Ectopic ACTH Syndrome

Ectopic ACTH syndrome (EAS) is a rare cause of Cushing’s syndrome (CS) that can be challenging to diagnose and manage, particularly in cases of severe, life-threatening hypercortisolism. Distinguishing clinical features are rapid onset, predominant catabolic signs and symptoms, and severe hypokalemia. Definitive diagnosis is established biochemically by high levels of ACTH and cortisol, and dynamic testing that might include high-dose dexamethasone suppression combined with CRH stimulation. CT, PET/CT, and/or somatostatin-based nuclear imaging is utilized to localize the source of ectopic ACTH secretion, but in some cases no definitive tumors are uncovered. Management of the sequelae of severe hypercortisolism needs to be swift, as it is an endocrine emergency, and can lead to severe hypertension, heart failure, hypokalemia, thromboembolism, gastrointestinal hemorrhage, hyperglycemia, infection, and altered mental status. Medical therapies to lower cortisol levels or action rapidly include etomidate, metyrapone, ketoconazole, and mifepristone. If the primary tumor is found, it should be surgically resected. However, if the primary tumor eludes detection, bilateral adrenalectomy may be necessary. Depending on the type of surgery, glucocorticoid and/or mineralocorticoid therapy will be required postoperatively. Patients with known primary tumors that are addressed promptly have successful outcomes.