Antithyroid Substances

Thyroid Factor

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Drugs that suppress thyroid secretion are called antithyroid substances. The best known of these substances are thiocyanate, propylthiouracil, and high concentrations of inorganic iodides. The mechanism by which each of these blocks thyroid secretion is different from the others, and they can be explained as follows.

Thiocyanate Ions Decrease Iodide Trapping. The same active pump that transports iodide ions into the thyroid cells can also pump thiocyanate ions, perchlorate ions, and nitrate ions. Therefore, the administration of thio-cyanate (or one of the other ions as well) in high enough concentration can cause competitive inhibition of iodide transport into the cell— that is, inhibition of the iodide-trapping mechanism.

The decreased availability of iodide in the glandular cells does not stop the formation of thyroglobulin; it merely prevents the thyroglobulin that is formed from becoming iodinated and therefore from forming the thyroid hormones. This deficiency of the thyroid hormones in turn leads to increased secretion of TSH by the anterior pituitary gland, which causes overgrowth of the thyroid gland even though the gland still does not form adequate quantities of thyroid hormones. Therefore, the use of thiocyanates and some other ions to block thyroid secretion can lead to development of a greatly enlarged thyroid gland, which is called a goiter.

Propylthiouracil Decreases Thyroid Hormone Formation. Propylthiouracil (and other, similar compounds, such as methimazole and carbimazole) prevents formation of thyroid hormone from iodides and tyrosine. The mechanism of this is partly to block the peroxidase enzyme that is required for iodination of tyrosine and partly to block the coupling of two iodinated tyrosines to form thyroxine or triiodothyronine.

Propylthiouracil, like thiocyanate, does not prevent formation of thyroglobulin. The absence of thyroxine and triiodothyronine in the thyroglobulin can lead to tremendous feedback enhancement of TSH secretion by the anterior pituitary gland, thus promoting growth of the glandular tissue and forming a goiter.

Iodides in High Concentrations Decrease Thyroid Activity and Thyroid Gland Size. When iodides are present in the blood in high concentration (100 times the normal plasma level), most activities of the thyroid gland are decreased, but often they remain decreased for only a few weeks. The effect is to reduce the rate of iodide trapping, so that the rate of iodination of tyrosine to form thyroid hormones is also decreased. Even more important, the normal endocytosis of colloid from the follicles by the thyroid glandular cells is paralyzed by the high iodide concentrations. Because this is the first step in release of the thyroid hormones from the storage colloid, there is almost immediate shutdown of thyroid hormone secretion into the blood.

Because iodides in high concentrations decrease all phases of thyroid activity, they slightly decrease the size of the thyroid gland and especially decrease its blood

Thyroid-stimulating hormone


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