建立液相色谱-串联质谱检测血浆游离变肾上腺素和去甲变肾上腺素诊断嗜铬细胞瘤的临床策略

黄斐; 陈方俊; 彭颖斐; 吴炯; 郭玮

doi:10.3760/cma.j.issn.1001-9030.2017.11.053

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中华实验外科杂志

• 临床研究 •

ENGLISH ABSTRACT

建立液相色谱-串联质谱检测血浆游离变肾上腺素和去甲变肾上腺素诊断嗜铬细胞瘤的临床策略

作者及单位信息

出版日期： 2017 -11 -08 ·

DOI： 10.3760/cma.j.issn.1001-9030.2017.11.053

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

Authors Info & Affiliations

Huang Fei

Department of Clinical Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China

Chen Fangjun

Peng Yingfei

Wu Jiong

Guo Wei

Published： 2017 -11 -08 ·

DOI： 10.3760/cma.j.issn.1001-9030.2017.11.053

315

APP内阅读

摘要

目的建立液相色谱-串联质谱(LC-MS/MS)平台检测血浆游离变肾上腺素(MN)和去甲变肾上腺素(NMN)诊断嗜铬细胞瘤的临床策略。

方法招募255例健康人以建立参考范围。另招募于复旦大学附属中山医院泌尿外科和内分泌科就诊患者，嗜铬细胞瘤组110例、疾病对照组1 262例和健康对照组500例，比较各组间MN和NMN水平。依据参考范围和由受试者工作特征曲线(ROC)得到最佳特异性切点制定诊断策略。

结果MN和NMN参考范围分别为<64.97 pg/ml和<185.83 pg/ml。嗜铬细胞瘤组MN和NMN水平显著高于疾病对照组( Z＝－17.410， P＝0.000； Z＝－17.278， P＝0.000)和健康对照组( Z＝－16.434， P＝0.000； Z＝－16.439， P＝0.000)。定义MN和NMN中任意一个超过参考范围上限为诊断策略A，MN和NMN中任意一个指标超过特异性诊断切点为诊断策略B，用于排除和辅助诊断嗜铬细胞瘤。

结论建立LC-MS/MS平台检测MN和NMN的参考范围，为临床提供嗜铬细胞瘤的诊断策略。

关键词：液相色谱-串联质谱法;变肾上腺素;去甲变肾上腺素;嗜铬细胞瘤

ABSTRACT

ObjectiveTo 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.

Methods255 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.

ResultsThe 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.

ConclusionThe reference intervals of plasma free MN and NMN by LC-MS/MS and diagnostic strategies of pheochromocytoma.

KEYWORDS： Liquid chromatography-tandem mass spectrometry;Metanephrine;Normetanephrine;Pheochromocytoma

Corresponding author: Guo Wei, Email: nc.defhsab.latipsoh-sziew.oug

FUNDING:

The State Key Laboratory of Clinical College Construction Project; The National Science & Technology Pillar Program during the 12th Five-year Plan Period (2012BAI37B01); National Natural Science Foundation of China (81572064); Key Developing Disciplines of Shanghai Municipal Commission of Health and Family Planning (2015ZB0201)

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All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.

引用本文

黄斐,陈方俊,彭颖斐,等. 建立液相色谱-串联质谱检测血浆游离变肾上腺素和去甲变肾上腺素诊断嗜铬细胞瘤的临床策略[J]. 中华实验外科杂志,2017,34(11)：1982-1984.

DOI:10.3760/cma.j.issn.1001-9030.2017.11.053

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嗜铬细胞瘤是一种神经内分泌肿瘤，大多源于肾上腺髓质，而少数源于肾上腺外的嗜铬细胞。由于肿瘤引起阵发或持续性儿茶酚胺(CA)的分泌 ^{[
1
]}，易导致患者血压异常以及代谢紊乱。部分患者因长期高血压致严重的心、脑、肾损害或高血压危象，因此及早发现、诊断和治疗嗜铬细胞瘤能避免上述情况发生。

传统辅助诊断嗜铬细胞瘤的生化指标包括血CA和尿CA、尿香草扁桃酸等，但缺乏敏感性和特异性。最新研究结果显示，相较于其他生物指标，变肾上腺素(MN)和去甲变肾上腺素(NMN)对嗜铬细胞瘤的辅助诊断具有较高价值 ^{[
2
]}。血浆游离MN和NMN的半衰期较CA长，因此其诊断性能更加稳定，可直接反映肿瘤细胞状态 ^{[
3
]}。为此，血浆游离MN和NMN逐渐成为嗜铬细胞瘤诊治指导中推荐的标志物 ^{[
4
]}。我们在对自建液相色谱-串联质谱(LC-MS/MS)平台行完整性能验证的基础上 ^{[
5
]}，进行后续研究以建立该平台检测MN和NMN的参考范围，为临床提供嗜铬细胞瘤的诊断策略。

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摘要
参考文献

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备注信息

通信作者：郭玮，Email： nc.defhsab.latipsoh-sziew.oug

基金项目：

"十二五"国家科技支撑计划 (2012BAI37B01) 查看更多基金信息

国家自然科学基金面上项目 (81572064)

上海市卫生计生系统重要薄弱学科建设项目 (2015ZB0201)

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