A. Kapoor 1 , J. Hefner 1 ; 1 University of Pittsburgh, Pittsburgh, PA (Tracking ID #76642) LEARNING OBJECTIVES: 1.) Recognize an unusual cause of persistent hypokalemia; 2.) Diagnose an atypical presentation of Cushing syndrome; 3.) Recognize the clinical presentation of an ectopic ACTH-producing tumor. CASE INFORMATION: A 77-year-old male with hypertension and Type II diabetes mellitus presented with a 2 month history of fatigue and weakness. He subsequently developed a gait dysfunction and had frequent falls. Outpatient potassium (K) was 1.9 and he was admitted for management of hypokalemia. Physical exam revealed a BP of 180/90, facial plethora and bilateral diffuse rales at the bases of the lungs. Proximal muscle strength was 4/5 in the upper and 3/5 in the lower extremities. Distal strength was 5/5. No moon facies, buffalo hump or abdominal striae were found. His K remained low despite aggressive replacement and secondary causes were investigated. Results of diagnostic testing included a urinary Na 17, K 52, pH 6 (4.8±8), serum Na 140, Cl 95, HCO3 40, BUN 28, Cr 1.4, renin 0.6 (<5 mcg/ml) and aldosterone 5.7 (2±9 mcg/ml). Urinary metanephrines were normal. Cortisol at 8 am was 100 (7±20 mcg/ml) and ACTH 380 (9±52 pg/ml). Post high-dose (8mg) dexamethasone suppression test (DST) cortisol was 118 and ACTH was 126 (2±8 pg/ml). FSH, LH, prolactin and IGF-1 were normal. Brain MRI revealed a normal sized pituitary. Chest CT showed pleural effusions, no masses or lymphadenopathy. Abdominal CT revealed a 3 cm renal mass and bilateral adrenal hypertrophy. Biopsy of the renal mass showed poorly differentiated small cell carcinoma (SCC). Treatment with ketoconazole failed to suppress his cortisol. The patient decompensated and expired. Autopsy revealed numerous nodules in the liver, the right renal mass with focal hemorrhage and no lung masses. Pathology revealed SCC of renal origin with metastasis to the liver. IMPLICATIONS/DISCUSSION: Cushing syndrome is an unusual cause of hypokalemia. Other causes include primary or secondary hyperaldosteronism, Type 2 renal tubular acidosis, Bartter syndrome, Liddle syndrome, diuretic use and VIPoma. Patients with ectopic Cushing secondary to carcinomas often lack the clinical manifestations associated with classic Cushing syndrome±the centripetal fat distribution, moon facies and striae. The metabolic abnormalities, however, are more common in ectopic ACTH syndrome namely hypokalemia, metabolic alkalosis, excessively high cortisol and elevated ACTH levels. Differentiation of ectopic from pituitary dependent Cushing is made by non-suppression of cortisol with the 8 mg DST. There have been reported cases of ectopic ACTH with lung SCC, bronchial carcinoid, medullary carcinoma of the thyroid, gastrointestinal and prostatic adenocarcinoma and pheochromocytoma. However, there are no reported cases of SCC of renal origin causing ectopic ACTH production as was present in our patient.