A Clinical Study On Lithium Carbonate Combined With ¹³¹I For Treatment Of Graves’ Disease With Leucocytopenia

Objective:Lithium carbonate is a common medicine in the treatment of manic-depressive psychosis.It is economic,and could be absorbed completedly in a short time in oral administration.It also has a stable plasma concentration,andusually concentrates in thyroidand and kidney.Recent researches found that li-ion couldinhabit the release ofthyroid hormones and hydrolyzethyroglobulin（Tg）.As a result,li-ion could relieve the side effects of the iodine treatment,such as symptoms of hyperthyroidism,or sudden aggregation of the complication,and,thus,decrease the risk of inducing thyroid crisis.Li-ion could also prolong the effective half-life of ¹³¹I in thyroid,and enhance the therapeutic effects of ¹³¹I treatment for Graves Disease（GD）.Moreover,li-ion acts on marrow,so it could increase the level of granulocyte colony stimulating factor,as well as the level of white blood cell（WBC）in peripheral blood.Therefore,lithium carbonate combined with¹³¹I are currently widely used as the treatment for severe GD,GD with huge goiter,GD with leucocytopenia,and GD with heart disease.However,there is no universal agreement about how to combine lithium carbonate and ¹³¹I to treat GD and its complication.There are two administration methods that are most frequently used.One is to simultaneously combine lithium carbonate and ¹³¹I for two weeks.The other one is to take lithium carbonate for two weeks,including one week before and after taking ¹³¹I.The main difference between these two methods is that the former one could shorten the preparation time of the ¹³¹I treatment,and avoid the inconvenience of second visit.But it remains unclear about the differences between these two administration methodsin the aspect of therapeutic effects and the side effects for GD with leucocytopenia.Our study was designed to explorethis question.The study aims to compare the differences between two administration methods of lithium carbonate combined with¹³¹I for treatment forincipient GD withleucocytopenia,including the therapeutic effects and side effects,and,thus,to provideevidence about which administration would be more effective,safer,and more convenient for patients of incipient GD with leucocytopenia.Methods:The data was collected from 2014 January to 2016 January.Patients were selected if they were first diagnosed GD with leucocytopenia,and had never received antithyroid drugs（ATD）treatment before.192 patients had been selected,49 male,143 female,with average age 39.65±12.18y in total.Random number table was utilized to divide the patients into three group,control group（n=60）which received only¹³¹I treatment,treatment group A（n=65）which received¹³¹I and lithium carbonate simultaneously for two weeks,and treatment group B（n=67）which received lithium carbonate one week before and after taking ¹³¹I（two weeks in total）.Indicators to be compared across the three groups included the following:cure rate and response rate at 3 months and 6 months after the treatment;the level of serum free Triiodothyronine（FT3）,free Thyroxine（FT4）,and WBC before treatment,at 2 week,1 month,3months,and 6 months after the treatment;adverse reaction rate（ADR）in each group within first two weeks after the treatment.Also,the research also compared the24-hour¹³¹I uptake between control group and treatment group B.The data was analyzed via ANOVA,t test with Bonferroni correction,and chi-square test.Results:1.In the treatment group B,there was a significant increase in 24-hour ¹³¹I uptake at one week after treatment of lithium carbonate,compared with that before treatment（82.75±6.37%vs63.9±7.2%）.There were no differences in the control group of 24-hour ¹³¹I uptake at one week after（65.27±6.48%vs64.5±7.4%）.Also,comparing the treatment group B and the control group,the 24-hour ¹³¹I uptake of the former was significantly higher than the latter（82.75±6.37%vs65.27±6.48%）.2.Compared with the date before the treatment,the level of FT3 and FT4 of both the two treatment groups were significantly lower at all measured time points after the treatments,which were two weeks,one month,3 months,and 6 months.In the control group,compared with the data before treatment,the level of FT3 and FT 4were slightly higher at two weeks after treatment,but became decreasing after one month after treatment.And at 3 months and 6 months after the treatment,the level of FT3 and FT4in the control group were significantly lower than that before treatment.3.Comparing the GD cure rate across the three groups,both the 3-month and6-month cure rate of both treatment group A and treatment group B were higher than those of control group（3-month:87.7%vs88.1%vs70.0%;6-month:89.2%vs89.6%vs71.7%）.Regarding the GD response rate across the three groups,there found no significant differences（3-month:98.5%vs97.0%vs91.7%;6-month:98.5%vs97.0%vs91.7%）.4.Regarding the level of WBC before the treatment,there were significant increases in both treatment group A and treatment group B at 3 months and 6 months after the treatment compared with the data before treatment.In the control group,compared with the WBC level before treatment,there was a slight increase at three months after treatment,but found a significant increase at 6 months after the treatment.Comparison of the degree of increasing of the WBC level at 3 months suggests that,the WBC level of both treatment group A and B were significantly higher than that of the control group（38.9±5.1%vs39.8±6.3%vs20.2±3.3%）.Comparing the level of WBC across the three groups at each time points,there found no significant differences.5.Both treatment group A and treatment group B had a significantly lower adverse reaction rate than control group（3.1%vs 14.9%vs30.0%）.Also,between the two treatment groups,the adverse reaction rate of treatment group A was lower than that of treatment group B.The differences reached the significant level.Conclusions:In ¹³¹I treatment for incipient GD patients with leucocytopenia,combining lithium carbonate could increase therapeutic effects to hyperthyroidism,increase the level of WBC,and reduce the adverse reaction rate after ¹³¹I treatment.Simultaneous combination of 131I treatment and lithium carbonate for two weeks,compared to separately using lithium carbonate for one week before and after ¹³¹I treatment（two weeks in total）,could significantly reduce the adverse reaction rate after ¹³¹I treatment,and increase the clinical safety of ¹³¹I treatment.