Clinical Information

Pheochromocytoma is a rare, though potentially lethal, tumor of chromaffin cells of the adrenal medulla that produces episodes of hypertension with palpitations, severe headaches, and sweating (spells). Patients with pheochromocytoma may also be asymptomatic and present with sustained hypertension or an incidentally discovered adrenal mass.

Pheochromocytomas and other tumors derived from neural crest cells (eg, paragangliomas and neuroblastomas) secrete catecholamines (epinephrine, norepinephrine, and dopamine). Metanephrine and normetanephrine are the 3-methoxy metabolites of epinephrine and norepinephrine, respectively. Metanephrine and normetanephrine are both further metabolized to vanillylmandelic acid. Pheochromocytoma cells also have the ability to oxymethylate catecholamines into metanephrines,  which are secreted into circulation.

In patients that are highly suspect for pheochromocytoma, it may be best to screen by measuring plasma free fractionated metanephrines (a more sensitive assay). The 24-hour urinary fractionated metanephrines (a more specific assay) may be used as the first test for low suspicion cases or as a confirmatory study in patients with a less than 2-fold elevation in plasma free fractionated metanephrines. This is highly desirable, as the very low population incidence rate of pheochromocytoma (<1:100,000 population per year) will otherwise result in large numbers of unnecessary, costly, and sometimes risky imaging procedures.

Complete 24-hour urine collections are preferred, especially for patients with episodic hypertension; ideally, the collection should begin at the onset of a spell.