Two Graves' disease patients who spontaneously developed hypothyroidism after antithyroid drug treatment: Characteristics of epitopes for thyrotropinreceptor antibodies

Few reports have identified blocking thyrotropin receptor antibodies (TSHRA bs) as a pathogenic mechanism explaining spontaneous hypothyroidism after a ntithyroid drug (ATD) treatment of Graves' disease. Here we report 2 Graves ' patients who showed different courses of hypothyroidism after ATD treatme nt. The first patient had Graves' hyperthyroidism and was treated with ATD for 1 year. After a short period of euthyroidism, she developed permanent h ypothyroidism with blocking TSHRAb. The second patient became euthyroid aft er 1 year of ATD treatment. After 3 years, however, she presented with hypo thyroidism with blocking TSHRAb activity. Her hypothyroidism was transient, and restoration of euthyroidism was followed by disappearance of blocking TSHRAb. Blocking and stimulating TSHRAbs activities of these 2 patients wer e serially measured using Chinese hamster ovary (CHO) cells transfected wit h wild-type human TSHR (CHO-hTSHR) and 2 TSHR chimeras with residues 8-165 (Mc1+2) or 90-165 (Mc2) substituted by equivalent residues of the luteinizi ng hormone/chorionic gonadotropin receptor (LH/CGR). During their hypothyro id phases, blocking TSHRAbs activities were positive in all 3 kinds of assa ys and stimulating TSHRAbs activities were negative in CHO-hTSHR or in Mc12 assay. Mc2 stimulating TSHRAb activity was detected in sera of hypothyroi d phase of the second patient who had transient hypothyroidism but not in t he first whose hypothyroidism was permanent. In these 2 cases, we demonstra te the causative role of blocking TSHRAb in the development of hypothyroidi sm after ATD treatment in Graves' patients. Interestingly, the difference i n the course of blocking TSHRAb-induced hypothyroidism was associated with the difference in epitope reactivities of TRAb during hypothyroid phase tha t developed after ATD treatment of Graves' disease.