Development of Thyrotoxicosis With Positive TSH Receptor Antibody and Transition to Hypothyroidism in a Patient With Unresectable Hepatocellular Carcinoma During Combined Atezolizumab and Bevacizumab Therapy: A Case Report and Review of the Literature

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Summary: A 65-year-old male with multiple hepatocellular carcinomas underwent hepatic artery chemoembolization in March X and was administered lenvatinib. In July X, 2 weeks after the initiation of this treatment, he developed latent hypothyroidism. However, he showed no response to these treatments. Consequently, a combination therapy consisting of an anti-programmed cell death protein-ligand 1 (PD-L1) antibody (atezolizumab) plus bevacizumab, administered every 3 weeks, was initiated in March X+1. During three cycles of this combination therapy, the patient developed thyrotoxicosis. Graves’ disease (GD) was suspected by TSH receptor antibody (TRAb) positivity and diffuse uptake in thyroid scintigraphy, although ^99mTcO₄^- uptake was normal. He was treated with methimazole. Notably, the hyperthyroidism was transient, rapidly transitioning to hypothyroidism. The emergence of GD during treatment with immune checkpoint inhibitors (ICPi) is a rare occurrence. To date, 26 cases of new-onset GD and/or thyroid eye disease (TED) have been reported. Approximately 71% of patients develop GD and/or TED within 3 months following the initiation of ICPi treatment. They quickly transition to a hypothyroid state, necessitating levothyroxine therapy. Furthermore, the presence of thyroid autoantibodies at baseline has been identified as a significant risk factor for thyroid immune-related adverse events (irAEs), highlighting the need for baseline measurements of these autoantibodies before treatment. Future prospective studies and further case report accumulations are essential to elucidate the role of thyroid irAEs during the combined therapy of ICPi and molecularly targeted drugs in advanced carcinoma cases.