{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:36:04Z","timestamp":1787686564909,"version":"build-2784847793"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T00:00:00Z","timestamp":1673136000000},"content-version":"vor","delay-in-days":101,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Symptoms of hyperandrogenism are common in patients with Cushing's disease (CD), yet they are not sufficiently explained by androgen concentrations. In this study, we analyzed the contribution of 11-oxygenated C19 steroids (11oxC19) to hyperandrogenemia in female patients with CD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed saliva day profiles in females with CD pre (n = 23) and post (n = 13) successful transsphenoidal surgery, 26 female controls, 5 females with CD treated with metyrapone and 5 treated with osilodrostat for cortisol, cortisone, androstenedione (A4), 11-hydroxyandrostenedione (11OHA4), testosterone (TS), 11-ketotestosterone (11KT), as well as metabolites of classic and 11-oxygenated androgens in 24-h urine. In addition, morning baseline levels of gonadotropins and estradiol, sex hormone-binding globulin, cortisol and dehydroepiandrosterone sulfate (DHEAS) in serum and adrenocorticotrophic hormone in plasma in patients and controls were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment-na\u00efve females with CD showed a significantly elevated area under the curve of 11OHA4 and 11KT in saliva throughout the day compared to controls (11OHA4 mean rank difference (mrd) 18.13, P = 0.0002; 11KT mrd 17.42; P = 0.0005), whereas A4, TS and DHEAS were comparable to controls. Gonadotropin concentrations were normal in all patients with CD. After transsphenoidal surgery, 11oxC19 and their metabolites dropped significantly in saliva (11OHA4 P &amp;lt; 0.0001; 11KT P = 0.0010) and urine (11-oxo-androsterone P = 0.0011; 11-hydroxy-androsterone P &amp;lt; 0.0001), treatment with osilodrostat and metyrapone efficaciously blocked 11oxC19 synthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hyperandrogenemia in CD is predominantly caused by excess of 11oxC19 steroids.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eje-22-0320","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T14:54:00Z","timestamp":1662648840000},"page":"663-673","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":30,"title":["11-Oxygenated C19 steroids are the predominant androgens responsible for hyperandrogenemia in Cushing's disease"],"prefix":"10.1093","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3791-9929","authenticated-orcid":false,"given":"Hanna F","family":"Nowotny","sequence":"first","affiliation":[{"name":"Medizinische Klinik and Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen , Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Braun","sequence":"additional","affiliation":[{"name":"Medizinische Klinik and Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen , Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8821-8968","authenticated-orcid":false,"given":"Frederick","family":"Vogel","sequence":"additional","affiliation":[{"name":"Medizinische Klinik and Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen , Munich, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-8332","authenticated-orcid":false,"given":"Matthias K","family":"Auer","sequence":"additional","affiliation":[{"name":"Medizinische Klinik and Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen , Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lottspeich","sequence":"additional","affiliation":[{"name":"Medizinische Klinik and Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, LMU M\u00fcnchen , Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan A","family":"Wudy","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology & Diabetology, Laboratory for Translational Hormone Analysis in Pediatric Endocrinology, Steroid Research & Mass Spectrometry Unit, Center of Child and Adolescent Medicine, Justus-Liebig-University , Giessen, 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