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Dietary Influences on Plasma and Urinary Metanephrines: Implications for Diagnosis of Catecholamine-Producing Tumors

Departments of Laboratory Medicine (W.H.A.d.J., F.A.J.M., I.P.K.), Epidemiology (W.J.P.), and Medical Oncology (E.G.E.d.V.), University Medical Center, University of Groningen, 9700 RB Groningen, The Netherlands; and Institute of Clinical Chemistry and Laboratory Medicine and Department of Medicine (G.E.), University of Dresden, 01187 Dresden, Germany

Address all correspondence and requests for reprints to: I. P. Kema, Ph.D., Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. E-mail: i.p.kema{at}lc.umcg.nl.

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 µmol dopamine and 1 µmol 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.