PHARM · Endocrine Axis

Hypothalamic & Pituitary Drugs

Six drug classes that rewrite the endocrine axis. Pulsatile stimulates. Continuous suppresses. Same molecule, opposite life.

Here is your patient: A 28-year-old woman receiving leuprolide for in vitro fertilization has her drug given in small doses every 90 minutes via a pump. What is the expected effect?
Ovarian suppression
Stimulation of LH and FSH release
Testosterone surge
Prolactin inhibition
Cortisol suppression
Ovarian suppression is what leuprolide does when given continuously, which is why it works for endometriosis and prostate cancer. The key here is the delivery pattern. The pituitary GnRH receptor only fires LH and FSH when it sees pulses roughly every 90 minutes; flood the receptor with constant drug and it downregulates, silencing the axis. Same drug, opposite effect based on pattern. Pulsatile leuprolide stimulates ovulation for IVF. Continuous leuprolide suppresses the gonadal axis for cancer and endometriosis.
Toggle The Pattern
Pulsatile GnRH · every 60 to 90 minutes the receptor fires, releases LH and FSH, and the gonads make estrogen and testosterone. This is normal physiology. Drug uses: infertility, hypogonadotropic hypogonadism, IVF priming.
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The Axis Map

Hypothalamus on top. Portal blood threads down to the anterior pituitary. Posterior pituitary stores ADH and oxytocin. Tap any glowing marker to meet the drug class that hijacks that node.

HYPOTHALAMUS GnRH · TRH · CRH · GHRH · Dopamine · Somatostatin RELEASING HORMONES portal blood axonal transport ANTERIOR PIT LH · FSH · TSH · ACTH · GH · PRL POST PIT ADH · Oxytocin GONADS testes · ovaries THYROID + adrenal LIVER GH / IGF-1 target KIDNEY ADH target 1 2 3 4 5 6 GnRH SOMATOSTATIN DOPAMINE ADH OXYTOCIN GH AXIS
Tap a marker
Six drug classes hijack this axis
Each marker is a node where a drug class either flips a switch on or jams it. Start with GnRH on the hypothalamus, finish at the kidney where ADH lands.
tap any numbered marker
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The Six Villains

Tap any card to flip. Front gives you the clue and the trap. Back gives you the board lock.

GnRH Analogues
Hypothalamic axis · LH/FSH gate
AgonistsLeuprolide, Nafarelin, Histrelin, Goserelin
AntagonistsCetrorelix, Ganirelix, Degarelix
KeyPulsatile = stimulate; continuous = suppress
TrapInitial testosterone flare with continuous agonist
The Paradox: same molecule, opposite endocrine life.
tap to flip →
Why It Works
Trace It
The GnRH receptor on the anterior pituitary fires LH/FSH only when stimulated in pulses every 60 to 90 minutes. Pulsatile dosing mimics physiology and drives gonadal hormone output. Continuous dosing downregulates the receptor within a couple of weeks, silencing the axis.
Uses
Pulsatile: infertility, IVF priming, hypogonadotropic hypogonadism. Continuous: prostate cancer, endometriosis, uterine fibroids, central precocious puberty.
Antagonist niche
Cetrorelix and ganirelix block the receptor directly with no flare. Used during IVF to prevent the premature LH surge.
Lock It
Stem says pump or pulse generator and asks expected effect on LH/FSH? Pulsatile leuprolide stimulates. Stem says continuous depot for prostate cancer or endometriosis? Continuous leuprolide suppresses.
Somatostatin Analogues
Octreotide · Lanreotide · Pegvisomant
TargetsGH, TSH, glucagon, insulin, gut peptides
Key usesAcromegaly, carcinoid syndrome, VIPoma, variceal bleed
ADRGallstones, steatorrhea, hyperglycemia
TrapPegvisomant blocks the GH receptor, not secretion
The Off Switch for half the endocrine pantry.
tap to flip →
Why It Works
Trace It
Octreotide mimics endogenous somatostatin: binds SST receptors and shuts down secretion of growth hormone, TSH, glucagon, insulin, and a long list of GI peptides such as VIP, serotonin, gastrin, secretin, and motilin.
Uses
Acromegaly: drops GH and IGF-1. Carcinoid syndrome: blocks serotonin and VIP flood causing flushing and diarrhea. VIPoma, glucagonoma, gastrinoma. Esophageal variceal bleed: splanchnic vasoconstriction.
Pegvisomant exception
Used in octreotide-refractory acromegaly. Blocks the peripheral GH receptor itself, so GH levels rise but IGF-1 falls. Different drug, different lane.
Lock It
Surgery patient with flushing, diarrhea, and bronchospasm intraoperatively? Carcinoid crisis. Reach for octreotide. Same drug for acute variceal bleed and refractory secretory diarrhea.
Dopamine Agonists
Cabergoline · Bromocriptine
Trace ItD2 agonism on lactotrophs → suppresses prolactin
First lineProlactinoma (medical, not surgical)
TrapHigh-dose cabergoline can fibrose heart valves
PearlCabergoline beats bromocriptine on tolerability and dosing
Tumors that shrink to a pill, not a knife.
tap to flip →
Why It Works
Trace It
Dopamine is the tonic brake on the lactotroph. Dopamine agonists slam that brake harder: prolactin falls and the tumor literally shrinks. This is the rare endocrine tumor where the drug is more effective than surgery.
Uses
Prolactinoma: shrinks tumor, restores menses and fertility. Hyperprolactinemia with amenorrhea and galactorrhea. Bromocriptine: type 2 DM adjunct, neuroleptic malignant syndrome rescue, Parkinson disease.
Cabergoline vs bromocriptine
Cabergoline has a long half-life (dosed twice weekly), less nausea, less orthostatic hypotension, and higher tumor shrinkage rates. Bromocriptine is preferred only in pregnancy because the safety data is longer.
Lock It
Woman with amenorrhea, galactorrhea, bitemporal hemianopia, and a sellar mass? Prolactinoma. First-line treatment is cabergoline. Surgery is reserved for failed medical therapy or apoplexy.
ADH Agonists & Vaptans
Desmopressin · Tolvaptan · Conivaptan
DDAVPV2 agonist for central DI, enuresis, vWD type 1, mild hemophilia A
VaptansV2 antagonist for SIADH, CHF and cirrhosis hyponatremia
TolvaptanHepatotoxic, max 30 days
TrapDDAVP does NOT work in nephrogenic DI
Two drugs, one receptor, opposite kidney plumbing.
tap to flip →
Why It Works
Trace It
V2 receptors on collecting duct principal cells insert aquaporin-2 channels and reabsorb free water. DDAVP turns this on; vaptans turn it off. The result is either water retention or selective water excretion (aquaresis, not diuresis, so sodium does not chase it out).
DDAVP uses
Central DI: replaces the missing ADH. Nocturnal enuresis in children. vWD type 1 and mild hemophilia A: releases vWF and factor VIII from endothelium.
Vaptan uses
SIADH and hypervolemic or euvolemic hyponatremia of CHF or cirrhosis. Never used in hypovolemic hyponatremia; that pattern needs isotonic saline.
Lock It
Central DI responds to DDAVP. Nephrogenic DI does not · treat with thiazide, amiloride, and salt restriction. SIADH and CHF hyponatremia respond to vaptans. Hypovolemic hyponatremia gets isotonic saline, not vaptans.
Oxytocin
Pitocin · nonapeptide cousin of ADH
ActionUterine contraction + milk letdown
UsesLabor induction and augmentation, postpartum hemorrhage
ADRHyponatremia at high doses, uterine hyperstimulation
TrapCross-acts on V2 receptors and behaves like ADH
Two amino acids away from ADH. It shows.
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Why It Works
Trace It
Oxytocin and ADH are nonapeptides that differ by only two amino acids and are both stored in the posterior pituitary. Oxytocin binds uterine OXT receptors during late pregnancy when receptor density is highest, driving rhythmic contractions and breast myoepithelial milk ejection.
Uses
Induction or augmentation of labor. Active management of third stage of labor. Postpartum hemorrhage from uterine atony.
Toxicities
Uterine tachysystole leading to fetal distress and possible rupture. At sustained high doses oxytocin cross-activates V2 receptors and behaves like ADH, retaining free water and dropping serum sodium.
Lock It
Laboring patient on prolonged high-dose oxytocin with serum sodium 128? That is ADH-like V2 cross-reactivity. Slow the infusion and check labs · do not chase it with more free water.
GH Axis Drugs
Somatropin · Sermorelin · Mecasermin
SomatropinRecombinant GH for deficiency states
UsesGH deficiency, Turner, Prader-Willi, CKD short stature, HIV wasting
ADRPseudotumor cerebri, SCFE, insulin resistance, acromegaly features
TrapNew hip or knee pain in a child on GH = SCFE
Growth has a price; the physis pays it.
tap to flip →
Why It Works
Trace It
Somatropin is recombinant human growth hormone. It signals at the hepatic GH receptor, releases IGF-1, and drives linear growth, lipolysis, and insulin antagonism. Sermorelin is a GHRH analogue used in diagnostic stimulation testing and selected therapeutic cases.
Uses
Pediatric GH deficiency, Turner syndrome, Prader-Willi, idiopathic short stature. Chronic kidney disease growth failure. Adult GH deficiency and HIV-associated wasting.
Toxicities
Pseudotumor cerebri presenting with headache, papilledema, and vision changes; slipped capital femoral epiphysis from rapid physeal growth; worsened insulin resistance; acromegaly-like coarsening with overuse.
Lock It
Child a few months into somatropin presents with a limp and hip or knee pain? Order a hip X-ray for slipped capital femoral epiphysis. Headache and papilledema on GH? Pseudotumor cerebri.
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Board Challenge

Six original stems. Read the last sentence first. Cover the choices. Build the board lock before you peek.

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