SUN-199 A Case of Ectopic Cushing’s Syndrome with Major Complications Leading to Treatment Dilemmas

Background: Ectopic ACTH syndrome is an uncommon cause of Cushing’s syndrome and patients are at high risk for serious complications including infections, thromboses, cardiovascular and neuropsychiatric complications; therefore, swift diagnosis and treatment is needed. Clinical Case: A 63-year old woman presented with lower extremity edema and severe lower back pain. She also reported a 2 month history of polyuria, polydipsia, and headaches. Initial labs showed hypernatremia, hypokalemia, alkalemia and hyperglycemia and an 8AM cortisol of 61.9 mcg/dL (N 5-25 mcg/dL) with an ACTH of 367 pg/mL (N 6-50pg/mL). Imaging showed a right middle lobe lung mass and 3 vertebral body compression fractures. A failed attempt at biopsy of the lung mass resulted in pneumothorax, air embolism, stroke, and cardiac arrest with shock liver. She was then transferred to our tertiary care center. On arrival at our center, her examination was notable for hypertension, upper and lower extremity edema and 4/5 strength in her right shoulder and hip flexor. She had left hemiparesis and a depressed mood. No facial plethora, acanthosis, buffalo hump or striae were observed. Her 24-hour Urinary Free cortisol (UFC) was 1,176 mcg/dL (n 3.5-45 mcg/24H) and her 8AM cortisol after 8 mg of dexamethasone was 58.3 mcg/dL (N <1.8mcg/dL). A pituitary MRI did not identify a lesion, and petrosal sinus sampling was considered too high-risk due to recent infarct and cerebral edema. A PET/CT-scan showed increased uptake in the right lung nodule, enlarged hyperactive adrenals, and a retroperitoneal lymph node. The patient’s course was further complicated by diffuse deep vein thromboses of her left leg and a subsequent retroperitoneal bleed while on anticoagulation, as well as an E.coli urinary tract infection. Interdisciplinary discussions regarding options for surgical management were ongoing, however given the patient’s fragile medical state, the endocrine team initiated medical therapy to treat her hypercortisolism while awaiting surgical decision. Initially, a continuous etomidate infusion was used that resulted in a 50% reduction in 24Hr UFC. When her liver function improved, she was transitioned to ketoconazole. She ultimately underwent a right middle lobectomy, revealing a 2.3cm typical carcinoid tumor with strongly diffusely positive ACTH staining on pathology. A day after surgery her ACTH level was 12 pg/mL, though cortisol was still elevated at 55.5 mcg/dL. Cortisol declined to 3.3 mcg/dL within one week. Her neuropsychiatric symptoms reversed almost entirely and she was discharged on a steroid taper. Conclusion: Ectopic ACTH syndrome is a rare paraneoplastic syndrome with significant comorbidity. In many cases, surgical excision can induce profound and rapid reversal of many of the symptoms of cortisol excess; however, if surgery is delayed, prompt medical treatment is vital to prevent compounding complications.