Prospective study of metyrapone in endogenous Cushing's syndrome (PROMPT).

IF 5.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

European Journal of Endocrinology Pub Date : 2025-08-29 DOI:10.1093/ejendo/lvaf181

Lynnette K Nieman, Marco Boscaro, Carla Scaroni, Timo Deutschbein, Emese Mezôsi, Natacha Driessens, Carmen E Georgescu, Marcin Motyka, Alicja Hubalewska-Dydejczyk, Barbara Jarzab, Dominique Maiter, Martin Reincke, Paola Loli, Benedetta Zampetti, Aysegul Atmaca, Corin Badiu, Albert Beckers, Marek Bolanowski, Francesco Cavagnini, Nicole Unger, Roberta Giordano, Felicia Alexandra Hanzu, Massimo Terzolo, Myriam Bou Nader, Ninet Sinaii, Judit Tőke, Miklós Tóth

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引用次数: 0

Abstract

Objective: We evaluated the safety and efficacy of metyrapone treatment for Cushing's syndrome (CS).

Design: International, prospective, single-arm, open-label study.

Methods: Fifty adults with endogenous CS (either unsuitable for or uncontrolled after surgery) and 3 urinary free cortisol (UFC) concentrations each ≥1.5-fold the upper limit of normal (ULN) were enrolled. After 12 weeks of metyrapone titration, participants with mean 24 h UFC (mUFC) ≤ 2-fold ULN could enter a 24-week extension phase. Safety was assessed, and doses adjusted at weeks 1-5, 8, 12, and 24. Pre-defined endpoints included normalization of mUFC at weeks 12 (primary), 24, and 36, and proportion of "responders" (normalization or ≥50% decrease of baseline mUFC), time to eucortisolemia, salivary cortisol day-curve, and quality of life (QoL).

Results: Of the 49 evaluable participants, 47 completed the 12-week visit; 40 were evaluated at week 24 and 35 at week 36. The primary endpoint was met in 46.9% of participants (95% CI 32.5%-61.7%), with efficacy maintained at week 24 (52.5%; 95% CI 37.5%-67.1%) and week 36 (48.6%; 95% CI 33.0%-64.4%). The responder rates were 80.9%, 77.5%, and 71.4% at weeks 12, 24, and 36, respectively. Forty-seven participants (94%) developed mild-to-moderate adverse events (AEs), mostly during the first 12 weeks and most commonly nausea (38%), fatigue (26%), and headache (22%); 8 experienced severe AEs. Six participants developed reversible adrenal insufficiency during titration. Clinical features and QoL improved.

Conclusion: Metyrapone is a safe and effective treatment for endogenous CS.

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美替拉酮治疗内源性库欣综合征（PROMPT）的前瞻性研究。

目的：评价美吡酮治疗库欣综合征（CS）的安全性和有效性。设计：国际、前瞻性、单臂、开放标签研究。方法：入选50例内源性CS（不适合手术或术后不受控制）和3例尿游离皮质醇（UFC）浓度（每bb0为正常上限（ULN）的1.5倍）的成年人。12周后，参与者的平均24小时UFC (mUFC)（基线mUFC降低50%）、皮质醇血症时间、唾液皮质醇日曲线和生活质量（QoL）。结果：在49名可评估的参与者中，47名完成了为期12周的访问；40只在第24周接受评估，35只在第36周接受评估。46.9%的参与者达到了主要终点（95%可信区间[CI] 32.5-61.7%），疗效维持在第24周（52.5%;95% CI 37.5-67.1%）和第36周（48.6%;95% CI 33.0-64.4%）。在第12周、第24周和第36周，应答率分别为80.9%、77.5%和71.4%。47名参与者（94%）出现轻中度不良事件（ae），主要发生在前12周，最常见的是恶心（38%）、疲劳（26%）和头痛（22%）；8例发生严重ae。6名参与者在滴定期间出现可逆性肾上腺功能不全。临床特征及生活质量均有改善。结论：Metyrapone是治疗内源性CS安全有效的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Endocrinology 医学-内分泌学与代谢

CiteScore

9.80

自引率

3.40%

发文量

354

审稿时长

1 months

期刊介绍： European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica. The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology. Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials. Equal consideration is given to all manuscripts in English from any country.