PSAT044 Management of Severe Cushing's Syndrome in a Patient with Cyclical Ectopic ACTH Production Treated with Osilodrostat.

INTRODUCTION: We are presenting a case of severe Cushing's syndrome with multiple complications treated medically with osilodrostat. CLINICAL CASE: A 71-year- old female with severe chronic obstructive pulmonary disease was noted to have episodes of hypokalemia, hyperglycemia, and hypertension lasting for several weeks. At the time of presentation to the clinic, she had normal vital signs and no physical exam findings suggestive of hypercortisolism except for mild proximal muscle weakness. Between 2019 and 2021, she had multiple episodes of the presenting symptoms along with elevated morning serum cortisol of 57 to 119 mcg/dl (normal 7-22 mcg/dl), 24-hour urine free cortisol 1343 to 2464 mcg/24 hours (normal 4.5-45 mcg/24 hours), midnight saliva cortisol 509 to 8870 ng/dl (normal <100 ng/dl), and ACTH 105 to 150 pg/ml (normal 5-52 pg/ml). Between episodes labs were normal. A diagnosis of cyclic ACTH-dependent Cushing's syndrome was made. Pituitary MRI was normal, with no evidence of pituitary adenoma. Inferior petrosal sinus sampling was done while cortisol level was elevated, and it showed petrosal sinus to peripheral ACTH ratio of 1.2 following stimulation, a ratio <3.0 suggests ectopic ACTH-dependent Cushing's syndrome. A Ga-65 DOTATATE scan did not localize the tumor. As she was considered a poor surgical candidate for bilateral adrenalectomy, she was started on osilodrostat 10 mg twice daily and hydrocortisone 10 mg twice daily for a block and replace strategy. She was admitted to the hospital 5 days later for increasing fatigue and severe hyperglycemia. Potassium level was 2.2 mmol/L (normal 3.5-5 mmol/L), blood glucose >500 mg/dl, Hemoglobin A1c 8.2%, and random cortisol level was 96 mcg/dl. She was hypertensive and had new acute rib fractures, right lower lobe pulmonary embolism, and deep vein thrombosis. She was given potassium supplements, insulin, anticoagulation, and spironolactone 100 mg bid. The dose of Osilodrostat was increased to 20 mg twice daily. Over 12 days, her cortisol level decreased gradually to 6.3 mcg/dl on the day of discharge. Spironolactone, insulin, and potassium were discontinued and hydrocortisone was prescribed for physiologic replacement. As an outpatient, she continues both osilodrostat and hydrocortisone and is doing quite well. CONCLUSION: Osilodrostat can rapidly and effectively decrease cortisol levels in patients with severe Cushing's syndrome. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.