Ectopic Cushing Syndrome due to Metastatic Medullary Thyroid Cancer

Background/Objective: Cushing syndrome (CS) is a life-threatening condition that occurs due to hypercortisolism. The most common cause of endogenous CS is adrenocorticotropic hormone (ACTH)-dependent CS caused by a pituitary adenoma (Cushing disease). Ectopic production of ACTH from tumors elsewhere in the body is rare and is most often associated with small cell lung cancer. This report describes a patient with ACTH-dependent CS secondary to metastatic medullary thyroid cancer (MTC), a rare cause of ectopic CS. Case Report: A 52-year-old man presented with progressive diarrhea, fatigue, muscle weakness, and hypokalemia. Initial investigations revealed metabolic alkalosis, elevated urinary potassium excretion, and fasting hyperglycemia. Evaluations confirmed ACTH-dependent hypercortisolism with elevated serum ACTH and urinary free cortisol levels. Imaging and fine needle aspiration confirmed MTC with metastatic lymph node involvement, supported by elevated serum calcitonin and carcinoembryonic antigen levels. Surgical intervention revealed extensive tumor invasion but was complicated by vascular injuries, resulting in postoperative hypoxic brain injury and fatality. Discussion: This case highlights the importance of early recognition and investigation of unexplained ACTH-dependent hypercortisolism. Delayed diagnosis complicates management, increases morbidity, and worsens outcomes. A systematic diagnostic approach-including biochemical markers, imaging, and cytology-is crucial in identifying rare causes of hypercortisolism. Conclusion: Early evaluation of persistent hypokalemia and hypercortisolism is essential to prevent delayed diagnosis of CS. This case highlights MTC as a rare source of ectopic ACTH secretion. (c) 2025 American Association of Clinical Endocrinologists. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).