@article{DetomasAltieriDeutschbeinetal.2022,
  author    = {Detomas, Mario and Altieri, Barbara and Deutschbein, Timo and Fassnacht, Martin and Dischinger, Ulrich},
  title     = {Metyrapone versus osilodrostat in the short-term therapy of endogenous Cushing's syndrome: results from a single center cohort study},
  series = {Frontiers in Endocrinology},
  volume    = {13},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2022.903545},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277477},
  year      = {2022},
  abstract  = {Background Although surgery is considered the first-line treatment for patients with endogenous Cushing's syndrome (CS), medical therapy is often required to control severe hypercortisolism. Metyrapone and osilodrostat are both steroidogenic inhibitors targeting the 11β-hydroxylase, however, their therapeutic effectiveness has not yet been directly compared. This study aimed to evaluate metyrapone and osilodrostat in the short-term therapy of CS. Methods Retrospective analysis of patients with endogenous CS treated with metyrapone or osilodrostat as monotherapy for at least 4 weeks. Main outcome measures were serum cortisol and 24h urinary free cortisol (UFC) at baseline (T0) and after 2 (T1), 4 (T2), and 12 weeks (T3) of therapy. Results 16 patients with endogenous CS were identified (pituitary n=7, adrenal n=4, ectopic CS n=5). Each 8 patients were treated with metyrapone and osilodrostat. Despite heterogeneity, both groups showed comparable mean UFC levels at T0 (metyrapone: 758 µg/24h vs osilodrostat: 817 µg/24h; p=0.93). From T0 to T1, the decrease of UFC was less pronounced under metyrapone than osilodrostat (-21.3\% vs -68.4\%; median daily drug dose: 1000 mg vs 4 mg). This tendency persisted at T2 (-37.3\% vs -50.1\%; median drug dose: 1250 mg vs 6 mg) while at T3 a decrease in UFC from T0 was more pronounced in the metyrapone group (-71.5\% vs -51.5\%; median dose 1250 mg vs 7 mg). Under osilodrostat, a QTc-interval prolongation was identified at T3 (mean 432 ms vs 455 ms). From T0 to T2, the number of antihypertensive drugs remained comparable under metyrapone and decreased under osilodrostat (n= -0.3 vs n= -1.0). Conclusion Although both drugs show comparable therapeutic efficacy, osilodrostat seems to reduce cortisol levels and to control blood pressure faster.},
  language  = {en}
}