A 45-year-old man with central obesity, moon facies, and striae is found to have 24-hour urinary free cortisol of 450 µg/day (normal <100). ACTH level is undetectable (<5 pg/mL). The most likely diagnosis is:

• A Cushing disease (pituitary ACTH-secreting adenoma)
• B Ectopic ACTH syndrome (small-cell lung carcinoma)
• C Pseudo-Cushing syndrome (alcoholism)
• D Adrenal adenoma (cortisol-secreting) ✓

Explanation

Undetectable ACTH (<5 pg/mL) in the setting of confirmed hypercortisolism indicates an ACTH-independent (adrenal) cause. Adrenal adenoma autonomously secretes cortisol, suppressing ACTH via negative feedback. Both Cushing disease and ectopic ACTH syndrome show elevated or inappropriately normal ACTH. Pseudo-Cushing's typically shows lesser cortisol elevation and resolves with abstinence.

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

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Written and medically reviewed by the StethoPrep medical team.