Endocrine Abstracts

Ipilimumab and tremelimumab are monoclonal antibodies directed against the extracellular domain of cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and have been used as the immunotherapies against immune checkpoints that suppress T cell activation. These anti-CTLA4 antibody-based therapies are effective in treating various cancers including metastatic melanoma. However, a few immune-related adverse events including hypophysitis and transient thyroiditis have been reported. We reported the first case of tremelimumab-induced Graves’ thyrotoxicosis.

A 55-year old man who was diagnosed with metastatic melanoma was enrolled into a phase II trial of anti-CTLA4 monoclonal antibody following a relapse of metastatic nodal and lung diseases. He completed 8 cycles of Tremelimumab in 2 years followed by 6-monthly Tremelimumab treatment with good response. However, the patient started to lose weight despite good appetite within a 6-month duration, after having intermittent Tremelimumab for 8 years. He has no personal or family history of thyroid or autoimmune diseases. He was clinically euthryoid and no goitre was palpable. There were no signs suggesting Graves’ ophthalmopathy. His serum TSH was suppressed with raised free thyroid free T3 13.0 pmol/l and free T4 27.6 pmol/l. Thyroid peroxidase antibodies (TPO) were elevated at >600 kU/l with raised thyrotropin receptor antibody (TRAB) at 5.0 IU/l. These results are consistent with Graves’ disease. He was then started on carbimazole 40 mg daily as part of the block and replace therapy. Further Tremelimumab therapy was deferred until he was rendered biochemically euthyroid.

The mechanistic profile of anti-CTLA4 induced thyroid dysfunction and the long-term endocrine safety of this therapeutic approach remains unclear. It is important to monitor thyroid functions in patients receiving anti-CTLA4 therapies as their effects on endocrine systems could be more latent or prolonged than the data from the current clinical trials suggests.