ACCURACY OF PLASMA FREE METANEPHRINES IN THE DIAGNOSIS OF PHEOCHROMOCYTOMA AND PARAGANGLIOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: Various studies have validated plasma free metanephrines (MNs) as biomarkers for pheochromocytoma and paraganglioma (PPGL). This meta-analysis aimed to estimate the overall diagnostic accuracy of this biochemical test for PPGL.

METHODS: We searched the PubMed, the Cochrane Library, Web of Science, Embase, Scopus, OvidSP, and ProQuest Dissertations & Theses databases from January 1, 1995 to December 2, 2016 and selected studies written in English that assessed plasma free MNs in the diagnosis of PPGL. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate the quality of the included studies. We calculated pooled sensitivities, specificities, positive and negative likelihood ratios, diagnostic odds ratios (DORs) and areas under curve (AUCs) with their 95% confidence intervals (95% CIs). Heterogeneity was assessed by I2 . To identify the source of heterogeneity, we evaluated the threshold effect and performed a meta-regression. Deeks' funnel plot was selected for investigating any potential publication bias.

RESULTS: Although the combination of metanephrine (MN) and normetanephrine (NMN) carried lower specificity (0.94, 95% CI 0.90-0.97) than NMN (0.97, 95% CI 0.92-0.99), NMN was generally more accurate than individual tests, with the highest AUC (0.99, 95% CI 0.97-0.99), DOR (443.35, 95% CI 216.9-906.23), and pooled sensitivity (0.97, 95% CI 0.94-0.98) values. Threshold effect and meta-regression analyses showed that different cut-offs, blood sampling positions, study types and test methods contributed to heterogeneity.

CONCLUSION: This meta-analysis suggested an effective value for combined plasma free MNs for the diagnosis of PPGL, but testing for MNs requires more standardization using tightly regulated studies.

ABBREVIATIONS: AUC = area under curve; CI = confidence interval; DOR = diagnostic odds ratio; EIA = enzyme immunoassay; LC-ECD = liquid chromatography-electrochemical detection; LC-MS/MS = liquid chromatography-tandem mass spectrometry; MN = metanephrine; NMN = normetaneprhine; PPGL = pheochromocytoma and paraganglioma; QUADAS-2 = Quality Assessment of Diagnostic Accuracy Studies 2.