7003 Comparative Study Of The Properties And Differences Of Steroidogenesis Inhibitors In Vitro

Abstract Disclosure: Y. Taki: None. T. Kono: None. S. Kono: None. N. Hashimoto: None. H. Nagano: None. T. Tanaka: None. Objective: Osilodrostat (Osi) is utilized as an inhibitor of cortisol (F) synthesis and is a potent inhibitor of CYP11B2, in addition to CYP11B1. Therefore, we investigated the aldosterone (Ald) and cortisol concentration-dependent inhibitory effects of Osi in vitro, using tissues from 9 cases [5 Aldosterone-producing adenoma (APA) and 4 Cortisol-producing adenoma (CPA)] operated at our institution. Methods: Adrenal tumor surgery specimens were treated with collagenase and cultured on plates. After 3 days, the medium was changed and incubated with osilodrostat or metyrapone (0.0001 to 10 µM). After another 3 days, the medium was collected, and Ald/F concentrations were measured. The IC50 of both drugs for Ald/F were then compared. Results: In APA cases, Osi inhibited at significantly lower concentrations (IC50: 0.003 µM) than Met (0.782 µM; p=0.0159) for Ald; in CPA cases, Osi inhibited with similar potency to Met (IC50: 0.061 µM vs 0.466 µM, p=0.2286) for F. In all cases, Osi inhibited at significantly lower concentrations for Ald than F (IC50: 0.003 µM vs 0.028 µM, p=0.0008). Discussion: Osi is a potent inhibitor of Ald and F production, and its use for PA alone is challenging because clinical trials of Osi for PA were terminated due to concerns about adrenal insufficiency. Therefore, we suggest that Osi may be useful in PA-associated CPA patients for whom surgery is not indicated or as a preoperative drug therapy. Presentation: 6/1/2024