PY8.1-7 | Endocrine Physiology — Gate Quiz

Correct! Glucose is the primary stimulus for insulin secretion. β-cells sense glucose via GLUT-2 transporters (high Km, not saturable at physiological glucose) → glucokinase phosphorylates glucose → ↑ATP → closes K_ATP channels → membrane depolarisation → voltage-gated Ca²⁺ influx → insulin exocytosis.

Key concept: Insulin secretion stimuli — Primary: ↑blood glucose; Secondary: amino acids (especially arginine, leucine), GIP/GLP-1 (incretins), vagal, sulphonylureas (K_ATP blockers). Biphasic response: Phase 1 (first 10 min, stored insulin) + Phase 2 (new synthesis). Sulphonylureas mimic glucose by blocking K_ATP channels. GLP-1 analogues (liraglutide) act in a glucose-dependent manner.

Incorrect. The primary stimulus for insulin secretion is increased blood glucose. The mechanism: GLUT-2 → glucokinase → ↑ATP/ADP ratio → K_ATP channel closure → depolarisation → Ca²⁺ influx → insulin release.

Correct! Insulin binds to its receptor (tyrosine kinase receptor) → IRS phosphorylation → PI3-K/Akt pathway → translocation of GLUT-4 vesicles from intracellular stores to the plasma membrane. This increases GLUT-4 density on the cell surface, dramatically increasing glucose uptake into muscle and fat cells.

Key concept: GLUT transporters — GLUT-1 (brain, RBC, ubiquitous, basal); GLUT-2 (liver, pancreatic β-cells, intestine, kidney — high Km glucose sensor); GLUT-3 (neurons, high affinity); GLUT-4 (muscle, adipose — insulin-regulated translocation). Insulin resistance = impaired GLUT-4 translocation → type 2 DM. Exercise also independently translocates GLUT-4 (via AMPK) — explains why exercise helps T2DM.

Incorrect. Insulin promotes glucose uptake into skeletal muscle and adipose tissue by translocating GLUT-4 vesicles from intracellular stores to the plasma membrane. This is the unique mechanism distinguishing insulin-sensitive tissues.

Correct! T3 (tri-iodothyronine) is the most biologically active thyroid hormone. T4 is the major secretory product of the thyroid (80%) but acts mainly as a prohormone — it is converted to T3 by 5'-deiodinase in peripheral tissues (especially liver, kidney). T3 binds to nuclear receptors with 10× greater affinity than T4.

Key concept: Thyroid hormone production — Thyroid secretes T4 (80%) + T3 (20%). Peripheral conversion of T4→T3 by 5'-deiodinase. T3 is 3–4× more potent than T4, shorter half-life (1 day vs 7 days for T4). Both are lipophilic, bound to TBG in plasma. Nuclear receptor activation → transcription of target genes. Actions: ↑BMR, ↑heart rate/contractility, growth, development, CNS maturation.

Incorrect. T3 is the biologically active form at the cellular level (binds nuclear receptor with 10× greater affinity than T4). T4 is a prohormone converted to T3 in peripheral tissues.

Correct! High TSH + low free T4 = primary hypothyroidism (thyroid gland failure). The pituitary correctly senses low T4 and increases TSH secretion (intact feedback axis). Clinical features — ↓BMR: weight gain, cold intolerance, fatigue; ↓cardiac: bradycardia; ↓GI: constipation; skin: dry, coarse; myxoedema; ↑cholesterol. Most common cause worldwide: iodine deficiency; in India: autoimmune (Hashimoto's).

Key concept: Thyroid function test interpretation — Primary hypothyroidism: ↑TSH, ↓fT4; Secondary: ↓TSH, ↓fT4 (pituitary failure); Primary hyperthyroidism (Graves'): ↓TSH, ↑fT4; Subclinical hypothyroidism: ↑TSH, normal fT4. Most common causes: Hypothyroidism = Hashimoto's (autoimmune), iodine deficiency (developing countries); Hyperthyroidism = Graves' disease (TSH-receptor antibodies).

Incorrect. High TSH + low free T4 = primary hypothyroidism. Secondary hypothyroidism (pituitary failure) would show low TSH + low T4. Hyperthyroidism shows low TSH + high T4.

Correct! Cortisol peaks in the early morning (6–8 AM, coinciding with waking) and is at its lowest around midnight. This rhythm is driven by CRH (hypothalamus) → ACTH (pituitary) → cortisol (adrenal cortex). Clinical relevance: cortisol samples should be taken in the morning (8 AM) for accurate assessment.

Key concept: Cortisol diurnal rhythm — Peak at 8 AM (waking), nadir at midnight. Driven by ACTH pulsatility (CRH → ACTH → cortisol, negative feedback). Cortisol testing: morning level >18 μg/dL = normal adrenal function; low morning cortisol = possible adrenal insufficiency (check with short Synacthen test). Loss of diurnal rhythm: Cushing's syndrome (high midnight cortisol). Stress response abolishes rhythm (cortisol rises in response to any stress).

Incorrect. Cortisol peaks in the early morning (around 6–8 AM at waking) and is lowest at midnight. Morning cortisol levels are used diagnostically.

Correct! Cortisol → cytoplasmic GR receptor → nucleus → induces transcription of lipocortin-1 (annexin-A1) → inhibits phospholipase A₂ → blocks arachidonic acid release from membrane phospholipids → reduces synthesis of ALL eicosanoids (prostaglandins, thromboxanes, leukotrienes). NSAIDs only block COX; steroids block PLA₂ (upstream of COX and LOX).

Key concept: Anti-inflammatory mechanisms of cortisol — ↓Lipocortin → ↓PLA₂ → ↓arachidonic acid → ↓prostaglandins + leukotrienes; ↓NF-κB → ↓cytokines (IL-1, TNF-α, IL-6); ↓macrophage activation; ↓ACTH → ↓inflammatory mediators; ↓capillary permeability; suppress T-cell function. Side effects of chronic steroids: Cushing's syndrome, hyperglycaemia, immunosuppression, osteoporosis, peptic ulcer, adrenal suppression.

Incorrect. Cortisol induces lipocortin-1 (annexin-A1) which inhibits phospholipase A₂, blocking arachidonic acid release — the upstream block that inhibits ALL eicosanoid synthesis.

Correct! PTH responds to hypocalcaemia by: (1) ↑osteoclast bone resorption → ↑Ca²⁺ from bone; (2) ↑renal Ca²⁺ reabsorption in distal tubule (and ↓phosphate reabsorption); (3) ↑1-α-hydroxylase in kidney → ↑calcitriol (1,25-dihydroxyvitamin D) → ↑intestinal Ca²⁺ absorption. Net effect: restores plasma Ca²⁺.

Key concept: Ca²⁺ homeostasis — PTH (↑when Ca²⁺ low): ↑bone resorption (osteoclasts), ↑renal Ca²⁺ reabsorption, ↑calcitriol; Calcitonin (thyroid C-cells, ↑when Ca²⁺ high): ↓bone resorption (↓osteoclasts); Vitamin D (calcitriol): ↑intestinal Ca²⁺ + PO₄ absorption, ↑bone mineralisation. Hypoparathyroidism (post-thyroidectomy): hypocalcaemia → tetany → treat with Ca²⁺ + vitamin D.

Incorrect. PTH responds to hypocalcaemia by: ↑bone resorption, ↑renal Ca²⁺ reabsorption (↓PO₄ reabsorption), and ↑calcitriol synthesis → ↑intestinal Ca²⁺ absorption.

Correct! In absolute insulin deficiency (T1DM), insulin normally suppresses hormone-sensitive lipase (HSL) in adipose tissue. Without insulin, HSL is unrestrained → massive lipolysis → ↑free fatty acids (FFAs) enter liver → overwhelm TCA cycle capacity → β-oxidation produces excess acetyl-CoA → ketogenesis (acetoacetate, β-hydroxybutyrate, acetone) → ketoacidosis.

Key concept: DKA pathway — ↓insulin (+ ↑glucagon) → ↑glycogenolysis + ↑gluconeogenesis (hyperglycaemia) + ↑lipolysis (↑FFA) → hepatic ketogenesis (acetoacetate, β-hydroxybutyrate) → ↓pH (metabolic acidosis) + osmotic diuresis (dehydration) + K⁺ shifts. DKA triad: hyperglycaemia + ketonaemia + metabolic acidosis. Treatment: IV fluids, insulin infusion, K⁺ replacement.

Incorrect. DKA mechanism: insulin deficiency → ↑HSL in adipose → ↑lipolysis → ↑FFA → hepatic β-oxidation → excess acetyl-CoA → ketone body synthesis → acidosis.

Correct! GH stimulates the liver (and locally in growth plates) to produce IGF-1 (also called somatomedin C). IGF-1 is the primary mediator of GH's growth-promoting effects on the growth plate (epiphyseal plate) chondrocytes. GH also has some direct effects but IGF-1 is the main effector for linear growth.

Key concept: GH-IGF-1 axis — Hypothalamus GHRH → pituitary GH → liver IGF-1 → growth plate chondrocyte proliferation. GH also has direct anti-insulin ("diabetogenic") effects: ↑gluconeogenesis, ↑lipolysis, ↓glucose uptake. Peak GH: puberty, deep sleep, exercise, fasting. GH excess in childhood: gigantism; in adults: acromegaly. GH deficiency in childhood: dwarfism (treatable with recombinant GH).

Incorrect. GH acts primarily through IGF-1 (insulin-like growth factor-1) produced by the liver. IGF-1 stimulates chondrocyte proliferation at epiphyseal growth plates for linear bone growth.

Correct! Adrenaline (epinephrine) mediates the fight-or-flight response: β₁ → ↑HR + ↑contractility; β₂ → skeletal muscle + coronary vasodilation + bronchodilation; α₁ → splanchnic/skin vasoconstriction; β₁/α₁ → ↑BP; β₁/β₃ → lipolysis; α₁/β₂ → glycogenolysis in liver/muscle → ↑blood glucose. Net: ↑cardiac output, ↑O₂ delivery to muscles, ↑fuel availability.

Key concept: Catecholamine effects — Adrenaline (adrenal medulla, 80%): β₁+β₂+α₁ (at high concentrations); Noradrenaline (sympathetic postganglionic, adrenal medulla 20%): α₁+α₂ dominant (↑BP, ↑SVR, reflex bradycardia). Phaeochromocytoma (catecholamine-secreting tumour): hypertensive crises, headache, palpitations, sweating (triad). Urine VMA/metanephrines for diagnosis.

Incorrect. Adrenaline in fight-or-flight: ↑HR (β₁), ↑cardiac output, skeletal muscle vasodilation (β₂), ↑blood glucose (glycogenolysis), bronchodilation (β₂). Visceral vasoconstriction redirects blood to muscles.