4项甲状腺自身抗体的变化特征及联合半定量评分在格雷夫斯甲亢131I治疗后疗效的相关性评估中的临床应用价值

The variation characteristics of four thyroid antibodies and the value of the combined semi-quantitative scores in the evaluation of the efficacy of Graves' hyperthyroidism after 131I therapy

    摘要
  • 摘要:
    目的 评估甲状腺球蛋白抗体（TgAb）、促甲状腺激素受体抗体（TRAb）、甲状腺过氧化物酶抗体（TPOAb）和促甲状腺激素受体刺激性抗体（TSAb）的变化特征及联合半定量评分在格雷夫斯甲亢（GH）131I治疗后疗效中的临床应用价值。
    方法 回顾性分析2000年1月至2021年8月在上海交通大学医学院附属瑞金医院行131I治疗的512例GH患者的临床资料，其中男性101例、女性411例，年龄（38±12）岁。根据疗效评估结果将131I治疗后的患者分为4组：甲状腺功能减退（简称甲减）组、完全缓解组、部分缓解组和无效组；前3组为有效组（A组），共431例，无效组（B组）81例。根据131I治疗后的时间将A组分成4小组：A1组（131I治疗后1年内），80例；A2组（131I治疗后1~4年），193例；A3组（131I治疗后5~9年），90例；A4组（131I治疗后10年以上），68例。入组的GH患者均于131I治疗后的第4周、第7周、第3个月、第6个月、第12个月或逐年进行游离三碘甲状腺原氨酸、游离甲状腺素、促甲状腺激素、TgAb、TRAb、TPOAb、TSAb水平的连续、联合测定。单项甲状腺抗体和TgAb、TRAb、TPOAb和TSAb 4项甲状腺抗体联合半定量评分范围分别为0~3分和0~12分。组间的比较采用配对t检验。
    结果 131I治疗后TgAb、TRAb、TPOAb和TSAb水平会有不同程度地升高，其中异常升高的状况可以分别持续29、21、26和26个月，之后会有不同程度地下降（直至阴性）。B组、A1组、A2组、A3组和A4组患者的4项甲状腺抗体联合半定量评分分别为（7.43±2.31）、（5.41±2.23）、（4.43±2.40）、（2.15±1.99）和（1.52±1.50）分；A1组与A2组、A2组与A3组、A3组与A4组、A1组与B组的组间比较，差异均有统计学意义（t=3.237、8.358、2.252、−5.639，均P<0.05）。在131I治疗后5年、10年以上，TPOAb、TgAb、TRAb、TSAb的阳性率分别为64.56%（102/158）和55.88%（38/68），34.81%（55/158）和33.82%（23/68）、18.35%（29/158）和11.76%（8/68）、24.68%（39/158）和17.65%（12/68）。
    结论 4项甲状腺抗体联合半定量评分可以评估甲状腺自身免疫状态的严重程度及其变化趋势：GH初发以TRAb水平明显升高为特征，131I治疗后5年抗体指标相对稳定，其TPOAb>50%的阳性率提示患者有以桥本甲状腺炎所引起的甲减的趋势。

     

    Abstract:
    Objective To evaluate the characteristics of changes in thyroglobulin antibody (TgAb), thyroid stimulating hormone receptor antibody (TRAb), thyroid peroxidase antibody (TPOAb) and thyroid stimulating antibody (TSAb) and the value of the combined semi-quantitative score in assessing the effectiveness of 131I treatment for Graves' hyperthyroidism (GH).
    Methods Retrospective analysis of clinical data of 512 patients with GH who underwent 131I treatment at Shanghai Ruijin Hospital, School of Medicine, Shanghai JiaoTong University from January 2000 to August 2021. The patients comprised 101 males and 411 females, aged (38±12) years. According to the efficacy evaluation, patients treated with 131I were divided into four groups: hypothyroidism group, complete remission group, partial remission group, and ineffective group. The first three groups were the effective group (Group A) with a total of 431 cases, and the ineffective group (Group B) had 81 cases. According to the time after 131I treatment, Group A was further divided into 4 groups: Group A1 (within 1 year after 131I treatment; 80 cases); Group A2 (1−4 years after 131I treatment; 193 cases), Group A3 (5−9 years after 131I treatment; 90 cases); Group A4 (more than 10 years after 131I treatment; 68 cases). The GH patients enrolled in the study underwent continuous and combined measurements of free triiodothyronine, free thyroxine, thyroid stimulating hormone, TgAb, TRAb, TPOAb, and TSAb levels were performed at 4 weeks, 7 weeks, 3 months, 6 months, 12 months, or annually after 131I treatment. The semi-quantitative score ranges for single and four combined thyroid antibodies (TgAb, TRAb, TPOAb and TSAb) were 0–3 and 0–12 points, respectively. The intergroup differences were compared using paired t-test.
    Results TgAb, TRAb, TPOAb, and TSAb increased to varying degrees after 131I treatment, and the abnormal increase period could last for 29, 21, 26, and 26 months, respectively. Thereafter, they exhibited different degrees of decline (until it could be negative). In group B, A1, A2, A3 and A4, the combined semi-quantitative scores of four thyroid antibodies were 7.43±2.31, 5.41±2.23, 4.43±2.40, 2.15±1.99 and (1.52±1.50) score respectively. The differences between groups A1 and A2, A2 and A3, A3 and A4, A1 and B, were statistically significant (t=3.237, 8.358, 2.252, −5.639, all P<0.05). After 131I treatment for 5 and more than 10 years, the positive rates were 64.56% (102/158) and 55.88% (38/68) for TPOAb, 34.81% (55/158) and 33.82% (23/68) for TgAb, 18.35% (29/158) and 11.76% (8/68) for TRAb, 24.68% (39/158) and 17.65% (12/68) for TSAb, respectively.
    Conclusions The semi-quantitative score of the combination of the four thyroid antibodies could be used to assess the severity of thyroid autoimmune status and its evolution. The initial onset of GH is characterized by a significant increase of TRAb, and the antibody index is relatively stable after 5 years of 131I treatment, and TPOAb positive rate of more than 50% suggests the presence of hypothyroidism resulting from Hashimoto's thyroiditis.

     

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