Journal article

Publication year: 2022

Pages: 663-673

Journal: European journal of endocrinology

Volume number: 187

Issue number: 5

ISSN: 0804-4643

eISSN: 1479-683X

Open access status: Hybrid

DOI Link: https://doi.org/10.1530/EJE-22-0320

Publisher: Oxford University Press

Abstract: 
BackgroundSymptoms 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. MethodsWe 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. ResultsTreatment-naive 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 < 0.0001; 11KT P = 0.0010) and urine (11-oxo-androsterone P = 0.0011; 11-hydroxy-androsterone P < 0.0001), treatment with osilodrostat and metyrapone efficaciously blocked 11oxC19 synthesis. ConclusionHyperandrogenemia in CD is predominantly caused by excess of 11oxC19 steroids.

Harvard Citation style: Nowotny, H., Braun, L., Vogel, F., Bidlingmaier, M., Reincke, M., Tschaidse, L., et al. (2022) 11-Oxygenated C19 steroids are the predominant androgens responsible for hyperandrogenemia in Cushing's disease, European journal of endocrinology, 187(5), pp. 663-673. https://doi.org/10.1530/EJE-22-0320

APA Citation style: Nowotny, H., Braun, L., Vogel, F., Bidlingmaier, M., Reincke, M., Tschaidse, L., Auer, M., Lottspeich, C., Wudy, S., Hartmann, M., Hawley, J., Adaway, J., Keevil, B., Schilbach, K., & Reisch, N. (2022). 11-Oxygenated C19 steroids are the predominant androgens responsible for hyperandrogenemia in Cushing's disease. European journal of endocrinology. 187(5), 663-673. https://doi.org/10.1530/EJE-22-0320