7162 Cushing’s Syndrome due to Metastatic Atypical Pulmonary Carcinoid and the Therapeutic Journey to Bilateral Adrenalectomy

Abstract Disclosure: P. Itersky: None. M.C. Pereira: None. S.J. Sternlieb: None. N. Manuel: None. J. Dahle: None. D. Englert: None. Background: Ectopic ACTH syndrome is an uncommon cause of Cushing’s syndrome. Carcinoid tumors are the most frequently reported cause of ectopic ACTH syndrome but there is a lack of consensus regarding the most efficacious treatment strategies in adults. We present the case of ectopic ACT syndrome due to metastatic bronchopulmonary carcinoma, refractory to ketoconazole that was ultimately treated with bilateral adrenalectomy. Clinical Case: A 61-year-old male with a history of atypical bronchopulmonary carcinoid diagnosed three years prior with metastasis to bone and pericardium was referred to endocrinology clinic for evaluation of elevated cortisol. He reported frequent falls, excessive weight gain, leg swelling and easy bruising. He had a long-standing history of resistant hypertension on four agents and poorly controlled type 2 diabetes mellitus requiring multiple daily insulin injections. On exam he had classic features of Cushing syndrome including moon facies, prominent supraclavicular fat pads, central fat distribution and peripheral edema. Morning cortisol was elevated at 40.00 ug/dL (4.30 – 22.40 ug/dL) and remained elevated at 26.4 ug/dL after administration of 1 mg dexamethasone overnight. There was intermittent hypokalemia dating back one year as low as 2.1 mmol/L (3.5 – 5.1 mmol/L). Baseline morning ACTH was elevated to 356 pg/mL (0 – 46 pg/mL). 24-hour urinary cortisol was elevated to 441 mcg/24h (3.5 – 45 mcg/24h). Pituitary MRI was normal. This constellation of findings was strongly suggestive of ectopic ACTH secretion. Treatment started with ketoconazole and initially provided a remarkable response. Urine cortisol levels initially decreased to 25 mcg/24h after two months of treatment. His weight decreased from 83.6 kg to a nadir of 69.4 kg and he demonstrated improvement in glycemic control and lowered insulin requirements. Three of four antihypertensives were discontinued. However, these improvements were short lived as urine cortisol levels subsequently increased despite increasing doses of ketoconazole. Glycemic control gradually worsened, and he developed recurrent weight gain, peripheral edema, hypertension and hypokalemia. Later, he was hospitalized for hypoglycemia and hypotension felt to be secondary to over treatment of Cushing syndrome. A block and replace strategy with ketoconazole and prednisone was attempted but was unsuccessful. Ultimately, he underwent bilateral adrenalectomy for definitive treatment of ectopic ACTH Cushing syndrome. Conclusion: This case highlights the challenging nature of medical management in ectopic ACTH syndrome with episodic variability in cortisol secretion. Definitive therapy with surgery should be considered in patients who respond poorly to medical management to prevent short and long term consequences of untreated Cushing syndrome. Presentation: 6/1/2024