MON-365 Immune Checkpoint Inhibitors: Endocrinopathies and Severe Electrolyte Abnormalities

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Background: Immune Checkpoint Inhibitors (ICPi) are promising therapies for advanced malignancies, including melanoma, lung cancer, and renal cancer. However, their use can induce mechanism-based toxicities called as immune-related adverse events (irAE) that can potentially affect various organ tissues, including the endocrine system. We present the case of a patient who developed secondary adrenal insufficiency & thyrotoxicosis within 9 weeks & severe electrolyte abnormalities within 13 weeks of starting therapy with ICPi. Case: A 56-year old woman with metastatic small cell lung cancer received 6 cycles of chemotherapy with carboplatin+etoposide, followed by whole brain radiation for multiple brain metastases. Subsequently, second-line therapy with ICPi was initiated, with a plan to administer four doses of combined ipilimumab (anti-CTLA-4 antibody) + nivolumab (anti-PD-1 antibody), followed by nivolumab alone every 2 weeks. Nine weeks post-initiation of ICPi therapy, she was hospitalized with symptoms of nausea & vomiting, she was hypotensive & an endocrine work-up confirmed adrenal insufficiency (AI). Possibility of immune-mediated AI was considered & she was started on hydrocortisone 30 mg/day & fludrocortisone 0.1 mg daily. However, subsequent evaluation confirmed the etiology of AI as secondary. Work-up during this hospitalization revealed a low TSH & low FT4 (central hypothyroidism vs. euthyroid sick syndrome). She did not have any symptoms or signs suggestive of hypophysitis & MRI brain did not reveal any pituitary pathology. Two months later, she was readmitted with confusion. Her thyroid function tests, this time, revealed severe thyrotoxicosis (with no increased TSI or anti-TPO antibodies); possibility of primary hyperthyroidism vs. destructive thyroiditis was considered, & pending thyroid scan, she was treated with methimazole and propranolol. She returned to the hospital in a week for nausea and vomiting; she had severe hypokalemia, hypocalcemia & hypomagnesemia requiring aggressive IV replacements. She required continued oral electrolyte replacements. At that point, nivolumab was discontinued. She had an endocrine clinic visit 3 weeks post-last hospitalization; she was asymptomatic, euadrenal and euthyroid, & had normal electrolytes. Dose of fludrocortisone was reduced & methimazole was discontinued (with decision to review post-thyroid scan). Conclusion: Novel ICPi can cause immune imbalance & irAE involving the endocrine system. Careful monitoring for & treatment of endocrinopathies is required during ICPi therapy. Nivolumab may likely induce severe electrolyte disturbances as well.