A Case Report of Graves' Disease Induced by the Anti-Human Programmed Cell Death-1 Monoclonal Antibody Pembrolizumab in a Bladder Cancer Patient

Abstract

Immune checkpoint inhibitors, such as anti-programmed cell death-1 (anti-PD-1), have been widely used in the treatment of malignancies. However, these drugs can cause immune-related adverse events resembling autoimmune diseases. There are some reports of Graves' disease (GD) induced by anti-cytotoxic T-lymphocyte-associated antigen 4 antibodies, but reports which discussed GD induced by anti-PD-1 antibodies are very rare. We report the case of a 61-year-old man with bladder cancer who presented with severe diarrhea, fatigue, palpitation, body weight loss, and hyperthyroidism after the fifth treatment with the anti-PD-1 monoclonal antibody pembrolizumab. His thyroid function prior to pembrolizumab administration had been subclinical hyperthyroidism, despite a negative thyroid-stimulating hormone receptor antibody (TRAb) level. On admission, pembrolizumab administration was discontinued. Graves' disease was diagnosed based on a positive TRAb test result and the ultrasonographic finding of increased blood flow in the superior thyroid artery. Based on colonoscopy findings, the cause of diarrhea was diagnosed as active colitis. His diarrhea was improved with prednisolone, and thyroid function was treated with potassium iodide and thiamazole. This case report of GD with positive TRAb induced by the anti-PD-1 antibody pembrolizumab may contribute to the understanding of the mechanism underlying the association between GD and autoimmune activation via PD-1.