Marked Increase in Thyrotropin Receptor Antibodies With the Development of Pretibial Myxedema After Total Thyroidectomy

A recent study revealed that the complex of thyrotropin receptors (TSHRs) and human leukocyte antigen (HLA) class II molecules within the thyroid gland, rather than TSHR alone, induces anti-TSHR autoantibody production by disrupting self-tolerance in Graves disease (GD). However, this complex has not yet been identified outside the thyroid gland. Complete removal of the thyroid gland typically reduces autoantibody titers by eliminating the antigen source. We present the case of a 51-year-old woman with GD and Graves ophthalmopathy who exhibited a marked increase in anti-TSHR autoantibodies concurrent with the development of pretibial myxedema (PTM) despite having undergone a total thyroidectomy. Immunohistological analysis of PTM tissues revealed the coexpression of TSHR and HLA class II molecules, forming a complex similar to that previously identified in the thyroid gland. These findings suggest that TSHR complexed with HLA class II molecules in PTM tissues may contribute to autoantibody production in this patient after total thyroidectomy, although the involvement of potential residual thyroid tissue cannot be entirely excluded. This case suggests that autoantibodies can be induced outside the thyroid gland and provides novel insights into the pathogenesis and progression of GD and related disorders.