MON-106 Effective Management of Ectopic Cushing's Syndrome with Orsilodrostat: A Clinical Case Study

Abstract Disclosure: W. Thi: None. P. Mikkilineni: None. ACTH producing extra-pituitary tumors are rarely reported and account for about 5-20% of Cushing’s syndrome cases. They exhibit diverse clinical courses, which are particularly challenging to manage. Diagnosis requires clinical suspicion, supported by biochemical tests and imaging findings. A multidisciplinary approach is recommended to address both hypercortisolism and underlying neoplasms. A 44-year-old White male with recently diagnosed small cell lung cancer, on chemotherapy (carboplatin and etoposide) and anti-PDL-1 Ab (atezolizumab), presented with proximal muscle weakness, easy bruising, uncontrolled hyperglycemia, and hypertension. He has known metastases to the liver, bone, and adrenal glands. Labs showed leukocytosis, anemia, mildly elevated ALT, hypokalemic alkalosis with HbA1c 9.1%. Further work-up showed elevated random serum cortisol 119.6mcg/dL at 7 pm, repeat 8 am cortisol levels were 71 and 81.2mcg/dL (3.7-19.4mcg/dL) on 2 separate days with ACTH 139pg/mL (7.2-63.3pg/mL). Markedly elevated 24-hour urine free cortisol 11009.2mcg/24h (5-64mcg/24h), and non-suppressed serum cortisol following the 8 mg dexamethasone suppression test. MRI brain did not reveal any pituitary lesions. He was initially started on ketoconazole 200mg TID for 3 days, then switched to osilodrostat 1mg BID due to concerns of hepatotoxicity from the combined use of ketoconazole and anti-PDL-1, as well as his treatment with voriconazole for invasive aspergillosis. Aldactone was initiated for the excess mineralocorticoid effect of Cushing’s. Type 2 diabetes was managed with basal bolus insulin. His antihypertensive and insulin doses significantly reduced, and he no longer required potassium supplements. After 1 week of treatment, his serum cortisol improved to 52.9mcg/dL, further decreasing to 11.3mcg/dL, and 24-hour urine cortisol down to 102mcg/24h after 2 weeks. He was discharged on osilodrostat 1mg QD, educated on adrenal insufficiency symptoms, given PO hydrocortisone tablets, with a plan to monitor 24-hour urine free cortisol biweekly for dose titration. Unfortunately, he was readmitted for septic shock and passed away shortly after his family chose to pursue comfort care. Ectopic secretion of ACTH, primarily caused by small cell lung cancer (45%), has a higher incidence of hypokalemic alkalosis compared to other causes. While bilateral adrenalectomy may improve survival, medical treatment is crucial for alleviating major clinical symptoms and comorbidities such as hyperglycemia, bleeding, thromboembolism, depression, and opportunistic infections. A once-daily potent steroidogenesis inhibitor, osilodrostat, with a titration regimen, normalizes cortisol levels in ectopic Cushing’s. Transient hypocortisolism may occur, but can be managed with hydrocortisone replacement. Patients and caregivers must be educated about possible adrenal insufficiency. Presentation: Monday, July 14, 2025