Biochemical Diagnosis of Pheochromocytoma

Which Test Is Best?

Lenders, Jacques W. M. MD, PhD
Pacak, Karel MD, PhD
Walther, McClellan M. MD
Linehan, W. Marston MD
Mannelli, Massimo MD
Friberg, Peter MD, PhD
Keiser, Harry R. MD
Goldstein, David S. MD, PhD
Eisenhofer, Graeme PhD

Author Affiliations: Department of Internal Medicine, St Radboud University Medical Center, Nijmegen, the Netherlands (Dr Lenders); Department of Clinical Pathophysiology, University of Florence, Florence, Italy (Dr Mannelli); Department of Clinical Physiology, Sahlgren's University Hospital, Göteborg, Sweden (Dr Friberg); Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development (Dr Pacak), Urologic Oncology Branch, National Cancer Institute (Drs Walther and Linehan), Hypertension Endocrine Branch, National Heart, Lung, and Blood Institute (Dr Keiser), and Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke (Drs Goldstein and Eisenhofer), National Institutes of Health, Bethesda, Md.

Corresponding Author and Reprints: Jacques W. M. Lenders, MD, PhD, Department of Internal Medicine, St Radboud University Medical Center, Geert Grooteplein Zuid 8, PO Box 9101, 6500 HB, Nijmegen, the Netherlands (e-mail: [email protected]).

JAMA: The Journal of the American Medical Association 287(11):p 1427-1434, March 20, 2002.

Context

Diagnosis of pheochromocytoma depends on biochemical evidence of catecholamine production by the tumor. However, the best test to establish the diagnosis has not been determined.

Objective

To determine the biochemical test or combination of tests that provides the best method for diagnosis of pheochromocytoma.

Design, Setting, and Participants

Multicenter cohort study of patients tested for pheochromocytoma at 4 referral centers between 1994 and 2001. The analysis included 214 patients in whom the diagnosis of pheochromocytoma was confirmed and 644 patients who were determined to not have the tumor.

Main Outcome Measures

Test sensitivity and specificity, receiver operating characteristic curves, and positive and negative predictive values at different pretest prevalences using plasma free metanephrines, plasma catecholamines, urinary catecholamines, urinary total and fractionated metanephrines, and urinary vanillylmandelic acid.

Results

Sensitivities of plasma free metanephrines (99% [95% confidence interval {CI}, 96%-100%]) and urinary fractionated metanephrines (97% [95% CI, 92%-99%]) were higher than those for plasma catecholamines (84% [95% CI, 78%-89%]), urinary catecholamines (86% [95% CI, 80%-91%]), urinary total metanephrines (77% [95% CI, 68%-85%]), and urinary vanillylmandelic acid (64% [95% CI, 55%-71%]). Specificity was highest for urinary vanillylmandelic acid (95% [95% CI, 93%-97%]) and urinary total metanephrines (93% [95% CI, 89%-97%]); intermediate for plasma free metanephrines (89% [95% CI, 87%-92%]), urinary catecholamines (88% [95% CI, 85%-91%]), and plasma catecholamines (81% [95% CI, 78%-84%]); and lowest for urinary fractionated metanephrines (69% [95% CI, 64%-72%]). Sensitivity and specificity values at different upper reference limits were highest for plasma free metanephrines using receiver operating characteristic curves. Combining different tests did not improve the diagnostic yield beyond that of a single test of plasma free metanephrines.

Conclusion

Plasma free metanephrines provide the best test for excluding or confirming pheochromocytoma and should be the test of first choice for diagnosis of the tumor.

JAMA.2002;287:1427-1434