title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology and Angiology I, University Heart Centre Freiburg, Freiburg, Germany. Roland.wolfgang.daerr@uniklinik-freiburg.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Därr
authors.affiliation: Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus at the TU Dresden, Dresden, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kuhn
authors.affiliation: Department of Cardiology and Angiology I, University Heart Centre Freiburg, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: Department of Medicine ΙΙI, University Hospital Carl Gustav Carus at the TU Dresden, Dresden, Germany.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.affiliation: Department of Medicine ΙΙI, University Hospital Carl Gustav Carus at the TU Dresden, Dresden, Germany.|Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jacques W M
authors.initials: JWM
authors.lastname: Lenders
authors.affiliation: Department of Medicine ΙΙI, University Hospital Carl Gustav Carus at the TU Dresden, Dresden, Germany.|Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the TU Dresden, Dresden, Germany.
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008676:Metanephrine / Q000032:analysis*; D010235:Paraganglioma / Q000175:diagnosis* / Q000378:metabolism; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013048:Specimen Handling / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D008676:Metanephrine
keywords: Diagnostic accuracy; High-performance liquid chromatography; Immunoassay; Metanephrines; Paraganglioma; Pheochromocytoma