Severe Ectopic ACTH-Dependent Cushing Syndrome Due to a Neuroendocrine Tumor of Occult Primary Origin Presenting with Widespread Metastases and Early Vertebral Fractures: A Rare Case Report.

Ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome is an uncommon cause of hypercortisolism, often associated with neuroendocrine tumors and challenges in localizing the primary source. We report a 30-year-old woman presenting with progressive lower limb weakness, generalized pain, and difficulty walking, along with recently diagnosed hypertension and diabetes. Clinical and biochemical findings were consistent with severe ACTH-dependent Cushing syndrome. Imaging revealed no definite pituitary lesion but demonstrated pulmonary and hepatic metastases with vertebral pathological fractures. Liver biopsy confirmed a metastatic neuroendocrine tumor of intermediate grade, with immunohistochemistry suggesting a possible pancreatic origin; however, the primary tumor remained occult, with no pancreatic lesion identified on imaging. Management included treatment of diabetes and hypertension, ketoconazole and osilodrostat for hypercortisolism, and supportive care for vertebral fractures, resulting in partial clinical improvement. This case highlights the aggressive presentation and diagnostic challenges of ectopic ACTH syndrome, particularly in low-resource settings, and underscores the importance of a multidisciplinary approach.