Environmental iodine intake affects the response to methimazole in patients with diffuse toxic goiter

The response to methimazole [1-methyl-2-mercaptoimidazole (MMI)] therapy was evaluated in 18 patients with diffuse toxic goiter residing in an area of iodine deficiency (Tehran) and in 18 patients residing in an area of iodine sufficiency (Boston). The mean free T4 index (FT4I) decreased from 22.9 +/- 4.8 (+/- SD) to 4.9 +/- 4.3 in Tehran and from 23.8 +/- 5.2 to 17.0 +/- 4.1 in Boston after 4 weeks of MMI administration (10 mg, three times daily). The mean free T3 index (FT3I) decreased from 489 +/- 124 to 117 +/- 58 in Tehran and from 512 +/- 250 to 368 +/- 152 in Boston. In patients residing in Tehran, the FT4I was normal in 9 (less than 6.3 in 6), above normal in 1, and subnormal in 8 (44%) after 4 weeks of MMI treatment. In 4 of 8 patients with subnormal FT4I, serum TSH was also above normal, and clinical findings of hypothyroidism were evident. MMI (10 mg, twice daily) was then given to 15 additional patients with diffuse toxic goiter in Tehran. Mean FT4I values were 22.7 +/- 6.8, 12.1 +/- 2.5, 10.8 +/- 2.8, and 6.0 +/- 4.3 before and 8, 14, and 28 days after treatment, respectively. Corresponding mean FT3I values were 415 +/- 90, 196 +/- 36, 162 +/- 44, and 117 +/- 46. At 28 days, FT4I was subnormal in 7 (46%) patients, of whom 1 had increased TSH. These results indicate that treatment with recommended doses of MMI rapidly causes hypothyroidism in patients residing in Tehran, an area of iodine deficiency. Furthermore, they support the hypothesis that the dosage of thionamide compounds and the duration of therapy with the initial doses necessary to induce euthyroidism may vary in various parts of the world.