Successful Treatment of Severe Ectopic ACTH-Dependent Cushing Syndrome Complicated by Hypocalcemia With Osilodrostat

Cushing syndrome due to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) is rare and may progress rapidly, making treatment very challenging. We report a 27-year-old woman with metastatic neuroendocrine tumor (NET) who presented with sudden onset and rapidly progressing fatigue, muscle weakness, and weight gain. Laboratory findings confirmed severe EAS with new onset hypocalcemia, hypokalemia, and hyperglycemia. The patient was hospitalized and initiated on high-dose osilodrostat. Cortisol levels rapidly decreased in response to osilodrostat. During treatment, she developed glucocorticoid withdrawal symptoms for which hydrocortisone treatment was started. Due to her ineligibility for bilateral adrenalectomy, bilateral adrenal arterial embolization was attempted but ultimately converted to right-only embolization due to hypertensive urgency and difficulty in catheterization. With significant improvement of cortisol levels, her hypocalcemia, hyperglycemia, and hypokalemia resolved. Her osilodrostat dose was gradually lowered during follow-up. Glucocorticoid replacement continued as part of the ongoing block-and-replace regimen.