First case report of ectopic Cushing's syndrome secondary to synchronous mediastinal neuroendocrine tumors

Background: Ectopic Cushing's syndrome (ECS) is a rare cause of hypercortisolism resulting from non-pituitary adrenocorticotropic hormone (ACTH) secretion, most associated with neuroendocrine tumors (NETs) of pulmonary or gastrointestinal origin. Mediastinal NETs are an extremely rare source. Case Presentation: We report the case of a 23-year-old male with no relevant medical history, presenting with progressive muscle weakness, hyperpigmentation, weight gain, and signs of severe hypercortisolism, including moon facies, ecchymosis, hypertension, hyperglycemia, and hypokalemia. Hormonal tests confirmed ECS with markedly elevated ACTH and cortisol levels. Imaging revealed two anterior mediastinal masses. Histopathological analysis of the surgical specimens confirmed ACTH-producing atypical NETs. Conclusions: This case highlights the importance of considering ectopic ACTH secretion from mediastinal neuroendocrine tumors in the differential diagnosis of severe, rapidly progressive hypercortisolism. Early recognition and timely surgical management can prevent life-threatening complications and improve patient outcomes, even in rare and aggressive presentations.