A patient on high-dose corticosteroids for 3 months develops secondary adrenal insufficiency. The pharmacological basis for this complication is:

• A Corticosteroids increase ACTH clearance by the kidney, reducing trophic stimulation of the adrenal cortex
• B Exogenous corticosteroids suppress CRH and ACTH secretion via negative feedback, causing HPA axis suppression and adrenocortical atrophy ✓
• C Exogenous corticosteroids competitively block aldosterone receptors in the adrenal cortex
• D Corticosteroids induce CYP11A1, converting cortisol to inactive cortisone, depleting adrenal reserves

Explanation

Prolonged exogenous glucocorticoid therapy suppresses the hypothalamic-pituitary-adrenal (HPA) axis via negative feedback. Supraphysiological glucocorticoid levels inhibit CRH secretion from the hypothalamus and ACTH secretion from the anterior pituitary. Without ACTH stimulation, the adrenal cortex (fasciculata and reticularis) undergoes disuse atrophy. Upon abrupt withdrawal, the atrophied cortex cannot respond to physiological stress with adequate cortisol secretion, causing secondary adrenal insufficiency (Addisonian crisis). This is why corticosteroids must be tapered gradually.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.