Acquired 11β-Hydroxylase deficiency in etomidate and (Iso)propoxate abusers: A nascent endocrine condition

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids Pub Date : 2025-05-30 DOI:10.1016/j.steroids.2025.109639

Yee-Ting Cheung , Choi-Yee Lau , Jeremiah Sik-Bit Tseung , Kelvin Yat-Chung Yu , Hoi-Ning Cheung , Chi-Chung Shek , Pak-Lam Sammy Chen , Yeow-Kuan Chong

{"title":"Acquired 11β-Hydroxylase deficiency in etomidate and (Iso)propoxate abusers: A nascent endocrine condition","authors":"Yee-Ting Cheung , Choi-Yee Lau , Jeremiah Sik-Bit Tseung , Kelvin Yat-Chung Yu , Hoi-Ning Cheung , Chi-Chung Shek , Pak-Lam Sammy Chen , Yeow-Kuan Chong","doi":"10.1016/j.steroids.2025.109639","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Etomidate, a general anaesthetic, is known to possess inhibitory activity on steroid 11β-hydroxylase at subanaesthetic concentrations. An emerging trend of abuse of etomidate as well as its analogues propoxate/isopropoxate has recently been observed. Their effects on adrenal steroidogenesis as drugs of abuse remain to be elucidated. Steroid excretion patterns of etomidate and propoxate/isopropoxate users were analysed for evidence of disrupted steroidogenesis.</div></div><div><h3>Method</h3><div>This is a retrospective, cross-sectional study. Urine steroid profiling by gas chromatography-mass spectrometry-based method was performed on spot urine specimens positive for etomidate, propoxate/isopropoxate and/or their metabolites by liquid chromatography-tandem mass spectrometry. Results were compared with routine clinical specimens with normal adult (≥ 18 years of age) urine steroid profiles, analysed between 1st January 2022 and 24th June 2024. Additional clinical and biochemical data were retrieved from the electronic patient records for review.</div></div><div><h3>Results</h3><div>Ten male and ten female adult users, aged 18 to 54 years, were included in this study. Their steroid excretion patterns were compared against 377 normal profiles. Hypokalaemia and concomitant drugs of abuse were present in the majority of cases. Psychiatric symptoms were noted in eight out of 20 cases. Multiple metabolites, including tetrahydro-11-deoxycortisol, tetrahydro-deoxycorticosterone and multiple adrenal androgen metabolites, were elevated in etomidate and propoxate/isopropoxate abusers. The pattern indicates 11β-hydroxylase inhibition.</div></div><div><h3>Conclusion</h3><div>11β-hydroxylase inhibition was demonstrated in recreational users of etomidate and/or its analogues, explaining the clinical features of hypokalaemia, and hyperandrogenism in female patients. Misuse of the compounds could be a harbinger of an increasing prevalence of acquired 11β-hydroxylase deficiency.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109639"},"PeriodicalIF":2.1000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Steroids","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0039128X25000807","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Etomidate, a general anaesthetic, is known to possess inhibitory activity on steroid 11β-hydroxylase at subanaesthetic concentrations. An emerging trend of abuse of etomidate as well as its analogues propoxate/isopropoxate has recently been observed. Their effects on adrenal steroidogenesis as drugs of abuse remain to be elucidated. Steroid excretion patterns of etomidate and propoxate/isopropoxate users were analysed for evidence of disrupted steroidogenesis.

Method

This is a retrospective, cross-sectional study. Urine steroid profiling by gas chromatography-mass spectrometry-based method was performed on spot urine specimens positive for etomidate, propoxate/isopropoxate and/or their metabolites by liquid chromatography-tandem mass spectrometry. Results were compared with routine clinical specimens with normal adult (≥ 18 years of age) urine steroid profiles, analysed between 1st January 2022 and 24th June 2024. Additional clinical and biochemical data were retrieved from the electronic patient records for review.

Results

Ten male and ten female adult users, aged 18 to 54 years, were included in this study. Their steroid excretion patterns were compared against 377 normal profiles. Hypokalaemia and concomitant drugs of abuse were present in the majority of cases. Psychiatric symptoms were noted in eight out of 20 cases. Multiple metabolites, including tetrahydro-11-deoxycortisol, tetrahydro-deoxycorticosterone and multiple adrenal androgen metabolites, were elevated in etomidate and propoxate/isopropoxate abusers. The pattern indicates 11β-hydroxylase inhibition.

Conclusion

11β-hydroxylase inhibition was demonstrated in recreational users of etomidate and/or its analogues, explaining the clinical features of hypokalaemia, and hyperandrogenism in female patients. Misuse of the compounds could be a harbinger of an increasing prevalence of acquired 11β-hydroxylase deficiency.

查看原文本刊更多论文

依托咪酯和（异）丙酸滥用者获得性11β-羟化酶缺乏症：一种新生内分泌疾病

背景：醋酸乙酯是一种全身麻醉剂，已知在亚麻醉浓度下对类固醇11β-羟化酶具有抑制活性。最近观察到一种滥用依托咪酯及其类似物丙酸/异丙酸的新趋势。它们作为滥用药物对肾上腺甾体生成的影响仍有待阐明。分析依托咪酯和丙酸酯/异丙酸酯使用者的类固醇排泄模式，以寻找类固醇生成中断的证据。方法回顾性、横断面研究。采用液相色谱-串联质谱法对依托咪酯、丙酸酯/异丙酸酯和/或其代谢物阳性的尿样进行气相色谱-质谱分析。将2022年1月1日至2024年6月24日期间的常规临床标本与正常成人（≥18岁）尿液类固醇谱进行比较。从电子病历中检索其他临床和生化数据进行审查。结果18 ~ 54岁成人用户男性10名，女性10名。将他们的类固醇排泄模式与377名正常人进行比较。在大多数病例中存在低钾血症和伴随滥用药物。20例患者中有8例出现精神症状。多种代谢物，包括四氢-11-脱氧皮质醇、四氢-脱氧皮质酮和多种肾上腺雄激素代谢物，在依托咪酯和丙酸/异丙酸滥用者中升高。该模式表明11β-羟化酶抑制。结论娱乐性使用依托咪酯和/或其类似物可抑制11β-羟化酶，这解释了女性患者低钾血症和高雄激素症的临床特征。滥用这些化合物可能是获得性11β-羟化酶缺乏症日益普遍的前兆。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Steroids 医学-内分泌学与代谢

CiteScore

5.10

自引率

3.70%

发文量

120

审稿时长

73 days

期刊介绍： STEROIDS is an international research journal devoted to studies on all chemical and biological aspects of steroidal moieties. The journal focuses on both experimental and theoretical studies on the biology, chemistry, biosynthesis, metabolism, molecular biology, physiology and pharmacology of steroids and other molecules that target or regulate steroid receptors. Manuscripts presenting clinical research related to steroids, steroid drug development, comparative endocrinology of steroid hormones, investigations on the mechanism of steroid action and steroid chemistry are all appropriate for submission for peer review. STEROIDS publishes both original research and timely reviews. For details concerning the preparation of manuscripts see Instructions to Authors, which is published in each issue of the journal.