SUN-919 Ectopic ACTH Syndrome: An Aggressive Presentation Due to Metastatic Liver Cancer of Unknown Primary

Abstract

Background: Ectopic Cushing’s Syndrome is a rare but often aggressive condition caused by ACTH-hypersecretion from non-pituitary tumors. In patients with metastatic cancer, as well as those with occult tumors, the diagnosis and management can be extremely challenging. Clinical Case: A 25-year old woman recently diagnosed with poorly differentiated metastatic liver carcinoma of unknown primary was admitted for lower extremity edema and worsening fatigue for the preceding month. Since being diagnosed with liver cancer, she developed uncontrolled hypertension, persistent severe hypokalemia and facial “puffiness”. Physical exam was remarkable for moon facies and truncal obesity but no evidence of striae. An overnight 1-mg dexamethasone suppression test resulted in an elevated morning cortisol level of 93.4 mcg/dL and elevated ACTH of 299 pg/mL. A 24-hour urine cortisol was significantly elevated at 4,448 mcg/24 hours. These findings were consistent with hypercortisolism due to hypersecretion of ACTH. An MRI of the sella revealed no pituitary abnormality. A high-dose dexamethasone suppresion test (single 8 mg dose) was performed and her morning cortisol level remained elevated at 98.6 mcg/dL, consistent with ectopic ACTH secretion. She was treated for the underlying malignancy with carboplatin and paclitaxel. After a thorough discussion of therapeutic options, she was prescribed Ketoconazole with the plan to medically control the hypercortisolism potentially followed by bilateral adrenalectomy. Ketoconazole was up-titrated and Spironolactone was added resulting in significant improvement of hypokalemia and hypertension. Unfortunately, one week after discharge she was re-admitted due to worsening performance status, watery diarrhea and abdominal pain. A serum cortisol level was elevated at 124 mcg/dL and Metyrapone was added to her regimen. Unfortunately, her performance status continued to decline due to progression of cancer and uncontrolled hypercortisolism. As a result, she was deemed a poor surgical candidate for bilateral adrenalectomy. The patient’s condition rapidly deteriorated and she developed malignant ascites as well as altered mental status. In accordance with her wishes, a DNR order was placed and she passed away shortly thereafter. Conclusion: Ectopic ACTH-syndrome is the etiology of 10–20% of cases of Cushing’s syndrome. Clinical presentation is often sudden and rapidly progressive. Severe hypertension and hypokalemia are seen more commonly than in Cushing’s disease. Cases secondary to occult tumors or metastatic cancer can be particularly challenging to treat when it is not possible to eliminate the source of ACTH hypersecretion via surgical or medical treatment. In patients such as this, early bilateral adrenalectomy should be considered after starting medical therapy in order to reduce morbidity and mortality due to hypercortisolism.