DURATION OF ANTITHYROID ACTION OF METHIMAZOLE ESTIMATED WITH AN INTRAVENOUS PERCHLORATE DISCHARGE TEST

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Abstract
We have used a method based on a perchlorate discharge test to estimate the duration of antithyroid effect of two doses of methimazole (MMI). Six patients with diffuse toxic goitre took 5 mg MMI twice daily and six took 20 mg twice daily over the study period of 12 weeks. Biochemical control of hyperthyroidism was achieved in all patients and thyroid hormone supplementation was required by all of the patients in the higher dose group to avoid hypothyroidism. Discharge of radioiodine from the thyroid by perchlorate diminished in both groups with time after MMI. After 5 mg MMI, perchlorate discharge as a percentage of the 30-minute uptake (mean .+-. SD), was 81.7 .+-. 3.3% at 2.2 h, 69.3 .+-. 18.9% at 5.9 h, 22.6-23.4% at 13-.4 h and 2.7-6.7% at 25.1 h. After 20 mg MMI, the discharge was 92.5 .+-. 1.9% at 2.2 h, 84.3 .+-. 8.8% at 6.3 h, 64.8 .+-. 24.1% at 13.3% h and 26.9-29.4% at 25.1 h. Only four patients (one in the lower dose group) showed a detectable discharge at 25 h and one of the patients treated with the lower dose showed no discharge at 13 h. These estimates of the effect of MMI on thyroidal iodide organification are not in keeping with published thyroidal MMI concentrations which do not show a fall between 3.6 h and 17-20 h after carbimazole. The explanation for this disparity is not clear but may be based on a redistribution of thioureylenes within the thyroid with time after dosage. The present data suggest that once daily is not the optimum dosage interval for MMI with respect to its effect on the organification of iodide.