Which biomarker is most sensitive for initial screening of pheochromocytoma?

• A. Plasma free metanephrines (or 24-hour urine metanephrines)
• B. Serum catecholamines
• C. Urinary VMA
• D. Plasma aldosterone

Answer: (A)

Measuring metanephrines is the most sensitive way to screen for pheochromocytoma because the tumor continuously produces these metabolites from catecholamines, so they remain elevated even when catecholamine release is not in flux. Plasma free metanephrines (or urinary metanephrines over 24 hours) capture this steady production and episodic secretion better than direct catecholamines, making them more reliable for initial screening.

Direct serum catecholamines can be normal between spells of tumor activity, which lowers their sensitivity. Urinary vanillylmandelic acid reflects end products of catecholamine metabolism and is an older test with lower sensitivity. Plasma aldosterone has no relevance to pheochromocytoma.