MON-081 ACTH Secretion from Gallbladder Neuroendocrine Tumor: A Rare Late-Onset Presentation of Ectopic Cushing’s Syndrome

Abstract Disclosure: T. Wolinsky: None. C. Gu: None. A. Nichol: None. C. Hupfeld: None. N. Shah: None. Introduction: Ectopic Cushing’s syndrome is most commonly caused by the secretion of adrenocorticotropic hormone (ACTH) from neuroendocrine tumors (NETs) and manifests with signs of hypercortisolism. Common sources of paraneoplastic ACTH production include small-cell lung cancer, thymic tumors, and pancreatic neoplasms. Cases arising from gallbladder NETs are exceedingly rare. Here, we present a unique case of ectopic Cushing’s syndrome that developed acutely ten months after gallbladder malignancy diagnosis. Case: A 72-year-old woman with a history of gallbladder adenocarcinoma (diagnosed ten months prior with subsequent radical cholecystectomy), prediabetes, hypertension, hyperlipidemia, and osteoporosis presented to our hospital with two weeks of progressive facial swelling. Her exam was notable for moon facies and abdominal distension. Laboratory findings revealed hypokalemia (serum potassium 2.8 mEq/L), hyperglycemia (serum glucose 453 mg/dL, A1c of 7.0%), and elevated cortisol. Morning cortisol was 45.3 µg/dL (compared to 18 µg/dL 33 days prior), ACTH 288 pg/mL, and urine free cortisol 1,263.1 µg/day. Late-night serum cortisol was 36.4 µg/dL, and AM cortisol post 8 mg dexamethasone suppression test was 49 µg/dL. Brain MRI revealed no pituitary lesion. CT abdomen showed enlarging hepatic metastases and unremarkable adrenal glands. Pathology of initial gallbladder resection demonstrated a 10.3 cm poorly differentiated adenocarcinoma that was negative for chromogranin A, synaptophysin, and insulinoma-associated protein 1 staining. Subsequent molecular profiling favored a neuroendocrine neoplasm with 87% predicted probability (73% large cell neuroendocrine cancer). Given the clinical presentation and imaging findings, metastases from her gallbladder cancer were suspected as the source of ectopic ACTH secretion. Osilodrostat 2 mg twice daily and second-line chemotherapy (carboplatin and etoposide) were initiated with rapid improvement of hypercortisolism. Five days after initiation of osilodrostat, her AM cortisol decreased to 18.6 µg/dL and hypokalemia resolved. Conclusion: Comprehensive literature review identified only six reported cases of ACTH secretion from gallbladder malignancies, all of which presented with hypercortisolism as the initial manifestation of their malignancy. This is a rare presentation of acute worsening severe hypercortisolemia presenting ten months after initial diagnosis of gallbladder adenocarcinoma. Ectopic Cushing’s syndrome is associated with significant morbidity. Early identification of ectopic Cushing’s syndrome is thus critical. This case underscores the importance of considering ectopic ACTH production from a known malignancy in patients presenting with symptoms of hypercortisolism. Presentation: Monday, July 14, 2025