How thyroid hormones work — mechanism and metabolic effects
T4 is the main secreted form but T3 is 3–4× more potent. T4 is converted to T3 by deiodinase enzymes in peripheral tissues (liver, kidney, muscle). T3 binds nuclear thyroid hormone receptors → activates gene transcription → increases: basal metabolic rate (BMR), O2 consumption, heat production, heart rate and contractility, carbohydrate and fat metabolism, protein synthesis and degradation, CNS development (critical in fetus). Propylthiouracil (PTU) blocks thyroid hormone synthesis AND peripheral T4→T3 conversion — used in thyroid storm. Methimazole blocks synthesis only.
T4 → T3
Deiodinase removes one iodine from T4. PTU blocks this conversion.
BMR ↑
Increases Na+/K+ ATPase → more ATP needed → more O2 consumed → more heat.
Direct effects (anti-insulin) + Indirect effects via IGF-1 (growth)
Growth hormone — direct and indirect effects, and its diabetogenic action
GH (somatotropin) from anterior pituitary has two types of effects. Direct effects: metabolic — lipolysis (breaks down fat), decreases glucose uptake (anti-insulin/diabetogenic), protein synthesis. Indirect effects via IGF-1 (insulin-like growth factor 1, from liver): linear bone growth (chondrocyte proliferation), organ growth. GH secretion is pulsatile — highest during deep sleep (delta sleep), exercise, fasting, hypoglycemia. Suppressed by: hyperglycemia (IGF-1 negative feedback), obesity, somatostatin. Deficiency in childhood → dwarfism. Excess before epiphyseal closure → gigantism. Excess after closure → acromegaly.
Direct (GH)
Lipolysis, anti-insulin, protein synthesis. Diabetogenic — raises blood glucose.
IGF-1
From liver — bone growth, chondrocyte proliferation, organ growth. Anabolic.
Low Ca2+ → PTH → Bone · Kidney · Gut (via Vit D) → Ca2+ UP
PTH raises Ca2+ three ways · Calcitonin lowers Ca2+
Calcium regulation physiology — how PTH orchestrates three organ systems
When Ca2+ falls: parathyroid glands release PTH → acts on three targets simultaneously. Bone: activates osteoclasts → bone resorption → Ca2+ + phosphate released. Kidney: increases Ca2+ reabsorption in DCT, decreases phosphate reabsorption (prevents Ca-phosphate precipitation), activates 1-alpha-hydroxylase (converts vitamin D to active form). Gut: via activated vitamin D → increases Ca2+ absorption from diet. Net result: blood Ca2+ rises. When Ca2+ rises: calcitonin from thyroid C cells inhibits osteoclasts → lowers Ca2+. PTH and calcitonin are physiological antagonists.
PTH → Bone
Activates osteoclasts → resorbs bone → releases Ca2+ and phosphate.
PTH → Kidney
↑Ca2+ reabsorption, ↓phosphate reabsorption, activates vitamin D.
PTH → Gut
Indirect via vitamin D → increases intestinal Ca2+ absorption.
Polyuria + Polydipsia + Polyphagia → osmotic diuresis from glucosuria.
DKA
No insulin → glucagon unopposed → lipolysis → ketones → anion gap metabolic acidosis.
Insulin vs Glucagon
In = IN (store it) · Glu = GO (release it)
📌 Glucose Regulation
Insulin stores glucose; glucagon releases it — opposite pancreatic hormones
Insulin (beta cells): released when blood glucose HIGH → promotes glucose uptake, glycogen synthesis, fat storage. Glucagon (alpha cells): released when blood glucose LOW → promotes glycogenolysis and gluconeogenesis. Together they maintain euglycemia (~70-100 mg/dL fasting).
Cortisol is the primary stress hormone — raises blood sugar and suppresses inflammation
Cortisol (glucocorticoid from zona fasciculata): raises blood glucose via gluconeogenesis, breaks down protein/fat, suppresses immune response, reduces inflammation. Chronically elevated = Cushing syndrome (buffalo hump, moon face, central obesity).
SStress hormone
UUp blood glucose
GGluconeogenesis promoted
AAnti-inflammatory
RRedistribute fat (central)
IImmune suppression
Thyroid Hormones
T3 = Active · T4 = Storage · TSH = Switch
📌 Thyroid Function
T4 is the storage form; T3 is the active form; TSH from pituitary controls both
Thyroid gland makes mostly T4 (thyroxine); peripheral tissues convert T4 → T3 (triiodothyronine, 3-4× more potent). TSH from anterior pituitary stimulates production. Both require iodine. Hypo = slow everything; Hyper = speed everything up.
T3Triiodothyronine — active form
T4Thyroxine — storage/transport form
TSHTSH from anterior pituitary — the switch
Calcium Regulation
PTH Picks Up Ca · Calcitonin Cuts it
📌 Mineral Homeostasis
PTH raises calcium; calcitonin lowers it — parathyroid vs thyroid C-cells
PTH (parathyroid glands): released when Ca²⁺ LOW → ↑ bone resorption, ↑ renal reabsorption, activates vitamin D → net rise in Ca²⁺. Calcitonin (thyroid C-cells): released when Ca²⁺ HIGH → inhibits osteoclasts → lowers Ca²⁺. Vitamin D essential for intestinal absorption.
PPTH = Picks up calcium (raises it)
CCalcitonin = Cuts calcium (lowers it)
DVitamin D = absorption from gut
🎓 Common Exam Questions
Q: What is the hypothalamic-pituitary axis and how does negative feedback work?
A: The hypothalamus releases releasing hormones (TRH, CRH, GnRH, GHRH) → anterior pituitary releases tropic hormones (TSH, ACTH, FSH/LH, GH) → target glands release final hormones (T3/T4, cortisol, sex steroids). Negative feedback: high levels of the final hormone suppress both the hypothalamus and pituitary. Example: high cortisol → suppresses CRH + ACTH → cortisol falls back. This is why exogenous steroid use suppresses the axis and causes adrenal atrophy.
Q: How do insulin and glucagon maintain blood glucose homeostasis?
A: After a meal (high glucose): beta cells release insulin → promotes glucose uptake by muscle/fat (GLUT4), glycogen synthesis in liver and muscle, protein synthesis, fat storage. Net effect: lower blood glucose. Fasting (low glucose): alpha cells release glucagon → promotes glycogenolysis (glycogen → glucose) and gluconeogenesis in liver. Net effect: raise blood glucose. In Type 1 DM: no insulin (beta cell destruction) → hyperglycemia + DKA. In Type 2 DM: insulin resistance → hyperglycemia despite insulin present.
Q: What are the effects of thyroid hormone deficiency vs excess?
A: Thyroid hormones (T3/T4) increase BMR, HR, GI motility, protein synthesis, and CNS development. Hypothyroidism (low T3/T4, high TSH): fatigue, weight gain, cold intolerance, constipation, bradycardia, dry skin, myxedema, cretinism if congenital. Most common cause: Hashimoto thyroiditis (autoimmune). Treat with levothyroxine (T4). Hyperthyroidism (high T3/T4, low TSH): weight loss, heat intolerance, tachycardia, diarrhea, anxiety, exophthalmos (Graves). Most common cause: Graves disease (TSI antibodies).
Q: How does PTH regulate calcium and what happens when it is excess or deficient?
A: PTH released when Ca2+ LOW → (1) bone resorption by osteoclasts → releases Ca2+, (2) renal reabsorption of Ca2+ in DCT, (3) activates vitamin D → intestinal Ca2+ absorption. Net: raises blood Ca2+. Hyperparathyroidism: excess PTH → hypercalcemia → "bones, stones, groans, moans" (bone pain, kidney stones, abdominal pain, neuropsychiatric symptoms). Hypoparathyroidism: low PTH → hypocalcemia → tetany, Chvostek sign, Trousseau sign, prolonged QT. Most common cause of hypoparathyroidism: accidental removal during thyroid surgery.
Q: What are the zones of the adrenal cortex and what does each produce?
A: Remember GFR: Glomerulosa → Fasciculata → Reticularis (outer to inner). Zona Glomerulosa (outermost): aldosterone (mineralocorticoid) — regulated by angiotensin II and K+; promotes Na+ retention, K+ excretion in kidney. Zona Fasciculata (middle, largest): cortisol (glucocorticoid) — regulated by ACTH; raises blood glucose, anti-inflammatory, immunosuppressive. Zona Reticularis (innermost): androgens (DHEA) — regulated by ACTH; precursors to sex steroids. The medulla (not cortex) produces epinephrine and norepinephrine.