Objective:

To evaluate dosing patterns, effectiveness, and safety of osilodrostat in patients with ACTH-dependent Cushing’s syndrome.

Approach:

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Key Findings:

• Osilodrostat was first-line therapy in 12 of 26 patients.
• A titration regimen was used in 21 patients, and a block-and-replace approach in five.
• A therapeutic effect was achieved in 92% of patients at a median dose of 5 mg/day within 14 days.
• Morning cortisol normalized in 92% of cases and urinary free cortisol in 75%.
• Median clinical score decreased from 9 to 4, and muscle strength increased from 50% to 75% of normal.
• Systolic/diastolic blood pressure decreased from 142/87 to 124/70 mmHg.
• Adverse events were mild to moderate, including fatigue and nausea (34.6% each), adrenal insufficiency (30.8%), and dizziness (23.1%).

Interpretation:

Osilodrostat provided biochemical control and clinical improvement in ACTH-dependent Cushing’s syndrome with a manageable safety profile.

Limitations:

• Small sample size of 26 patients.
• Retrospective nature may limit the generalizability of findings.
• Exclusion of patients treated in clinical trials may affect the results.

Conclusion:

Osilodrostat demonstrates effective dosing and safety in real-world settings for ACTH-dependent Cushing’s syndrome.