Pheochromocytomas are rare chromaffin cell tumors that nevertheless must be
excluded in large numbers of patients who develop sustained or episodic hy
pertension as well as in many others with suggestive symptoms or with a fam
ilial history of pheochromocytoma. Diagnosis of pheochromocytoma depends im
portantly on biochemical evidence of excess catecholamine production by a t
umor. Imperfect sensitivity and specificity of commonly available biochemic
al tests and the low incidence of the tumor among the tested population mea
n that considerable time and effort can be expended in confirming or ruling
out pheochromocytoma in patients where the tumor is suspected. Measurement
s of plasma free metanephrines provide a superior test compared to other av
ailable tests for diagnosis of pheochromocytoma. In particular, the high se
nsitivity of plasma free metanephrines means that a normal test result reli
ably excludes all but the smallest of pheochromocytomas so that no other te
sts are necessary. Measurements of plasma free metanephrines, when systemat
ically combined with other diagnostic procedures outlined in this review, p
rovide a more efficient, reliable and cost-effective approach for diagnosis
of pheochromocytoma than offend by previously available approaches.