Endocrine Abstracts

Context: Osilodrostat (Osi), a potent inhibitor of 11β-hydroxylase, blocks the conversion of 11-deoxycortisol to cortisol and improves hypercortisolism in patients with Cushing’s syndrome (CS). Here, we report a study evaluating the efficacy of Osi in five non-Cushing’s disease (CD) CS patients treated with Osi in Japan.

Subjects and Results: Five patients with non-CD CS were treated with Osi at Chiba University [primary disease breakdown: 4/5 patients with adrenal Cushing’s syndrome (cortisol-producing adenoma (CPA): 3, primary macronodular adrenal hyperplasia (PMAH): 1) and 1 with an adrenocorticotropic hormone (ACTH)-producing tumor originating from the thymus]. The mean age was 38.4 years, the male to female ratio was 1:4, and the mean duration of treatment was 3.4 months for the 3 patients who underwent CPA surgery after receiving Osi, 15 months for the patient with an ACTH-producing tumor and 18 months for the patient with PMAH. The maximum dose of Osi ranged from 4 mg/day to 10 mg/day. Three patients had been treated with metyrapone before Osi was administered. The maximum dose of metyrapone ranged from 1000 mg/day to 5000 mg/day. Osi was administered after approximately one-month wash-out period. The mean urinary free cortisol level before administration was 2162 μg/day (251-5420), which decreased markedly to a mean of 13 μg/day (8.3-20.6) after treatment, all of which were normalized. Laparoscopic surgeries were performed safely. The major adverse events were related to the Osi mechanism of action, such as adrenal insufficiency/hypofunction and fatigue, and no grade 4 adverse events were observed. The three patients with CPA were cured by surgery after preoperative Osi administration. None of the patients discontinued Osi because of safety.

Conclusion: Osi efficiently normalized symptoms and rapidly and persistently lowered urinary cortisol levels in patients with CS due to adrenal or ectopic ACTH. Our findings show that Osi is an effective treatment option and contributes to safely undergoing surgery for CPA patients.