SAT-584 Pembrolizumab-Related Graves' Disease: A Rare Adverse Effect of an Anti-PD-1 Antibody Cancer Immunotherapy

Background: Immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) have emerged as important anticancer therapies and are sometimes associated with thyrotoxicosis. With anti-PD-1 antibody therapy, most often this is related to destructive thyroiditis. We present a rare case of Graves’ disease related to pembrolizumab. Clinical Case: A 37‐year old woman presented with a 1-week history of lightheadedness, fatigue and nausea. She had a history of grade 3 diffuse oligodendroglioma diagnosed during evaluation for focal seizures three years ago. She had completed chemotherapy with temozolomide and then was found to have extension of the tumor into the right anterior temporal lobe. She underwent tumor resection and began pembrolizumab treatment shortly thereafter. She completed two infusions of pembrolizumab at the time of her presentation with the above symptoms. In the ED she was noted to be orthostatic and had a HR of 110 bpm. Labs were consistent with thyrotoxicosis: elevated FT3 of 10.5 pg/mL (2.3-4.2), FT4 3.7 ng/dL (0.9-1.8) and a suppressed TSH of < 0.01 mcU/mL. She was treated with IVF and started on propranolol 10 mg three times daily. A thyroid ultrasound revealed a hyperemic, diffusely heterogenous gland. Antibody testing demonstrated an elevated TSI of 10.8 IU/L (< 0.55), confirming a diagnosis of Graves’ disease. She was subsequently started on methimazole 10 mg twice daily and had improvement of both her symptoms and biochemical indices over several weeks. Up to 5% of patients receiving anti-PD-1 antibody immunotherapy develop thyrotoxicosis, with most reported patients having destructive thyroiditis.(1) To our knowledge this is one of the first reports of thyrotoxicosis due to Graves’ disease related to anti-PD-1 antibody therapy. Interestingly there are two reports in the literature of Graves’ ophthalmopathy without thyrotoxicosis (one with pembrolizumab therapy alone and another with the combination of durvalumab and tremelimumab therapy).(2)(,3) Our case demonstrates the importance of a thorough evaluation for the cause of thyrotoxicosis in patients receiving anti-PD-1 antibody therapy, as a prompt diagnosis allows for etiology-targeted management. Conclusion: This is the one of the first case reports demonstrating Graves’ disease as a specific thyroid-related endocrinopathy linked to PD-1 antagonist use. Clinicians must consider Graves’ disease as a potential cause of thyrotoxicosis in patients taking these medications. References: (1) Ferrari SM, Fallahi P, et al. Rev in Endocr and Metab Dis. 2018; Sep 21. Epub ahead of print. (2) Park ESY, Rabinowits G, et al. J of AAPOS. 2018;22(4):310-312 (3) Sabini E, Sframeli A, Marino M. J of Endocr Investig. 2018;41:877-878.