8295 Development of Type 1 Diabetes and Primary Adrenal Insufficiency Secondary to Immunotherapy Treatment for Chordoma in a Patient With Hypopituitarism

Abstract Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None. Background: Cranio-cervical chordomas are rare locally aggressive, invasive, and slow-growing bone neoplasms. Treatment involves a combination of excision and radiation therapy, and sometimes immunotherapy for recurrent disease. Endocrine-related toxicities from immune checkpoint inhibitors are well recognized and include autoimmune thyroid disease, hypophysitis, and less commonly, type 1 diabetes mellitus (T1DM) and primary adrenal insufficiency (PAI). We present a case of a patient with hypopituitarism secondary to a recurrent and aggressive skull base chordoma with leptomeningeal spread who developed T1DM and PAI after treatment with nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody. Diagnosis of PAI was delayed because patient was on hydrocortisone replacement for secondary adrenal insufficiency. Case Report: A 38 year old male with history of primary hypothyroidism underwent endoscopic endonasal transsphenoidal resection and adjuvant proton beam radiation therapy for a sellar chordoma after presenting with diplopia. Testing was consistent with hypopituitarism and the patient was started on hydrocortisone, levothyroxine, and testosterone replacement. Due to recurrent disease and leptomeningeal spread, he subsequently underwent three additional surgeries and two courses of gamma knife radiosurgery. Five months after starting systemic therapy with nivolumab, the patient developed insulin dependent diabetes presumed to be T1DM secondary to immunotherapy. He was continued on nivolumab, and six months into treatment developed hyperkalemia and hyponatremia requiring inpatient admission. He was treated with diuretics and fluid restriction initially without improvement in his electrolyte abnormalities although he remained relatively asymptomatic. Laboratory evaluation showed a renin activity of 66 ng/mL/H and aldosterone < 4.0 ng/dL (<= 21) with sodium of 128 mmol/L (135-145) and potassium 5.8 mml/L (3.3-4.9). Due to suspicion for PAI secondary to checkpoint-inhibitor induced adrenalitis, 21-hydroxylase antibody was checked and was positive. It was felt that the patient had not had other signs or symptoms classic for PAI such as nausea and/or vomiting because he had already been on glucocorticoid replacement for his hypopituitarism. Ultimately, the patient was started on fludrocortisone, with resolution of his hyponatremia and hyperkalemia. Conclusion: Adrenal insufficiency from immunotherapy is most commonly caused by hypophysitis. T1DM and PAI due to adrenalitis are less common. In patients on steroid replacement for hypopituitarism, the development of electrolyte abnormalities with or without symptoms in a patient on immunotherapy should raise the suspicion for rarer endocrine side effects such as primary adrenal insufficiency. Presentation: 6/3/2024