MON-682 Acquired Generalized Lipodystrophy Treated With Metreleptin in a Patient With Total Body Irradiation and Chronic Graft-Versus-Host Disease

Abstract Disclosure: T. Moazezi: None. B. Salehian: None. Background: Acquired lipodystrophy, both partial and generalized, is a rare disease that can be seen in patients with a history of total-body irradiation (TBI) and hematopoietic stem cell transplantation (HSCT). The widespread metabolic complications that arise from this disorder warrant attention and treatment. Clinical Case: A 25-year-old female with a history of Non-Hodgkin Lymphoma status post TBI and HSCT in 2000 and 2004 complicated by chronic graft-versus-host disease (GVHD) presented with multiple endocrinopathies to the endocrinology clinic. She presented with type 2 diabetes mellitus with severe insulin resistance, severe hypertriglyceridemia, and non-alcoholic steatohepatitis. The patient weighed 36.7 kg with a BMI of 14.3 kg/m2. On physical exam, the patient had complete loss of subcutaneous fat mass in the chest, abdomen, upper and lower extremities, and palmar-plantar region; there was minimal appreciable subcutaneous fat in the face and supraclavicular region. Abdominal exam revealed visceral fat and hepatomegaly with percussion of the liver 5 cm below the costal margin. The quantitative adiponectin level was low at 3.1 ug/mL (2.0-19.3 ug/mL), and the diagnosis of acquired generalized lipodystrophy (AGL) was made. Laboratory work-up was notable for SGOT 50 U/L (15-46 U/L), SGPT 88 U/L (7-56 U/L), glucose of 435 mg/dL (80-128 mg/dL), hemoglobin A1c 14.4% (<=6.4%), C-peptide 9.7 ng/mL (0.8-3.5 ng/mL), fasting triglyceride 4268 mg/dL (<=150 mg/dL), total cholesterol 297 mg/dL (<=200 mg/dL), HDL 34 mg/dL (>=39 mg/dL), and LDL 32 mg/dL (<=100 mg/dL). Abdominal ultrasound with elastography showed hepatomegaly, fatty liver, mild-moderate fibrosis. The patient was treated with statin, fish oil, gemfibrozil, Humulin R U-500 insulin, insulin pump, pioglitazone, and multiple oral hypoglycemic agents, and her metabolic complications were refractory to these standard therapies. She was started on treatment with metreleptin by subcutaneous injection for treatment of AGL. The dose was titrated upwards as tolerated, and the patient had improvement in her metabolic parameters while on treatment, including improved insulin sensitivity and lipoprotein profile. Metreleptin was discontinued after two years due to significant pain at the injection site. She was referred to plastic surgery to assess for auto-transplantation of adipose tissue, which was not an option due to complete loss of subcutaneous adipose tissue. Conclusion: Childhood cancer survivors with a history of TBI and HSCT can develop acquired lipodystrophy with associated metabolic complications later in life. This case demonstrates the role of metreleptin in improving insulin sensitivity and lipoprotein profiles in a patient with AGL. Presentation: Monday, July 14, 2025