For suspected Cushing's syndrome, which laboratory tests are most appropriate?

• A. Plasma drug levels of quinidine, digoxin, and hydralazine
• B. Plasma levels of ACTH and cortisol
• C. 24-hour urine for metanephrine and catecholamine
• D. Spot urine for creatinine and white blood cells

Answer: (B)

A key approach when Cushing's syndrome is suspected is to confirm hypercortisolism and determine its origin by looking at both cortisol and ACTH levels. Measuring morning plasma cortisol confirms there is excess cortisol. Checking plasma ACTH alongside it helps distinguish whether the excess cortisol is ACTH-dependent (ACTH present or high) or ACTH-independent (ACTH suppressed). This classification guides further testing and management: an ACTH-suppressed result points toward an adrenal source, while an ACTH-normal or elevated result points toward a pituitary or ectopic source. The other options don’t address cortisol excess or its regulation and are used for different conditions (for example, pheochromocytoma with metanephrines, or unrelated drug levels or urine findings).