***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND The effect of supplementation with a fixed combination of antioxidants ( vitamins C and E , beta-carotene and selenium ) was monitored on the speed of attaining euthyroidism in a group of patients with Graves ' disease , treated with methimazole .  METHODS The activity of glutathione peroxidase in whole blood and the concentrations of selenium , pituitary and thyroid hormones in serum were measured , prior to commencement of therapy and after 30 and 60 days . RESULTS Patients who received supplementation with antioxidants in addition to therapy with methimazole  ( Group A , n=29 ) attained euthyroidism faster than the patients treated with only methimazole  ( Group B , n=28 ) . The concentration of selenium in the serum of patients in Group A increased significantly during treatment ( p<0.001 ) , while there was no statistically significant change in the patients in Group B. The concentration of selenium in the serum between the groups differed statistically significantly 30 days ( p<0.05 ) and 60 days ( p<0.01 ) after the commencement of therapy . Activity of glutathione peroxidase in whole blood increased during treatment in both groups of patients . However , a statistically more significant increase occurred in Group A compared to Group B , 30 days after the commencement of therapy ( p<0.01 ) . CONCLUSION The results of the study clearly indicate that supplementation with antioxidants in the treatment of Graves ' disease is justified , particularly those containing selenium We compared the effects of high and low dosages of antithyroid drugs in 113 patients with Graves ' hyperthyroidism . The patients were r and omly divided into 2 groups . In group A , 65 patients received either methimazole ( MMI ) : 60 + /- 14.5 mg/day ( mean + /- SD ) ; range 40 - 100 mg/day , or propylthiouracil ( PTU ) : 693 + /- 173 mg/day ; range 500 - 1200 mg/day . These high doses were maintained throughout treatment with later addition of 50 - 75 micrograms T3 daily . Forty eight patients ( group B ) were treated with lower doses of MMI or PTU without thyroid hormone addition . The maintenance dose of MMI was 13.6 + /- 7 mg/day ( range 5 - 25 mg/day ) and that of PTU was 180 + /- 58 mg/day ( range 100 - 300 mg/day ) . The treatment period was 15.1 + /- 4.2 ( range 10 - 30 ) months for group A and 13.5 + /- 2.2 ( range 12 - 20 ) months for group B. Remission occurred in 75.4 % patients from group A and in 41.6 % patients from group B ( P less than 0.001 ) . The mean follow-up was 42 + /- 14 months ( 17 - 81 months ) . The free T4 index ( FT4I ) in group A remained below the normal range during treatment . The mean FT4I , obtained during the course of treatment , of patients who went into remission from group A was significantly ( P less than 0.001 ) lower than in relapsed patients ( 4.8 vs. 6.5 ) . Moreover , there was an inverse correlation between mean FT4I and maintenance daily dose of either MMI ( r = -0.567 ; P less than 0.001 ) , or PTU ( r = -0.379 ; P less than 0.01 ) . A fall in microsomal antibody ( MCHA ) titer occurred mainly in remission patients , and was more significant ( P less than 0.05 ) in group A patients . In contrast , 11 ( 7 from group B ) of the 16 patients with an increase of microsomal antibody levels relapsed . The frequency of negative tests of thyroid-stimulating antibody was higher in group A patients ( 71 % ) than in group B ( 29 % ) at the end of therapy ( P less than 0.01 ) . No correlation was found between thyroid T3 suppressibility and either mean FT4I or thyroid-stimulatory antibody activity during treatment . Our findings show that patients treated with high doses of PTU or MMI throughout treatment have a higher remission rate when compared to those treated with a more conventional regimen . These results support the hypothesis that large antithyroid drug doses may have greater immunosuppressive effects than low dosage regimens . Furthermore , a high dosage regimen could permit the restoration of the immune surveillance mechanisms and , thus , lasting remission of Graves ' disease UNLABELLED Graves ' disease ( GD ) patients treated with antithyroid drugs ( ATD )  have overall relapse rates of 30 - 50 % after ATD discontinuation . Conflicting data have been reported with regard to the usefulness of adding thyroxine ( I-T4 ) during and after ATD treatment . Also , clinicians are still in search of useful factors to predict remission/recurrence after ATD withdrawal . Eighty two consecutive patients were treated with  ATD for 15 months , combined with 12 months of I-T4 . Then , patients were r and omized ( placebo-controlled double blind protocol ) to continuing I-T4 versus a placebo for one year . RESULTS I-T4 administration during and after ATD treatment did not affect favorably the outcome , the final recurrence rate being 31 % , in both placebo and I-T4 groups . Two factors were identified as independent and synergistic markers of a significantly increased risk of recurrence after ATD withdrawal : smoking and TSH receptor antibodies ( TSHR-Ab ) remaining positive at the end of ATD . Non smoking patients with a negative TSHR-Ab ( end ATD ) had a low ( 18 % ) recurrence risk , while smoking patients also with a negative TSHR-Ab had a higher ( 57 % ) recurrence risk . Non smoking patients with a positive TSHR-Ab ( end ATD ) had a 86 % recurrence risk . Finally , smoking patients with a positive TSHR-Ab ( end ATD ) all recurred within 6 months . CONCLUSIONS 1 ) T4 administration after ATD withdrawal does not improve recurrence rates ; 2 ) two parameters , smoking and positive TSHR-Ab ( at end ATD ) , were valid -- albeit not absolute-predictors of the risk of recurrence in ATD-treated patients with Graves ' disease BACKGROUND Antithyroid drugs are effective in patients with hyperthyroidism due to Graves ' disease , but the rate of recurrence after treatment is high . In a recent Japanese study , adjunctive treatment with thyroxine ( T4 ) was associated with a recurrence rate 20 times lower than that among patients who received only an antithyroid drug . If these results are confirmed , combined therapy with an antithyroid drug and T4 might become the treatment of choice for all patients with Graves ' hyperthyroidism . METHODS We treated 111 patients ( 89 women and 22 men ) who had Graves ' hyperthyroidism . All patients initially received 40 mg of carbimazole daily for one month . Then one group received carbimazole alone for 17 months ( 52 patients ) , and the other group received carbimazole plus T4 for 17 months and T4 alone for 18 months ( 59 patients ) . In the carbimazole group , the dose was adjusted after one month to maintain a normal serum thyrotropin concentration . In the carbimazole-T4 group , the dose of carbimazole was not changed , but 100 micrograms of T4 per day was added to the regimen and the dose was adjusted to maintain an undetectable serum thyrotropin concentration ( < 0.04 microU per milliliter ) . RESULTS At the time of our analysis , 53 of the 111 patients had completed at least 3 months of follow-up ( median , 12 months ) after carbimazole was withdrawn . Hyperthyroidism recurred in eight patients in each group after a mean ( + /- SD ) of 6 + /- 4 months in the carbimazole group and 7 + /- 4 months in the carbimazole-T4 group . There was no difference between the recurrence rates in the two groups , despite the fact that serum thyrotropin concentrations were undetectable in 73 percent of patients in the carbimazole-T4 group on at least 75 percent of their visits . CONCLUSIONS The administration of T4 to patients with Graves ' disease during carbimazole treatment and after its withdrawal neither delays nor prevents the recurrence of hyperthyroidism OBJECTIVE In Graves ' hyperthyroidism treated with antithyroid drugs ( ATD ) , the overall relapse rate reaches 30 - 50 % following ATD discontinuation . Conflicting results have previously been reported with regard to the usefulness of combining ATD with thyroxine ( l-T4 ) , and thereafter maintaining l-T4 treatment after ATD withdrawal . Also , clinicians are in search of useful parameters to predict the risk of a recurrence of hyperthyroidism after ATD treatment . DESIGN Eighty-two consecutive patients ( 70 women and 12 men ; mean age 36 years ) with a first episode of Graves ' hyperthyroidism were investigated prospect ively ; they were treated with ATD for a total of 15 months , combined with l-T4 ( for at least 12 months ) after they had reached euthyroidism , with the aim of maintaining serum TSH below 2.5 mU/l during the combined therapy . Following ATD discontinuation , the patients were r and omly assigned ( double-blind placebo-controlled trial ) to taking 100 microg/day l-T4 ( vs placebo ) for an additional year . METHODS The following determinations were carried out at initial diagnosis : serum total T4 and tri-iodothyronine ( T3 ) , free T4 and T3 , TSH , TSH-receptor antibodies ( TSHR-Ab ) , thyroid scintigraphy and echography . During ATD treatment , serum free T4 and T3 and TSH concentrations were recorded after 1 ( optional ) , 2 , 4 , 6 , 9 , 12 and 15 months , and echography at the end of ATD treatment . During the r and omized trial , serum free T4 and T3 and TSH concentrations were checked every 3 months ( or until a recurrence ) . TSHR-Ab titers were measured at initial diagnosis , after 6 months with ATD , and at the end of ATD treatment . RESULTS l-T4 administration , both during and after ATD treatment , did not improve the final outcome and recurrence rates were similar in placebo and l-T4-treated patients ( 30 % ) . Two parameters were identified that might be useful to help predict recurrence risks after ATD : ( i ) positive TSHR-Ab ( at the end of ATD treatment ) was significantly associated with a greatly increased recurrence risk ; and ( ii ) despite the relatively small number of patients who were smokers , regular cigarette smoking was shown , for the first time , to be significantly associated with an increased recurrence risk . Also , the deleterious effect of smoking was shown to manifest its impact independently of TSHR-Ab titers at the end of ATD treatment . Thus , compared with the overall 30 % recurrence risk , non-smoking patients with a negative TSHR-Ab ( at the end of ATD ) had a lower ( 18 % ) recurrence risk ; smoking patients with negative TSHR-Ab ( at the end of ATD ) had a 57 % recurrence risk ; non-smoking patients with positive TSHR-Ab ( at the end of ATD ) had a high ( 86 % ) recurrence risk ; the recurrence risk was 100 % in those few patients who both smoked and maintained a positive TSHR-Ab at the end of ATD treatment . CONCLUSIONS The present study confirmed that l-T4 administration during and after ATD withdrawal did not improve remission rate . Two factors , namely positive TSHR-Ab at the end of ATD treatment and regular smoking habits may represent clinical ly useful ( albeit not absolute ) predictors of the risk of recurrence in patients with Graves ' hyperthyroidism treated with ATD . However , due to the relatively small number of smoking patients in the present cohort , this conclusion needs to be confirmed by a larger study CONTEXT Although methimazole ( MMI ) and propylthiouracil ( PTU ) have long been used to treat hyperthyroidism caused by Graves ' disease ( GD ) , there is still no clear conclusion about the choice of drug or appropriate initial doses . OBJECTIVE The aim of the study was to compare the MMI 30 mg/d treatment with the PTU 300 mg/d and MMI 15 mg/d treatment in terms of efficacy and adverse reactions . DESIGN , SETTING , AND PARTICIPANTS Patients newly diagnosed with GD were r and omly assigned to one of the three treatment regimens in a prospect i ve study at four Japanese hospitals . MAIN OUTCOME MEASURES Percentages of patients with normal serum free T(4 ) ( FT4 ) or free T(3 ) ( FT3 ) and frequency of adverse effects were measured at 4 , 8 , and 12 wk . RESULTS MMI 30 mg/d normalized FT4 in more patients than PTU 300 mg/d and MMI 15 mg/d for the whole group ( 240 patients ) at 12 wk ( 96.5 vs. 78.3 % ; P = 0.001 ; and 86.2 % , P = 0.023 , respectively ) . When patients were divided into two groups by initial FT4 , in the group of the patients with severe hyperthyroidism ( FT4 , 7 ng/dl or more , 64 patients ) MMI 30 mg/d 
    Output:
    
The titration ( low dose ) regimen had fewer adverse effects than the block-replace ( high dose ) regimen and was no less effective .
Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism .