局部注射免疫抑制剂治疗复发性毒性弥漫性甲状腺肿伴功能亢进症的疗效和安全性

Therapeutic effect and safety of local intrathyroid injection of immunosuppressive agents in the treatment of recurrent toxic diffuse goiter associated with hyperthyroidism

目的:探讨甲状腺局部注射免疫抑制剂地塞米松(Dex)、环磷酰胺(CTX)和奥曲肽治疗复发性毒性弥漫性甲状腺肿伴功能亢进症(又称Graves病)的疗效和安全性。方法:采用随机单盲法将300例复发性Graves病病人分为两组,两组病人均常规口服甲巯咪唑或丙硫氧嘧啶。治疗组病人甲状腺局部注射Dex(4mg/次)、CTX(50mg/次)和奥曲肽(0.1mg/次),每周1次,连续3个月;每两周1次,连续2个月;每月1次,连续4个月。观察治疗期间病人的甲状腺体积,甲状腺功能[包括总三碘甲状腺原氨酸(TT3)、总甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、超敏促甲状腺激素(sTSH)、促甲状腺激素受体抗体(TRAb)、甲状腺球蛋白抗体(TGAb)和甲状腺过氧化酶抗体(TPOAb)的水平],肝、肾功能及血、尿常规的改变。结果:治疗组病人的甲状腺体积与对照组相比明显缩小:3个月时,(21.3±6.9)vs(28.7±9.2)cm3(P<0.01);6个月时,(16.4±7.8)vs(25.6±8.2)cm3(P<0.01);治疗2年时,(7.9±6.1)vs(20.9±8.5)cm3(P<0.001)。治疗6个月后,治疗组的甲状腺抗体转阴率明显高于对照组:TRAb(31.3±12.5)vs(62.8±11.3)%(P<0.01),TGAb(20.7±9.5)vs(52.3±8.2)%(P<0.01),TPOAb(24.7±12.8)vs(55.8±10.9)%(P<0.01)。治疗组和对照组病人的甲状腺功能分别在治疗6个月和12个月时全部恢复正常。治疗组停药2年后只有21%复发,而对照组的复发率高达70%。整个治疗过程中,两组病人的肝、肾功能,血、尿常规无显著变化。结论:甲状腺局部注射免疫抑制剂用于治疗复发性Graves病疗效和安全性良好,其机制可能与缓解甲状腺肿大,抑制甲状腺相关抗体水平的升高有关。

Objective：To investigate the therapeutic effect and safety of local intrathyroid injection of immunosuppressive agents dexamethasone（Dex）, cyclophosphamide（CTX） and octreotide in the treatment of recurrent toxic diffuse goiter associat- ed with hyperthyroidism（Graves＇ disease）. Methods：Three hundred patients with recurrent Graves＇ disease were randomly di- vided into 2 groups by single blind method. Patients in both groups were treated with conventional oral therapy of thiamazole or propylthiouracil. Patients in the treatment group were treated with Dex（4 mg）,CTX（50 mg） and octreotide（0. 1 mg） by local intrathyroid injection,once a week for three months, then once every two weeks for two months, and once a month for 4 months. Changes in size and function of thyroid, including plasma concentrations of total triiodothyronine（TT：~ ）, total thyroxine （TT~）, free triiodothyronine （FT3）, free thyroxine （FT,）, sensitive thyroid-stimulating hormone （sTSH）, thyroid-stimulating hormone receptor antibody （ TRAb）, thyroid globulin antibody （TGAb） and thyroid peroxidase antibody （ TPOAb）, liver and kidney functions, blood and urine routine were examined. Results：Thyroid sizes of the patients in the treatment group were sig- nificantly decreased than those of the control group： （21.3±6.9） vs （28.7±9.2） cm3 （P〈0.01） in the 3rd month; （16.4± 7.8） vs （25.6±8.2） cm3（P〈0.01） in the 6＇h month and （7.9±6. 1） vs （20.9±8. 5） cm3（P〈0.001） at the end of 24th month, respectively. The negative conversion rates of thyroid-related antibodies within 6 months were significantly higher in the treatment group than those in the control group：TRAb （31.3±12.5） vs （62.8±11.3）%（P〈0.01）,TGAh （20.7±9.5） vs （52.3±8.2）%（P〈0.01）,TPOAb（24.7±12.8） vs （55.8±10.9）% （ P〈 0. 01） . Thyroid function of the patients in both the treatment and control groups returned to normal,following treatment for 6 and 12 months respectively. The relapse rate was on-ly 21st in the treatment group after two years,whihe that of the control group was 70 uA. In the whole process ot treatment,no significant changes could be noted in liver and kidney functions, blood and urine routines in the patients of both groups. Conclusion：Local intrathyroid injection of immunosuppression agents is safe and effective in the treatment of recurrent Graves＇ disease. The mechanism of which might be related with the alleviation of thyroid enlargement and the restricated level of thy- roid-related antibodies.