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Utility of Plasma Free Metanephrines for Detecting Childhood Pheochromocytoma

Developmental Endocrinology Branch (M.W.), Pediatric and Reproductive Endocrinology Branch (D.P.M., K.P.), National Institute of Child Health and Human Development; Clinical Neurocardiology Section (G.E.), National Institute of Neurological Disorders and Stroke; Urologic Oncology Branch (M.M.W.), National Cancer Institute; and the Warren Grant Magnuson Clinical Center (D.P.M.), National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Graeme Eisenhofer, Ph.D., Building 10, Room 6N252, National Institutes of Health, 10 Center Drive, MSC 1620, Bethesda, Maryland 20892-1620. E-mail: . ge{at}box-g.nih.gov

Abstract

Measurements of plasma free metanephrines, normetanephrine (NMN) and metanephrine (MN), provide a sensitive test for diagnosis of pheochromocytoma in adults but have not been evaluated in children. We therefore established reference ranges for plasma and urinary metanephrines and the catecholamines, norepinephrine (NE) and epinephrine (E), in 86 healthy children (age 5–17). A group of 158 healthy adults (age 18–72) served as a comparison group. Pediatric reference ranges were applied to examine the diagnostic utility of the various tests in 45 children evaluated for pheochromocytoma (age 8–17; 38 with von Hippel-Lindau syndrome), with tumors found on 12 occasions. Upper reference limits for E and MN were higher and those for NE and NMN lower in children than in adults. Boys had higher plasma levels of E and MN and higher urinary excretion of all four amines than girls. Plasma free metanephrines provided a diagnostic test with values for sensitivity (100%) and specificity (94%) that were equal to or higher than those of other tests. In two children screened for pheochromocytoma on multiple occasions, use of pediatric reference ranges for plasma free metanephrines indicated the tumor a year earlier than indicated using adult reference ranges. The findings indicate that plasma free metanephrines provide a sensitive tool for detection of pheochromocytoma in children. Age appropriate reference ranges should be used and gender differences should be considered.

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