A 52-year-old man presents with central obesity, bruising, hypertension, and hyperglycemia. 24-hour urinary free cortisol is 450 μg/day (normal <50). Overnight 1 mg dexamethasone suppression test fails to suppress cortisol below 1.8 μg/dL. Plasma ACTH is undetectable. What is the MOST likely diagnosis?

• A Pituitary corticotroph adenoma (Cushing's disease)
• B Ectopic ACTH syndrome from small cell lung carcinoma
• C Pseudo-Cushing's syndrome due to depression
• D Adrenal adenoma causing ACTH-independent Cushing's syndrome ✓

Explanation

Undetectable ACTH with excess cortisol indicates ACTH-independent hypercortisolism, strongly pointing to a primary adrenal source — most commonly an adrenal adenoma. Pituitary Cushing's disease and ectopic ACTH syndrome both have elevated or detectable ACTH. Pseudo-Cushing's from depression rarely elevates UFC to more than twice normal. Next step would be adrenal CT to localise the adenoma.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.