抗甲状腺药物治疗Graves病复发风险模型的构建与评估

Construction and evaluation of recurrence risk model of Graves′disease treated with antithyroid drugs

目的构建并评估抗甲状腺药物(ATD)治疗初发Graves病停药后复发风险预测模型。方法纳入2012年至2019年南京中医大学附属中西医结合医院内分泌科Graves病患者308例,ATD规范治疗后停药,据随访2年内是否复发进入复发组或缓解组,建立发现队列,bootstrap重抽样数据为验证队列。比较两组基线人口学特征、临床表现和Graves病相关检查指标。Cox回归筛选与Graves病复发相关危险因素并构建Graves病复发风险评估系统(GRES)预测模型。评价GRES模型预测效应并与Graves病治疗后复发事件评分(GREAT评分)模型进行比较。结果170例完成随访,90例停药2年内复发。Graves病家族史,年轻(<30岁),中重度甲状腺肿(Ⅱ度~Ⅲ度),高促甲状腺激素受体抗体(TRAb≥13 IU/L)水平,较大甲状腺体积(≥26.4 cm^(3))和低25羟维生素D水平[25(OH)D<14.7 ng/mL]6项因素进入预测模型:个体预后指数(PI)=0.672×家族史+0.405×年龄+0.491×甲状腺肿大程度+0.808×TRAb水平+1.423×甲状腺体积+0.579×25(OH)D水平。PI值≥1.449,停药后2年内复发风险较高。GRES模型评估Graves病患者停药后2年内是否复发的区分度与准确度均较好,且优于GREAT评分。结论本研究构建的GRES模型可用于评估初发Graves病患者停药后2年内的复发风险,指导临床医师根据预测的复发风险高低,合理选择治疗方案,提高缓解率。

Objective To establish and evaluate a predictive model for recurrence risk of Graves′disease after antithyroid drugs(ATD)withdrawal.Methods Among 308 patients with newly onset Graves′disease taking ATD from 2012 to 2019,170 patients who completed follow-up were enrolled and divided into relapse and remission groups according to whether hyperthyroidism reoccurred within 2 years after ATD withdrawal to establish the discovery cohort.An internal validation cohort was constructed by repeating the sampling with bootstrap.Cox regression analysis was used to screen risk factors and establish a predictive model,named Graves′Recurrence Evaluation System(GRES).The differentiation and accuracy of GRES model were evaluated and compared with the GREAT score.Results Of 170 patients,90 Graves′disease cases relapsed within 2 years after ATD withdrawal.According to Cox regression analysis,family history of Graves′disease,younger age(<30 years),gradeⅡ-Ⅲgoiter,high level of TRAb(≥13 IU/L),large thyroid volume(≥26.4 cm^(3))and low 25(OH)D(<14.7 ng/mL)were included in the predictive model:PI=0.672×family history+0.405×age+0.491×severity of goiter+0.808×TRAb+1.423×thyroid volume+0.579×25(OH)D.PI≥1.449 was associated with a higher risk of recurrence after drug withdrawal.The GRES model has good prediction in assessing Graves′disease relapse within 2 years after ATD withdrawal and better than GREAT score.Conclusion GRES model can be used to evaluate the recurrence risk within 2 years for patients with newly onset Graves′disease after ATD withdrawal,and facilitate clinicians to reasonably select treatment modalities in order to improve the remission rate.