Measurement of Urinary Metanephrines to Screen for Pheochromocytoma in an Unselected Hospital Referral Population

Background: Despite the rarity of pheochromocytoma, diagnosis is important because of the dangers of uncontrolled severe hypertension and the availability of very effective surgical treatment. Urinary or plasma catecholamines or catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, and sex may better predict tumors in populations with a low pretest probability. Methods: We retrospectively studied outcomes of an unselected population (1819 patients) referred to a tertiary hospital laboratory for urinary metanephrine testing and investigated the usefulness of some simple derivative measures for detecting pheochromocytoma. We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range. We then compared pheochromocytoma prediction by the use of products of these normalized measures with the gold standard of biopsy-confirmed tumor. Results: The product of the excretion of normalized metanephrine (nMAD) and normalized normetanephrine (nNMT) (nMAD·nNMT) was a highly sensitive (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%. ROC curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. The test for nMAD·nNMT gave higher sensitivity and specificity than the tests for either substance alone. Conclusion: The test for nMAD·nNMT is a useful measure for identifying pheochromocytoma in a population with a low pretest probability.