RESPONSE TO METHIMAZOLE IN GRAVES-DISEASE

OBJECTIVE A variety of regimens continue to be used in the treatment o f Graves' disease with antithyroid drugs. We have investigated the fac tors which determine the initial response to methimazole (time until e uthyroidism is achieved) in Graves' disease. PATIENTS Five hundred and nine patients with Graves' disease in different European countries wi th normal and subnormal iodine supply. Patients were randomized to tre atment with either 10 or 40 mg of methimazole per day for one year, wi th levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months. MEASUREMENTS Response was assessed by seri al measurements of serum thyroid hormones. TSH receptor antibodies, th yroid autoantibodies and urinary iodide excretion were measured centra lly. Twenty-minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as we ll as a stepwise logistic regression model were used to examine the re lations between methimazole dose, age, goitre size, presence of endocr ine eye signs, thyroid hormone levels, urinary iodide excretion, thyro id uptake, index of disease severity (Crooks), presence of TSH recepto r antibodies and duration of the hyperthyroid phase. RESULTS Within 3 weeks, 40.2% of patients responded to 10mg of methimazole and 77.5% re sponded within 6 weeks. The corresponding figures for 40 mg of methima zole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroidism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor a ntibodies (TBIAb), index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed in patien ts with large goitres, iodine excretion of greater than or equal to 10 0 mu g/g creatinine, high pretreatment thyroid hormone levels, elevate d levels of TBIAb and treatment with only 10 mg of methimazole. In the 10-mg group, 46% of patients were euthyroid within 3 weeks when urina ry iodide was <50 mu g/g of creatinine, and only 27% when iodide was a bove 100 mu g/g. By stepwise logistic regression, the main factors for the response to methimazole were daily dose, pretreatment T3 levels, and goitre size. CONCLUSION Methimazole dose, pretreatment serum T3 le vels, and goitre size are the main determinants of the therapeutic res ponse to methimazole in Graves' disease, at least in areas comprising low, subnormal and normal iodine supply.