en Endocrinology Endocrinology case report case report <span style="font-size:14px;"><span style="font-family:Times New Roman;"><span style="line-height:14.3pt"><b><i><span style="color:blue">Background:</span></i></b> Ectopic Cushing&#39;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.</span><br> <span style="line-height:14.3pt"><b><i><span style="color:blue">Case Presentation: </span></i></b>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.</span><br> <span style="line-height:14.3pt"><b><i><span style="color:blue">Conclusions:</span></i></b> 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.</span></span></span><br> &nbsp; Ectopic ACTH Syndrome, Cushing Syndrome, Neuroendocrine Tumors, Mediastinal Neoplasms, Case Reports. 681 687 http://caspjim.com/browse.php?a_code=A-10-1924-7&slc_lang=en&sid=1 Edita Guadalupe Ruiz-Huaranga guadaluperuizh200194.gr@gmail.com 100319475328460057976 100319475328460057976 No Division of Endocrinology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Perú Maria del Pilar Quinones Avila mpilarquinones@gmail.com 100319475328460057977 100319475328460057977 No Division of Pathology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Perú Rosa Laurie Marcilla Truyenque rosa.marcilla@essalud.gob.pe 100319475328460057978 100319475328460057978 No Division of Endocrinology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Perú. Marcio Jose Concepcion-Zavaleta marcio_conc_zav@outlook.es 100319475328460057979 100319475328460057979 Yes Universidad Científica del Sur, Lima, Peru Jose Paz-Ibarra jose.paz1@unmsm.edu.pe 100319475328460057980 100319475328460057980 No Division of Endocrinology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Perú Jenyfer Fuentes-Mendoza jenyferfuentesmendoza73@gmail.com 100319475328460057981 100319475328460057981 No Universidad Científica del Sur, Lima, Peru Juan Eduardo Quiroz-Aldave jquirozaldave@hotmail.com 100319475328460057982 100319475328460057982 No Division of Research, Hospital de Apoyo Chepén, Chepén, Perú.