Biochemical Diagnosis of Pheochromocytoma: How to Distinguish True- from False-Positive Test Results
Graeme Eisenhofer,
David S. Goldstein,
McClellan M. Walther,
Peter Friberg,
Jacques W. M. Lenders,
Harry R. Keiser and
Karel Pacak
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke (G.E., D.S.G.); the Urologic Oncology Branch, National Cancer Institute (M.M.W.); the Hypertension Endocrine Branch, National Heart Lung and Blood Institute (H.R.K.); and the Pediatric and Reproductive Endocrinology Branch (K.P.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; the Department of Clinical Physiology (P.F.), Sahlgren’s University Hospital, S-41345 Gothenburg, Sweden; and the Department of General Internal Medicine (J.W.M.L.), St. Radboud University Hospital, 6525 GA Nijmegen, The Netherlands
Address all correspondence and requests for reprints to: Graeme Eisenhofer, Building 10, Room 6N252, NIH, 10 Center Drive, Bethesda, Maryland 20892-1620. E-mail: ge{at}box-g.nih.gov.
Measurements of plasma normetanephrine and metanephrine providea highly sensitive test for diagnosis of pheochromocytoma, butfalse-positive results remain a problem. We therefore assessedmedication-associated false-positive results and use of supplementarytests, including plasma normetanephrine responses to clonidine,to distinguish true- from false-positive results. The studyincluded 208 patients with pheochromocytoma and 648 patientsin whom pheochromocytoma was excluded. Clonidine-suppressiontests were carried out in 48 patients with and 49 patients withoutthe tumor. Tricyclic antidepressants and phenoxybenzamine accountedfor 41% of false-positive elevations of plasma normetanephrineand 44–45% those of plasma and urinary norepinephrine.High plasma normetanephrine to norepinephrine or metanephrineto epinephrine ratios were strongly predictive of pheochromocytoma.Lack of decrease and elevated plasma levels of norepinephrineor normetanephrine after clonidine also confirmed pheochromocytomawith high specificity. However, 16 of 48 patients with pheochromocytomahad normal levels or decreases of norepinephrine after clonidine.In contrast, plasma normetanephrine remained elevated in allbut 2 patients, indicating more reliable diagnosis using normetanephrinethan norepinephrine responses to clonidine. Thus, in patientswith suspected pheochromocytoma and positive biochemical results,false-positive elevations due to medications should first beeliminated. Patterns of biochemical test results and responsesof plasma normetanephrine to clonidine can then help distinguishtrue- from false-positive results.
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