Does The Initial Dose Of Methimazole Correlate To The Efficacy And Hypothyroxinemia In The Course Of The Treatment Of Hyperthyroidism?

Objective: Antithyroid drug therapy is the main treatment for Grave’s disease. As the new guidelines of ATA/AACE(American Thyroid Association/American Association of the Clinical Endocrinologists) in 2011 recommend, ATD therapy initial dose of methimazole(MMI) 10~20mg/d or propylthiouracil(PTU) 150~450mg/d, but in terms of the initial dose of the right medication, are still lack of strong evidence-medical support.Meanwhile, for the GD patients taking ATD occurred hypothyroxinemia phenomenon,Analysis of related factors of hypothyroxinemia during ATD therapy,then discusses the course of GD treatment in combination with L-thyroxine(L-T4) or not impact on the course of the disease. GD current treatment very irregular, and has a lot of randomness.The course of treatment in combination with L-T4 whether or not the impact on the course of inconclusive. Many clinical endocrinologist usually choose to add or not add L-T4 according to their own experience. This study investigated the efficacy of treatment and after its relationship with the occurrence of hypothyroxinemia among former administration of different doses of MMI retrospective.Compare the use of low-dose(MMI15mg/d),moderate dose(MMI20mg/d) and high-dose(MMI130mg/d) methimazole therapy efficacy and safety. And through observation whether or not combined with L-T4 to the response rate for GD to provide reference for clinical medicine.Method: In this study, we selected hyperthyroidism patients who came to the first Affiliated Hospital of Dalian Medical University for treatment from May 2013 to September 2014. The diagnosis of the patients based on clinical symptoms, physical examination, thyroid function, TRAb and ECT. According to the inclusion and exclusion criteria, 146 cases were included. Before the treatment, we preserve the serum sample of the patients and record their sex, age, symptoms, TSH, FT3, FT4, TRAb, Tg Ab, TPOAb, biochemical parameters, liver function, absolute value of leukocyte and neutrophil. 146 patients in FT4<40pmol/L were given MMI15mg/d, group MMI15mg(low dose group, n=60); FT4 is between 40~60 pmol/L were treated with MMI20mg/d, group MMI20mg(middle dose group, n=39); FT4>60 pmol/L MMI30mg/d, MMI30 group(high dose group, n=47). Before treatment with mild neutropenia(neutrophil count ranged from 1.5×109/L to 2×109/L) or mild abnormal liver function(ALT or AST increased but did not reach 2.5 times the normal value), regardless of the initial level of FT4, were treated with MMI15mg/d. According to the initial treatment period, reduction period, maintenance period and standardized medication.Follow-up once every two weeks. At least 16 weeks of follow-up. Collected before and after general information,thyroid function,blood,Liver function related blood biochemical parameters. EXCEL2003 software was used for data entry and SPSS 22.0 statistical software was adopted for statistical processing.Measurement data were presented as mean±standard deviation( x ±s) indicate.Data between the two groups were compared using t test. Data among the three groups were compared using analysis of variance. X2 test was used to compare the percentage. To "whether there is a hypothyroxinemia after ATD treatment" as the dependent variable,With "sex, age, before treatment FT4, TRAb, TgAb, TPOAb and MMI initial dose level" as the independent variable line logistic regression analysis. Respectively, "FT4 standard time", "TSH standard time" as the dependent variable, With "sex, age,medication before the FT4, TRAb, Tg Ab, TPOAb levels,MMI initial dose,whether in combination with L-T4" as the independent variable line multiple linear regression analysis,P <0.05 was considered with statistically significance.Results:1.Three different dose MMI groups treatment GD can all achieve good results. FT4 level after16-weeks’ treatment decreased significantly in all the three groups(P< 0.01). Three groups of FT4 before treatment, MMI30 mg group were higher than those in MMI15 mg group and MMI20 mg group, the difference was statistically significant(P<0.01); Comparison between the three groups after treatment of FT 4, no significant difference(P>0.05); After treatment, MMI30 mg group, FT4 decreased significantly than that in group MMI15 mg and group MMI20mg(P<0.01).Three groups of TSH level after 16-weeks’ treatment showed a rising trend, and difference was statistically significant in MMI 30 mg group(P <0.05).2. "whether there is a hypothyroxinemia after ATD treatment" was considered as the dependent variable,with "sex, age, before treatment FT4,TRAb,TgAb, TPOAb and MMI initial dose level" as the independent variable line logistic regression analysis. The results show that these indicators are not related to hypothyroxinemia(P> 0.05).3.There were 65 patients had hypothyxinemia during MMI treatment of GD patients, which in combination with L-T4 in 23 cases, not in combination with L-T4 in 42 cases.Not in combination with L-T4 group of hypothyxinemia slightly earlier than normal time combined with L-T4 group. But between the two groups, the difference was not statistically significant(P>0.05). In combination with L-T4 group of hypothyxinemia 65.22% response rate, slightly higher than in combination with L-T4 not group 52.38%. Between the two groups were compared using the x2 test, the difference was not statistically significant(P> 0.05).4.TSH and FT4 standard time comparing three groups within groups, FT4 standard time was earlier than TSH standard time. And group MMI15 mg statistically significant differences(P<0.01). Comparison of TSH standard time among the three groups, TSH standard time MMI20 mg group most slow. There are significant differences between the groups with and MMI15 mg MMI30mg group. The difference was statistically significant(P<0.05). There was no significant difference between group 15 mg and group 30mg(P>0.05) TSH standard time. While the time required for FT4 reaching to the standard among the three groups showed no statistical difference(P>0.05).5.Respectively, "FT4 standard time", "TSH standard time" as the dependent variable,with "sex, age, medication before the body FT4, TRAb, Tg Ab, TPOAb levels, MMI initial dose, whether in combination with L-T4" as the independent variable line multiple linear regression analysis.The results show that these indicators are not related to FT4 and TSH standard time.6.Three groups of treatment process of the 96 cases of GD patients with FT 4 decreased to normal, MMI15 mg group of FT4 remission rate was 84.62%, higher than that of MMI20 mg group and MMI30 mg group.But the three groups were compared by x2 test, no significant difference(P>0.05). When FT4 returned to normal, in 16 cases at TSH remission normal, not relieved in 80 cases. Among them, MMI15 mg group of TSH response in 9 cases, remission rate was 20.45%, higher than that of MMI20 mg group and MMI30 mg group. But the three groups were compared by x2 test, no significant difference(P>0.05).Conclusion:1. According to the initial FT4 level, the treatment of different doses of MMI can effectively control hyperthyroidism, and the efficacy of different dosage groups is similar, and the efficacy has nothing to do with dose.2. Occurrence of hypothyroxinemia in the course of the treatment of MMI showed no correlation with sex, age, serum FT4 level, TRAb, Tg Ab, TPOAb levels and even the initial dose of MMI.3. Combined application of L-T4 for hypothyroxinemia did not affect the rate of recovery of hyperthyroidism,also do not show advantage.