard plot show?
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Answer
Kd = hormone concentration at which 50% of receptors are bound. Lower Kd = HIGHER affinity. Insulin receptor Kd ≈ 10⁻⁹ M. Scatchard plot: x-axis = Bound hormone; y-axis = Bound/Free. Straight line with negative slope = single receptor class; curved = multiple classes or cooperativity. Slope = −1/Kd; x-intercept = Bmax (total receptor number).
LO 6 · GPCR Diseases FA 3.14 · BnB 5.06
Pair each disease/toxin to its G-protein defect: cholera · pertussis · McCune-Albright · PHP 1a · nephrogenic DI.
Define EC50. List three ways to shift cellular sensitivity.
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Answer
EC50 = hormone concentration producing half the maximal cellular response; lower EC50 = more sensitive. Three shifts (in-house slide): (1) different receptor isoforms with different affinities; (2) post-translational modification of the receptor; (3) changing receptor number (up/down-regulation).
LO 7 · Insulin Resistance In House · Petersen & Shulman 2018
Describe the curve shift in insulin resistance and explain the compensatory hyperinsulinemia of early T2DM.
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Answer
RIGHTWARD shift of the insulin dose-response curve = higher EC50 (more insulin for same effect). In severe disease the plateau also falls. Mechanism: chronic hyperinsulinemia → insulin receptor down-regulation + post-receptor defects (SOCS proteins, IRS-1 serine phosphorylation) + lipotoxicity. Early T2DM: β-cells compensate with hyperinsulinemia (climb the shifted curve → glucose stays near-normal). Late T2DM: β-cell exhaustion → insulin falls, glucose rises.
LO 7 · Down- vs Up-Regulation FA · BnB
What triggers each? Clinical example of each.
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Answer
Down-regulation: chronic HIGH hormone → receptor internalization + post-receptor desensitization → loss of sensitivity. Example: T2DM insulin resistance; continuous GnRH agonism (leuprolide) → medical castration. Up-regulation: chronic LOW hormone → ↑ receptor number → supersensitivity. Example: denervation hypersensitivity; prolonged fasting ↑ insulin receptors.
LO 7 · Permissiveness FA · Physio
Define hormone permissiveness and give a high-yield example.
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Answer
Permissiveness: one hormone is required for another hormone's full effect, even though hormone A alone has no direct effect. Classic:Cortisol permits catecholamine vasoconstriction — Addisonian crisis presents with hypotension refractory to pressors because NE/Epi can't vasoconstrict without permissive cortisol. Give stress-dose hydrocortisone. Also: T3 permits β-adrenergic sensitivity → tachycardia in hyperthyroidism.
LO 7 · Hormone Resistance FA · BnB
How is "hormone resistance" distinguished from hormone deficiency biochemically?
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Answer
Hormone resistance: serum hormone is HIGH (or normal) but target-tissue effect is LOW → receptor/post-receptor defect. Classic examples: Type 2 DM (insulin receptor), Laron syndrome (GHR mutation — ↑GH, ↓IGF-1), pseudohypoparathyroidism (Gsα, PTH resistance), androgen insensitivity (AR mutation), Type A insulin resistance (insulin-R mutation). Contrast: hormone deficiency — hormone LOW, response restored by exogenous hormone.
LO 2/5 · Oral Bioavailability FA · Pharm
Why can levothyroxine/cortisol be given PO while insulin/GH must be injected?
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Answer
Lipid-soluble hormones (PO): steroids, thyroid hormone, vitamin D — resistant to GI proteases + cross intestinal membrane + reach liver for carrier binding. Hydrophilic peptides (inject): insulin, GH, teriparatide, calcitonin, ACTH, GnRH analogs — digested by pepsin/trypsin within minutes + cannot cross intestinal epithelium. Nasal: desmopressin (small peptide, specialized delivery). Transdermal estrogen avoids first-pass.
LO 2 · C-peptide FA · Anki
What is C-peptide and why is it clinically useful?
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Answer
C-peptide is cleaved from proinsulin in the Golgi and released in equimolar amounts with endogenous insulin. Factitious hypoglycemia: insulin ↑ but C-peptide ↓ → exogenous insulin injection. Insulinoma: both ↑. Sulfonylurea abuse: both ↑ (stimulates endogenous release) — confirm with urine sulfonylurea screen. T1DM: both LOW (β-cell destruction). Directly tests peptide-hormone processing (LO 2).
LO 7 · Feedback Loops Bootcamp 1.03
Contrast negative, positive, and feedforward regulation with endocrine examples.
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Answer
Negative: target-organ hormone suppresses upstream release — cortisol → ↓CRH + ↓ACTH; T4 → ↓TSH. Positive: rising hormone further stimulates its own release — mid-cycle estradiol surge → LH surge (ovulation); oxytocin during labor (Ferguson reflex). Positive loops are self-terminating. Feedforward: anticipatory signal prepares target before stimulus arrives — cephalic insulin release before glucose load.
Step 1-Style MCQs: single best answer. Each question is cross-referenced to the in-house LO and the mapped 3rd-party resource that teaches it.
Question 1 of 10 · LO 1 — Signaling Modes In House
Somatostatin released from δ-cells of a pancreatic islet diffuses across the interstitium to suppress insulin release from neighboring β-cells within the same islet. Which mode of intercellular communication best describes this effect?
AEndocrine
BParacrine
CAutocrine
DNeural
EJuxtacrine
B — Paracrine. Signal acts on ADJACENT cells without entering blood. Endocrine (A) = into bloodstream to distant targets. Autocrine (C) = self-signaling. Neural (D) = across a synapse with neurotransmitter release. Juxtacrine (E) = direct cell–cell contact via membrane-anchored ligand.
Question 2 of 10 · LO 2 — Hormone Classes In House · FA 3.14
A hormone is hydrophilic, circulates free in plasma, has a half-life of minutes, and signals through a G-protein-coupled receptor. Which class most likely describes this hormone?
ASteroid hormone
BThyroid hormone
CCatecholamine (amino acid derivative)
DVitamin D (secosteroid)
ERetinoic acid
C — Catecholamine. Hydrophilic + free in plasma + short ½-life + GPCR all fit catecholamines (Epi, NE, DA) which act on α/β adrenergic or D receptors. Steroid, thyroid, vitamin D, retinoic acid are hydrophobic, carrier-bound, long-t½, and signal through nuclear receptors.
Question 3 of 10 · LO 2 — Glycoprotein Subunits In House · FA
A 28-year-old woman at 14 weeks' gestation presents with palpitations and tremor. TSH <0.01, free T4 elevated, β-hCG 530,000 mIU/mL. Ultrasound: "snowstorm" uterus, no fetal heart tones. Which structural feature best explains the hyperthyroidism?
AhCG-β and TSH-β are identical in sequence
BhCG and TSH share an identical α-subunit; at extreme hCG concentrations, partial β similarity allows TSH-receptor cross-activation
ChCG binds directly to thyroid peroxidase
DhCG stimulates hepatic TBG synthesis
EMolar tissue secretes a distinct thyroid-stimulating immunoglobulin
B. TSH, LH, FSH, hCG all share identical α-subunits; the β-subunit confers specificity. At extreme hCG (>100,000 mIU/mL — molar pregnancy, choriocarcinoma, hyperemesis), partial structural similarity in β allows cross-activation at the TSH receptor → secondary thyrotoxicosis with suppressed TSH (normal pituitary feedback intact). Resolves after tumor evacuation.
Question 4 of 10 · LO 3 — Catecholamine Rate-Limiting Step In House · BnB 3.02
A 34-year-old woman with episodic headaches, sweating, and palpitations has BP 210/120 during attacks. Imaging: 3-cm right adrenal mass. 24-hour urine metanephrines are markedly elevated. Which enzyme's activity is most upregulated in the neoplastic chromaffin cells?
ATyrosine hydroxylase
BDOPA decarboxylase
CPNMT
DCatechol-O-methyltransferase (COMT)
EMonoamine oxidase (MAO)
A — Tyrosine hydroxylase. Pheochromocytoma overproduces catecholamines. The RATE-LIMITING step is TH (Tyr → L-DOPA, BH4 cofactor) — the first committed step is almost always the regulated one. COMT/MAO degrade catecholamines (explains why metanephrines are the best screen). PNMT only makes Epi in the adrenal medulla but isn't rate-limiting for overall catecholamine output. Metyrosine (α-methyltyrosine) blocks TH for pre-op control.
Question 5 of 10 · LO 4 — Steroid Initial Step In House · FA 3.15
An adrenal cortical cell is stimulated by ACTH. Which step does ACTH accelerate first, committing the pathway toward cortisol?
A21α-hydroxylase conversion of progesterone to 11-deoxycorticosterone
B17α-hydroxylase conversion of pregnenolone
CStAR-mediated cholesterol transfer + desmolase conversion to pregnenolone
D11β-hydroxylase conversion of 11-deoxycortisol to cortisol
EAromatase aromatization of testosterone
C. All steroid hormones begin with cholesterol → pregnenolone via desmolase (CYP11A1 / P450scc) on the inner mitochondrial membrane. The true rate-limiting element is StAR — it shuttles cholesterol from outer → inner mito membrane. ACTH (and LH in gonads) acts through Gs → cAMP → PKA → StAR phosphorylation + transcription. Options A, B, D are downstream steps unique to cortisol or aldosterone branches. Aromatase (E) is an estrogen-specific late step.
Question 6 of 10 · LO 4 — CAH BnB · FA · Anki
A 3-week-old female neonate presents with vomiting, ambiguous genitalia, Na⁺ 128, K⁺ 6.4, glucose 52. Serum 17-hydroxyprogesterone is markedly elevated. Which enzyme is deficient?
A11β-hydroxylase
B17α-hydroxylase
C21-hydroxylase
DDesmolase (CYP11A1)
EAromatase
C. 21-hydroxylase deficiency is the most common CAH (~90%). Loss of 21-OH → no cortisol, no aldosterone (salt-wasting hyponatremia + hyperkalemia); precursors shunt into androgen pathway → virilization. 17-OH-progesterone accumulates upstream. 11β (A) = HTN + virilization; 17α (B) = HTN, no sex steroids. Desmolase (D) shuts all steroid synthesis.
Question 7 of 10 · LO 5 — Free Hormone Hypothesis In House · FA
A 28-year-old pregnant woman at 18 weeks has total T4 18.4 μg/dL (upper limit 12), TSH 1.3 mIU/L, feels well, no tremor. What is the best next step?
AStart methimazole for hyperthyroidism
BRadioactive iodine uptake scan
COrder FREE T4 to confirm euthyroid state
DBegin propranolol
EStart levothyroxine
C. Pregnancy ↑↑ estrogen → ↑ hepatic TBG → ↑ total T4 (more bound) but FREE T4 unchanged. Normal TSH confirms euthyroidism. Always order the FREE fraction — it is the biologically active form (free hormone hypothesis, in-house LO 5 slide). RAI (B) contraindicated in pregnancy; A/D/E inappropriate when patient is euthyroid.
Question 8 of 10 · LO 6 — GPCR Signaling / PHP 1a FA 3.14 · BnB 5.06
A 22-year-old woman with short stature, round face, and shortened 4th/5th metacarpals has Ca²⁺ 6.8, Pi 6.2, and PTH 220. Infusion of synthetic PTH fails to raise urinary cAMP. Which molecular defect best explains these findings?
AAutoimmune destruction of parathyroid glands
BLoss-of-function mutation of the PTH receptor
CLoss-of-function mutation of Gsα (GNAS)
DChronic hypomagnesemia
EActivating mutation of the calcium-sensing receptor
Question 9 of 10 · LO 7 — Receptor Sensitivity / T2DM In House · FA
A 48-year-old obese man has fasting glucose 148, HbA1c 8.1%, fasting insulin 42 μIU/mL (normal 2–25), C-peptide 4.8 (normal). Over the next 5 years his fasting insulin progressively declines and glucose worsens. Which statement best explains this trajectory?
AAutoimmune destruction of β-cells has occurred
BInitial insulin-receptor down-regulation caused resistance; β-cell exhaustion later reduced output
B. Classic T2DM trajectory — the disease explicitly referenced in the in-house insulin-resistance slide. Chronic hyperinsulinemia → receptor down-regulation + post-receptor defects → resistance. β-cells compensate (early hyperinsulinemia + high C-peptide) then exhaust (late insulin falls, glucose rises). A describes T1DM.
Question 10 of 10 · LO 2 — Bioavailability FA · Pharm
A 52-year-old woman with primary hypothyroidism takes oral levothyroxine with good effect. Her husband with T1DM must inject his insulin subcutaneously. What BEST explains the difference?
BT4 is lipid-soluble and resistant to GI proteases; insulin is a hydrophilic peptide rapidly digested
CInsulin requires an intestinal transporter that is saturated
DT4 is stored in thyroglobulin which protects it in the gut
EInsulin is subject to first-pass metabolism while T4 is not
B. Hormone class → solubility → route of administration. Hydrophobic hormones (T4, steroids, vitamin D) resist GI proteolysis + cross intestinal epithelium easily → effective PO. Hydrophilic peptides (insulin, GH, PTH) are hydrolyzed by pepsin/trypsin within minutes — must be injected (SC/IM/IV) or delivered nasally (desmopressin). Molecular weight (A) contributes but isn't the mechanism; T4 stored in thyroglobulin (D) is irrelevant to oral administration.
Integrated Vignettes: longer clinical scenarios crossing multiple LOs, drawn from the mapped 3rd-party workbook content (FA, BnB, Bootcamp, Pathoma) in scope for end01.
Vignette 1 of 6 · LO 2/6 — Molar Pregnancy / hCG Cross-Reactivity FA · BnB
A 28-year-old G2P1 at 14 weeks presents with hyperemesis, palpitations, tremor, and warm moist skin. BP 148/92, pulse 118. TSH <0.01, free T4 ↑, β-hCG 530,000 mIU/mL, TPO antibodies negative. Ultrasound: enlarged uterus with "snowstorm" appearance and no fetal heart tones.
AGraves disease coincident with pregnancy
BToxic multinodular goiter
ChCG-mediated hyperthyroidism from a complete hydatidiform mole
DFactitious thyrotoxicosis
ESubacute thyroiditis
C. Classic buzzwords: snowstorm uterus, absent fetal heart tones, hCG >500,000, negative autoantibodies. hCG and TSH share α-subunit; at extreme hCG, partial β similarity activates the TSH-R. Integrates LO 2 (glycoprotein structure) + LO 6 (receptor cross-reactivity). Resolves after molar evacuation.
Vignette 2 of 6 · LO 4 — CAH with HTN (11β-OH) BnB · FA
A 5-year-old girl presents with clitoromegaly, pubic hair, and hypertension (BP 142/88, 99th percentile). Labs: K⁺ 2.9, renin suppressed, aldosterone low, but 11-deoxycorticosterone (DOC) and 11-deoxycortisol markedly elevated. DHEA very high.
A21-hydroxylase deficiency
B11β-hydroxylase deficiency
C17α-hydroxylase deficiency
DAromatase deficiency
EDesmolase deficiency
B — 11β-hydroxylase. Block at 11β-OH → no cortisol, no aldosterone, but DOC (weak mineralocorticoid) accumulates → HTN + hypokalemia. Androgen precursors shunt into virilization. 21-OH (A) → salt-wasting, NOT HTN. 17α (C) → HTN but NO virilization.
Vignette 3 of 6 · LO 6 — Nephrogenic DI / V2 Receptor BnB 5.06 · FA
A 55-year-old man on chronic lithium for bipolar disorder has polyuria (8 L/day) and polydipsia. Na⁺ 152, urine osm 120 mOsm/kg. After water deprivation urine osm rises to 180. After desmopressin, urine osm still does not rise above 200.
ACentral diabetes insipidus
BNephrogenic DI (V2 / aquaporin-2 dysfunction)
CPrimary polydipsia
DSIADH
EOsmotic diuresis
B. Central DI corrects with desmopressin; nephrogenic does NOT because defect is downstream of ADH — V2-receptor/aquaporin-2 signaling. Lithium disrupts V2 → cAMP coupling. Tests LO 6 (Gs-cAMP signaling disease) + LO 7 (drug-altered receptor function). Tx: stop lithium if possible, HCTZ + low-salt, amiloride.
Vignette 4 of 6 · LO 5 — Carrier Protein Change in Pregnancy In House · FA
A 26-year-old woman on combined oral contraceptives is referred for "high cortisol." Morning total cortisol 32 μg/dL (upper normal 22); no Cushing features. 24-h urine free cortisol normal, late-night salivary cortisol normal, dexamethasone suppression intact.
ACushing disease (pituitary)
BAdrenal adenoma secreting cortisol
CEstrogen-induced ↑ CBG with normal free cortisol
DFactitious glucocorticoid use
ECyclic Cushing syndrome
C. Estrogen (OCPs, pregnancy) induces hepatic CBG → ↑ total cortisol but free cortisol unchanged → patient remains eucortisolic. Normal urine free cortisol, normal late-night salivary cortisol, intact dexamethasone suppression confirm. Tests LO 5 free-hormone hypothesis directly.
Vignette 5 of 6 · LO 6/7 — Laron Syndrome (Hormone Resistance) FA · BnB
A 6-year-old boy has severe growth failure; doll-like facies with prominent forehead. GH 58 ng/mL (HIGH), IGF-1 28 ng/mL (VERY LOW). He fails to respond to exogenous GH. Consanguineous parents of normal stature.
C. Paradigm of hormone resistance: ↑↑ hormone + LOW effect because the receptor is broken. AR inheritance (consanguinity). GHR mutation → failed JAK2-STAT5 signaling → no hepatic IGF-1 → growth failure. Treat with recombinant IGF-1 (mecasermin) bypassing the receptor. Integrates LO 6 (JAK-STAT) + LO 7 (resistance as the inverse of deficiency).
Vignette 6 of 6 · LO 2/7 — C-peptide / Factitious Hypoglycemia FA · Anki
A 32-year-old nurse is found with diaphoresis, confusion, and fingerstick glucose 38. Labs during the episode: insulin 85 μIU/mL (HIGH), C-peptide 0.3 ng/mL (LOW), proinsulin undetectable. Which best explains the findings?
AInsulinoma
BSurreptitious exogenous insulin administration
CSulfonylurea abuse
DGlucagonoma
EAdrenal insufficiency
B. Endogenous insulin is cleaved from proinsulin → equimolar insulin + C-peptide. Exogenous insulin has NO C-peptide. Pattern: ↑ insulin + ↓↓ C-peptide = injection (classic factitious case, medical personnel). Insulinoma (A) = both ↑ + ↑ proinsulin. Sulfonylureas (C) = both ↑ (stimulates endogenous release; urine sulfonylurea screen confirms). Directly tests LO 2 peptide-hormone processing.
Step 1 Traps: each statement is TRUE or FALSE. Many reverse or mix facts that routinely trip students up.
Trap 01 · LO 1 — Paracrine Definition In House
"A paracrine hormone is secreted into the bloodstream and acts on adjacent cells."
FALSE. Paracrine = local DIFFUSION to neighboring cells, NO bloodstream. Endocrine = into blood → distant targets. The word "paracrine" literally means "alongside" — no circulation.
Trap 02 · LO 2 — Storability In House
"Steroid hormones, unlike peptide hormones, are stored in secretory vesicles and released on demand."
FALSE — reversed.Peptides are stored preformed in granules → released in seconds of stimulus. Steroids are lipid-soluble and cannot be stored in membrane-bound granules; they are synthesized de novo from cholesterol upon stimulus (StAR → desmolase). ACTH → cortisol appears in minutes–hours, peaking ~30–60 min later.
Trap 03 · LO 2 — Glycoprotein Subunits In House · FA
"TSH, LH, FSH, and hCG all share a common β-subunit, with the α-subunit being unique."
FALSE — reversed. The α-subunit is IDENTICAL across all four; the β-subunit is UNIQUE and gives each receptor specificity. β-hCG is what pregnancy tests measure.
Trap 04 · LO 2 — Thyroid Hormone Class In House
"Thyroid hormone and cortisol are both steroid hormones derived from cholesterol."
FALSE. Thyroid hormone is an amine (tyrosine + iodine on thyroglobulin). Cortisol IS a steroid. However, thyroid hormone BEHAVES like a steroid — lipid-soluble, carrier-bound to TBG, nuclear receptor, long half-life. This dual classification is a classic source of confusion.
Trap 05 · LO 3 — Rate-Limiting Step In House · BnB 3.02
"The rate-limiting enzyme of catecholamine synthesis is dopamine β-hydroxylase."
FALSE. Rate-limiting = tyrosine hydroxylase (Tyr → L-DOPA; BH4 cofactor). DβH is downstream (DA → NE inside vesicle). Rate-limiting is almost always the FIRST committed step.
Trap 06 · LO 3 — PNMT Location In House
"PNMT is distributed across all sympathetic postganglionic neurons, which is why NE and Epi are both released at peripheral synapses."
FALSE. PNMT is found only in the adrenal medulla. Its expression requires high local cortisol delivered via an intra-adrenal portal system from the cortex. Sympathetic nerves release primarily NE; adrenal medulla releases ~80% Epi / 20% NE.
Trap 07 · LO 4 — StAR vs Desmolase FA 3.15
"StAR and desmolase are interchangeable names for the enzyme that converts cholesterol to pregnenolone."
FALSE.StAR (steroidogenic acute regulatory protein) TRANSPORTS cholesterol from outer to inner mitochondrial membrane. Desmolase (CYP11A1 / P450scc) is the ENZYME that cleaves the side chain → pregnenolone. Both are required; without StAR, desmolase has no substrate. StAR is the acutely regulated rate-limiting element.
Trap 08 · LO 5 — Free Hormone In House
"A pregnant woman with elevated total T4 but normal free T4 is hyperthyroid and should be treated with methimazole."
FALSE. Classic free-hormone trap. Estrogen ↑ hepatic TBG → ↑ total T4, but free T4 is unchanged → patient is euthyroid. No treatment needed. Always use FREE T4 to judge thyroid status in pregnancy / OCPs.
Trap 09 · LO 6 — Receptor Logic In House · FA
"Insulin and glucagon both signal through G-protein coupled receptors using cAMP."
FALSE. Insulin uses a receptor tyrosine kinase (RTK) → IRS-1 → PI3K/MAPK. Only glucagon uses a Gs-coupled GPCR → cAMP. Despite being counter-regulatory hormones, their receptors are architecturally opposite.
Trap 10 · LO 6 — Nuclear Receptor Onset In House · FA
"Nuclear receptors like the glucocorticoid receptor produce rapid effects (within seconds) by directly gating ion channels."
FALSE. Nuclear receptors alter gene transcription → mRNA → new protein → effect. This is SLOW (hours–days). Rapid (seconds–minutes) effects are signature of hydrophilic hormones on MEMBRANE receptors (GPCR, RTK) using second messengers. Some steroids do have non-genomic rapid membrane effects but these aren't the canonical pathway.
Trap 11 · LO 6 — GPCR Toxins FA 3.14 · BnB 5.06
"Cholera toxin ADP-ribosylates Gi, causing diarrhea by lowering intracellular cAMP."
FALSE.Cholera toxin ADP-ribosylates Gs → locks Gs ON → adenylyl cyclase constitutive → massive ↑cAMP → PKA → CFTR Cl⁻ secretion → rice-water stool. Pertussis toxin is the one that targets Gi (locks it OFF). Don't mix them up.
Trap 12 · LO 7 — Down-regulation Direction In House · FA
"Up-regulation of receptors is the defensive response to chronic HIGH hormone exposure."
FALSE — reversed.Down-regulation is the response to chronic HIGH hormone (e.g., T2DM insulin resistance). Up-regulation follows chronic LOW hormone (denervation hypersensitivity; prolonged fasting → ↑ insulin receptors). Rule: "Lots of hormone → Lose receptors; Little hormone → Lots of receptors."
Trap 13 · LO 7 — EC50 Shift In House · Petersen & Shulman
"A patient with insulin resistance has a LEFT-shifted insulin dose-response curve because they need more insulin to produce the same effect."
FALSE — reversed. Insulin resistance = RIGHT shift (↑ EC50). More hormone is required for the same response. A LEFT shift = sensitization (lower hormone for max effect) — the opposite of resistance.
Trap 14 · LO 7 — Cortisol & Catecholamines FA · Physio
"Patients in adrenal crisis are hypotensive because cortisol directly mediates vascular tone independent of catecholamines."
FALSE — but close. Cortisol has no direct vasoconstrictive effect. Its role is PERMISSIVE: cortisol is required for catecholamines to exert α₁-mediated vasoconstriction. Without cortisol, pressors lose effect — give stress-dose hydrocortisone. Classic LO 7 permissiveness example.
Matching drills: click an item on the left, then its match on the right. Correct pairs turn green; wrong pairs flash red. Four drills covering hormone class, signaling pathway, carrier proteins, and G-protein diseases.
Drill 1 · LO 2/6 — Hormone → Signaling Pathway
Match each hormone to its principal receptor/pathway. Every entry is named in in-house slides, FA 3.14, or BnB 5.06.
Hormone
Insulin
Thyroxine (T4)
Epinephrine
Cortisol
TSH / LH / FSH / hCG
Growth hormone
ANP / BNP
Receptor Pathway
Membrane guanylyl cyclase → cGMP
Nuclear (TR) — pre-bound to DNA; de-repression on hormone binding
JAK2 → STAT5 (cytokine receptor)
RTK → IRS-1 → PI3K / MAPK
Gs-coupled GPCR (shared α-subunit)
GPCR (α / β-adrenergic)
Cytoplasmic GR → HSP90 released → nucleus → HRE
Score: 0/7 correct
Drill 2 · LO 5 — Carrier Protein → Hormone Cargo
Knowing carrier-protein specificity is required for interpreting Total vs Free hormone labs.
Blocks PERIPHERAL DOPA decarboxylase (does NOT cross BBB)
Cholesterol → Pregnenolone; inner mito; stimulated by ACTH / LH
Score: 0/6 correct
Clinical correlates + HY testing notes: the signature diseases and testing patterns that connect each LO to mapped 3rd-party step-1 content. Click Expand for mechanism.
LO 3 · Catecholamines BnB 3.02 · Bootcamp 10.04 · FA
Pheochromocytoma — The "5 P's" & Rule of 10s
Chromaffin-cell tumor of the adrenal medulla producing catecholamines. Classic 5 P's: pressure, pain, palpitations, perspiration, pallor. Rule of 10s: 10% bilateral, 10% extra-adrenal (organ of Zuckerkandl), 10% malignant, 10% familial (MEN 2A/2B, NF1, VHL).
Biochemistry: TH activity upregulated → massive NE/Epi synthesis. Continuous COMT/MAO degradation → measure 24-h urine fractionated metanephrines or plasma free metanephrines (more sensitive). Pharmacology: α-blockade (phenoxybenzamine) FIRST, then β-blocker. Never β-block first — unopposed α can precipitate hypertensive crisis. Metyrosine (α-methyltyrosine) blocks TH for pre-op control.
LO 4 · Steroid Biosynthesis BnB · FA 3.15 · In-House Anki
Congenital Adrenal Hyperplasia — Three Enzyme Defects
Autosomal recessive defects of adrenal steroidogenesis. Always three presentations: 21-OH (most common), 11β-OH, 17α-OH — each has a distinct cortisol / aldosterone / androgen / BP profile.
21-hydroxylase (90%): ↓ cortisol, ↓ aldosterone, ↑↑ androgens → salt-wasting, hyperkalemia, hypotension, virilization. ↑ 17-OH-progesterone (screening marker). 11β-hydroxylase: ↓ cortisol, ↓ aldo, but 11-DOC (weak MC) accumulates → HTN + hypokalemia + virilization. 17α-hydroxylase: ↑ MC precursors → HTN + hypokalemia; ↓ sex steroids → ambiguous genitalia / sexual infantilism. Mnemonic: 21 low BP · 11 high BP + virile · 17 high BP, no sex steroids.
LO 5 · Carrier Proteins In House · FA · BnB 5.06
TBG / CBG in Pregnancy & OCPs — Free Hormone Hypothesis in Action
Estrogen (pregnancy or OCPs) stimulates hepatic TBG and CBG synthesis → total T4 and total cortisol rise, but FREE fractions stay the same. Patient is clinically euthyroid/eucortisolic.
The principle: Carrier proteins do NOT change endocrine activity — they buffer delivery and extend half-life. Only FREE hormone can bind receptors. Always order FREE T4 or late-night salivary/urine free cortisol — not totals — when evaluating pregnant or OCP patients. Same logic: hyperthyroidism ↑SHBG → ↑total T but ↓free T → hypogonadism symptoms despite normal total T. Obesity ↓SHBG → ↑free androgens (PCOS-like features).
LO 6 · GPCR Signaling FA 3.14 · BnB 5.06
Pseudohypoparathyroidism 1a — Hormone Resistance via Gsα Loss
Classic GPCR-signaling disease: inactivating GNAS mutation → loss of Gsα → PTH receptor cannot signal cAMP → end-organ resistance despite elevated PTH.
Mechanism: PTH-R is Gs-coupled. Without Gsα, PTH binding cannot raise cAMP in kidney/bone → end-organ resistance. Labs: ↑PTH, ↓Ca²⁺, ↑Pi. Phenotype — Albright hereditary osteodystrophy: short stature, short 4th/5th metacarpals, round face, obesity. Multi-hormone resistance (TSH, LH, FSH also Gs-coupled). Diagnostic test: Ellsworth-Howard — PTH infusion fails to raise urinary cAMP (true hypoparathyroidism would respond). Maternal imprinting: phenotype requires inheritance from mother.
LO 6 · GPCR Signaling FA 3.14 · BnB 5.06
Cholera vs. Pertussis Toxin — G-Protein Poisoning
Both bacterial exotoxins ADP-ribosylate G-protein α-subunits but at opposite sites, producing opposite electrolyte / respiratory pictures.
Cholera toxin (Vibrio cholerae): ADP-ribosylates Gsα at an arginine residue → locks Gs GTP-bound active → adenylyl cyclase permanently ON → massive ↑cAMP → PKA → CFTR phosphorylation → Cl⁻ + Na⁺ + H₂O secretion → rice-water stool, severe dehydration, hypokalemic metabolic acidosis. Treat: aggressive rehydration, doxycycline. Pertussis toxin (Bordetella pertussis): ADP-ribosylates Giα at cysteine → locks Gi OFF → loss of adenylyl cyclase inhibition → relative ↑cAMP in respiratory epithelium + immune cells → whooping cough, lymphocytosis. DTaP prevents. Mnemonic:Cholera = Gs ON, Pertussis = Gi OFF.
Somatic post-zygotic activating GNAS (Gsα) mutation → constitutive cAMP in affected tissues. Features are patchy because germline activating GNAS is embryonic lethal — disease survives only in mosaic pattern.
Classic triad (Albright 1937): (1) precocious puberty (ovarian Gs activation autonomous of LH/FSH → LH/FSH LOW — peripheral PP, not central); (2) café-au-lait macules with "coast of Maine" borders (melanocyte Gs activation); (3) polyostotic fibrous dysplasia (bone osteoblast Gs activation). GNAS is imprinted: maternal activating mutation = MA syndrome; maternal inactivating = PHP 1a. Opposite ends of the same gene.
LO 6 · V2 Receptor FA 3.14 · BnB 5.06
Nephrogenic DI — Downstream of ADH
ADH is released normally but the V2 receptor / Gs → cAMP → aquaporin-2 cascade is broken → renal collecting duct cannot reabsorb water → polyuria with dilute urine, hypernatremia, no response to desmopressin.
Causes: V2-R mutation (X-linked), aquaporin-2 mutation (AR), drugs — lithium (disrupts V2/cAMP signaling — reversible if caught early, irreversible later); hypercalcemia; amphotericin. Desmopressin test: central DI responds (urine osm rises >50%); nephrogenic does NOT. Tx: stop offending drug, HCTZ + low-salt diet (paradoxical effect), amiloride (for lithium-induced).
LO 7 · Receptor Regulation In House · Petersen & Shulman 2018 · FA · BnB
Insulin Resistance in T2DM — Down-Regulation Personified
The in-house slide example for LO 7. Chronic overnutrition → chronic ↑insulin → insulin receptor down-regulation + post-receptor defects → resistance. β-cells hypersecrete early (hyperinsulinemia + high C-peptide), exhaust late (low insulin, low C-peptide).
Dose-response curve: RIGHTWARD shift (↑ EC50); severe disease also lowers plateau. Visualized in Petersen & Shulman 2018 (cited on in-house slide). Post-receptor defects: SOCS protein induction, IRS-1 serine phosphorylation (instead of tyrosine), lipotoxicity, intramyocellular lipid accumulation → impaired GLUT4 trafficking. Pharmacology: metformin (↑ sensitivity), TZDs (PPAR-γ), GLP-1 agonists (β-cell preservation + sensitivity), SGLT2 inhibitors. Exogenous insulin always works (bypasses receptor issue via mass-action).
Adrenal insufficiency → loss of cortisol → catecholamines lose their α₁-mediated vasoconstriction → refractory hypotension despite pressors. Classic LO 7 permissiveness scenario.
Cortisol upregulates α₁-adrenergic receptor expression and downstream signaling components. Without cortisol, NE/Epi cannot drive vasoconstriction effectively. Treatment: stress-dose hydrocortisone restores responsiveness within hours. Inverse concept: T3 permits β-adrenergic sensitivity — why hyperthyroid patients have tachycardia / tremor out of proportion to catecholamine levels, and why β-blockers help symptomatically.
LO 1 · Historical In House (Horsley/Murray 1890s)
The First Hormone Therapy — Thyroid Extract for Myxedema
1890s: Victor Horsley and George Murray demonstrated that implanting sheep thyroid or injecting extract reversed myxedema/cretinism. One of the first examples of endocrine replacement therapy — named explicitly on the in-house slide.
Horsley/Murray established that a molecule secreted by a gland travels through blood to restore function at a distant organ. The earlier Berthold rooster experiment (1849) had shown reimplanted testes restored secondary sex characteristics without nervous reconnection — blood-borne signaling principle. Modern descendants: insulin for T1DM, levothyroxine for hypothyroidism, hydrocortisone for Addison's, testosterone/estrogen for hypogonadism, recombinant GH for deficiency.
High-Yield Testing Notes
Pattern-matching, buzzwords, and rules that recur on Step 1 for LOs 1–7.
Buzzword → Diagnosis Pattern Bank
"Snowstorm uterus" + hyperthyroid: hCG-mediated hyperthyroidism in molar pregnancy (LO 2/6). "Round face, short 4th/5th metacarpals, ↑PTH + ↓Ca": Pseudohypoparathyroidism 1a (Gsα loss) (LO 6). "Coast of Maine café-au-lait + precocious puberty": McCune-Albright (activating Gs) (LO 6). "Episodic HTN + headache + sweating": Pheochromocytoma (LO 3). "Virilized female + salt-wasting": 21-OH CAH (LO 4). "Virilized female + HTN + hypokalemia": 11β-OH CAH (LO 4). "Pregnant + ↑total T4 + normal free T4": Estrogen ↑ TBG (LO 5). "↑Insulin + ↓C-peptide": Exogenous (factitious) insulin (LO 2). "Rice-water diarrhea": Cholera toxin (Gs ON) (LO 6). "↑GH but ↓IGF-1 in a short child": Laron syndrome (GH-R mutation) (LO 6/7).
Rate-Limiting Enzymes (Must Know) High-Yield
Catecholamine synthesis:Tyrosine hydroxylase (Tyr → L-DOPA; cofactor BH4). Named in slides as "the key enzyme that begins the synthetic pathway (and is the rate-limiting step)" — LO 3. Steroid biosynthesis:Desmolase (CYP11A1); regulated by StAR protein + ACTH/LH — LO 4. Vitamin D activation:1α-hydroxylase in renal PCT; ↑ by PTH, ↓ by FGF23 — LO 4.
Do NOT confuse: α/β glycoprotein subunits (α shared, β unique). Do NOT confuse: Down-regulation (high hormone) vs up-regulation (low hormone). Do NOT confuse: Total vs FREE hormone — only free is biologically active. Do NOT confuse: Thyroid hormone is an AMINE, not a steroid — it just ACTS like one. Do NOT confuse: L-DOPA crosses BBB; dopamine does NOT. Carbidopa blocks peripheral DOPA decarboxylase. Do NOT confuse: PNMT is only in adrenal medulla — sympathetic nerves release NE. Do NOT confuse: StAR (shuttle) vs desmolase (enzyme) — both in step 1 of steroid synthesis, different molecules. Do NOT confuse: Cholera toxin = Gs ON (↑cAMP); Pertussis toxin = Gi OFF (relative ↑cAMP). Different G proteins, different tissues.
Hormone Class — Master Comparison
Feature
Peptide
Catecholamine (amine)
Thyroid Hormone (amine)
Steroid
Eicosanoid
Precursor
Amino acids (gene-encoded)
Tyrosine
Tyrosine + I₂ on thyroglobulin
Cholesterol
Arachidonic acid (membrane PLs)
Solubility
Hydrophilic
Hydrophilic
Hydrophobic
Hydrophobic
Hydrophobic (acts locally)
Stored?
YES (vesicles)
YES (chromaffin granules)
YES (extracellular colloid as Tg)
NO (de novo)
NO (local, on demand)
Plasma transport
Free
Free
Carrier (TBG)
Carrier (CBG, SHBG, DBP, albumin)
Local — mostly paracrine/autocrine
Half-life
Minutes
Seconds–minutes
Days (T4 ~7 d)
Hours
Seconds–minutes
Receptor
Membrane (GPCR, RTK, JAK-STAT, GC)
Membrane (GPCR)
Nuclear (TR)
Cytoplasmic/nuclear
Membrane GPCR (EP, TP, IP, DP, LT)
Signaling
Indirect (2nd msgrs)
Indirect (2nd msgrs)
Direct (transcription)
Direct (transcription)
Indirect (2nd msgrs)
Oral OK?
No — digested
No — first-pass
YES — levothyroxine
YES — prednisone, estradiol
Varies — misoprostol, latanoprost
Thyroid hormone is an amine but behaves like a steroid (hydrophobic, carrier-bound, nuclear receptor, long half-life). Eicosanoids are lipid-derived but act locally via membrane GPCRs like hydrophilic hormones.
Steroids (cortisol, aldo, E2, T), T3/T4, vit D, retinoic acid
Androgen insensitivity syndrome (AR mutation)
Free Hormone Hypothesis — When Total ≠ Free
Clinical State
Carrier Change
Total
Free
Status
Pregnancy (estrogen ↑)
↑TBG, ↑CBG, ↑SHBG
↑Total T4, ↑Total cortisol, ↑Total T
Normal free T4, free cortisol; ↓ free T slightly
Euthyroid / eucortisolic
OCPs
↑TBG, ↑CBG
↑Total T4, ↑Total cortisol
Normal free
Normal
Nephrotic syndrome
↓ albumin, ↓ DBP
↓ Total hormones
Normal free (often)
Usually normal
Hyperthyroidism
↑ SHBG
↑ Total T
↓ Free T
Hypogonadism symptoms despite "normal total"
Obesity / exogenous androgens
↓ SHBG
↓ Total E2, ↓ Total T
↑ Free E2, ↑ Free T
PCOS-like; gynecomastia risk in males
Board rule: whenever a total hormone measurement looks abnormal, ask whether a carrier-protein change is the cause. Always order the FREE fraction (or surrogate — late-night salivary cortisol, 24-h urine free cortisol, free testosterone) before treating.
Mapped 3rd-Party Coverage for end01
Resource
Section (primary for end01)
Cards / Slides
Best Use
In-house lecture
Module Intro & Intro to Hormones
PDF slides + LO doc
Baseline — LOs 1-7, slide content
In-house Anki
Bioch::ENDO::01-Intro-Hormones
26 cards
Facts emphasized in this specific lecture
BnB
5.06 Signaling Pathways
64 cards (primary) + 3.02 Phe/Tyr (xref 76)
Depth on receptor classes + catecholamine biochem
First Aid
3.14 Signaling pathways of endocrine hormones + 3.15 Steroid signaling