A patient with Cushing's syndrome secondary to ectopic ACTH secretion from a small cell lung carcinoma has a plasma ACTH of 380 pg/mL, serum cortisol 78 µg/dL, and fails high-dose dexamethasone suppression. Which drug acts by inhibiting 11β-hydroxylase to rapidly reduce cortisol in this setting?
- A Metyrapone ✓
- B Cabergoline
- C Mifepristone
- D Pasireotide
Correct answer: A. Metyrapone
Explanation
Metyrapone inhibits 11β-hydroxylase (CYP11B1), the final step in cortisol synthesis, making it the agent of choice for rapid cortisol reduction in ectopic ACTH syndrome when the primary tumor cannot be resected immediately. It is fast-acting and effective. Mifepristone blocks glucocorticoid receptors but does not reduce cortisol levels, making monitoring difficult. Cabergoline (dopamine agonist) and pasireotide (somatostatin analogue) are used in Cushing's disease of pituitary origin, not ectopic ACTH.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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