Immune checkpoint inhibitors, anti-PD1 and anti-CTLA-4, have become widely utilized and proven effective in treating various forms of cancer. Although the discovery of immunotherapy has been a major advancement in the field of oncology, a series of endocrinopathies have been described and research is still ongoing. We would like to report a case of diabetes mellitus with positive glutamic acid decarboxylase (GAD) antibodies secondary to pembrolizumab therapy for locally advanced Merkle Cell Carcinoma. A 70-year-old male with no history of diabetes presented to the ER with severe hyperglycemia after his fifth cycle of pembrolizumab. His labs revealed a blood glucose of 659 mg/dL, an A1c of 8.5%, creatinine of 1.45 mg/dL, and urine negative for ketones. He demonstrated elevated anti-GAD antibodies (>250 IU/mL), suggesting type 1 diabetes. The patient was started on both long acting insulin glargine and prandial short acting insulin with improved glycemic control. The first case reports of pembrolizumab induced diabetes and diabetic ketoacidosis were published in 2015. During the initial clinical trials, only 0.1% of patients using pembrolizumab developed type 1 DM, but a review of current literature suggests that it has become more prevalent with rates as high as 2%. The rise in cases has also demonstrated that the majority of immunotherapy induced diabetes results primarily in patients receiving anti-PD1 therapy. A study done on mice demonstrated PD-L1 expression in inflamed pancreatic beta cells of mice that had developed diabetes. These results suggest that pembrolizumab causes destruction of insulin producing cells, releasing intracellular proteins such as GAD, and triggering the immune system to create autoantibodies. This emphasizes the need for further studies investigating the relationship between immunotherapy and autoimmune diabetes. In addition, it is essential that clinicians become aware and remain vigilant of this potentially life-threatening complication.
S. Spyropoulos: None. A. Manessis: Advisory Panel; Self; Medtronic, Research Support; Self; IQVIA, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., MannKind Corporation, Sanofi US.
