Two cases of Graves' disease with antithyroid hormone antibodies: implication on the role of thyroglobulin as an antigen.

We have experienced two cases of Graves' disease with antithyroid hormone autoantibodies (Case 1: anti-T4; Case 2: anti-T3) who finally underwent subtotal thyroidectomy after antithyroid drug treatment. Using serial sera obtained before and after operation, the correlation between titers of antithyroglobulin (anti-Tg) and anti-T4 or anti-T3 autoantibodies was examined in each case. There was a significant positive correlation between titers of anti-T4 (Case 1, r = 0.90, p less than 0.05), or anti-T3 (Case 2, r = 0.64, p less than 0.01) and anti-Tg antibodies. Using the homogenate of the thyroid tissue, it was found that the sole iodoprotein in the thyroid gland in each patient was 660 KDa Tg. In addition, Tg purified from the thyroid gland from Case 2 showed different immunological activity with normal Tg in two out of four murine monoclonal anti-Tg antibodies tested. On the other hand, Tg from Case 1 had identical immunological activity with normal Tg in every four monoclonal antibodies. These results are consistent with the view that the antigen responsible for the development of antithyroid hormone autoantibodies is Tg, at least in our two cases. The reason for the persistence of anti-T3 autoantibodies in Case 2, despite the subtotal thyroidectomy, could be due to some unidentified structural abnormalities of Tg which was detected only by the monoclonal anti-Tg antibodies.