Hidden in the Mediastinum: A Grade 1 Neuroendocrine Tumor Revealed by Refractory Hypokalemia and Ectopic Adrenocorticotropic Hormone (ACTH)-Dependent Cushing's Syndrome

Ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) is a rare, fulminant variant of endogenous hypercortisolism that demands rapid localization of the ACTH source to achieve a cure. A 51-year-old woman presented with progressive proximal muscle weakness, centripetal obesity, new-onset hypertension with a blood pressure of 150/90 mmHg at arrival, and persistent hypokalemia (2.2 mmol/L). Biochemical testing confirmed severe hypercortisolism that failed to suppress after an overnight 1-mg dexamethasone test. Plasma ACTH was markedly elevated (798 pg/mL), indicating ACTH-dependent disease. Pituitary MRI showed no adenoma, so an ectopic source was suspected. Contrast-enhanced thoracoabdominal CT revealed a 24 × 14-mm anterior mediastinal node, which was excised via video-assisted thoracoscopic surgery (VATS). Histopathology confirmed a grade 1 neuroendocrine tumor with diffuse positivity for synaptophysin, chromogranin A, and neuron-specific enolase. Twenty-four hours after surgery, serum cortisol decreased to 11.1 µg/dL and ACTH to 2.0 pg/mL; serum potassium normalized without supplementation. Octreotide receptor scintigraphy showed no residual or metastatic disease, and the patient remained normotensive and normokalemic at follow-up. Rapidly progressive hypercortisolism accompanied by refractory hypokalemia should prompt consideration of ectopic ACTH secretion. A stepwise diagnostic approach, including biochemical confirmation, exclusion of pituitary disease, and targeted thoracic localization, enabled early minimally invasive resection and biochemical cure in this case. Early recognition and surgery remain the cornerstones of management for ectopic ACTH-producing neuroendocrine tumors. Prompt identification and anatomical localization of the ectopic source are essential to prevent prolonged exposure to severe hypercortisolism and its associated metabolic and cardiovascular complications. Timely surgical resection allows rapid biochemical remission and improvement in short- and long-term outcomes.