How Basic Concepts Explain Clinical Scenarios
Why does Addison's disease cause dark skin? Primary adrenal failure → no cortisol → no negative feedback → massive ACTH excess. ACTH is derived from POMC, which also contains MSH (melanocyte-stimulating hormone) sequences. Excess ACTH mimics MSH → melanocyte activation → increased melanin → hyperpigmentation. Clinical clue: darkening in sun-exposed areas, skin creases, and buccal mucosa.
Why is insulin injected, not taken as tablets? Insulin is a 51-amino acid peptide (water-soluble). Proteases in the GI tract digest peptide bonds → insulin is destroyed before absorption. Must be injected subcutaneously to bypass digestion. Contrast: steroid hormones (oral prednisolone) are lipid-soluble → absorbed across gut epithelium intact.
Why must steroid therapy be tapered gradually? Chronic exogenous corticosteroid → continuous negative feedback on HPA axis → CRH and ACTH suppressed → adrenal cortex atrophies from disuse. Abrupt cessation: exogenous supply removed + endogenous supply cannot respond (atrophied adrenals) → acute cortisol deficiency (Addisonian crisis). Gradual tapering allows HPA axis recovery.
Why is TSH the best thyroid screening test? The TSH-T4 feedback is exquisitely sensitive. A small drop in T4 causes a proportionally large TSH rise (logarithmic relationship). TSH detects thyroid dysfunction long before T4 leaves the normal range or symptoms appear. It is the most cost-effective single test for thyroid disease.
Why do antipsychotic drugs cause galactorrhoea? Antipsychotics block dopamine D2 receptors. Dopamine (PIF) tonically inhibits prolactin. Blocking dopamine → prolactin rises (hyperprolactinaemia) → stimulates mammary glands → milk secretion (galactorrhoea), even in non-pregnant individuals. Also causes menstrual irregularities (prolactin suppresses GnRH).
Why do athletes sometimes use recombinant GH? GH (via IGF-1) stimulates protein synthesis in muscle → muscle hypertrophy. GH also promotes lipolysis → reduced fat. Side effects of GH abuse: acromegalic features, glucose intolerance (GH is anti-insulin), joint pain, carpal tunnel syndrome.