SAT-493 A Case of Profound Hypothyroidism Secondary to Immune Check Point Inhibitors

Background: The discovery of immune check-point inhibitors (ICI) revolutionized cancer treatment. CTLA-4, anti-PD-1 and anti-PD-L1 monoclonal antibodies have been approved in recent years. However, the advantageous clinical outcomes can also be associated with potentially severe immune related adverse effects (irAEs) such as hypophysitis, thyroiditis, type 1 diabetes mellitus, and adrenal insufficiency [1]. We report to highlight the importance of awareness of irAEs and collaboration of endocrinology and oncology specialties in managing oncology patients with ICI in an underserved community hospital in Brooklyn, NY. Clinical case: 62 years old woman with unremarkable thyroid history presented with chronic mid-chest pain and dysphagia in 2016 found to have a mass in middle third of esophagus. Biopsies revealed invasive squamous cell carcinoma (T3N0). She underwent radiotherapy and esophagectomy. On 1/2018, surveillance imaging detected a new tracheobronchial angle lymph node, which was confirmed as hypermetabolic and likely malignant by PET scan. Patient received additional 5 cycles of radiotherapy followed with 5 cycles of chemotherapy with Oxaliplatin and Capecitabine. Since post-chemotherapy PET scan showed local recurrence, patient was started on PD1 inhibitor, Pembrolizumab 200 mg Q3 week. After 3 doses patient developed cold intolerance, weight gain and low mood. Her TSH was 173 uIU/ml (0.27-0.42), FT4 <0.1 ng/dL (0.9-1.8) and referred to endocrine clinic. Repeat TSH was 190 uIU/ml, FT4 0.2 ng/dL, TPOAbs 619 IU/ml (<35) and TSI<0.1 IU/L (<0.55). Adrenal insufficiency was ruled out and started on levothyroxine 50 mcg in the morning, increased to 75 mcg. After 2 months of levothyroxine use, TSH was 11.8 uIU/ml and FT4 1.3. Pembrolizumab therapy is restarted shortly after. Conclusion: National Comprehensive Cancer Network guideline for management of immunotherapy related toxicities recommends routine monitoring of TSH and FT4 at baseline and every 4-6 weeks during immunotherapy, follow up every 12 weeks and TPO antibodies if TSH is high. This patient’s clinical symptoms of hypothyroidism might be confused by nonspecific symptoms of underlying malignancy. Combination radiotherapy and immunotherapy place this patient at higher risk of developing hypothyroidism. This case showed the successful collaboration of endocrinology and oncology team in giving vulnerable patient an optimized care with good clinical outcome. References: (1). Ferrari SM, et al. Autoimmune Endocrine Dysfunctions Associated with Cancer Immunotherapies. Int J Mol Sci. 2019;20(10):2560. Published 2019 May 24. (2). John A. Thompson, et al. Management of ImmunotherapyRelated. Toxicities, Version 1.2019J Natl Compr Canc Netw 2019;17(3):255–289