Kinetics of [123I]iodide uptake and discharge by perchlorate in studies of inhibition of iodide binding by antithyroid drugs

Thyroidal binding of idoide was studied by kinetic analysis of [123I]iodide uptake and its discharge by perchlorate in 80 hyperthyroid subjects receiving antithyroid drug therapy. Five dosage regimens ranging from 5 mg carbimazole twice daily to 15 mg methimazole twice daily were studied. Binding inhibition was estimated at 5–7 h after drug as an index of the mean effect of the 12 hourly regimen. In all cases, except one in the lowest dose group, binding was found to be markedly reduced with mean binding rates ranging from 0.002 to 0.020 min−1 (normal > 0.15 min−1). The net clearance of iodide in the lowest dose group was reduced to a mean value near the upper limit of the euthyroid range, whereas in the highest dose group it lay at the lower limit of the euthyroid range. These results were reflected in the serum thyroid hormone response. There was a reducing incidence of inadequate control of hyperthyroidism and an increasing incidence of hypothyroidism with increasing thiourylene dose. The exit rate constant of free iodide for the various doses showed values from 0.048 to 0.055 min−1. Corresponding mean values for the discharge rate constant after perchlorate were 0.087 to 0.105 min−1. This suggests that perchlorate increases the rate of iodide release from the thyroid gland. Studies at a later interval after drug (12–14 h) showed no change in discharge rate constant. This leads to the conclusion that perchlorate may further inhibit iodide binding in subjects receiving antithyroid drug therapy.