{ "abstract": "Objective: By inhibiting 11β-hydroxylase, metyrapone may increase androgen precursors; however, systematic prospective data on potential correlation with treatment-emergent hirsutism are limited. We evaluated longitudinal changes in hirsutism severity, and their association with testosterone and baseline CS severity, in women with Cushing’s syndrome (CS) treated with metyrapone for 36 weeks in the PROMPT study, and reviewed the published literature.\n\nMethods: Of 34 women enrolled in PROMPT, a prospective, single-arm, open-label study, 32 with an evaluable baseline modified Ferriman-Gallwey (mFG) score were analyzed. CS severity was classified from baseline mean 24-hour urinary free cortisol (mUFC) as mild (>1.5–2-fold), moderate (>2–5-fold) or severe (>5-fold the upper limit of normal). Overall and body area-specific mFG scores were assessed at baseline and weeks 12, 24 and 36, and serum testosterone at baseline and weeks 12 and 36. Group-level changes were analyzed with linear mixed-effects models, and individual trajectories were classified using an operational ≥2-point threshold. Spearman correlation and exploratory ROC analyses examined testosterone changes in relation to mFG changes. A targeted PubMed search was done to identify the reporting of hirsutism in previous studies.\n\nResults: At baseline, 21 women (65.6%) had hirsutism (mFG ≥8), predominantly mild. Model-estimated mean mFG did not change significantly (9.41 [95% CI: 7.17–11.65] at baseline; 9.63 [7.36–11.91] at week 36), including among women with baseline hirsutism (all Holm-adjusted p≥0.696). Worsening occurred in 4/32 women (12.5%), de novo in one of them. Testosterone increased during treatment, but its changes were not significantly correlated with mFG changes at week 12 or week 36, and its ability to predict worsening could not be reliably determined. Baseline CS severity (defined by mUFC) was not associated with hirsutism severity. Across 12 published studies (384 women), relatively few cases of hirsutism were reported, although ascertainment was heterogeneous, and only three discontinuations were attributed to it.\n\nConclusions: Hirsutism was frequently observed among women with CS; however, group-level mFG scores did not significantly increase during 36 weeks of metyrapone therapy. No clear association between testosterone levels and changes in hirsutism was demonstrated in this cohort. These preliminary findings are consistent with the published literature.", "abstract_shown": true, "affiliations": [ "Department of Internal Medicine and Oncology, Semmelweis University", "Endocrinology Unit, Department of Medicine, Hospital-University", "Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg", "Medicover Oldenburg MVZ", "Department of Internal Medicine, University Medical School", "Hôpital Universitaire de Bruxelles Hôpital Erasme, Université Libre de Bruxelles", "Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy and Cluj County Emergency Hospital", "Department of Endocrinology, Oncologic Endocrinology and Nuclear Medicine, University Hospital in Krakow", "Endocrinology Department, Jagiellonian University Medical College", "Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology", "Department of Endocrinology and Nutrition, UCLouvain Hospital Saint-Luc", "Department of Medicine, Klinikum der Universität, Ludwig-Maximilians-Universität München", "Endocrinology Department, Clinica San Carlo, Paderno Dugnano", "Endocrinology Unit, Azienda Socio-Sanitaria Territoriale (ASST) Grande Ospedale Metropolitano Niguarda", "Department of Internal Medicine, Division of Endocrinology and Metabolism, Ondokuz Mayis University", "Department of Endocrinology IV, “C.I Parhon”, National Institute of Endocrinology, “D. Davila” University of Medicine and Pharmacy", "Endocrinology Department, University Hospital", "Department of Endocrinology and Internal Medicine, Medical University Wroclaw", "Endocrinology Clinic, Istituto Auxologico Italiano", "Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen", "Department of Biological and Clinical Sciences, University of Turin", "Endocrinology Department, Hospital Clinic, University of Barcelona", "Department of Clinical and Biological Sciences, Internal Medicine, San Luigi Gonzaga Hospital", "Esteve S.A.", "Biostatistics and Clinical Epidemiology Service, National Institutes of Health Clinical Center, National Institute of Health", "National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health" ], "article_type": null, "arxiv": null, "author_total": 28, "authors": [ { "affs": [ 0 ], "name": "Miklós Tóth" }, { "affs": [ 1 ], "name": "Marco Boscaro" }, { "affs": [ 1 ], "name": "Carla Scaroni" }, { "affs": [ 2, 3 ], "name": "Timo Deutschbein" }, { "affs": [ 4 ], "name": "Emese Mezôsi" }, { "affs": [ 5 ], "name": "Natacha Driessens" }, { "affs": [ 6 ], "name": "Carmen E. Georgescu" }, { "affs": [ 7 ], "name": "Marcin Motyka" }, { "affs": [ 8 ], "name": "Alicja Hubalewska-Dydejczyk" }, { "affs": [ 9 ], "name": "Barbara Jarzab" }, { "affs": [ 10 ], "name": "Dominique Maiter" }, { "affs": [ 11 ], "name": "Martin Reincke" }, { "affs": [ 12 ], "name": "Paola Loli" }, { "affs": [ 13 ], "name": "Benedetta Zampetti" }, { "affs": [ 14 ], "name": "Aysegul Atmaca" }, { "affs": [ 15 ], "name": "Corin Badiu" }, { "affs": [ 16 ], "name": "Albert Beckers" }, { "affs": [ 17 ], "name": "Marek Bolanowski" }, { "affs": [ 18 ], "name": "Francesco Cavagnini" }, { "affs": [ 19 ], "name": "Nicole Unger" }, { "affs": [ 20 ], "name": "Roberta Giordano" }, { "affs": [ 21 ], "name": "Felicia Alexandra Hanzu" }, { "affs": [ 22 ], "name": "Massimo Terzolo" }, { "affs": [ 23 ], "name": "Myriam Bou Nader" }, { "affs": [ 23 ], "name": "Arnau Domenech" }, { "affs": [ 24 ], "name": "Ninet Sinaii" }, { "affs": [ 0 ], "name": "Judit Toöke" }, { "affs": [ 25 ], "name": "Lynnette K. Nieman" } ], "bibtex": "https://research.draconitic.com/paper/6w3cky9rqvwye.bib", "cited_by": 0, "doi": "10.3389/fendo.2026.1928037", "fulltext_url": null, "id": "6w3cky9rqvwye", "issns": [ "1664-2392" ], "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1928037/full", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [], "openalex": null, "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-11-05", "publisher": "Frontiers Media SA", "ris": "https://research.draconitic.com/paper/6w3cky9rqvwye.ris", "sources": [ { "first_seen": "2026-11-05T12:21:29Z", "native_id": "10.3389/fendo.2026.1928037", "source": "crossref", "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1928037/full" } ], "subjects": [ { "field": "medicine", "origin": "issn:1664-2392", "subfield": "endocrinology-metabolism" } ], "title": "Hirsutism in Cushing’s syndrome: prospective evidence from the PROMPT study and available literature", "title_text": "Hirsutism in Cushing’s syndrome: prospective evidence from the PROMPT study and available literature", "type": "peer-reviewed", "updated_at": "2026-11-07T00:21:25Z", "url": "https://research.draconitic.com/paper/6w3cky9rqvwye", "venue": "Frontiers in Endocrinology", "versions": [] }