6372 Changes in Blood Steroid Hormone Profile after Switching from Metyrapone to Osilodrostat

Abstract Disclosure: K. Yokozeki: None. H. Kameda: None. A. Miya: None. H. Nomoto: None. A. Nakamura: None. S. Jin: None. K. Matoba: None. T. Atsumi: None. Background: The new steroidogenesis inhibitor osilodrostat has recently been approved for use in Cushing's syndrome. However, there are limited studies on changes in blood steroid hormone profiles after switching from existing drugs including metyrapone. Purpose: To study the changes in steroid hormone profiles with switching from metyrapone to osilodrostat in patients with Cushing's disease and to examine the differences in clinical efficacy. Case 1: A woman in her 40s underwent transsphenoidal pituitary tumor surgery (TSS) for Cushing's disease in X-12, but was not in remission and was treated with 1000 mg/day of metyrapone and oral hydrocortisone. In X-3, the patient complained of masculinization and was started pasireotide LAR 10 mg per month, which was subsequently increased to 30 mg. Despite the addition of 240 mg/day of trilostane in X-2, the patient did not show improvement. Switched the steroidogenesis inhibitors to osilodrostat 4 mg/day in year X, blood cortisol and testosterone levels decreased and the symptoms of virilization disappeared.Case 2: A woman in her 40s experienced edema in her face and limbs, increased appetite and weight gain since Y-13. After endocrinological examination, she was diagnosed with Cushing's disease. TSS was performed and she was in remission. However, she suffered a relapse in Y-4 and was started on metyrapone, which was titrated up to 4,000 mg/day. Due to gastric discomfort, metyrapone was switched to osilodrostat 52 mg/day in year Y, leading to an improvement of her gastric symptoms and stabilized blood cortisol level. Case 3: A woman in her 70s underwent TSS for Cushing's disease in Z-6, but the tumor remained and she was prescribed metyrapone 1,500 mg/day. The disease was stable and complications were under control with metyrapone. In Z-1, the patient developed elevated blood pressure and worsening leg edema, and metyrapone was switched to osilodrostat 3 mg/day in year Z, resulting decreased blood cortisol level and blood pressure. Results: Liquid chromatograph mass spectrometry (LC-MS) analysis of blood steroid hormone profiles in above three cases demonstrated a decrease in 17-OH pregnenolone, 17-OH progesterone, and 11-deoxycorticosterone after switching the steroidogenesis inhibitors. Discussion and Conclusion: It has been noted that osilodrostat lowers serum cortisol in a shorter period of time compared to metyrapone and may also decrease the number of antihypertensive medications used. Under metyrapone administration, hypertrichosis, hypertension, and hypokalemia are often observed with increased mineralocorticoid precursors, but osilodrostat may have a different clinical effect as a result of its different pattern of steroid hormone synthase inhibition. Presentation: 6/2/2024