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Comparison of Diagnostic Accuracy of Urinary Free Metanephrines, Vanillyl Mandelic Acid, and Catecholamines and Plasma Catecholamines for Diagnosis of Pheochromocytoma

Division of Cardiovascular and Medical Sciences (J.G.B., C.G.P., J.M.C.C.), Western Infirmary, University of Glasgow, Glasgow G12 8TA, United Kingdom; and Department of Biochemistry (D.F.D.), Crosshouse Hospital, Kilmarnock KA2 0BE, United Kingdom

Address all correspondence and requests for reprints to: Professor John M. C. Connell, BHF Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom. E-mail: jfg2t{at}clinmed.ac.gla.uk.

Context: Recent evidence suggests that plasma-free metanephrines provide a highly sensitive test in patients requiring exclusion of pheochromocytoma. The diagnostic efficacy of urinary free metanephrines, however, has not been evaluated.

Objective, Design, Setting, Patients, and Outcome Measures: We compared retrospectively the diagnostic efficacy of 24-h urinary free metanephrines with our currently available measurements of 24-h urinary vanillyl mandelic acid (VMA), urinary catecholamines, and plasma catecholamines in 159 outpatients tested in a tertiary referral center for pheochromocytoma over a 4-yr period.

Results: The sensitivity of urinary free metanephrines was 100% [25 of 25 patients; 95% confidence interval (CI) 86–100%)] compared with the sensitivity of 84% (21 of 25; 95% CI 64–95%) for urinary catecholamines; 72% (18 of 25; 95% CI 51–88%) for urinary VMA; and 76% (16 of 21; 95% CI 53–92%) for plasma catecholamines. The specificity of urinary free metanephrines was 94% (116 of 123; 95% CI 89–98%), compared with the specificity of 99% (127 of 129; 95% CI 96–100%) for urinary catecholamines; 96% (130 of 134; 95% CI 91–98%) for urinary VMA; and 88% (66 of 75; 95% CI 78–94%) for plasma catecholamines. Receiver operating characteristic curves for all test groups were generated. Pairwise comparisons of the area under the receiver operating characteristic curve for urinary free metanephrines with that of each of the other three test groups individually were: 0.993 (95% CI 0.962–0.999) vs. 0.919 (95% CI 0.862–0.957, P = 0.032) for urine catecholamines; 0.993 (95% CI 0.962–0.999) vs. 0.846 (95% CI 0.778–0.900, P = 0.002) for urine VMA; and 0.992 (95% CI 0.945–0.998) vs. 0.852 (95% CI 0.762–0.918, P = 0.009) for plasma catecholamines. Testing with urinary free metanephrines failed to misidentify a single case of pheochromocytoma, compared with four missed cases for urinary catecholamines, seven missed cases for urinary VMA, and five missed cases for plasma catecholamines.

Conclusion: Urinary free metanephrines were superior to urinary VMA, urinary catecholamines, and plasma catecholamines and can provide a valuable test for diagnosis of pheochromocytoma in adults.