Histopathological evidence of osilodrostat-induced regression of a cortisol-producing adrenocortical adenoma

We describe histopathological and ultrastructural evidence of osilodrostat-induced regression of a cortisol- and possibly aldosterone-producing adrenocortical adenoma. An 82-year-old woman with adrenal Cushing syndrome received preoperative osilodrostat therapy. Seventy days after starting osilodrostat, the patient developed an adrenal crisis, and the adrenal tumor obviously decreased in size. Laparoscopic adrenalectomy was performed 11 months after osilodrostat plus hydrocortisone treatment. Histological examination revealed no evident hemorrhage, necrosis, or conspicuous apoptosis. Instead, diffuse and extensive infiltration of CD163-positive histiocytes was observed, outnumbering the tumor cells. Residual neoplastic cells exhibited a global reduction in the expression of cortisol-synthesizing enzymes. Notably, focal weak CYP11B2 (aldosterone synthase) positivity was detected in the tumor, whereas adjacent nontumorous cortex showed preserved rather prominent CYP11B2 expression. Electron microscopy showed a marked loss of organelles essential for steroidogenesis. These findings suggest that osilodrostat exerts biochemical suppression of both cortisol and aldosterone secretion and modulates the morphology and function of the adrenocortical adenoma tissue.