Symptom management with osilodrostat in multiple endocrine neoplasia type 1 with a Cushing syndrome presentation

Multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare autosomal dominant disorder characterized by predisposition to a multitude of endocrine neoplasms. Cushing syndrome (CS) within MEN1 presents complex diagnostic and therapeutic challenges. We report a case of a 36-year-old male with adrenocorticotropic hormone (ACTH)-dependent Cushing disease and MEN1 syndrome with thymic and pancreatic neuroendocrine tumors. The patient presented with weight gain, weakness and proximal myopathy. Biochemical testing confirmed ACTH-dependent hypercortisolism. Imaging revealed a pituitary microadenoma, a large anterior mediastinal mass, and pancreatic lesions. Genetic analysis confirmed a pathogenic heterozygous MEN1 frameshift variant. After thymectomy, he declined further surgery. Treatment with thymectomy and octreotide long-acting release (LAR) was ineffective. Initiation of osilodrostat (titrated to 5 mg twice daily) resulted in a 76% reduction in urinary cortisol levels and a 47 kg weight loss, with significant functional improvement. Pancreatic and pituitary lesions remained stable. This is the first reported case of successful symptom management of MEN1-associated Cushing disease with osilodrostat, establishing it as an effective therapeutic option for medically complex MEN1 cases where surgery is not feasible or is declined.