AUTHOR=Detomas Mario , Altieri Barbara , Deutschbein Timo , Fassnacht Martin , Dischinger Ulrich 

TITLE=Metyrapone Versus Osilodrostat in the Short-Term Therapy of Endogenous Cushing’s Syndrome: Results From a Single Center Cohort Study

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.903545

DOI=10.3389/fendo.2022.903545

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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 <italic>vs</italic> osilodrostat: 817 µg/24h; <italic>p</italic>=0.93). From T0 to T1, the decrease of UFC was less pronounced under metyrapone than osilodrostat (-21.3% <italic>vs</italic> -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 <italic>vs</italic> 6 mg) while at T3 a decrease in UFC from T0 was more pronounced in the metyrapone group (-71.5% <italic>vs</italic> -51.5%; median dose 1250 mg <italic>vs</italic> 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 <italic>vs</italic> n= -1.0).</p></sec><sec><title>Conclusion</title><p>Although both drugs show comparable therapeutic efficacy, osilodrostat seems to reduce cortisol levels and to control blood pressure faster.</p></sec>