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Graeme Eisenhofer, Biochemical Diagnosis of Pheochromocytoma—Is it Time to Switch to Plasma-Free Metanephrines?, The Journal of Clinical Endocrinology & Metabolism, Volume 88, Issue 2, 1 February 2003, Pages 550–552, https://doi.org/10.1210/jc.2002-021913
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Current recommendations for biochemical diagnosis of pheochromocytoma remain more often based on institutional experience with certain methods than on evidence of carefully designed studies carried out to compare available tests. Experts from some centers emphasize measurements of plasma catecholamines, whereas others advocate urinary measurements. Emerging evidence now indicates that measurements of catecholamines, when carried out alone, are not sufficiently sensitive for reliable diagnosis. In particular, plasma and urinary catecholamines can be normal when testing is carried out between spells or when normotensive and asymptomatic patients with pheochromocytoma are screened for the tumor because of a hereditary predisposition or the incidental finding of an adrenal mass by imaging studies.
Realization that pheochromocytomas may secrete catecholamines intermittently or in low amounts has led to recommendations that diagnosis should entail a combination of tests, and include measurements of metanephrines, the O-methylated metabolites of catecholamines (1, 2). Measurements of urinary metanephrines originally involved spectrophotometric methods where normetanephrine, the O-methylated metabolite of norepinephrine, and metanephrine, the O-methylated metabolite of epinephrine, are measured together in total as a single analyte—hence, the term “urinary total metanephrines.” These methods have now been superseded by techniques involving liquid chromatography that allow separation of normetanephrine and metanephrine into fractionated components that can be measured individually—hence, the term “urinary fractionated metanephrines.” Most of these latter methods also allow additional measurements of methoxytyramine, the O-methylated metabolite of dopamine.
