Long-term corticosteroid therapy causes adrenal suppression through which mechanism?

• A Direct cytotoxic destruction of zona fasciculata cells by exogenous glucocorticoids
• B Negative feedback suppression of CRH and ACTH release from hypothalamus and pituitary, resulting in adrenal cortex atrophy from chronic ACTH deprivation ✓
• C Competitive blockade of mineralocorticoid receptors in the adrenal cortex
• D Inhibition of cholesterol side-chain cleavage enzyme (CYP11A1) in adrenocortical cells

Explanation

Exogenous glucocorticoids exert negative feedback at the hypothalamic level (suppressing CRH) and pituitary level (suppressing ACTH). Without trophic ACTH stimulation, the zona fasciculata and zona reticularis of the adrenal cortex undergo progressive atrophy. Abrupt withdrawal after long-term therapy can precipitate acute adrenal insufficiency because the suppressed HPA axis cannot respond quickly to physiological cortisol demand. Recovery of HPA function may take 6–12 months. Exogenous glucocorticoids are not directly cytotoxic to adrenal cells and do not block cholesterol side-chain cleavage.

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

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