A 48-year-old man presents with proximal muscle weakness, central obesity, hyperglycemia, and hypokalemic metabolic alkalosis. Plasma ACTH is markedly elevated at 480 pg/mL. Pituitary MRI shows no adenoma. Chest CT reveals a 4 cm right hilar mass. Which finding best supports an ectopic source of ACTH rather than Cushing disease?
- A Suppression of cortisol on high-dose dexamethasone testing
- B Elevated ACTH with normal serum potassium
- C Cortisol that fails to suppress even with high-dose dexamethasone ✓
- D Loss of circadian cortisol rhythm
Correct answer: C. Cortisol that fails to suppress even with high-dose dexamethasone
Explanation
Ectopic ACTH secretion from small cell lung carcinoma is autonomous, so cortisol does not suppress even with high-dose dexamethasone, whereas corticotroph adenomas usually retain partial suppressibility. Hypokalemic metabolic alkalosis from mineralocorticoid effects of extreme cortisol levels strongly favors ectopic secretion. Loss of circadian rhythm occurs in all causes of endogenous Cushing syndrome, and normal potassium argues against the ectopic form.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
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