Hirsutism in Cushing’s syndrome: prospective evidence from the PROMPT study and available literature
26 affiliations
- 1Department of Internal Medicine and Oncology, Semmelweis University
- 2Endocrinology Unit, Department of Medicine, Hospital-University
- 3Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg
- 4Medicover Oldenburg MVZ
- 5Department of Internal Medicine, University Medical School
- 6Hôpital Universitaire de Bruxelles Hôpital Erasme, Université Libre de Bruxelles
- 7Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy and Cluj County Emergency Hospital
- 8Department of Endocrinology, Oncologic Endocrinology and Nuclear Medicine, University Hospital in Krakow
- 9Endocrinology Department, Jagiellonian University Medical College
- 10Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology
- 11Department of Endocrinology and Nutrition, UCLouvain Hospital Saint-Luc
- 12Department of Medicine, Klinikum der Universität, Ludwig-Maximilians-Universität München
- 13Endocrinology Department, Clinica San Carlo, Paderno Dugnano
- 14Endocrinology Unit, Azienda Socio-Sanitaria Territoriale (ASST) Grande Ospedale Metropolitano Niguarda
- 15Department of Internal Medicine, Division of Endocrinology and Metabolism, Ondokuz Mayis University
- 16Department of Endocrinology IV, “C.I Parhon”, National Institute of Endocrinology, “D. Davila” University of Medicine and Pharmacy
- 17Endocrinology Department, University Hospital
- 18Department of Endocrinology and Internal Medicine, Medical University Wroclaw
- 19Endocrinology Clinic, Istituto Auxologico Italiano
- 20Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen
- 21Department of Biological and Clinical Sciences, University of Turin
- 22Endocrinology Department, Hospital Clinic, University of Barcelona
- 23Department of Clinical and Biological Sciences, Internal Medicine, San Luigi Gonzaga Hospital
- 24Esteve S.A.
- 25Biostatistics and Clinical Epidemiology Service, National Institutes of Health Clinical Center, National Institute of Health
- 26National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
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.
Methods: 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.
Results: 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.
Conclusions: 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.
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BibTeX
@article{toth2026hirsutism,
title = {{Hirsutism in Cushing’s syndrome: prospective evidence from the PROMPT study and available literature}},
author = {Miklós Tóth and Marco Boscaro and Carla Scaroni and Timo Deutschbein and Emese Mezôsi and Natacha Driessens and Carmen E. Georgescu and Marcin Motyka and Alicja Hubalewska-Dydejczyk and Barbara Jarzab and Dominique Maiter and Martin Reincke and Paola Loli and Benedetta Zampetti and Aysegul Atmaca and Corin Badiu and Albert Beckers and Marek Bolanowski and Francesco Cavagnini and Nicole Unger and Roberta Giordano and Felicia Alexandra Hanzu and Massimo Terzolo and Myriam Bou Nader and Arnau Domenech and Ninet Sinaii and Judit Toöke and Lynnette K. Nieman},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.1928037},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1928037/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hirsutism in Cushing’s syndrome: prospective evidence from the PROMPT study and available literature
AU - Miklós Tóth
AU - Marco Boscaro
AU - Carla Scaroni
AU - Timo Deutschbein
AU - Emese Mezôsi
AU - Natacha Driessens
AU - Carmen E. Georgescu
AU - Marcin Motyka
AU - Alicja Hubalewska-Dydejczyk
AU - Barbara Jarzab
AU - Dominique Maiter
AU - Martin Reincke
AU - Paola Loli
AU - Benedetta Zampetti
AU - Aysegul Atmaca
AU - Corin Badiu
AU - Albert Beckers
AU - Marek Bolanowski
AU - Francesco Cavagnini
AU - Nicole Unger
AU - Roberta Giordano
AU - Felicia Alexandra Hanzu
AU - Massimo Terzolo
AU - Myriam Bou Nader
AU - Arnau Domenech
AU - Ninet Sinaii
AU - Judit Toöke
AU - Lynnette K. Nieman
PY - 2026
DA - 2026/11/05
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1928037
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1928037/full
AB - 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. Methods: 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. Results: 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. Conclusions: 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.
SN - 1664-2392
ER -