Ectopic Adrenocorticotropic Hormone Syndrome Due to Extensive-stage Small-cell Lung Cancer Treated with Multimodal Therapy Including Osilodrostat: a Case Report

Background. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) caused by lung cancer presents significant therapeutic challenges due to complications associated with hypercortisolemia. Case Presentation. A 65-year-old woman presented with limb weakness and dyspnea. Although pathological confirmation was not obtained, clinical and radiological findings supported a diagnosis of EAS due to lung cancer. Multidisciplinary management addressed complications including transudative pleural effusion, muscle weakness, electrolyte imbalance, hyperglycemia, gastrointestinal bleeding, febrile neutropenia, enterococcal bacteremia, pulmonary aspergillosis, and cytomegalovirus infection. Chemotherapy resulted in tumor shrinkage and normalization of ACTH levels, but could not be continued due to persistent complications. A "titration strategy" using metyrapone led to adrenal insufficiency. Subsequently, a "block and replace strategy" with osilodrostat and hydrocortisone maintained stable cortisol levels. The patient died on hospital day 150. A postmortem examination confirmed small-cell lung cancer positive for ACTH on immunohistochemistry. Conclusion. A "block and replace strategy" involving osilodrostat may represent a potential treatment approach for EAS secondary to lung cancer, particularly when metyrapone is not tolerated.