Establishment a diagnostic strategy of pheochromocytoma by plasma free metanephrines determined by liquid chromatography-tandem mass spectrometry

Objective To set up reference intervals of plasma free metanephrine (MN) and normetanephrine (NMN) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and diagnostic strategies of pheochromocytoma. Methods 255 healthy people were recruited to set up reference intervals.110 patients with pheochromocytoma were also enrolled, in addition to 1 262 subjects taken as disease control group and 500 subjects taken as health control group. Positive rates of plasma free MN and NMN were compared among different groups. Diagnostic strategies were designed according to reference intervals and cut-off value with optimal specificity determined by receiver operating characteristic (ROC) curve. Results The reference intervals of MN and NMN are <64.97 pg/ml and <185.83 pg/ml, respectively. Significant differences in the level of MN and NMN were found between not only pheochromocytoma group and disease control group (Z=-17.410, P=0.000; Z=-17.278, P=0.000), but also pheochromocytoma group and health control group (Z=-16.434, P=0.000; Z=-16.439, P=0.000). We establish diagnostic strategy A for either of MN and NMN above the upper limit of the reference range and B for either of MN and NMN above specific diagnostic cutoff value to rule in or rule out the diagnosis of pheochromocytoma. Conclusion The reference intervals of plasma free MN and NMN by LC-MS/MS and diagnostic strategies of pheochromocytoma. Key words: Liquid chromatography-tandem mass spectrometry; Metanephrine; Normetanephrine; Pheochromocytoma