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Free or Total Metanephrines for Diagnosis of Pheochromocytoma: What Is the Difference?

¹ Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, E-mail graeme@catecholamine.org

Pheochromocytomas, although a rare cause of hypertension, are dangerous tumors that require consideration in large numbers of patients. The resulting low prevalence of these tumors among the tested population and the inadequate sensitivity and specificity of commonly used biochemical tests make diagnosis of pheochromocytoma difficult and time-consuming.

As outlined in two articles in this issue of the Journal (1)(2), measurements of plasma concentrations of metanephrines provide a promising, new, highly sensitive test for diagnosis of pheochromocytoma. A negative test result for plasma metanephrines means that a pheochromocytoma is highly unlikely so that no other tests are necessary (3)(4). Thus, measurements of plasma metanephrines provide a particularly good initial diagnostic test for exclusion of pheochromocytoma.

The diagnostic superiority of plasma metanephrines over plasma or urinary catecholamines and urinary vanillylmandelic acid is clear (3)(4)(5)(6). What remains unclear, as illustrated in the two articles in this issue of the Journal (1)(2), is whether measurements of plasma free (unconjugated) metanephrines or total metanephrines provide the better diagnostic test, and how these tests differ. Also unclear is how these tests differ from measurements of urinary metanephrines.

Part of the confusion about tests of urinary total or fractionated metanephrines and plasma free, unconjugated, or total metanephrines stems from the unfortunate and confusing terminology used to distinguish these analytes. The term "metanephrines" . . . [Full Text of this Article]

References

The following articles in journals at HighWire Press have cited this article:

				J. G. Boyle, D. F. Davidson, C. G. Perry, and J. M. C. Connell Comparison of Diagnostic Accuracy of Urinary Free Metanephrines, Vanillyl Mandelic Acid, and Catecholamines and Plasma Catecholamines for Diagnosis of Pheochromocytoma J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4602 - 4608. [Abstract] [Full Text] [PDF]

				W. H.A. de Jong, K. S. Graham, J. C. van der Molen, T. P. Links, M. R. Morris, H. A. Ross, E. G.E. de Vries, and I. P. Kema Plasma Free Metanephrine Measurement Using Automated Online Solid-Phase Extraction HPLC Tandem Mass Spectrometry Clin. Chem., September 1, 2007; 53(9): 1684 - 1693. [Abstract] [Full Text] [PDF]

				N. Unger, C. Pitt, I. L. Schmidt, M. K Walz, K. W Schmid, T. Philipp, K. Mann, and S. Petersenn Diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass. Eur. J. Endocrinol., March 1, 2006; 154(3): 409 - 417. [Abstract] [Full Text] [PDF]

				R. J. Singh, S. K. Grebe, B. Yue, A. L. Rockwood, J. C. Cramer, Z. Gombos, G. Eisenhofer, and S. Binder Precisely Wrong? Urinary Fractionated Metanephrines and Peer-Based Laboratory Proficiency Testing * A representative for Bio-Rad responds: Clin. Chem., February 1, 2005; 51(2): 472 - 474. [Full Text] [PDF]

				J. W. M. Lenders, K. Pacak, M. M. Walther, W. M. Linehan, M. Mannelli, P. Friberg, H. R. Keiser, D. S. Goldstein, and G. Eisenhofer Biochemical Diagnosis of Pheochromocytoma: Which Test Is Best? JAMA, March 20, 2002; 287(11): 1427 - 1434. [Abstract] [Full Text] [PDF]

				R. L. Taylor and R. J. Singh Validation of Liquid Chromatography-Tandem Mass Spectrometry Method for Analysis of Urinary Conjugated Metanephrine and Normetanephrine for Screening of Pheochromocytoma Clin. Chem., March 1, 2002; 48(3): 533 - 539. [Abstract] [Full Text] [PDF]

				D. K. Crockett, E. L. Frank, and W. L. Roberts Rapid Analysis of Metanephrine and Normetanephrine in Urine by Gas Chromatography-Mass Spectrometry Clin. Chem., February 1, 2002; 48(2): 332 - 337. [Abstract] [Full Text] [PDF]