{"title":"库欣病患者从美替拉酮转为奥西洛他后的血液类固醇激素谱和临床结果","authors":"Kei Yokozeki, Hiraku Kameda, Aika Miya, Shigeki Jin, Kotaro Matoba, Akinobu Nakamura, Tatsuya Atsumi","doi":"10.1507/endocrj.EJ25-0089","DOIUrl":null,"url":null,"abstract":"<p><p>Steroidogenesis inhibitors such as metyrapone and osilodrostat, target 11β-hydroxylase to inhibit cortisol synthesis, are used in inoperable or recurrent Cushing disease. While osilodrostat has been reported to be more effective at lower doses than metyrapone, there are only a few reports describing the difference between osilodrostat and metyrapone in clinical practice. In this study, we evaluated the changes in steroid hormone profiles and clinical outcomes in seven Cushing disease patients switched from metyrapone to osilodrostat after incomplete remission post-transsphenoidal sinus surgery. Three of the seven patients were using trilostane, which was discontinued at the same time as metyrapone. Steroid hormone concentrations, including cortisol, progesterone (Prog), pregnenolone (Preg), deoxycorticosterone, corticosterone, 17-hydroxyprogesterone (17Prog), 17-hydroxypregnenolone (17Preg), and 11-deoxycortisol, were measured using high-performance liquid chromatography-mass spectrometry. No adverse events occurred after switching to osilodrostat. Potassium and ACTH levels increased significantly, and dehydroepiandrosterone sulfate and testosterone levels decreased significantly. Cortisol levels did not change significantly, whereas the ratios reflecting CYP17A1 activity (17Preg/Preg and 17Prog/Prog) decreased significantly, suggesting superior inhibition of CYP17A1 with osilodrostat. Clinical improvements included reduced antihypertensive medication requirements, decreased masculinization, and resolved gastric discomfort. Different inhibition patterns of the steroid synthetic enzymes may explain the observed clinical outcomes between these drugs. These data suggest that in patients with Cushing disease receiving metyrapone, switching to osilodrostat may benefit cases with inadequate disease control and complications including hypertension, manifestation of masculinization, and gastric discomfort.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":" ","pages":""},"PeriodicalIF":2.1000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Blood steroid hormone profile and clinical outcomes following switching from metyrapone to osilodrostat in patients with Cushing disease.\",\"authors\":\"Kei Yokozeki, Hiraku Kameda, Aika Miya, Shigeki Jin, Kotaro Matoba, Akinobu Nakamura, Tatsuya Atsumi\",\"doi\":\"10.1507/endocrj.EJ25-0089\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Steroidogenesis inhibitors such as metyrapone and osilodrostat, target 11β-hydroxylase to inhibit cortisol synthesis, are used in inoperable or recurrent Cushing disease. While osilodrostat has been reported to be more effective at lower doses than metyrapone, there are only a few reports describing the difference between osilodrostat and metyrapone in clinical practice. In this study, we evaluated the changes in steroid hormone profiles and clinical outcomes in seven Cushing disease patients switched from metyrapone to osilodrostat after incomplete remission post-transsphenoidal sinus surgery. Three of the seven patients were using trilostane, which was discontinued at the same time as metyrapone. Steroid hormone concentrations, including cortisol, progesterone (Prog), pregnenolone (Preg), deoxycorticosterone, corticosterone, 17-hydroxyprogesterone (17Prog), 17-hydroxypregnenolone (17Preg), and 11-deoxycortisol, were measured using high-performance liquid chromatography-mass spectrometry. No adverse events occurred after switching to osilodrostat. Potassium and ACTH levels increased significantly, and dehydroepiandrosterone sulfate and testosterone levels decreased significantly. Cortisol levels did not change significantly, whereas the ratios reflecting CYP17A1 activity (17Preg/Preg and 17Prog/Prog) decreased significantly, suggesting superior inhibition of CYP17A1 with osilodrostat. Clinical improvements included reduced antihypertensive medication requirements, decreased masculinization, and resolved gastric discomfort. Different inhibition patterns of the steroid synthetic enzymes may explain the observed clinical outcomes between these drugs. These data suggest that in patients with Cushing disease receiving metyrapone, switching to osilodrostat may benefit cases with inadequate disease control and complications including hypertension, manifestation of masculinization, and gastric discomfort.</p>\",\"PeriodicalId\":11631,\"journal\":{\"name\":\"Endocrine journal\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrine journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1507/endocrj.EJ25-0089\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1507/endocrj.EJ25-0089","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Blood steroid hormone profile and clinical outcomes following switching from metyrapone to osilodrostat in patients with Cushing disease.
Steroidogenesis inhibitors such as metyrapone and osilodrostat, target 11β-hydroxylase to inhibit cortisol synthesis, are used in inoperable or recurrent Cushing disease. While osilodrostat has been reported to be more effective at lower doses than metyrapone, there are only a few reports describing the difference between osilodrostat and metyrapone in clinical practice. In this study, we evaluated the changes in steroid hormone profiles and clinical outcomes in seven Cushing disease patients switched from metyrapone to osilodrostat after incomplete remission post-transsphenoidal sinus surgery. Three of the seven patients were using trilostane, which was discontinued at the same time as metyrapone. Steroid hormone concentrations, including cortisol, progesterone (Prog), pregnenolone (Preg), deoxycorticosterone, corticosterone, 17-hydroxyprogesterone (17Prog), 17-hydroxypregnenolone (17Preg), and 11-deoxycortisol, were measured using high-performance liquid chromatography-mass spectrometry. No adverse events occurred after switching to osilodrostat. Potassium and ACTH levels increased significantly, and dehydroepiandrosterone sulfate and testosterone levels decreased significantly. Cortisol levels did not change significantly, whereas the ratios reflecting CYP17A1 activity (17Preg/Preg and 17Prog/Prog) decreased significantly, suggesting superior inhibition of CYP17A1 with osilodrostat. Clinical improvements included reduced antihypertensive medication requirements, decreased masculinization, and resolved gastric discomfort. Different inhibition patterns of the steroid synthetic enzymes may explain the observed clinical outcomes between these drugs. These data suggest that in patients with Cushing disease receiving metyrapone, switching to osilodrostat may benefit cases with inadequate disease control and complications including hypertension, manifestation of masculinization, and gastric discomfort.
期刊介绍:
Endocrine Journal is an open access, peer-reviewed online journal with a long history. This journal publishes peer-reviewed research articles in multifaceted fields of basic, translational and clinical endocrinology. Endocrine Journal provides a chance to exchange your ideas, concepts and scientific observations in any area of recent endocrinology. Manuscripts may be submitted as Original Articles, Notes, Rapid Communications or Review Articles. We have a rapid reviewing and editorial decision system and pay a special attention to our quick, truly scientific and frequently-citable publication. Please go through the link for author guideline.