SUN-084 A Case of Central Diabetes Insipidus Following CAR-T Cell Therapy

Abstract Disclosure: J. Lung: None. N. Bang: None. M. Pandey: None. E. Punni: None. I. Goyal: None. Introduction: Chimeric antigen receptor T-cell therapy (CAR-T) cell therapy is used for treatment for several lymphomas and leukemias. However, endocrine-related toxicities are reported rarely. We present an adult male with central diabetes insipidus (DI) related to CAR-T cell therapy. Case presentation: A 33-year-old male presented to the hospital to start CAR-T therapy. He had a notable past medical history of hypothyroidism, testicular seminoma treated with orchiectomy and chemotherapy 8 years ago, and stage IV high-grade B-cell lymphoma diagnosed 8 months ago with bone marrow and bone involvement. He started chemotherapy R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) for 1 cycle, dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) for 5 cycles completed 3 months ago. He had relapse with CNS involvement within weeks of chemotherapy completion. He then started salvage chemotherapy with cytarabine and methotrexate 2 months ago. He received whole brain radiotherapy and jaw mass radiotherapy 1 month ago. Six days after starting CAR-T therapy, the patient developed hypernatremia with a sodium of 162 mmol/L (136-145) and increased 24-hour urine output of 5.8 L. The patient never had hypernatremia prior to admission. He was treated with IV fluids and 1 mcg desmopressin (DDAVP) with improvement in sodium to 146 mmol/L and urine osmolality of 577 mOsm/kg (300-900). An MRI pituitary showed a decrease in the CNS lymphoma lesions involving the infundibulum and hypothalamus compared to 2 months ago with the posterior pituitary bright spot present. The patient matched oral intake with urine output. After IV fluids were stopped, he developed hypernatremia with increased urine output. Endocrinology ordered a water deprivation test overnight. Post water deprivation test, the patient had subsequent urine osmolality of 148 mOsm/kg with serum sodium of 153 mmol/L. A morning 8am cortisol level was adequate at 14.28 µg/dL (2.5-16.6). He had suppressed TSH 0.01 uIU/mL (0.35-4.89) and normal free T4 1.1 ng/dL (1.0-2.1), thus his home levothyroxine dose was adjusted. The patient was started on DDAVP 0.1 mg daily with improvement in urine osmolality and sodium levels. The DDAVP dose was increased to 0.1 mg twice daily prior to discharge, with stable sodium levels in the following months. Discussion: Our case demonstrates a rare cause of central DI related to CAR-T cell therapy. With a normal cortisol level and known previous hypothyroidism, the patient did not have panhypopituitarism, normally seen in CNS lymphoma involvement. Moreover, there was a decrease in CNS lymphoma lesions following CAR-T therapy. Instead, the patient developed acute hypernatremia following CAR-T cell therapy initiation. The pathophysiology is uncertain but may be related to an inflammatory reaction by immunological attack of CAR-T cells. Presentation: Sunday, July 13, 2025