SUN-431 Seizure Due to Symptomatic Hyponatremia, An Unusual Presentation of Nivolumab-induced Central Adrenal Insufficiency and Hypothyroidism

Abstract Disclosure: L. Vako: None. S. Kalik: None. N.E. Cusano: None. Background: Nivolumab is a Programmed Cell Death-1 (PD-1) immune checkpoint inhibitor used in cancer treatment. Nivolumab has been shown to cause endocrine-related adverse events, most commonly hypothyroidism, hypophysitis and adrenal insufficiency. Presentations can vary from vague symptoms to severe illness. Case Presentation: A 67-year-old man with bladder urothelial carcinoma was treated with a combination of gemcitabine, cisplatin, and nivolumab followed by nivolumab monotherapy. Prior to arrival in the emergency department, he had two episodes of new-onset absence seizures followed by a period of unresponsiveness while at an outpatient oncology appointment. These episodes resolved within a few minutes. Outpatient evaluation that morning showed: serum Na 124 mmol/L [reference range (RR): 135-145 mmol/L], AM cortisol 2.48 ug/dL (RR: 6.02-18.4 ug/dL), ACTH 17.4 pg/mL (RR: 7.2-63.3 pg/mL), TSH 9.93 uIU/mL (RR: 0.27-4.20 uIU/mL], and free T4 0.8 ng/dL (RR: 0.9-1.8 ng/dL). These results suggested new secondary adrenal insufficiency (AI) and primary hypothyroidism. He was hemodynamically stable. Admission evaluation showed: serum Na 128 mmol/L, serum osmolarity 265 mosm/kg (RR: 280-301 mosm/kg), urine osmolarity 111 mosm/kg (RR: 300-900 mosm/kg). He had reported drinking more water recently. He received one dose of hydrocortisone 100 mg IV for suspected AI and was placed on fluid restriction for suspected polydipsia. After four days, laboratories showed: AM cortisol 7.05 ug/dL, ACTH 15.9 pg/mL, TSH 6.52 uIU/mL, and free T4 0.624 ng/dL. He tested negative for thyroglobulin and thyroid peroxidase antibodies. There was otherwise normal anterior pituitary function of all other axes. CT scan of the head did not show any metastasis or acute processes. He did not undergo MRI as his symptoms improved rapidly. Na improved with one dose of steroid and fluid restriction. No further episodes of seizure-like activity occurred in the hospital. Additional steroids were held until the cosyntropin stimulation test was performed, demonstrating a baseline cortisol of 1.3 ug/dL with ACTH 10.4 pg/mL, and after 60 minutes, a suboptimal cortisol level of 11.3 ug/dL, confirming suspected secondary AI. He was started on hydrocortisone 10 mg in AM and 5 mg in PM. He was also started on levothyroxine 25 mcg for primary hypothyroidism. Na levels remained normal at 141 mmol/L after 1 month and he remained normotensive and seizure-free. Conclusion: This case highlights seizure as a severe presenting symptom of hyponatremia caused by Nivolumab-induced secondary AI and hypothyroidism. It is important to recognize adverse endocrine events related to check point inhibitors and initiate appropriate therapy. Presentation: Sunday, July 13, 2025