Case Report: Long-lasting adrenal insufficiency following successful osilodrostat therapy with subsequent recurrence of Cushing’s syndrome

Osilodrostat is an effective steroidogenesis inhibitor used in the treatment of Cushing’s syndrome (CS). One of the clinically significant adverse events associated with this therapy is adrenal insufficiency (AI). Here, we report a patient with CS who developed delayed-onset AI during osilodrostat therapy, that persisted for four years despite drug discontinuation and was followed by recurrence of hypercortisolism. A 52-year-old female was admitted with suspicion of CS. Diagnostic evaluation suggested pituitary CS. Ketoconazole was initiated as a preoperative treatment, however, transsphenoidal surgery (TSS) proved non-radical. The patient declined reoperation, and was therefore treated with metyrapone within a clinical trial (NCT02297945), followed by transition to osilodrostat after the trial’s completion. After two years of successful treatment with a stable dose of osilodrostat the patient developed AI. The drug was discontinued, however AI persisted for the next 4 years. The symptoms suggestive of CS recurred, which led to another TSS, that resulted in remission. After 10 months of remission, hypercortisolism recurred again. This case highlights the need for careful long-term monitoring in patients receiving adrenostatic therapy. It is particularly notable for delayed onset of AI, despite long-term treatment with a stable, relatively low dose of osilodrostat. The prolonged persistence of AI and the subsequent late recurrence of hypercortisolism further distinguish this case from previously reported cases. Overall, this case underscores the need for continued clinical vigilance during long-term osilodrostat treatment.