Introduction: Endogenous Cushing's syndrome (CS) is a rare, multi-systemic condition resulting from chronic glucocorticoid excess sustained by a pituitary adenoma (Cushing's disease, CD), an adrenal adenoma or, less frequently, a neuroendocrine tumor. The optimal first-line option is surgery, but when it is contraindicated/refused, or in case of severe, life-threatening disease, medical treatment is a first-line choice. Osilodrostat (LCI699, Isturisa®) is a new, orally active adrenal steroidogenesis inhibitor currently approved by the FDA and EMA for the treatment of endogenous CS.
Areas covered: We illustrate the pharmacologic profile of osilodrostat and summarize the efficacy and safety of osilodrostat from the first phase I studies to the most recent evidence.
Expert opinion: Osilodrostat acts as a potent, reversible inhibitor of 11β-hydroxylase (CYP11B1) and 18-hydroxylase (or aldosterone synthase, CYP11B2), counteracting both gluco- and mineralocorticoid production. According to the results of the LINC1, LINC2, and LINC3 studies and the preliminary findings of LINC4, osilodrostat offers an excellent efficacy in controlling hypercortisolism with a good tolerability. The non-negligible risk of adrenal insufficiency/steroid withdrawal symptoms, hypokalemia, and hyperandrogenism disorders, and the possibility, albeit rare, of pituitary tumor enlargement, require further confirmation and careful monitoring.
Keywords: Steroidogenesis inhibitor; glucocorticoid excess; hypercortisolism; medical therapy.