Accuracy of recommended sampling and assay methods for the determination of plasma-free and urinary fractionated metanephrines in the diagnosis of pheochromocytoma and paraganglioma: a systematic review
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Purpose To determine the accuracy of biochemical tests for the diagnosis of pheochromocytoma and paraganglioma.Methods A search of the PubMed database was conducted for English-language articles published between October 1958 and December 2016 on the biochemical diagnosis of pheochromocytoma and paraganglioma using immunoassay methods or high-performance liquid chromatography with coulometric/electrochemical or tandem mass spectrometric detection for measurement of fractionated metanephrines in 24-h urine collections or plasma-free metanephrines obtained under seated or supine blood sampling conditions.Results Application of the Standards for Reporting of Diagnostic Studies Accuracy Group criteria yielded 23 suitable articles. Summary receiver operating characteristic analysis revealed sensitivities/specificities of 94/93% and 91/93% for measurement of plasma-free metanephrines and urinary fractionated metanephrines using high-performance liquid chromatography or immunoassay methods, respectively. Partial areas under the curve were 0.947 vs. 0.911. Irrespective of the analytical method, sensitivity was significantly higher for supine compared with seated sampling, 95 vs. 89% (p < 0.02), while specificity was significantly higher for supine sampling compared with 24-h urine, 95 vs. 90% (p < 0.03). Partial areas under the curve were 0.942, 0.913, and 0.932 for supine sampling, seated sampling, and urine. Test accuracy increased linearly from 90 to 93% for 24-h urine at prevalence rates of 0.0-1.0, decreased linearly from 94 to 89% for seated sampling and was constant at 95% for supine conditions.Conclusions Current tests for the biochemical diagnosis of pheochromocytoma and paraganglioma show excellent diagnostic accuracy. Supine sampling conditions and measurement of plasma-free metanephrines using high-performance liquid chromatography with coulometric/electrochemical or tandem mass spectrometric detection provides the highest accuracy at all prevalence rates.
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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 [202]
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- Authors
- Därr, R., Kuhn, M., Bode, C., Bornstein, S. R., Pacak, K., Lenders, J. W. M., & Eisenhofer, G.
- Affiliations
- University of Freiburg (DE)
- University Hospital Carl Gustav Carus (DE)
- Radboud University Medical Center (NL)
- Corresponding author
- Därr, Roland
- Venue
- Endocrine
- Published
- 2017-04-12
- Volume
- 56
- Issue
- 3
- Pages
- 495-503
- ISSN
- 0969-711X (ISSN-L)
- 1355-008X
- 1559-0100
- PMC
- PMC6297899
- OpenAlex
- W2607207406
- Cited by
- 105
- References
- 60
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 11 · 2023: 10 · 2022: 16 · 2021: 16 · 2020: 13 · 2019: 13 · 2018: 12 · 2017: 2
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Endocrine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (DE) (DA 1630/2-1)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Keywords
- pheochromocytoma, paraganglioma, metanephrine, plasma free metanephrines, 24-hour urine collection, diagnostic accuracy, immunoassay, HPLC, tandem mass spectrometry, biochemical diagnosis
- MeSH terms
- Adrenal Gland Neoplasms, Chromatography, High Pressure Liquid, Humans, Metanephrine, Paraganglioma, Pheochromocytoma, Sensitivity and Specificity, Specimen Handling, Tandem Mass Spectrometry
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