Plasma Metanephrines in the Diagnosis of Pheochromocytoma

  1. Jacques W. M. Lenders;
  2. Harry R. Keiser;
  3. David S. Goldstein;
  4. Jacques J. Willemsen;
  5. Peter Friberg;
  6. Marie-Cecile Jacobs;
  7. Peter W. C. Kloppenborg;
  8. Theo Thien; and
  9. Graeme Eisenhofer
  1. From the National Institutes of Health, Bethesda, Maryland. St. Radboud University Hospital, Nijmegen, the Netherlands. The University of Goteborg, Goteborg, Sweden. Requests for Reprints: Jacques W.M. Lenders, MD, Division of General Internal Medicine, Department of Internal Medicine, St. Radboud University Hospital, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, the Netherlands. Acknowledgments: The authors thank Dr. Irwin J. Kopin for his support and critical review of the manuscript and Dr. Andre Verbeek for his assistance in the statistical analysis.

    Abstract

    Objective: To examine whether tests for plasma metanephrines, the o-methylated metabolites of catecholamines, offer advantages for diagnosis of a pheochromocytoma over standard tests for plasma catecholamines or urinary metanephrines.

    Design: Cross-sectional study.

    Setting: 3 clinical specialist centers.

    Patients: 52 patients with a pheochromocytoma; 67 normotensive persons and 51 patients with essential hypertension who provided reference values; and 23 patients with secondary hypertension and 50 patients with either heart failure or angina pectoris who served as comparison groups.

    Measurements: Plasma concentrations of catecholamines (norepinephrine and epinephrine) and metanephrines (normetanephrine and metanephrine) were measured in all patients. The 24-hour urinary excretion of metanephrines was measured in 46 patients with pheochromocytoma.

    Results: Pheochromocytomas were associated with increases in plasma concentrations of metanephrines that were greater and more consistent than those in plasma catecholamine concentrations. No patient with a pheochromocytoma had normal plasma concentrations of both normetanephrine and metanephrine. The sensitivity of these tests was 100% (52 of 52 patients [95% CI, 94% to 100%]), and the negative predictive value of normal plasma concentrations of metanephrines was 100% (162 of 162 patients). Tests for plasma catecholamines yielded eight false-negative results and a sensitivity of 85% (44 of 52 patients [CI, 72% to 93%]). The negative predictive value of normal plasma concentrations of catecholamines was 95% (156 of 164 patients). Tests for urinary metanephrines yielded five false-negative results and a sensitivity of 89% (41 of 46 patients [CI, 76% to 96%]). Because no statistical difference was noted in the number of false-positive results between tests for plasma metanephrines (15%) and tests for plasma catecholamines (18%), the specificities of the two tests did not differ.

    Conclusions: Normal plasma concentrations of metanephrines exclude the diagnosis of pheochromocytoma, whereas normal plasma concentrations of catecholamines and normal urinary excretion of metanephrines do not. Tests for plasma metanephrines are more sensi-tive than tests for plasma catecholamines or urinary metanephrines for the diagnosis of pheochromocytoma.

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