LC-MS/MS检测类固醇激素谱在诊断原发性醛固酮增多症中的应用

doi:10.16352/j.issn.1001-6325.2022.12.1835

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (12): 1835-1840.doi: 10.16352/j.issn.1001-6325.2022.12.1835

LC-MS/MS检测类固醇激素谱在诊断原发性醛固酮增多症中的应用

高寅洁¹, 谢绍伟², 刘世颖³, 陆艺⁴, 张芳⁵, 邱玲^2*, 童安莉^1*

1.中国医学科学院北京协和医学院北京协和医院内分泌科国家卫生健康委员会内分泌重点实验室;
2.检验科疑难重症及罕见病国家重点实验室,北京 100730;
3.赤峰市医院内分泌科,内蒙古赤峰 024099;
4.长沙市第三医院内分泌科,湖南长沙 410035;
5.河北医科大学第二医院内分泌科,河北石家庄 050004

收稿日期:2022-05-05 修回日期:2022-06-28 出版日期:2022-12-05 发布日期:2022-11-23
通讯作者: ^* tonganli@hotmail.com;lingqiubj@163.com
基金资助:
国家自然科学基金(81770427,82070822);郑洛新国家自主创新示范区创新引领型产业集群专项(201200211100)

Application of the steroid profiling detecting by LC-MS/MS in the diagnosis of primary aldosteronism

GAO Yin-jie¹, XIE Shao-wei², LIU Shi-ying³, LU Yi⁴, ZHANG Fang⁵, QIU Ling^2*, TONG An-li^1*

1. Key laboratory of Endocrinology, National Health Commission, Department of Endocrinology;
2. State Key Laboratory of Complex Severe and Rare Diseases, Department of Clinical Laboratory, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730;
3. Department of Endocrinology, Chifeng Hospital, Chifeng 024099;
4. Department of Endocrinology, the Third Hospital of Changsha, Changsha 410035;
5. Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang 050004, China

Received:2022-05-05 Revised:2022-06-28 Online:2022-12-05 Published:2022-11-23
Contact: ^* tonganli@hotmail.com;lingqiubj@163.com

摘要/Abstract

摘要： 目的探究原发性醛固酮增多症(PA)患者的类固醇激素谱特征,并评估代谢产物18-氧-皮质醇和18-羟-皮质醇对该疾病的诊断效能。方法纳入2020年11月至2021年11月于北京协和医院内分泌科就诊的PA患者59例[醛固酮产生腺瘤(APA)41例,特发性醛固酮增多症(IHA)18例]及原发性高血压(EH)患者42例(对照组)。收集患者基本情况及临床特征,采用液相色谱-串联质谱(LC-MS/MS)法检测8种类固醇激素(包括6种肾上腺盐皮质激素:孕烯醇酮、孕酮、11-脱氧皮质酮、皮质酮、18-羟-皮质酮和醛固酮,以及2种代谢产物18-氧-皮质醇和18-羟-皮质醇)。比较不同组间各种类固醇激素水平的差异并评估诊断效能。结果 APA组患者孕酮水平高于EH组(P＜0.05);APA组和IHA组患者11-脱氧皮质酮水平均高于EH组(均P＜0.001);APA组患者18-羟-皮质酮水平高于EH组(P＜0.001);APA组和IHA组患者醛固酮水平均高于EH组(均P＜0.01);APA组患者18-氧-皮质醇水平高于IHA组高于EH组(均P＜0.05);APA组患者18-羟-皮质醇水平高于EH组(P＜0.001)。利用代谢产物18-氧-皮质醇和18-羟-皮质醇鉴别PA和EH,当18-氧-皮质醇切点值为0.06 ng/mL时,敏感性74.6%,特异性88.1%;当18-羟-皮质醇切点值为1.44 ng/mL时,敏感性71.2%,特异性69.0%。18-氧-皮质醇和18-羟-皮质醇识别APA,当18-氧-皮质醇切点值为0.11 ng/mL时,敏感性73.2%,特异性95.2%;当18-羟-皮质醇切点值为1.77 ng/mL时,敏感性68.3%,特异性78.6%。结论 PA患者的多种类固醇激素前体物质及代谢产物水平显著高于EH患者,类固醇激素谱的质谱法检测对该疾病的诊断和分型具有重要作用,尤其是18-氧-皮质醇和18-羟-皮质醇在APA的识别中显示了特有的优势。

关键词: 原发性醛固酮增多症, 液相色谱-串联质谱, 类固醇激素谱, 18-氧-皮质醇, 18-羟-皮质醇

Abstract: Objective To explore the characteristics of steroid hormone spectrum in patients with primary aldoste- ronism (PA) and to evaluate the diagnostic efficacy of 18-oxocortisol and 18-hydroxycortisol. Methods Fifty-nine PA patients including 41 cases of aldosterone-producing adenoma (APA) and 18 cases of idiopathic hyperaldosteronism (IHA)and 42 essential hypertension (EH) patients as control group diagnosed in Department of Endocrinology of Peking Union Medical College Hospital from November 2020 to November 2021 were enrolled in this study. The basic information and clinical characteristics of patients were collected and 8 kinds of steroid hormones,including mineral corticoids (pregnenolone,progesterone, 11-deoxycorticosterone, corticosterone, 18-OH-corticoster-one) and aldosterone, and metabolites 18-oxocortisol as well as 18-hydroxycortisol were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The differences of steroid hormone level from different groups were compared and their diagnostic efficacy was evaluated. Results The average level of progesterone in APA group was higher than that in EH group (P＜0.05). The average level of 11-deoxycorticosterone in APA and IHA group was higher than that in EH group (both P＜0.001). The average level of 18-OH-corticosterone in APA group was higher than that in EH group (P＜0.001). The average level of aldosterone in APA and IHA group were higher than that in EH group(P＜0.01). The average level of 18-oxocortisol in APA group was higher than that in IHA group and higher than that in EH group (all P＜0.05). The average level of 18-hydroxycortisol in APA group was higher than that in EH group (P＜0.001). As for the diagnostic efficiency of 18-oxocortisol and 18-hydroxycortisol differentiating PA from EH, when the cut-off value of 18-oxocortisol was 0.06 ng/mL, the sensitivity reached 74.6% with specificity as 88.1%; when the cut-off value of 18-hydroxycortisol was 1.44 ng/mL, the sensitivity was 71.2% and the specificity was 69.0%. As for the diagnostic efficiency of 18-oxocortisol and 18-hydroxycortisol recognizing APA, when the cut-off value of 18-oxocortisol was 0.11 ng/mL, the sensitivity was 73.2% and the specificity was 95.2%; when the cut-off value of 18-hydroxycortisol was 1.77 ng/mL, the sensitivity was 68.3% and the specificity was 78.6%. Conclusions The level of various steroid hormone precursors and metabolites in PA patients is significantly higher than those in EH patients. The detection of steroid hormone profiling by LC-MS/MS plays an important role in the diagnosis and typing of PA. In particular, 18-oxocortisol and 18-hydroxycortisol show unique advantages in the recognition of APA.

Key words: primary aldosteronism, liquid chromatography-tandem mass spectrometry, steroid hormone spectrum, 18-oxocortisol, 18-hydroxycortisol

中图分类号:

R586.9

高寅洁, 谢绍伟, 刘世颖, 陆艺, 张芳, 邱玲, 童安莉. LC-MS/MS检测类固醇激素谱在诊断原发性醛固酮增多症中的应用[J]. 基础医学与临床, 2022, 42(12): 1835-1840.

GAO Yin-jie, XIE Shao-wei, LIU Shi-ying, LU Yi, ZHANG Fang, QIU Ling, TONG An-li. Application of the steroid profiling detecting by LC-MS/MS in the diagnosis of primary aldosteronism[J]. Basic & Clinical Medicine, 2022, 42(12): 1835-1840.

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LC-MS/MS检测类固醇激素谱在诊断原发性醛固酮增多症中的应用

Application of the steroid profiling detecting by LC-MS/MS in the diagnosis of primary aldosteronism

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