Evaluation of an enzyme immunoassay for plasma-free metanephrines in the diagnosis of catecholamine-secreting tumors

Objective: To define the test characteristics of an enzyme immunoassay (EIA) for plasma-free metanephrines (metanephrine and normetanephrine) in the diagnosis of pheochromocytoma and paraganglioma. Design: Prospective observational design from a single University Hospital. Twenty-four hour urine for catecholamines and plasma for free metanephrines were collected from patients with a clinical suspicion of pheochromocytoma or paraganglioma. Patient records were reviewed for clinical data, follow-up, imaging and laboratory results to establish or exclude the diagnosis of pheochromocytoma. Patients and methods: Out of 178 consecutive patients, 10 had a paraganglioma and 12 had a pheochromocytoma: 156 were finally judged not to harbour active tumors and were therefore considered as controls. The main outcome measure was the diagnosis or exclusion of paraganglioma or pheochromocytoma and test characteristics of plasma-free metanephrines measured by EIA. Results: Urinary epinephrine had a sensitivity of 45.5% and norepinephrine a sensitivity of 75% (98.8% specificity) for the diagnosis of pheochromocytoma. Plasma-free metanephrine and normetanephrine both had a sensitivity of 66.7% and a specificity of 100%, but when combined (either positive) they demonstrated a 91.7% sensitivity with a preserved specificity of 100%. For the diagnosis of paraganglioma, urinary norepinephrine gave slightly better results than plasma-free metanephrines, but combined testing was of no additional value. Conclusions: Plasma-free metanephrines measured by EIA have better diagnostic test characteristics than urinary catecholamines in the diagnosis of pheochromocytoma. The EIA offers a simple and effective measurement of plasma-free metanephrines.