ODP570 Immunotherapy and its Implications for the Future of Endocrinology: A Case Discussion of Pembrolizumab Induced Myxedema Coma

Abstract

Abstract Introduction Immunotherapy is a relatively new type of cancer treatment that has been successful in prolonging survival time and improving quality of life for patients with a wide variety of cancers.1 While these therapies do not usually have the same systemic toxicities seen in traditional chemotherapies, they can lead to significant autoimmune disorders due to their method of action.2 We present a case of pembrolizumab induced Hashimoto's thyroiditis leading to myxedema coma. Case A 67-year-old male presented to the hospital ED via EMS after being found unconscious in his car by his neighbor. On arrival, he was confused, lethargic, unable to answer questions, and had a Glasgow Coma Scale of 12. He was hypotensive 87/55 mmHg, bradycardic 55 bpm, respirations 12 breaths/min, SpO2 99% on room air, temperature 37 °C. Past medical history included type 2 diabetes mellitus on insulin and non-small cell lung cancer metastatic to bone and brain treated with pembrolizumab, denosumab, steroids, and radiation therapy. Initial labs revealed elevated TSH of 47. 01 with undetectable T3 and T4, glucose 514 mg/dL and elevated beta hydroxybutyrate 1.61, WBCs 3.9, hemoglobin 11.7, platelets 105. TPO antibodies were elevated 44.5IU/ml. Patient was treated with IV levothyroxine, hydrocortisone, insulin, and fluids and his condition improved rapidly. Patient was transitioned to oral levothyroxine with plans for outpatient endocrinology follow upon discharge. Thyroid tests done during a prior hospitalization following the initiation of pembrolizumab six months earlier demonstrated a low TSH of <0. 003 and an elevated free T4 of 2. 09. The diagnosis of autoimmune thyroiditis induced by immunotherapy was made. Discussion Pembrolizumab is one of several immune-checkpoint inhibitors (ICIs) used to treat cancer by blocking the programmed-death (PD-1) receptor, allowing T-cells to detect malignant cells and mount an immune response. ICIs are part of a larger therapeutic class known as immunotherapy which acts to enhance the body's own detection and elimination of cancerous cells.1 As a result, approximately 10% of patients treated with immunotherapy develop autoimmune reactions.2 In this case, the patient had positive thyroid autoantibodies for Hashimoto's thyroiditis, that eventually lead to his profound hypothyroid state and myxedema coma. As these therapies become more widely utilized, the incidence and prevalence of autoimmune induced endocrine disorders will naturally increase. Awareness of the mechanisms and implications of immunotherapy in patients presenting with endocrine disorders will led to early recognition, treatment and improved patient outcomes. Waldman AD, et al Nat Rev Immunol. 2020;20(11): 651-668. Barroso-Sousa R, et al. . JAMA Oncol. 2018;4(2): 173-182. Presentation: No date and time listed