Tremelimumab-Induced Graves Hyperthyroidism

Abstract

• Transient thyroiditis and Graves disease usually take place within the first 12 weeks following anti-CTLA-4 therapy. • In this case, Graves disease developed after 8 years of tremelimumab therapy for metastatic melanoma. • Antithyroid drug therapy was safe and effective alongside anti-CTLA-4 therapy without compromis-ing antitumour treatment efficacy. Abstract Tremelimumab and ipilimumab are monoclonal antibodies directed against the extracellular domain of cytotoxic T-lym-phocyte-associated antigen 4 (CTLA-4) and have been used as immunotherapies against immune checkpoints that sup-press T-cell activation. Anti-CTLA-4 antibody-based thera-pies have been shown to be effective in treating various cancers including metastatic melanoma. However, a few immune-related adverse events including hypophysitis and thyroid disorder have been reported, mostly developed within the first year of receiving treatment. We report a case of tremelimumab-induced Graves hyperthyroidism in a 55-year-old man who was diagnosed with metastatic mela-noma after 8 years of tremelimumab therapy. He had no per-sonal or family history of thyroid or autoimmune diseases. His biochemical profile was in keeping with Graves disease, with raised serum free thyroid hormones, suppressed thy-roid-stimulating hormone concentration, and raised thyro-tropin receptor antibody level. He was treated with carbima-zole as part of the block and replace therapy, without complications. Tremelimumab therapy was temporarily dis-continued and recommenced when he was rendered bio-chemically euthyroid. There has been no further relapse of Graves hyperthyroidism since the discontinuation of block and replace therapy. The mechanistic profile of anti-CTLA-4-induced thyroid dysfunction and the long-term endocrine safety of this therapeutic approach remain unclear. It is im-portant to monitor thyroid functions in patients receiving anti-CTLA-4 therapies, as their effects on endocrine systems could be more latent or prolonged than the data from cur-rent clinical trials suggest. Antithyroid drug therapy was safe and effective alongside anti-CTLA-4 therapy without com-promising antitumour treatment efficacy.