Prolonged Adrenal Insufficiency After Osilodrostat Exposure With Eventual Recovery of Adrenal Function

Osilodrostat is an 11β-hydroxylase inhibitor used in the treatment of adult patients with Cushing disease. Prolonged adrenal insufficiency (AI) after osilodrostat use is a rare but significant adverse effect. We present the case of a 41-year-old woman treated with osilodrostat for persistent hypercortisolism following pituitary surgery and Gamma Knife radiosurgery. After 11 months of osilodrostat therapy, she reported AI symptoms, and biochemical testing revealed low serum cortisol following cosyntropin stimulation as well as high plasma adrenocorticotropic hormone (ACTH). The patient was started on physiologic replacement dose of hydrocortisone, which was discontinued 23 months after last osilodrostat exposure when laboratory testing revealed recovery of endogenous cortisol production. The mechanism responsible for the prolonged AI noted with osilodrostat use is unclear and unexpected, given the short half-life of the drug. Although prolonged AI after osilodrostat use is not well understood, providers should be aware of this potential adverse effect and have a low threshold to test for AI in patients reporting AI-related symptoms.