Antithyroid Drugs Thionamides

Antithyroid drugs, a class of drugs known as thionamides, block the formation of thyroid hormone by thyroid cells. If hyperthyroidism is caused by single or multiple autonomous toxic nodules (ATNs, see Chapter 8), antithyroid drugs can be used to temporarily lower thyroid hormone levels but are not useful for long-term management since ATNs don't spontaneously get better over time. On the other hand, they're often used to treat hyperthyroidism in Graves' disease, since roughly one-quarter of people with Graves' disease will see a permanent end to Graves' thyrotoxicosis after a year of treatment with thionamides (known as a remission or resolution). Although some people take thionamides for many years, I (Ken) don't advise taking them longer than one year because of potential toxicity (explained later) and because these spontaneous remissions of Graves' disease are much less likely to occur if they do not happen within the first year of thionamide treatment.

You'll find regional differences in the methods physicians use to treat Graves' disease. In the United States physicians including myself (Ken) prefer to treat Graves' disease patients with radioactive iodine (see Chapter 12), with the exception of patients who are pregnant (see Chapter 13) or young children (see Chapter 15). On the other hand, physicians in Japan and Europe tend to use thionamides more often, and radioactive iodine less often, than their American counterparts.

Thionamides are the only safe and effective form of treatment to control hyper-thyroidism during pregnancy, aside from surgery to remove the thyroid gland. This is because radioactive iodine can't be given to a pregnant woman without causing harm to the fetus within her. Surgery is an option for treatment; however, this can be a problem during pregnancy and usually can be avoided. Also, if hyperthyroidism is caused by Graves' disease (see Chapter 6) the thyroid-stimulating antibodies causing stimulation of the mother's thyroid will cross through the placenta into the blood supply of the fetus, stimulating the fetal thyroid gland. Thionamides, given to the mother, will also cross through the placenta into the fetal blood supply, treating both the mother and the fetus to prevent overproduction of thyroid hormone.

The two thionamide drugs used today are propylthiouracil (PTU) and methimazole (Tapazole). These drugs were developed in the 1940s when they were found to cause goiters in laboratory animals. They work similarly to block the formation of thyroid hormone within the thyroid cells. It is possible that they may also have effects on suppressing the immune system, decreasing the autoimmune effects of Graves' disease.

PTU seems to have an additional effect, not shared by methimazole, of decreasing the conversion of T4 to T3.

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