Chung H K, Kim W B, Park D J, Kohn L D, Tahara K, Cho B Y
Department of Internal Medicine, Seoul National University College of Medicine, Korea.
Thyroid. 1999 Apr;9(4):393-9. doi: 10.1089/thy.1999.9.393.
Few reports have identified blocking thyrotropin receptor antibodies (TSHRAbs) as a pathogenic mechanism explaining spontaneous hypothyroidism after antithyroid drug (ATD) treatment of Graves' disease. Here we report 2 Graves' patients who showed different courses of hypothyroidism after ATD treatment. The first patient had Graves' hyperthyroidism and was treated with ATD for 1 year. After a short period of euthyroidism, she developed permanent hypothyroidism with blocking TSHRAb. The second patient became euthyroid after 1 year of ATD treatment. After 3 years, however, she presented with hypothyroidism 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 were serially measured using Chinese hamster ovary (CHO) cells transfected with 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 luteinizing hormone/chorionic gonadotropin receptor (LH/CGR). During their hypothyroid phases, blocking TSHRAbs activities were positive in all 3 kinds of assays and stimulating TSHRAbs activities were negative in CHO-hTSHR or in Mc 1+2 assay. Mc2 stimulating TSHRAb activity was detected in sera of hypothyroid phase of the second patient who had transient hypothyroidism but not in the first whose hypothyroidism was permanent. In these 2 cases, we demonstrate the causative role of blocking TSHRAb in the development of hypothyroidism after ATD treatment in Graves' patients. Interestingly, the difference in the course of blocking TSHRAb-induced hypothyroidism was associated with the difference in epitope reactivities of TRAb during hypothyroid phase that developed after ATD treatment of Graves' disease.
很少有报告将促甲状腺素受体抗体（TSHRAbs）确定为解释抗甲状腺药物（ATD）治疗格雷夫斯病后自发性甲状腺功能减退的致病机制。在此，我们报告2例格雷夫斯病患者，他们在接受ATD治疗后出现了不同病程的甲状腺功能减退。首例患者患有格雷夫斯甲亢，接受ATD治疗1年。在短暂的甲状腺功能正常期后，她出现了伴有阻断性TSHRAb的永久性甲状腺功能减退。第二例患者在接受ATD治疗1年后甲状腺功能恢复正常。然而，3年后，她出现了伴有阻断性TSHRAb活性的甲状腺功能减退。她的甲状腺功能减退是短暂的，甲状腺功能恢复正常后阻断性TSHRAb消失。使用转染了野生型人促甲状腺素受体（CHO-hTSHR）的中国仓鼠卵巢（CHO）细胞以及2种促甲状腺素受体嵌合体（其8-165位残基（Mc1+2）或90-165位残基（Mc2）被促黄体生成素/绒毛膜促性腺激素受体（LH/CGR）的等效残基取代），对这2例患者的阻断性和刺激性TSHRAbs活性进行了连续检测。在她们的甲状腺功能减退期，在所有3种检测中阻断性TSHRAbs活性均为阳性，而在CHO-hTSHR检测或Mc 1+2检测中刺激性TSHRAbs活性为阴性。在第二例患有短暂性甲状腺功能减退患者的甲状腺功能减退期血清中检测到了Mc2刺激性促甲状腺素受体抗体活性，而在首例患有永久性甲状腺功能减退的患者中未检测到。在这2例病例中，我们证明了阻断性TSHRAb在格雷夫斯病患者接受ATD治疗后甲状腺功能减退发生中的致病作用。有趣的是，阻断性TSHRAb诱导的甲状腺功能减退病程差异与格雷夫斯病接受ATD治疗后出现的甲状腺功能减退期促甲状腺素受体抗体（TRAb）表位反应性差异有关。
