{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:28:46Z","timestamp":1793917726719,"version":"4.8.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"HRA Pharma","id":[{"id":"https:\/\/ror.org\/059jy0w68","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017521","name":"ESTEVE","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017521","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We evaluated the safety and efficacy of metyrapone treatment for Cushing's syndrome (CS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>International, prospective, single-arm, open-label study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fifty adults with endogenous CS (either unsuitable for or uncontrolled after surgery) and 3 urinary free cortisol (UFC) concentrations each \u22651.5-fold the upper limit of normal (ULN) were enrolled. After 12 weeks of metyrapone titration, participants with mean 24\u2005h UFC (mUFC) \u2264 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 \u201cresponders\u201d (normalization or \u226550% decrease of baseline mUFC), time to eucortisolemia, salivary cortisol day-curve, and quality of life (QoL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Metyrapone is a safe and effective treatment for endogenous CS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf181","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T12:03:59Z","timestamp":1757592239000},"page":"391-402","source":"Crossref","is-referenced-by-count":14,"title":["Prospective study of metyrapone in endogenous Cushing's syndrome (PROMPT)"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0534-8025","authenticated-orcid":false,"given":"Lynnette K","family":"Nieman","sequence":"first","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Building 10, CRC, 1 East, Rm 1-3140, 10 Center Dr, MSC 1109, Bethesda, MD 20892-1109 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Oldenburg MVZ , Oldenburg, 26122 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emese","family":"Mez\u00f4si","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Medical School , Pecs, 7624 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5992-2486","authenticated-orcid":false,"given":"Natacha","family":"Driessens","sequence":"additional","affiliation":[{"name":"H\u00f4pital Universitaire de Bruxelles H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles , Brussels, 1070 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen E","family":"Georgescu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy and Cluj Country Emergency Hospital , Cluj-Napoca, 400012 ,","place":["Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Motyka","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Oncologic Endocrinology and Nuclear Medicine, University Hospital in Krakow , Krakow, 30-688 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Hubalewska-Dydejczyk","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Jagiellonian University Medical College , Krakow, 30-688 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Jarzab","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch , Gliwice, 44-102 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-637X","authenticated-orcid":false,"given":"Dominique","family":"Maiter","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, UCLouvain Hospital Saint-Luc , Brussels, 1200 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-9875","authenticated-orcid":false,"given":"Martin","family":"Reincke","sequence":"additional","affiliation":[{"name":"Department of Medicine 4, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen , Munich, 80336 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Loli","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Clinica San Carlo , Paderno Dugnano, Milan, 20037 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Zampetti","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, ASST Grande Ospedale Metropolitano Niguarda , Milan, 20162 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysegul","family":"Atmaca","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology and Metabolism, Ondokuz Mayis University , Samsun, 55200 ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8087-8125","authenticated-orcid":false,"given":"Corin","family":"Badiu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology IV, \u201cC.I Parhon\u201d, National Institute of Endocrinology, \"D. Davila\" University of Medicine and Pharmacy , Bucharest, 011863 ,","place":["Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Beckers","sequence":"additional","affiliation":[{"name":"Endocrinology Department, University Hospital , Liege, 4000 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Bolanowski","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine, Medical University Wroclaw , Wroclaw, 50-367 ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cavagnini","sequence":"additional","affiliation":[{"name":"Endocrinology Clinic, Istituto Auxologico Italiano , Milan, 20100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Unger","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen , Essen, 45127 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8713-3532","authenticated-orcid":false,"given":"Roberta","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Biological and Clinical Sciences, University of Turin , Turin,10100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-4023","authenticated-orcid":false,"given":"Felicia Alexandra","family":"Hanzu","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Hospital Clinic, University of Barcelona , Barcelona, 080336 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Terzolo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Internal Medicine, San Luigi Gonzaga Hospital , Orbassano, 10043 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,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology, Semmelweis University , Budapest, H-1083 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"issue":"1","key":"2026091613263738400_lvaf181-B1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41572-024-00588-w","article-title":"Cushing syndrome","volume":"11","author":"Nieman","year":"2025","journal-title":"Nat Rev Dis Primers"},{"issue":"9996","key":"2026091613263738400_lvaf181-B2","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/S0140-6736(14)61375-1","article-title":"Cushing's 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