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Cited by 1,134Adrenal and Paraganglionic TumorsNeuroendocrine Tumor Research AdvancesMetabolism and Genetic Disorders

Biochemical Diagnosis of Pheochromocytoma: Which Test Is Best?

Lenders, Jacques W. M., Pacak, Karel, Walther, McClellan M., Linehan, W. Marston, Mannelli, Massimo, Friberg, Peter, Keiser, Harry R., Goldstein, David S. +1 more·2002·JAMA
DOI 10.1001/jama.287.11.1427
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Abstract

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.

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  • Evaluation for pheochromocytoma is best made by measuring plasma metanephrines.

    “Evaluation for pheochromocytoma is best made by measuring plasma metanephrines (67).”

    From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [67]

  • Plasma free or 24-hour urine fractionated metanephrines are recommended as the screening test of choice for pheochromocytoma with a sensitivity of 90% to 95%.

    “Plasma free or 24-hour urine fractionated metanephrines are recommended as the screening test of choice for pheochromocytoma with a sensitivity of 90% to 95% (202, 203).”

    From Adrenal incidentaloma (2020) · cites this paper as [203]

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Authors
Lenders, J. W. M., Pacak, K., Walther, M. M., Linehan, W. M., Mannelli, M., Friberg, P., Keiser, H. R., Goldstein, D. S., & Eisenhofer, G.
Affiliations
Radboud University Medical Center (NL)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2002-03-20
Volume
287
Issue
11
Pages
1427-34
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.287.11.1427
OpenAlex
W1979422997
Cited by
1,134
References
26
Citations by year
2026: 15 · 2025: 25 · 2024: 30 · 2023: 47 · 2022: 44 · 2021: 45 · 2020: 48 · 2019: 44 · 2018: 33 · 2017: 46 · 2016: 33 · 2015: 55 · 2014: 62 · 2013: 63 · 2012: 53
FWCI
43.82
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
pheochromocytoma, biochemical diagnosis, plasma free metanephrines, urinary vanillylmandelic acid, urinary catecholamines, plasma catecholamines, sensitivity and specificity, diagnostic accuracy, catecholamine synthesis, predictive value, diagnostic test selection
MeSH terms
Adolescent, Adrenal Gland Neoplasms, Adult, Aged, Catecholamines, Child, Female, Humans, Male, Metanephrine, Middle Aged, Pheochromocytoma, Predictive Value of Tests, ROC Curve, Sensitivity and Specificity, Cohort Studies

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