Dietary influences on plasma and urinary metanephrines: implications for diagnosis of catecholamine-producing tumors

Context: Measurements of the 3-O-methylated metabolites of catecholamines [metanephrines (MNs)] in plasma or urine are recommended for diagnosis of pheochromocytoma. It is unclear whether these tests are susceptible to dietary influences. Objective: The aim of the study was to determine the short-term influence of a catecholamine-rich diet on plasma and urinary fractionated MNs. Design, Setting, and Participants: We conducted a crossover study in a specialist medical center involving 26 healthy adults. Interventions: Subjects consumed catecholamine-rich nuts and fruits at fixed times on one day (about 35 mu mol dopamine and 1 mu mol norepinephrine) and catecholamine-poor products on another day. Blood and urine samples were collected at timed intervals before, during, and after experimental and control interventions. Main Outcome Measures: Isotope-dilution mass spectrometry-based measurements of plasma and urinary concentrations of free and deconjugated 3-methoxytyramine (3-MT), normetanephrine (NMN), and MN were made. Results: The catecholamine-rich diet had substantial effects (up to 3-fold increases) on plasma concentrations and urinary outputs of free and deconjugated 3-MT. Dietary catecholamines had negligible influences on free NMN in plasma and urine, but substantial effects (up to 2-fold increases) on deconjugated NMN in plasma and urine. Concentrations of free and deconjugated MN in plasma and urine remained unaffected. Conclusions: Dietary restrictions should be considered to minimize false-positive results for urinary and plasma deconjugated MNs during diagnosis of pheochromocytoma. Similar considerations appear warranted for plasma and urinary free 3-MT, but not for free NMN or MN, indicating advantages of measurements of the free compared to deconjugated metabolites. (J Clin Endocrinol Metab 94: 2841-2849, 2009