Sustained shrinkage of bilateral adrenal adenomas during long-term osilodrostat therapy

Introduction Surgery remains the first-line therapy for all forms of Cushing syndrome; medical therapy may be appropriate when surgery is not feasible or as adjunctive therapy in severe hypercortisolism. Case presentation A 70-year-old woman was hospitalized for hemorrhagic shock due to massive abdominal bleeding. Abdominal CT scan detected bilateral adrenal masses. Hormonal evaluation revealed ACTH-independent hypercortisolism. Given her frail condition, medical treatment was started while surgery was deferred. Metyrapone and ketoconazole were discontinued for inefficacy or hepatotoxicity. Osilodrostat was initiated and progressively titrated up to 6 mg/day, achieving sustained clinical and biochemical control of hypercortisolism at a maintenance dose of 1 mg/day. Adrenal masses began to shrink after 18 months of treatment, with progressive reduction through the 54-month follow-up. The patient developed adrenal insufficiency (AI), requiring osilodrostat discontinuation and glucocorticoid replacement. Conclusions Osilodrostat showed marked clinical and biochemical efficacy. This case suggests that osilodrostat may contribute to adrenal mass reduction, warranting further investigation.