Plasma Metanephrines: the Optimal Diagnostic Tool for Pheochromocytoma?

Diagnosis of pheochromocytoma depends on biochemical evidence of catecholamine production by the tumor, but the best test for establishing the diagnosis remains unsettled. The objective of this study was to determine which biochemical test or combination of tests provides the optimal method for diagnosis of pheochromocytoma.; Tests of plasma catecholamines, plasma free metanephrines, and urinary catecholamines, total and fractionated metanephrines and vanillylmandelic acid (VMA) were compared in 858 patients tested for pheochromocytoma on clinical suspicion of the tumor. Pheochromocytoma was confirmed in 214 patients and excluded in 644 patients according to independent standard criteria (surgical pathology, imaging studies, follow-up).; Sensitivities of plasma free metanephrines (99%) and urinary fractionated metanephrines (97%) were higher than those for plasma catecholamines (84%), urinary catecholamines (86%), urinary total metanephrines (77%) or VMA (64%). Specificity was highest for urinary VMA (95%) and urinary total metanephrines (93%), intermediate for plasma free metanephrines (89%), urinary catecholamines (88%) and plasma catecholamines (81%) and lowest for urinary fractionated metanephrines (69%). As shown by receiver-operating characteristic curves, aggregate sensitivity and specificity values at different upper reference limits were highest for plasma free metanephrines. Combining different tests did not improve the diagnostic yield significantly beyond that of a single test of plasma free metanephrines.; Measurements of plasma free metanephrines or urinary fractionated metanephrines are equally effective in excluding pheochromocytoma. However, due to the higher specificity of plasma than urinary fractionated metanephrines, plasma free metanephrines should be the test of first choice in the diagnostic work-up of a patient with suspected pheochromocytoma.