The mechanism of the antithyroid action of iodide ion and of the aromatic thyroid inhibitors.

Two general classes of compounds interfere with the synthesis of the hormone thyroxine in the thyroid gland. These are the thiocarbamides and what will be referred to here as the “aromatic” antithyroid compounds. The present state of knowledge on the mechanism and locus of action of these substances has been reviewed recently (l-3). There appears to be general agreement that the thiocarbamides exert a direct chemical reducing action in the gland; thus the oxidation required to convert inorganic iodide to organically bound iodine is impossible. This result,s in the cessation of the synthesis of thyroxine and its intermediates in the gland. In contrast to this, there is no generally acceptable explanation for the mechanism of action of the aromatic antithyroids. This class of substances was discovered by Mackenzie et al. (4) who found that sulfaguanidine produced enlargement and hyperplasia of the thyroid glands of rats to which it was administered. This action was found to be common to a number of sulfonamide derivatives as well as to many other compounds containing an amino-substituted benzene ring (5). These compounds were shown to inhibit the synthesis of thyroxine by surviving slices of thyroid tissue in vitro and it was shown that a series of aromatic hydroxy compounds had this same effect (6). It would appear from information at present in the literature that all aromatic compounds with an electron-donating group on t’he ring are capable of inhibiting the synthesis of the thyroid hormone. For this reason the authors feel that this class of compound should be referred to as the “aromatic” rather than the “sulfonamide” or “aminobenzene” type of inhibitor. We feel that the data presented in this paper establish the finding that the aromatic thyroid inhibitors act by binding the elementall iodine formed in the gland. They do this either by forming a molecular compound with