Study On Drug Responsiveness In Early Stage Of Hyperthyroidism Caused By Graves' Disease Treated With Methimazole

BackgroundMethimazole?MMI?is one of the main therapeutic drugs for GD.It is absorbed by the thyroid gland from the blood and mainly inhibits the synthesis of thyroid hormone by inhibiting thyroid peroxidase.However,it has been found in clinical practice that the efficacy varies greatly among individuals.Some patients have a slow recovery of thyroid function after use while others may suffer from severe drug-induced hypothyroidism during treatment.In the early stage of drug therapy,we expect to restore thyroid function quickly and make stable with appropriate dose,and meanwhile reduce the occurrence of adverse drug reactions as much as possible.Therefore,more simple and easier methods are needed to predict the different responses to drug therapy in individuals.In many clinical studies related to drug reactions and efficacy,due to the lack of unified and objective definition of drug responsiveness,the results of studies were different.The definition of different therapeutic effects or drug reactions,such as the time of restoration of thyroid function and whether severe hypothyroidism occurs,cannot exclude the subjective influence of doctors on drug adjustment.Recently,a literature proposed to apply mathematical model to define drug responsiveness,which we explored and compared with earlier literatures,and compared the occurrence of adverse reactions in different drug reaction groups.Objective:The purpose of this study was to verify the role of mathematical model in defining methimazole drug responsiveness and to explore the individual differences of different drug response groups and whether there are differences in adverse drug reactions in different groups which provided the basis for the choice of clinical drug treatment plan for Graves'disease.Then we preliminarily discussed its possible mechanism.Methods:We retrospectively analyzed the general data?including onset age,sex,smoking history,thyroid size by palpation,etc?,serological examination?including blood routine,thyroid function,thyroid-associated antibodies,liver function test,etc?and imaging indexes?thyroid iodine uptake?of outpatients with Graves'disease before and after treatment with methimazole.The data of patients with 30mg?taken orally three times?per day on the starting were selected,and the continuously monitored serum free thyroxine levels were used for linear regression to establish the mathematical model of"drug response coefficient".The patients were further divided into"slow response group"and"rapid response group".The therapeutic effects between the two groups were observed,including the recovery time of free thyroxine?FT₄?,whether severe drug-induced hypothyroidism?TSH?10uIU/ml?and the first month occurred during the treatment.The"reaction coefficient"was verified by the decrease of free thyroxine level.Compared the baseline data between the two groups to predict the difference of drug response among different individuals.Finally,the adverse reactions of patients with different drug reactions were compared to provide a basis for clinical treatment.Results:1.The median of"drug response coefficient"was 0.0438.The patients were divided into"rapid response group"and"slow response group"according to the median,and there was no significant difference in the goodness of fit of linear equation between them?p=0.542?.2.The recovery time of serum FT₄ in the"rapid response group"was significantly shorter than that in the"slow response group"?p<0.01?.The decrease level and rate of free thyroxine in the first month of patients in the"rapid response group"were higher than those in the"slow response group"?p<0.01?.The occurance of severe drug-induced hypothyroidism in the"rapid response group"was significantly higher than that in the"slow response group",and the difference was statistically significant?p<0.01?.3.Univariate analysis showed that serum levels of FT₃?p<0.01?,FT₄?p<0.01?and TRAb?p<0.01?in the"rapid response group"before treatment were significantly higher than those in the"slow response group",with statistically significant differences.4.The single-factor ROC curve showed that the sensitivity and specificity of the"fast response group"were 0.564 and 0.883,AUC=0.784?p<0.01?when 23.4pmol/L of serum FT₃ was used as the cutting point.The sensitivity and specificity were 0.713and 0.809,AUC=0.788?p<0.01?when 51.1 pmol/L of serum FT₄ was used as the cutting point.The sensitivity and specificity were 0.681 and 0.798,AUC=0.804?p<0.01?when 16.3?IU/L of serum TRAb was used as the cutting point.5.Multivariate Logistic regression?progressive method?showed that FT₄ and TRAb were included in the equation,the overall model fitted well,and the area under the multivariate ROC curve was 0.903?p<0.01?.The regression coefficient of FT₄ was0.084,OR=1.088,and the 95%confidence interval was 1.056-1.121?p<0.01?.The regression coefficient of TRAb was 0.132,OR=1.142,and the 95%confidence interval was 1.092-1.193?p<0.01?.6.The occurance of biochemical abnormalities?including granulocyte abnormalities and liver function abnormalities?in the"rapid response group"was higher than that in the"slow response group",and the difference was statistically significant?p=0.022?.The occurance of granulocytopenia?p=0.721?and abnormal liver function?p=0.080?in the"rapid response group"was not statistically different compared to the"slow response group".Conclusion:Patients with higher levels of serum free thyroxine or thyrotropin receptor antibodies before treatment responded better to drug therapy and were more likely to have adverse drug reactions.