SUN-059 A Case of Cyclical Ectopic Cushing Syndrome: A Diagnostic Dilemma

Abstract Disclosure: T. Aggarwal: None. R. Sandooja: None. A. Fingeret: None. J.B. Shank: None. M.B. Mulder: None. L.M. Vargas: None. Background: Endogenous hypercortisolism secondary to ectopic ACTH syndrome (EAS) is a rare condition with a reported incidence of 6-10%. The most common sources are bronchial carcinoid tumors, followed by small cell lung carcinoma. Pancreatic EAS is uncommon (7-14%) and in 12-18% of cases, the source remains occult. Cyclical ectopic Cushing syndrome (CS) is an exceptionally rare variant of EAS, with only a few cases reported in the literature. While no standard definition of cyclical CS exists, diagnosis usually requires at least two hypercortisolemic peaks interspersed with eucortisolemic troughs. Case Presentation: A 74-year-old male presented with a three-month history of progressive proximal muscle weakness, new onset type 2 diabetes mellitus, and severe hypokalemia requiring hospitalization. Axial imaging of the abdomen noted bilateral adrenal hyperplasia. Biochemical evaluation demonstrated an elevated baseline morning cortisol level of 27.2 µg/dL (n 6.7-22.6 µg/dl) with ACTH of 50.5 pg/mL (n 7.2-63.3 pg/mL). A 1mg and 8mg dexamethasone suppression test (DST) revealed non-suppressible cortisol levels of 53.3µg/dl (<1.8µg/dL) and 33.6 µg/dL (n <1.8 µg/dL) respectively. ACTH levels post 1 mg and 8 mg DST were 50.5 pg/mL and 40.7 pg/mL (n 7.2-63.3 pg/mL) respectively. Bedtime salivary cortisol levels were elevated > 0.1µg/dl on multiple occasions. Initial 24-hour urine free cortisol (UFC) levels were also elevated at 225 µg (n <60µg). MRI pituitary with dynamic protocol was unremarkable. Given the suspicion for EAS, PET DOTATATE was performed which identified a small focus of increased DOTATATE avidity in pancreatic tail which was confirmed on a CT abdomen with pancreas protocol. Subsequent UFC levels normalized at 44.8 µg (n <60µg) after one month but showed a marked elevation to over 1500 µg (n <60µg) the following month. The patient's reported symptoms, including proximal muscle weakness, correlated with his cortisol levels. After multidisciplinary discussion, the patient underwent bilateral adrenalectomy and distal pancreatectomy to address the biochemical and clinical consequences of recalcitrant cyclical CS. Intraoperative ACTH levels were unreliable due to the administration of dexamethasone during surgery. Pathology revealed a 5 mm pancreatic neuroendocrine tumor; however, definitive proof of ACTH secretion by the NET could not be established due to absence of direct ACTH staining.Conclusion: This case demonstrates the diagnostic and management challenges of cyclical EAS due to fluctuating biochemical testing and adds to the existing literature on this rare entity. Collaboration within a multidisciplinary team is crucial due to the heterogeneity of the patient's presentation and the rarity of the condition. Presentation: Sunday, July 13, 2025