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Biochemical Diagnosis of Pheochromocytoma: How to Distinguish True- from False-Positive Test Results

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 provide a highly sensitive test for diagnosis of pheochromocytoma, but false-positive results remain a problem. We therefore assessed medication-associated false-positive results and use of supplementary tests, including plasma normetanephrine responses to clonidine, to distinguish true- from false-positive results. The study included 208 patients with pheochromocytoma and 648 patients in whom pheochromocytoma was excluded. Clonidine-suppression tests were carried out in 48 patients with and 49 patients without the tumor. Tricyclic antidepressants and phenoxybenzamine accounted for 41% of false-positive elevations of plasma normetanephrine and 44–45% those of plasma and urinary norepinephrine. High plasma normetanephrine to norepinephrine or metanephrine to epinephrine ratios were strongly predictive of pheochromocytoma. Lack of decrease and elevated plasma levels of norepinephrine or normetanephrine after clonidine also confirmed pheochromocytoma with high specificity. However, 16 of 48 patients with pheochromocytoma had normal levels or decreases of norepinephrine after clonidine. In contrast, plasma normetanephrine remained elevated in all but 2 patients, indicating more reliable diagnosis using normetanephrine than norepinephrine responses to clonidine. Thus, in patients with suspected pheochromocytoma and positive biochemical results, false-positive elevations due to medications should first be eliminated. Patterns of biochemical test results and responses of plasma normetanephrine to clonidine can then help distinguish true- from false-positive results.

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