Which of the following best explains why high-dose dexamethasone (8 mg overnight) suppresses urinary free cortisol in Cushing's disease but NOT in ectopic ACTH syndrome?

• A Ectopic ACTH-producing tumors lack glucocorticoid receptors, so dexamethasone cannot act on them
• B The pituitary corticotroph adenoma in Cushing's disease retains glucocorticoid negative feedback at higher threshold, while ectopic tumors are insensitive to feedback ✓
• C Dexamethasone binds mineralocorticoid receptors in ectopic tumors, blocking cortisol measurement
• D High-dose dexamethasone directly suppresses adrenal cortisol synthesis, which fails in ectopic disease due to bilateral adrenal hyperplasia

Explanation

Corticotroph adenomas in Cushing's disease retain some glucocorticoid negative feedback sensitivity, but the set-point is reset upward; high pharmacologic doses of dexamethasone (8 mg) can overcome this threshold and suppress ACTH/cortisol by ≥50%. Ectopic ACTH tumors (e.g., small cell lung cancer) lack this feedback sensitivity and secrete ACTH independently of circulating glucocorticoid levels. Dexamethasone does not act directly on the adrenal gland to suppress cortisol; suppression occurs via pituitary ACTH suppression.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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