Endocrine Physiology
Usually weeks 6-8 of a medical physiology courseEndocrine physiology is the homeostasis unit at full size: every gland is a sensor, a hormone, and a negative feedback loop, and nearly every exam question is solved by drawing that loop and asking which piece broke. Start with the rules that apply to every hormone — how its chemistry predicts its receptor, half-life, and transport — then walk the axes from hypothalamus to target gland. The high-yield outputs are the feedback patterns that separate primary from secondary disease, the actions of each hormone (so you can predict its excess and its deficiency), and the three regulators of calcium.
This guide is the frame. The exams are written from your lectures— drop this unit's slides on the dashboard to get flashcards and board-style questions from your own course, and quiz them all semester (a course whose exams re-test earlier units rewards nothing more than early, repeated self-testing). The physiology playbook has the weekly loop.
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AI-authored study notes, not faculty-reviewed and not medical advice. Verify every mechanism against your course materials and faculty; programs differ in emphasis.
High-Yield Pearl
Draw the loop — sensor, hormone, target, feedback — and read the pair of values together: when the target hormone and its driver move in opposite directions the gland is the problem, and when they move together the driver is.
What the exam asks
Mechanisms, curves, and what happens when each one fails.
- Hormone chemistry predicts behavior. PEPTIDE and protein hormones (insulin, glucagon, the pituitary hormones, PTH) are water-soluble: made in advance and stored in granules, carried free in plasma, short half-lives, and they act on MEMBRANE receptors through second messengers — fast onset. STEROID hormones (cortisol, aldosterone, sex steroids, and the secosteroid calcitriol) are made from cholesterol on demand, travel bound to carrier proteins, cross membranes, and bind INTRACELLULAR receptors that alter gene transcription — slower, longer-lasting effects. The amines split: catecholamines behave like peptides; THYROID hormone behaves like a steroid (protein-bound, nuclear receptor).
- Receptor mechanisms worth sorting. Gs → adenylyl cyclase → cAMP: TSH, ACTH, LH, FSH, PTH, glucagon, calcitonin, the V2 action of ADH, β-adrenergic effects. Gq → phospholipase C → IP3 and Ca2+: GnRH, TRH, oxytocin, the V1 action of ADH, angiotensin II, α1 effects. Receptor tyrosine kinase: insulin and IGF-1. Cytokine receptors with JAK-STAT: growth hormone and prolactin. Guanylyl cyclase → cGMP: ANP and nitric oxide. Intracellular receptors: steroids, thyroid hormone, and vitamin D.
- Axes, feedback, and free hormone. Hypothalamic releasing hormones (TRH, CRH, GnRH, GHRH) travel down the HYPOPHYSEAL PORTAL SYSTEM to the anterior pituitary, whose tropic hormones (TSH, ACTH, LH/FSH, GH) drive the target glands; the target hormones then feed back negatively on both the pituitary and hypothalamus. That structure is diagnostic: in PRIMARY gland failure the target hormone is low and the pituitary hormone HIGH; in SECONDARY (pituitary) failure both are low. Only the FREE fraction of a bound hormone is active and fed back on, so changes in binding protein (thyroxine-binding globulin rises with pregnancy and estrogen) change the total level while free hormone and feedback stay normal.
- The posterior pituitary and prolactin — two exceptions. ADH and oxytocin are made in hypothalamic neurons (supraoptic and paraventricular nuclei) and shipped down axons to be released from the posterior pituitary — true neurosecretion. ADH responds most sensitively to plasma osmolality (a 1–2% rise) and, with a larger threshold, to falling blood volume; via V2 receptors it inserts aquaporin-2 into the collecting duct, and via V1 it constricts vessels. Oxytocin drives milk letdown and labor contractions. Prolactin is the one anterior pituitary hormone held under predominant INHIBITION — by hypothalamic dopamine — so a pituitary stalk lesion or a dopamine-blocking drug raises prolactin while the other anterior hormones fall.
- Growth hormone and IGF-1. GH is secreted in pulses, largest in deep sleep, stimulated by GHRH, ghrelin, hypoglycemia, exercise, and stress, and inhibited by somatostatin and by IGF-1 feedback. It acts directly as an ANTI-INSULIN hormone (raises glucose, promotes lipolysis) and indirectly through IGF-1 made by the liver, which drives linear growth and protein synthesis. Excess before the growth plates close causes gigantism; after, acromegaly. Because GH pulses, the screening test is IGF-1, and the confirmatory test is failure of an oral glucose load to suppress GH.
- Thyroid hormone — synthesis and action. Follicular cells trap iodide with the sodium-iodide symporter; thyroid peroxidase oxidizes it, attaches it to tyrosines on thyroglobulin (organification), and couples them into T4 and T3, which are stored in the colloid and released by proteolysis. The gland secretes mostly T4; peripheral deiodinases convert it to the more potent T3. Thyroid hormone raises basal metabolic rate and heat production (more Na+/K+-ATPase), increases cardiac output and β-adrenergic sensitivity, and is essential for brain development and growth — untreated congenital deficiency causes permanent intellectual disability, which is why newborns are screened.
- The adrenal cortex and medulla. Zona glomerulosa makes aldosterone, driven mainly by ANGIOTENSIN II and plasma K+ (ACTH plays only a minor role); zona fasciculata makes cortisol under ACTH; zona reticularis makes adrenal androgens (DHEA). Cortisol raises glucose (gluconeogenesis, anti-insulin effects), breaks down protein and fat, suppresses inflammation and immunity, is permissive for catecholamine vasoconstriction, and peaks in the early morning. Aldosterone acts on principal cells to reabsorb Na+ and secrete K+ (and on intercalated cells to secrete H+). The medulla is a modified sympathetic ganglion whose chromaffin cells release mostly epinephrine — the enzyme that makes it (PNMT) is induced by the cortisol draining through from the cortex.
- The endocrine pancreas. Beta cells take up glucose through GLUT2; metabolism raises ATP, which CLOSES ATP-sensitive K+ channels; the cell depolarizes, L-type Ca2+ channels open, and insulin granules fuse (sulfonylureas close the same channel). Insulin moves GLUT4 transporters into muscle and fat membranes, builds glycogen, fat, and protein, suppresses hepatic glucose output and lipolysis, and drives K+ into cells. Glucagon from alpha cells does the reverse at the liver: glycogenolysis, gluconeogenesis, and ketogenesis. Gut incretins (GLP-1, GIP) amplify insulin release, so ORAL glucose produces more insulin than the same glucose given IV. Glucagon, epinephrine, cortisol, and GH are the counter-regulatory hormones that defend against hypoglycemia.
- Calcium and phosphate — three regulators. Only IONIZED calcium is regulated, sensed by the calcium-sensing receptor on parathyroid chief cells. When it falls, PTH rises and (1) increases bone resorption (acting through osteoblasts, which signal osteoclasts via RANKL), (2) increases Ca2+ reabsorption in the distal tubule, (3) DECREASES phosphate reabsorption in the proximal tubule, and (4) activates renal 1α-hydroxylase to make calcitriol. Calcitriol (active vitamin D) raises intestinal absorption of both calcium and phosphate and supports bone mineralization. Calcitonin from thyroid C cells lowers calcium but matters little in adult humans. FGF23 from bone lowers phosphate and calcitriol.
Worth drilling · 38 concepts
Each with the one fact that identifies it. Your course's slides are the authority; use this to check your list against.
- 1Peptide hormone — water-soluble, stored in granules, membrane receptor, short half-life
- 2Steroid hormone — cholesterol-derived, protein-bound, intracellular receptor, alters transcription
- 3Thyroid hormone — an amine that behaves like a steroid: bound in plasma, nuclear receptor
- 4Catecholamines — tyrosine-derived amines acting through membrane G-protein receptors
- 5cAMP second messenger — Gs-coupled; TSH, ACTH, LH, FSH, PTH, glucagon
- 6IP3–calcium second messenger — Gq-coupled; GnRH, TRH, oxytocin, angiotensin II
- 7Receptor tyrosine kinase — the insulin and IGF-1 receptor type
- 8JAK-STAT pathway — growth hormone and prolactin receptor signaling
- 9Long-loop feedback — target-gland hormone suppresses its hypothalamic and pituitary drivers
- 10Hypophyseal portal system — carries hypothalamic releasing hormones to the anterior pituitary
- 11Primary gland failure — target hormone low, pituitary tropic hormone high
- 12Free hormone — the unbound fraction that acts and is sensed by feedback
- 13Thyroxine-binding globulin — carries most T4; rises in pregnancy without changing free T4
- 14Antidiuretic hormone — V2 receptors insert aquaporin-2 in the collecting duct
- 15Oxytocin — posterior pituitary hormone for milk letdown and uterine contraction
- 16Dopamine (hypothalamic) — tonic brake on prolactin; stalk damage raises prolactin
- 17Growth hormone — pulsatile, peaks in deep sleep, anti-insulin, acts largely via IGF-1
- 18IGF-1 — liver-made growth mediator; the screening test for acromegaly
- 19Somatostatin — inhibits growth hormone, insulin, glucagon, and most gut hormones
- 20Sodium-iodide symporter — traps iodide into thyroid follicular cells
- 21Thyroid peroxidase — oxidizes, organifies, and couples iodine on thyroglobulin
- 22Peripheral deiodinase — converts T4 to the more active T3 in tissues
- 23Zona glomerulosa — aldosterone; driven by angiotensin II and plasma K+
- 24Zona fasciculata — cortisol; driven by ACTH
- 25Zona reticularis — adrenal androgens such as DHEA
- 26Cortisol — gluconeogenic, catabolic, anti-inflammatory; peaks in the early morning
- 27Aldosterone — principal-cell Na+ reabsorption with K+ secretion
- 28Adrenal medulla — chromaffin cells releasing mostly epinephrine
- 29ATP-sensitive K+ channel — closes as beta-cell ATP rises, triggering insulin release; sulfonylurea target
- 30GLUT4 — insulin-regulated glucose transporter in muscle and fat
- 31Glucagon — alpha-cell hormone driving glycogenolysis, gluconeogenesis, and ketogenesis
- 32Incretin effect — oral glucose releases more insulin than IV glucose (GLP-1, GIP)
- 33Counter-regulatory hormones — glucagon, epinephrine, cortisol, and GH defend against hypoglycemia
- 34Parathyroid hormone — raises Ca2+ via bone and kidney; makes the kidney waste phosphate
- 35Calcium-sensing receptor — chief-cell sensor that suppresses PTH as ionized Ca2+ rises
- 36Calcitriol — active vitamin D; raises gut absorption of calcium and phosphate
- 371-alpha-hydroxylase — renal enzyme PTH switches on to make calcitriol
- 38FGF23 — bone-derived hormone that lowers phosphate and calcitriol
Practice it
Active recall over the drill list — flip and claim, match the pairs, produce the answers cold, fill in the diagram, or read the curves like the exam does.
Every concept on the drill list, one card at a time — the name up front, the fact that identifies it on the flip. Claim each card honestly and the deck learns what to lead with next time. Progress lives in this browser only.
What everyone misses
The distinctions that lose points on this material, year after year.
- Total hormone is not free hormone. A pregnant patient's total T4 is high and her TSH is normal — because estrogen raised thyroxine-binding globulin, not because she is hyperthyroid. Feedback senses FREE hormone. Any vignette with a binding-protein change (pregnancy, oral estrogen, liver disease, nephrotic syndrome) wants you to look at the free level before diagnosing.
- Primary vs secondary is read off the pituitary hormone. Low T4 with high TSH is primary hypothyroidism (the gland failed; the pituitary is shouting). Low T4 with low or inappropriately normal TSH is secondary (the pituitary failed). The same logic runs cortisol-ACTH and testosterone-LH. Students memorize the lab patterns separately; draw the loop once and derive all of them.
- Aldosterone follows angiotensin II and potassium, not ACTH. In secondary adrenal insufficiency (pituitary failure) ACTH is gone but the renin-angiotensin system still drives the glomerulosa, so aldosterone is preserved — no hyperkalemia, no severe salt wasting. In primary adrenal insufficiency (Addison) the whole cortex is destroyed, so aldosterone falls too, and high ACTH darkens the skin. The hyperkalemia is the discriminator.
- PTH raises calcium but LOWERS phosphate. Because PTH and vitamin D both raise calcium, students assume they move phosphate the same way. PTH makes the proximal tubule dump phosphate, so primary hyperparathyroidism shows high calcium with LOW phosphate; vitamin D raises both. Hypoparathyroidism is the mirror: low calcium, high phosphate.
- Insulin moves potassium into cells. Students learn insulin as a glucose hormone and forget its K+ effect. It stimulates the Na+/K+-ATPase, so insulin (with glucose) is an emergency treatment for hyperkalemia — and in DKA, serum K+ is often high while total body K+ is depleted, so potassium must be replaced as insulin drives it back into cells.
- Prolactin is under inhibition. Every other anterior pituitary hormone falls when the stalk is cut; prolactin rises, because its dominant hypothalamic control is dopamine's brake. Antipsychotics (dopamine blockers) cause galactorrhea and amenorrhea for the same reason, and dopamine agonists treat prolactinomas.
Clinical correlations
Where this unit shows up again — in clinic, on rotations, and on the boards.
- Primary adrenal insufficiency (Addison disease). Fatigue, weight loss, salt craving, hypotension, hyponatremia, hyperkalemia, and hyperpigmentation: the cortex is destroyed (usually autoimmune), cortisol and aldosterone fall, and the pituitary's surge of ACTH — cleaved from POMC alongside melanocyte-stimulating hormone — darkens the skin. Adrenal crisis is a hypotensive emergency treated with IV hydrocortisone and fluids.
- Cushing syndrome. Central obesity, proximal weakness, purple striae, easy bruising, hypertension, and hyperglycemia from cortisol excess. The most common cause is exogenous glucocorticoids. For endogenous disease, screening tests the feedback loop: a normal person's cortisol is suppressed by low-dose dexamethasone overnight; a patient with Cushing syndrome escapes suppression. ACTH then separates a pituitary or ectopic source (high ACTH) from an adrenal tumor (low ACTH).
- Graves disease vs Hashimoto thyroiditis. Graves: antibodies that STIMULATE the TSH receptor — hyperthyroidism with suppressed TSH, a diffuse goiter, ophthalmopathy, and pretibial myxedema. Hashimoto: autoimmune destruction (anti-TPO antibodies) — hypothyroidism with high TSH, the most common cause of hypothyroidism where iodine is sufficient. Both are exercises in reading the feedback loop.
- Diabetic ketoacidosis. With no insulin, lipolysis floods the liver with fatty acids, glucagon-driven ketogenesis produces an anion-gap acidosis, hyperglycemia causes an osmotic diuresis and dehydration, and K+ shifts out of cells. Treatment is fluids, insulin, and potassium — the physiology of insulin's actions run in reverse.
- SIADH and diabetes insipidus. Too much ADH (SIADH — small cell lung cancer, CNS disease, many drugs) retains free water: euvolemic hyponatremia with inappropriately concentrated urine. Too little ADH effect (diabetes insipidus) produces large volumes of dilute urine and a rising sodium; desmopressin corrects the central form but not the nephrogenic form, where the kidney can't respond (lithium is a classic cause).
- Primary hyperparathyroidism. Usually a single parathyroid adenoma, often found on routine labs: high calcium, low phosphate, and high (or inappropriately normal) PTH. Symptoms follow the mnemonic stones, bones, abdominal groans, and psychiatric moans — kidney stones, bone loss, constipation and pancreatitis, and depression or confusion.
- Acromegaly and prolactinoma. Growing hands and feet, coarse features, and jaw prognathism point to a GH-secreting adenoma — screen with IGF-1, confirm with GH that fails to suppress after oral glucose. Galactorrhea, amenorrhea, or low libido point to a prolactinoma, the most common functioning pituitary tumor, usually treated first with a dopamine agonist rather than surgery.