Endocrine Abstracts

JOINT1977

Introduction: Osilodrostat, approved in 2020, is a second-line therapy for Cushing’s syndrome (CS) when surgery is ineffective, contraindicated, or as bridging therapy before surgery. While urinary free cortisol (UFC) is the standard for assessing treatment efficacy, prolonged processing time can limit its utility.

Objectives: Retrospective assessment of the efficacy of osilodrostat therapy in CS patients from a single reference endocrinology center by assessing the reduction of serum cortisol levels and the impact on CS complications.

Materials and Methods: We analyzed medical records of 25 CS patients treated with osilodrostat (2020-2025). Due to UFC processing delays (>7 days), response was assessed based on morning serum cortisol and clinical parameters. We evaluated time to reduce:.

- serum cortisol concentration(CR)- time to 50% cortisol reduction or achieve level <15 μg/dl.

- potassium supplementation(PS) - any reduction.

-antihypertensive(aHT) and antidiabetic therapy(aDT) - any reduction.

Results: Of 23 analyzable patients (13 CD, 10 ECS), mean diagnosis age was 57.8 years; 61% were women. Seven (30.4%) died. Mean morning serum cortisol at diagnosis: 42.7 μg/dl; ACTH: 180.3 pg/ml. Osilodrostat was first-line in 11, second-line in 10 (after metyrapone, ketoconazole, or pasireotide), and third/fourth-line in 2. Treatment was changed to osilodrostat in 7/12 cases due to incomplete clinical/biochemical remission, in 1/12 due to intolerance, and in 4/12 after short-term use of another drug as a bridge before osilodrostat. Four patients received a “block and replace” regimen, including two with cyclic CS. At osilodrostat initiation: 17 required potassium supplementation (9 needed spironolactone), 19 had diabetes (9 on insulin), 21 had hypertension. Mean treatment duration: 221.5 days (CD), 156 days (ECS). CR was achieved in 22/23 patients at a mean dose of 7.2 mg/day (5.8 mg in CD; 9.5 mg in ECS).

Key outcomes:

Discussion: Morning serum cortisol combined with clinical assessment is effective for monitoring osilodrostat treatment. In ECS, the most rapid improvement was seen in potassium supplementation reduction. Higher doses of osilodrostat were associated with faster improvements in blood pressure and glycemic control. There is the necessity of further research to optimize and personalize osilodrostat therapy.