A patient with Addison's disease on hydrocortisone replacement develops an acute febrile illness. Which physiological principle mandates an immediate doubling or tripling of his hydrocortisone dose?

• A Cortisol acts as a permissive hormone that potentiates catecholamine-mediated cardiovascular responses to stress ✓
• B Glucocorticoids directly suppress fever by inhibiting PGE2 synthesis
• C Illness increases cortisol clearance by hepatic CYP3A4 induction
• D ACTH secretion is stimulated by fever, requiring more substrate

Explanation

Cortisol's critical role during physiological stress is its 'permissive' action on the cardiovascular response to catecholamines. Cortisol upregulates alpha and beta adrenoreceptors and maintains vascular responsiveness to epinephrine and norepinephrine. In adrenal insufficiency during illness, despite adequate catecholamine secretion, the vasculature cannot respond appropriately, leading to vasodilatory shock. Doubling/tripling the steroid dose ('sick day rules') mimics the normal 3–5-fold rise in cortisol secretion during serious illness.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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