Which of the following is used in the evaluation of pheochromocytoma?

• A. Plasma metanephrines, normetanephrine and VMA (HPLC)
• B. Clonidine suppression test
• C. Glucagon suppression test
• D. All of the above

Answer: (D)

When evaluating a suspected pheochromocytoma, you look for excess catecholamine production or its metabolites, using a mix of biochemical and provocative tests to confirm and localize the tumor. The most sensitive initial screen is measuring plasma free metanephrines and normetanephrines, often with HPLC or similar methods, because these metabolites are produced continuously by the tumor and can reveal even small secretory activity. Urinary fractionated metanephrines and vanillylmandelic acid (VMA) have long been used as well; VMA reflects end products of catecholamine metabolism but is less sensitive than metanephrines, so it’s useful in conjunction with other tests.

The clonidine suppression test is a functional test you might use when results are ambiguous. In normal physiology, clonidine reduces sympathetic outflow and freezes plasma catecholamine levels. If levels remain elevated and do not suppress, this supports autonomous catecholamine release from a pheochromocytoma rather than a stress-related or exogenous source.

The glucagon stimulation test is another provocative approach that has historical use. It aims to provoke a larger catecholamine response and hypertensive reaction in someone with pheochromocytoma, helping distinguish it from other causes of elevated catecholamines, though it’s less commonly used today due to safety concerns and advances in more specific testing.

All of these tools play a role in evaluating suspected pheochromocytoma, chosen based on the clinical context and test results.