A patient on long-term glucocorticoids undergoes elective surgery. Perioperative 'stress dosing' is required. Which physiological mechanism necessitates supraphysiological perioperative corticosteroid coverage?

• A Surgery increases hepatic CYP3A4 activity, rapidly degrading circulating cortisol requiring supplementation
• B Exogenous glucocorticoids suppress the hypothalamic-pituitary-adrenal (HPA) axis via negative feedback; surgery-induced stress requires cortisol surge of 200–500 mg/day that a suppressed HPA axis cannot generate, causing addisonian crisis ✓
• C Surgical trauma increases corticosteroid-binding globulin, reducing free cortisol availability
• D Inflammation activates mineralocorticoid receptors, requiring glucocorticoid supplementation for aldosterone competition

Explanation

The HPA axis is the primary stress-response system. Exogenous glucocorticoids (≥5 mg prednisone equivalent for >3 weeks) suppress CRH (hypothalamus) and ACTH (pituitary) release via glucocorticoid receptor-mediated negative feedback. The adrenal cortex atrophies and cannot mount an adequate stress response. Major surgery triggers cortisol surges of 200–500 mg hydrocortisone equivalent/day. Without stress dosing, these patients develop adrenal crisis (hypotension, hyponatremia, hypoglycemia, circulatory collapse). Hydrocortisone 50–100 mg IV every 6–8 hours perioperatively is standard coverage.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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