***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: 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, 53 of the 111 patients had completed at least 3 months of follow-up ( median , 12 months ) after carbimazole was withdrawn .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 BACKGROUND Antibodies to thyroid-stimulating hormone ( TSH ) receptors that stimulate the thyroid gl and cause hyperthyroidism in patients with Graves ' disease , and their production during antithyroid drug treatment is an important determinant of the course of the disease . One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy . We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole . METHODS AND RESULTS The levels of antibodies to TSH receptors were measured during treatment with methimazole , either alone or in combination with thyroxine , in 109 patients with hyperthyroidism due to Graves ' disease . The patients first received 30 mg of methimazole daily for six months . All were euthyroid after six months , and their mean ( + /- SD ) level of antibodies to TSH receptors decreased from 64 + /- 9 percent to 25 + /- 15 percent ( P less than 0.01 ; normal , 2.9 + /- 1.4 percent ) . Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year . In the thyroxine-treated group , the mean serum thyroxine concentration increased from 108 + /- 16 nmol per liter to 145 + /- 11 nmol per liter ( P less than 0.01 ) , and the level of antibodies to TSH receptors decreased from 28 + /- 10 percent to 10 + /- 3 percent after one month of combination therapy . In the patients who received placebo and methimazole , the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change . Methimazole , but not thyroxine or placebo , was discontinued in each group 1 1/2 years after the beginning of treatment . The level of antibodies to TSH receptors further decreased ( from 6.6 + /- 3.2 percent at the time methimazole was discontinued to 2.1 + /- 1.2 percent one year later ) in the patients who continued to receive thyroxine , but it increased ( from 9.1 + /- 4.8 percent to 17.3 + /- 5.8 percent during the same period ) in the patients who received placebo . One patient in the thyroxine-treated group ( 1.7 percent ) and 17 patients in the placebo group ( 34.7 percent ) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole . CONCLUSIONS The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism Antithyroid drugs are effective in restoring euthyroidism in Graves ' disease , but many patients experience relapse after withdrawal . Prevention of recurrence would therefore be a desirable goal . In a prospect i ve study , patients with successful outcome of 12 to 15 months antithyroid drug therapy  were stratified for risk factors and r and omly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment . The levothyroxine group was r and omized to continue or discontinue levothyroxine after 1 year . End points included relapse of overt hyperthyroidism .  Of 346 patients with Graves ' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal  and were r and omly assigned to receive levothyroxine ( 114 patients ) or no treatment ( controls , 111 patients ) . Of those not r and omized , 39 patients showed early relapse within 4 weeks , 61 endogenous TSH suppression , 7 TSH elevation , and 14 had to be excluded . Dropout rate during the study were 13.3 % . Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group ( 20 % after 1 year , 32 % after 2 years ) and the r and omized controls ( 18 % , 24 % ) , whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH ( 33 % , 49 % ) . Levothyroxine therapy did not influence TSH-receptor antibody , nor did it reduce goiter size . The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs ( posttreatment TSH ) . The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker Although antithyroid drugs ( ATD ) are widely used in the treatment of Graves ' disease , management protocol s , especially treatment duration , remain a subject of debate . The rate of relapse after short‐term regimens of less than 6 months with ATD at decreasing doses is higher than after longer treatments from 12 to 24 months . As no prospect i ve study has provided data on even longer protocol s exceeding 2 years , we conducted a prospect i ve trial to determine potential benefits of a 42‐month treatment compared with an 18‐month treatment Medical treatment of Graves ' disease involves antithyroid drugs with or without the addition of exogenous T4 . There have been conflicting reports as to whether the addition of T4 improves remission rates or delays relapse . To evaluate this issue in a North American population , 199 patients were treated with methimazole until they were euthyroid . They were then r and omized to either methimazole alone in a dose sufficient to normalize TSH ( group 1 ) , or to 30 mg methimazole daily plus sufficient T4 to maintain TSH in the upper normal range ( group 2 ) , or to 30 mg methimazole daily plus sufficient T4 to suppress TSH below 0.6 mIU/L ( group 3 ) . After 18 months , methimazole was stopped , and T4 was continued in groups 2 and 3 . Because not all patients in groups 2 and 3 achieved their target TSH concentration , they were reassigned to group A ( TSH > or = 1.0 ) or group B ( TSH < 1.0 ) , based on the mean TSH achieved during methimazole treatment . One hundred forty-nine patients have been followed for at least 6 months after stopping methimazole  ( mean 27 months ) . Fifty-eight percent of patients have relapsed . There were no significant differences in relapse rates after stopping methimazole . Among those patients who did relapse , however , there was a significant difference in the months to relapse after stopping methimazole between groups B and 1 ( group 1 : 3.3 + /- 0.7 , group A : 5.6 + /- 0.8 , group B : 7.4 + /- 1.7 ; P = 0.01 for the comparison between groups B and 1 ) . We conclude that the addition of T4 to methimazole does not improve long-term remission rates in Graves ' disease A prospect i ve r and omized study was performed in patients with hyperthyroid Graves ' disease ( GD ) in order to compare long ( 18 months ) and short term ( 6 months ) antithyroid drug treatment on the remission rate . A therapeutic protocol was offered to all GD patients who had not been treated for this disease previously . All patients studied who followed the protocol were rechecked 2 yr after treatment was withdrawn , or earlier in the case of relapse . Of the patients having undergone long term treatment , 61.8 % still were in remission 2 yr after treatment withdrawal , whereas only 41.7 % of the patients treated for 6 months were in remission ( P less than 0.05 ) . Such findings clearly establish that treatment duration has a direct beneficial incidence on the remission rate . These results were confirmed by the fact that treatment for 18 months result ed in remission in 7 of 15 patients who had previously relapsed after a 6-month course of therapy . This improvement in relation to treatment duration might be due to the immunosuppressive action of carbimazole . No significant difference was observed between relapse and remission groups , regardless of treatment duration , for HLA ABDr , serum T3 and T4 , and T3/T4 ratio determined before treatment . Only the thyroid-stimulating antibody levels determined at the time of diagnosis and at the end of treatment were higher in the relapse group , a difference that was relevant only globally , due to value scattering . Furthermore , thyroid-stimulating antibody levels at the end of treatment may indicate remission or , conversely , continuance of the pathological process . ( ABSTRACT TRUNCATED AT 250 WORDS Sixty patients with Graves ' disease ( GD ) hyperthyroidism were distributed in two r and omized groups . Patients in group A ( n = 30 ) received carbimazole by a titration regimen , and patients in group B ( n = 30 ) were treated with higher doses of carbimazole plus T4 .  Clinical and analytical evaluations were done at baseline , during treatment ( 18.4 + /- 2.6 months ) , and after , until the relapse of hyperthyroidism , or for 4.98 + /- 1.6 yr in patients who did not relapse . There were no differences in clinical parameters , thyroid hormones , or TSH binding inhibitory immunoglobulins ( TBII ) levels between the two groups , either at baseline or at the end of treatment . Serum TSH persisted undetectable in 16 out of 60 patients ( group A : 9 ; group B : 7 ) , after treatment . Relapse occurred in 38 patients ( 63.3 % ) , ( group A : 18 ( 60 % ) vs. group B : 20 ( 66.7 % ) ) . Patients who relapsed had bigger goiters at baseline ( P = 0.02 ) and at the end of treatment ( P = 0.03 ) . Eighty-seven percent ( 14/16 ) of patients with undetectable TSH after therapy relapsed , vs. 54.5 % ( 24/44 ) of those with normal TSH ( P = 0.01 ) . Undetectable TSH at the end of treatment was the only independent variable in the logistic analysis to predict relapse . Treatment modality did not influence the relapse rate . This study has found that , in Spanish patients , the use of high doses of carbimazole with T4 offers no advantages in the treatment of GD hyperthyroidism Antithyroid drugs are commonly used as first-line treatment for Graves ' disease , but the optimum regimen for inducing remission remains unclear . We gave the block-replace regimen of carbimazole plus thyroxine to 100 patients for 6 or 12 months , to determine whether prolonged treatment is associated with fewer relapses . The remission rate one year after cessation of treatment was 59 % with the 6 month course and 65 % with 12 months ; this was not significantly different . We also analysed HLA markers identified by restriction fragment length polymorphisms and could not confirm the recently reported associations of outcome with HLA-DR4 or with an HLA-DQA2 allele . These results show that six months treatment with a block-replace regimen of antithyroid drugs is probably sufficient , in the 
    Output:
    
Prescribing replacement thyroxine , either with the anti-thyroid drug treatment , or after this was completed , had no significant effect on relapse .
Limited evidence suggested 12 - 18 months of anti-thyroid drug treatment should be used .
The titration regimen appeared as effective as the Block-Replace regimen , and was associated with fewer adverse effects .
However , relapse rates over 50 % and high participant drop-out rates in trials mean that the results should be interpreted with caution , and may suggest that other strategies for the management of Graves ' disease , such as radioiodine , should be considered more frequently as first-line therapy .