Risk Factors For The Relapse Of Graves’ Disease Treated With Antithyroid Drugs

Objective:Anti-thyroid drug(ATD)have almost always been the first choice for the treatment of GD worldwide.However,the high rucurrence rate is regarded as the most important trouble after drug withdrawal.We try to assess related factors for the recurrence of GD by this study,thus to find the appropriate time for GD patients to stop taking drugs and reduce recurrence.Methods:GD patients,who were newly diagnosed in the affiliated hospital of Qingdao university from January 2016 to December 2019,were enrolled in this study.According to the normal reference range of TSH(0.55-4.78 m IU/L),all the patients were divided into three groups based on serum TSH level at the time of ATD withdrawal: Group A:0.55≤TSH<1.96 m IU/L,Group B: 1.96≤TSH<3.37 m IU/L and Group C:3.37≤TSH<4.78 m IU/L.The general data and thyroid function related indexes of in each group were compared.The correlations between age,sex,duration of maintenance therapy with low-dose ATD,serum levels of Thyrotropin receptor antibody(TRAb),TSH level,Free triiodiothyronine(FT3),Free thyroxine(FT4),serum FT3 to FT4ratios(FT3/FT4),were analyzed.Univariate analysis was used to find the factors related to the recurrence of GD.We used Cox proportional hazard regression model to assess the relationship between the above factors level and recurrence in patients with GD after ATD treatment.Result:1.The baseline characteristics of 218 Graves’ disease patients ranged in age from 14 to76 years.Patients < 40 years old accounted for 54.13%,patients ≥40 years old for45.87%,women for 79.36%,and men for 20.64%.When discontinued,192 patients(88.07%)had normal TRAb,18 patients(8.26%)had high TRAb,and 8 patients(3.67%)had absent TRAb.There were 70 patients(32.11%)who received low-dose drug maintenance treatment for less than 6 months,147 patients(62.73%)who received low-dose drug maintenance treatment for more than 6 months,and 1 patient(0.46%)whose maintenance time was unknown.Median values of FT3,FT4,TSH and FT3/FT4 were 4.58 m IU/L,14.44 m IU/L,1.98 m IU/L and 0.32 when discontinuous.2.age,sex,serum levels of FT3,FT4,FT3 / FT4 at the time of ATD withdrawal were not correlated with recurrence in GD patients treated with ATD.3.When serum TSH value was used as a continuous variable after ATD withdrawal,univariate survival analysis showed that recurrence of Graves’ disease was correlated with TSH value(HR= 0.55,95%CI= 0.40-0.75,P=0.00),in another word,the risk of recurrence decreased by 45% for every 1 m IU/L increase in TSH.the level of serum TSH was negatively correlated with recurrence in GD patients treated with ATD(HR=0.43,95%CI= 0.22-0.86,P=0.02).4.the level of serum TRAb was correlated with recurrence in GD patients treated with ATD(HR=2.99,95%CI=1.43-6.22,P=0.00).5.the duration of maintence therapy with low-dose ATD was correlated with recurrence in GD patients treated with ATD(HR=0.53,95%CI=0.31-0.94,P=0.03).Conclusions:1.Serum TSH is an independent protective factor in patients with Graves disease.The level of serum TSH at the time of drug withdrawal can predict the risk of recurrence after drug withdrawal.Higher TSH concentration(1.96≤TSH<4.78 m IU/L)may be used as a basis for selecting the appropriate time for drug withdrawal in patients with Graves disease.2.The level of serum TRAb in patients with Graves disease is related to the prognosis.The risk of recurrence in patients with abnormal serum TRAb is 2.99 times higher than that in patients with normal level.3.The risk of recurrence of Graves disease patients with drug maintenance therapy less than 6 months is 1.89 times higher than that of patients with more than 6 months.4.The ATD withdrawal should be considerd when serum TSH level is a little bit higher among normal range(>1.96 m IU/L),the serum TRAb activity is negtive.And low-dose maintenance therapy ≥ 6 months.5.The age,sex and serum FT3,FT4 and FT3/FT4 of patients with Graves disease are not related to the prognosis of Graves disease.