***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: In 1976 we initiated a prospect i ve study to specify the usefulness of thyroid stimulating antibody ( TSAb ) determinations in predicting the outcome of post‐antithyroid drug treatment for Graves ' disease . This study was carried out on 55 patients , who were either treated for six ( n= 16 ) or 18 months ( n= 39 ) and followed up for an additional two‐year period . TSAb was determined on whole serum in 29 patients before and at the end of treatment , and in 26 patients at the end of treatment only . These determinations were carried out using a sensitive and reproducible microassay based on cAMP accumulation in human thyroid cell cultures . Before treatment , TSAb ranging from 170 to 1529 % was present in 28/29 patients and reached significantly low levels at the end of treatment whatever its duration . TSAb was undetectable in 24/55 patients at the end of treatment . 8/16 ' short‐treated ’ and 18/39‘long‐treated ’ patients remained in remission . As expected , initial TSAb levels had no predictive value . End‐treatment TSAb values , when low ( ±350 % ) or negative did not correlate with later evolution : in these 39 patients , relapse rate was 41 % . In contrast , 13/16 patients with end‐treatment TSAb ± 350 % relapsed . Relapses tended to occur earlier in patients with the highest TSAb levels . TSAb determined again during follow‐up was negative in each of the 18 patients in remission , and positive in 8/10 patients at the time of relapse , whatever its level at the end of the drug course . This study confirms that only high end‐treatment TSAb levels are predictive of relapse . In the other cases , TSAb had no prognostic value . Overall , it was shown that TSAb levels appear to reflect only partially , the activity of the underlying disturbances of Graves ' disease Although many research ers have reported clinical and laboratory parameters for prediction of remission in Graves ' disease during or after anti-thyroid drug therapy , there is no reliable one to assure the complete remission . We prospect ively examined a practical therapy with minimum maintenance dose of anti-thyroid drugs for prediction of remission in Graves ' disease . Fifty-seven patients with Graves ' disease were treated with anti-thyroid drugs at the initial dose of 30 mg/day of methimazole ( MMI ) or 300 mg/day of propylthiouracil ( PTU ) . Then , doses were gradually decreased , and finally discontinued when the patients were able to maintain euthyroid ( normal FT4 and TSH ) for at least 6 months with the minimum maintenance dose ( MMI 5 mg every other day or PTU 50 mg every other day ) . After discontinuation of drugs , FT4 , FT3 , TSH and TSH-binding inhibitory immunoglobulin ( TBII ) were measured every one to two months for the first 6 months and every 3 - 4 months for the next 18 months to confirm continuous remission . After 2 years of drug cessation , 46 ( 81 % ) of 57 patients were in remission and the other 11 patients had relapsed into thyrotoxicosis . At the time of drug discontinuation , the serum concentration of FT4 , FT3 and TSH , titers of anti-thyroglobulin antibodies and anti-thyroid microsomal antibodies , goiter size were not different between the remission and relapse groups . At the time of drug cessation , the activities of TBII and thyroid-stimulating antibodies ( TSAb ) overlapped between the two groups , although they were significantly lower in the remission group than in the relapse group ( p<0.01 ) . Forty percent ( 4/10 ) of TBII positive patients and 71 % ( 23/32 ) of TSAb positive patients continued to be in remission . On the other h and , thyrotoxicosis relapsed in 5 ( 11 % ) of 47 TBII negative and 2 ( 8 % ) of 25 TSAb negative patients . These data indicate that minimum maintenance therapy to keep euthyroid ( normal FT4 and TSH ) for 6 months is a practical measure for 81 % prediction of remission in Graves ' disease . The measurement of TBII or TSAb gave little additional information for predicting remission 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 To determine the influence of age on the signs and symptoms of hyperthyroidism we prospect ively examined 880 patients and matched them by age , sex , race , and visit date with similarly examined euthyroid control subjects .  Many signs and symptoms showed little change with age until after the fifth decade of life when they began to decrease gradually . Findings that increased with age were weight loss and atrial fibrillation , while those that decreased most markedly with age were increased appetite and weight gain . The diagnosis is more difficult as age progresses because there are fewer findings and because the significance of those present may not be appreciated . Identification of the most sensitive and specific signs and symptoms in each age decade should improve the early detection 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 A prospect i ve study was carried out to determine the factors which influence response to  antithyroid drug treatment  in Graves ' disease and to assess their predictive value . Eleven variables were included in the assessment and were subjected to discriminant analysis , log rank test and " survival " analysis . The patients were observed for a considerable period ( mean duration 51 months ) .  Carbimazole ( mean total dose 8 g ) was given in combination with thyroxine for an average of eight months to 72 patients . Thirty-five patients relapsed and 37 remain in remission . Thyrotrophin binding inhibiting immunoglobulins ( TBII ) were detectable in 74 per cent of patients at diagnosis and thyroid stimulating antibodies detectable in 70 per cent . At the end of treatment thyrotrophin binding inhibiting immunoglobulins and thyroid stimulating antibodies were present in 36 and 27 per cent of patients respectively . Levels of thyrotrophin binding inhibiting immunoglobulins were significantly higher both before and after treatment in the group who relapsed , but were not of prognostic significance in an individual patient unless the value was extremely high ( TBII index greater than 70 ) . The presence of thyroid stimulating antibodies was of no value in predicting outcome . HLA typing confirmed the known association of Graves ' disease with HLA B8 and HLA DR3 but neither of these antigens conferred and increased likelihood of relapse . The likelihood of relapse is shown to be directly related to the severity of the disease at the time of diagnosis , as measured by the serum total T3 , and to the size of the thyroid gl and ; it is not affected by age , family history of thyroid disease or ophthalmopathy . The data indicate that antithyroid drug treatment can be expected to induce long-term remission in patients with mild disease ( T3 less than 5 nmol/l ) and small thyroids ; carbimazole at this dose level is inappropriate for patients with severe disease ( T3 
    Output:
    
IMPLICATION S This analysis revealed that certain risk factors were associated with GD relapses such as younger age , larger goiter size or thyroid volume , and the higher free triiodothyronine or free thyroxine level in the diagnosing phase of GD .