THEORETICAL ASPECTS OF ANTITHYROID DRUG-T REATMENT

Antithyroid drugs (thionamides such as carbimazole and its active meta bolite methimazole, and propyl thiouracile) are taken up by the thyroi d gland just as the other anions similar to iodide (perchlorate, thioc yanate, pertechnetate). Their target is the thyroid peroxidase. They b lock the iodation of tyrosine residues and the coupling of iodotyrosin es into iodothyronines. However, beyond the inhibition of thyroid horm one synthesis, antithyroid drugs appear to have the capacity of interf ering with the immunological abnormalities involved in Graves' hyperth yroidism: they cure 50% of the patients provided they are maintained f or at least 12 months and they significantly decrease the titers of an tithyroid antibodies in most of the patients. Potential immunomodulato ry effects of antithyroid drugs seem to involve thyroid depletion of i odine which might reduce antigen expression, and scavenging of reactiv e free radicals generated from oxygen and/or iodide during peroxidatio n. A direct toxic effect of thionamides on immuno-competent cells seem s unlikely. Whatever the mechanisms, more accurate elucidation of the immunomodulatory action of antithyroid drugs might contribute to a bet ter understanding of the thyroid-immune derangements involved in the i nitiation or perpetuation of Graves' hyperthyroidism.