Abstract

THE discovery of the antithyroid activity of certain drugs furnished a tool and a renewed stimulus for the study of the mechanism of thyroid function. One of these agents, thiouracil, was early recognized as an effective chemotherapeutic agent for the control of thyrotoxicosis. Unfortunately, thiouracil, the most active of these early agents, proved not to be an unmixed blessing since it possesses properties which lead to many undesirable reactions. Despite the study and publication of results on several hundred compounds, no ideal antithyroid agent has been found.

The mechanism of action of the antithyroid agents is not clear. Evidence indicates there is an interference by these agents with the thyroid content of oxidative enzymes. Moreover, it appears that the conversion of iodide to free iodine and thus the conversion of iodide to organic forms is blocked. For example, the formation of diiodotyrosine is depressed. Iodine participates in many vital reactions in the thyroid gland. According to De Robertis (1) it prevents the breakdown of the globulin portion of thyroglobulin by inhibiting proteolytic enzymes of the thyroid. The fixation of iodide in the production of thyroxine is catalyzed by thyroid-stimulating hormone (TSH). ExcessiveJevels of iodide inhibit this and other actions of TSH. Thus the actual formation of active thyroid hormone depends upon the quantitative relationship of iodine to thyrotropin, the rate of activation and inactivation of TSH, the level of oxidase activity in the thyroid, and probably many other unknown factors (2, 3).

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