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

Abstract

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” describes two catecholamine metabolites: …