Graves’ disease is a condition of autoimmune hyperthyroidism. Graves’ disease typically runs its course and then resolves as the immune system heals. Worldwide, antithyroid drugs (ATDs) are the most common treatment for hyperthyroidism. Since the introduction of radioiodine as an ablative treatment for Graves’ disease in the 1940s, it has remained a first-line treatment approach in the United States. With recognition of the dangers of radioiodine, and the Internet's role in medical education and patient empowerment, more patients are requesting drug therapies for Graves' disease.
Antithyroid Drug Use in the United States
Antithyroid drugs are medicines that reduce thyroid hormone production. In addition, ATDs mildly suppress the immune system, reducing production of the thyroid antibodies that cause hyperthyroidism in Graves’ disease. Like most synthetic drugs, antithyroid drugs are modeled after plant compounds. In the 1940s researchers discovered that plants known as goitrogens contain sulfur (thiol) molecules that inhibit thyroid hormone production. The word goitrogen refers to their ability to cause hypothyroidism and thyroid gland enlargement (goiter) when consumed excessively. Goitrogens include raw broccoli, cabbage, cauliflower, squash, peanuts, almonds, maize, kohlrabi and other plants.
Consequently, antithyroid drugs, which were introduced in the mid-1940s, contain thiol derivatives and are often referred to as thionamides. In the United States, antithyroid drugs, which have been in use for more than 60 years, include propylthiouracil (PTU) and methimazole (Tapazole).
In 2010, David Cooper and his team at Johns Hopkins Medical School began a study of ATD prescribing habits in the United States. The results showed that between 1991 and 2008, methimazole, which was introduced several years after PTU, became the most frequently prescribed ATD. Prior to this study, PTU accounted for two-thirds of all prescriptions. Between 1991 and 2008 there was a 19 percent increase in PTU (from 348,000 to 415,000 prescriptions annually) and a 9-fold (800 percent) increase in methimazole (from 158,000 to 1.36 million prescriptions annually).
Methimazole’s popularity compared to PTU is related to its superior side effect profile, greater efficacy in severely hyperthyroid patients and its longer mode of action. In addition, in the 1990s, methimazole became available as a generic, causing it to be more affordable than in the past. PTU, which now has a black box warning due to its potential to cause liver problems, is generally reserved for patients who are pregnant, allergic to methimazole and in possibly life-threatening conditions of thyroid storm. The Johns Hopkins study showed that 30 percent of methimazole prescriptions were written by endocrinologists; 20 percent by internists, general practitioners, and family medicine physicians and 13 percent by doctors of osteopathy. For PTU, endocrinologists and internists each accounted for 27 percent of prescriptions, and doctors of osteopathy accounted for 24 percent. Pediatricians accounted for 2 percent of all methimazole prescriptions and 2 percent of all PTU prescriptions.
How Antithyroid Drugs Work
Thyroid hormone results from the linking of iodine molecules to the amino acid tyrosine. Antithyroid drugs exert their antithyroid effects primarily by inhibiting thyroid hormone production by interfering with the oxidation and organic binding of iodide into thyroglobulin molecules (thyroid hormone precursors). In addition, PTU, but not MMI, inhibits the peripheral conversion of T4 (thyroxine) to the more potent T3 hormone by deiodinase enzyme. ATDs also have a mild immunosuppressant effect demonstrated by their ability to reduce TSH receptor antibodies.
Treatment Changes in Graves’ Disease
There is a trend in the United States for patients to be more involved in their own healthcare. Because of federal government changes, patients have a right to know about all aspects of their condition and all treatment options. With patient involvement, there has been more of a demand for medical treatment that induces remission rather than thyroid gland destruction. The Johns Hopkins team predicts that the use of PTU will begin to fall and the United States will catch up with the rest of the world, with methimazole as the mainstay treatment for Graves’ disease.
Source:
- Ana B. Emiliano, Laura Governale, Mary Parks, and David S. Cooper. 2010. “Shifts in Propylthiouracil and Methimazole Prescribing Practices: Antithyroid Drug Use in the United States from 1991 to 2008,” Journal of Clinical Endocrinology and Metabolism. May; 95(5): 2227-2233.
Disclaimer: The information contained in this article is for educational purposes only and should not be used for diagnosis or to guide treatment without the opinion of a health professional. Any reader who is concerned about his or her health should contact a doctor for advice.
Elaine Moore - I'm a retired medical technologist and medical writer with more than 30 years experience working in hospital laboratories. Currently, I ...
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