Stability and reference intervals of spot urinary fractionated metanephrines and methoxytyramine by tandem mass spectrometry as a screening method for pheochromocytoma and paraganglioma.

ABSTRACT

PURPOSE: The 24 h urinary-fractionated metanephrine (MN) and normetanephrine (NMN) are recommended as the preferred indicators for laboratory diagnosis of pheochromocytoma and paraganglioma (PPGL). However, it might cause missed diagnosis for some type of PPGL, in addition, 24-h urine collection is inconvenient and prone to error, so we aimed to develop a better screening method. METHODS: Urine samples from patients of primary hypertension (n = 317) or PPGL (n = 64) were collected randomly and in a 24-h cycle. Samples were prepared by solid phase extraction (SPE) and analyzed with LC-MS/MS. Sample stability under different storage conditions was investigated. The gender-specific reference intervals of spot urinary catecholamine metabolites adjusted by creatinine were established and the diagnostic performance was evaluated. RESULTS: Urinary MN, NMN (MNs), and 3-methoxytyramine (3-MT) were stable at room temperature or 4 °C for at least 4 days without adding any preservatives and at -20 °C for at least 11 weeks. Reference intervals of spot urinary MN, NMN and 3-MT adjusted by creatinine were 20.2-174.0, 47.6-452.0, and 20.6-398.5 µg/g for male and were 15.3-202.0, 34.4-461.0, and 38.0-392.6 µg/g for female. The sensitivity and specificity of spot urinary MN, NMN, and 3-MT were similar with that of 24-h urine (P > 0.05). Regardless of urine sample type, combined application of MNs or MNs and 3-MT can improve the diagnosis efficiency of MN and 3-MT alone. CONCLUSIONS: Adding 3-MT to diagnosis model can improve diagnostic sensitivity to some extent, and the analysis of spot urinary MNs and 3-MT can provide reliable diagnostic information in a much shorter diagnostic time, it may reduce the medical expenses indirectly.