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New Advances in the Biochemical Diagnosis of Pheochromocytoma

Moving beyond Catecholamines



    1. Department of Internal Medicine, St. Radboud University Medical Center, Nijmegen, the Netherlands
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    1. Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
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    Corresponding author
    1. Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
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Address for correspondence: Graeme Eisenhofer, Building 10, Room 6N252, National Institutes of Health, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620. Voice: 301-496-8925; fax: 301-402-0180;


Abstract: Pheochromocytomas are dangerous tumors that, although a rare cause of hypertension, require consideration among large numbers of patients. The resulting low prevalence of the tumor among tested populations and the inadequacies of commonly used biochemical tests make excluding or confirming the tumor an often difficult and time-consuming task. Recognition that catecholamines are metabolized to free metanephrines within pheochromocytoma tumor cells, and that this process is independent of catecholamine release, provides a rationale for use of these metabolites in the biochemical diagnosis of pheochromocytoma. Here we briefly review the history of biochemical diagnosis of pheochromocytoma in relation to recent data about the diagnostic utility of plasma free metanephrines for detection of these tumors. Measurements of urinary or plasma catecholamines have reasonable sensitivity for detection of most pheochromocytomas, particularly those in patients with sustained hypertension. False-negative test results can, however, occur in asymptomatic patients tested because of an adrenal incidentaloma or a familial predisposition for pheochromocytoma, or when sampling is carried out between episodes of paroxysmal hypertension. Measurements of urinary total metanephrines or vanillylmandelic acid are less reliable and are of little value as initial screening tests. In contrast, measurements of plasma concentrations or free metanephrines or 24-hour urinary outputs of fractionated normetanephrine and metanephrine almost always reveal the tumor. Although, both tests have similarly high sensitivity, the relatively low specificity of urinary fractionated metanephrines means that pheochromocytomas can be more efficiently excluded or confirmed using measurements of plasma free metanephrines.