Ectopic ACTH syndrome in an adult with metastatic Ewing sarcoma

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) accounts for 8-18% of Cushing syndrome cases and is typically due to neuroendocrine tumors such as small cell lung carcinoma and bronchopulmonary neuroendocrine tumors. EAS arising from Ewing sarcoma (EwS) is rare, with only 9 pediatric and 5 adult cases reported to date. We present the case of a 40-year-old woman with refractory, metastatic EwS who developed progressive swelling, fatigue, hypokalemia, profound proximal muscle weakness, and intermittent confusion over 2 months. Physical examination revealed facial plethora, supraclavicular fat pads, hirsutism, ecchymoses, and bilateral lower extremity weakness. Laboratory evaluation was consistent with severe ACTH-dependent hypercortisolism, confirmed to be secondary to EAS after further evaluation, including the radiographic finding of rapid-onset bilateral adrenal hyperplasia. She started metyrapone, an 11-β hydroxylase inhibitor, which resulted in rapid biochemical improvement and allowed for discontinuation of insulin and potassium therapies. Due to the refractory, progressive EwS and the patient's poor performance status, she transitioned to palliative care at home, continuing metyrapone for hypercortisolism management until her death 4 months later. Herein, we summarize the existing literature of EAS in EwS, emphasize the importance of prompt recognition of the condition, and highlight the therapeutic challenges of managing paraneoplastic EAS.