Establishment of reference intervals for plasma metanephrines in seated position measured by LC-MS/MS and assessment of diagnostic performance in pheochromocytoma/paraganglioma

Abstract

Background The use of supine reference intervals instead of the corresponding seated reference intervals for seated plasma-free metanephrines (MNs) in pheochromocytoma/paraganglioma (PPGL) screening has been controversial in recent years. Each clinical laboratory should choose the optimal sampling posture and diagnostic strategy according to local conditions. Methods The reference population consisted of 736 cases aged 14–92 years old and the validation population consisted of 1068 patients aged 8–87 years old. Seated MNs were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the reference intervals and diagnostic cut-off values were established and the diagnostic performance compared with reference intervals established in a supine position. Results There was no correlation between seated plasma MNs and age ( p > 0.05) and there were differences in MNs among the various disease groups ( p < 0.05). MNs were different in gender ( p < 0.0001). The upper reference limit (URL) established in this study had the same sensitivity (100%) and better specificity (94.6% vs 83.5%) compared with the published age-adjusted supine reference intervals. The proportion of suspected patients with MNs within the URL-2×URL range was lower using seated reference intervals compared to supine intervals (5.3% vs 15.7%). Conclusion Using the corresponding seated reference intervals for seated plasma MNs can reduce the unnecessary re-examinations of suspected patients with slightly elevated MNs. The cut-off value established by seated plasma MNs has good diagnostic performance in PPGL. Use of seated sampling is an acceptable practice and is more convenient and economical than supine sampling.