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

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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.

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Acknowledgements

The authors like to thank Beijing Health Biotech Co., Ltd for their participation. Thanks are also extended to the many clinicians and their patients who participated in this study.

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Authors and Affiliations

  1. Center of Laboratory Medicine, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 100037, Beijing, China

    Kaijuan Wang, Xiaojing Gao, Hongying Cong, Wei Zhang, Xiaocui Shi, Shuming Dai & Zhou Zhou

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  1. Kaijuan Wang
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  2. Xiaojing Gao
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Correspondence to Zhou Zhou.

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The authors declare that they have no conflict of interest.

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This study was approved by ethic committee of Fuwai Hospital, china and complies with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was funded by Innovation Project for Medicine and Health Science and Technology form CAMS (grant numbers: 2016-12M-1-016).

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Wang, K., Gao, X., Cong, H. et al. Stability and reference intervals of spot urinary fractionated metanephrines and methoxytyramine by tandem mass spectrometry as a screening method for pheochromocytoma and paraganglioma. Endocrine 69, 188–195 (2020). https://doi.org/10.1007/s12020-020-02267-8

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