Patient information: Antithyroid drugs

ANTITHYROID DRUGS OVERVIEW

Antithyroid drugs (also called thionamides) are most often used to treat an overactive thyroid (hyperthyroidism) caused by Graves' disease. These drugs block the formation of thyroid hormone by the thyroid gland. (figure 1) (See "Patient information: Hyperthyroidism".)

The use of antithyroid drugs has several benefits and a few risks. It is therefore important to learn as much as possible about the treatment of Graves' disease and to discuss all of the possible effects of antithyroid drugs with a healthcare provider. (See "Treatment of Graves' hyperthyroidism".)

FUNCTION OF ANTITHYROID DRUGS

Antithyroid drugs decrease the levels of the two hormones produced by the thyroid, thyroxine (T4) and triiodothyronine (T3). (See "Patient information: Hyperthyroidism".)

Antithyroid drugs may be used as a short-term treatment to prepare people with Graves' hyperthyroidism for thyroid surgery or radioiodine; alternatively, they may be used alone for long-term treatment. Approximately 30 percent of people with Graves' disease will have a remission after prolonged treatment with antithyroid drugs. (See "Thionamides in the treatment of Graves' disease".)

Antithyroid drugs may also be used to treat hyperthyroidism associated with toxic multinodular goiter or a toxic adenoma ("hot nodule"), and to treat women with hyperthyroidism during pregnancy.

Antithyroid drugs require at least three weeks (usually six to eight weeks or longer) to lower thyroid hormone levels because they only block formation of new thyroid hormone; they do not alter the effects of thyroid hormones that are already present in the thyroid and the blood stream.

TYPES OF ANTITHYROID DRUGS

Two antithyroid drugs are currently available in the United States: propylthiouracil (PTU) and methimazole (MMI, Tapazole). Carbimazole (which is converted into MMI in the body) is available in Europe, but not in the United States.

Higher doses of antithyroid drug are often prescribed early in treatment and for people with large goiters and severe hyperthyroidism. Spreading these higher doses out over the course of the day can help minimize gastrointestinal side effects.

Methimazole (MMI) — MMI is usually preferred over PTU because it reverses hyperthyroidism more quickly and has fewer side effects. MMI requires an average of 6 weeks to lower T4 levels to normal and is often given before radioactive iodine treatment. MMI can be taken once per day.

Propylthiouracil (PTU) — PTU blocks the conversion of T4 to T3 in non-thyroid tissue, but it does not reverse hyperthyroidism as rapidly as MMI. PTU must be taken two to three times per the day.

Antithyroid drugs during pregnancy — PTU used to be the drug of choice during pregnancy because it is thought to have a lower risk of causing birth defects. But experts now recommend that PTU be given during the first trimester only. This is because there have been rare cases of liver damage in people taking PTU. After the first trimester, women should switch to methimazole for the rest of the pregnancy.

For women who are nursing, methimazole is probably a better choice than PTU (to avoid liver side effects).

If you take antithyroid drugs, you should discuss your treatment with your doctor before becoming pregnant. Having radioiodine treatment at least six months before becoming pregnant can eliminate the need for antithyroid treatment during pregnancy. (See "Patient information: Hyperthyroidism" and "Diagnosis and treatment of hyperthyroidism during pregnancy".)

Antithyroid drug side effects — Most of the side effects of antithyroid drugs are minor, but major side effects can occur. Because there is no way to predict who will experience side effects, it is important to discuss all possible side effects before starting treatment. (See "Pharmacology and toxicity of thionamides".)

If you cannot tolerate antithyroid treatments, you can consider radioiodine treatment or surgery. (See "Radioiodine in the treatment of hyperthyroidism" and "Surgery in the treatment of hyperthyroidism".)

Minor side effects — Up to 15 percent of people who take an antithyroid drug have minor side effects. Both MMI and PTU can cause itching, rash, hives, joint pain and swelling, fever, changes in taste, nausea, and vomiting.

If one medication causes side effects, switching to the other drug may be helpful. However, half of those who have side effects with one drug will also have side effects with the other drug. The nausea and vomiting may depend on the dose; therefore, spreading large total daily doses out over through day can reduce side effects.

Major side effects — Fortunately, the major side effects of antithyroid drugs are very rare.

• Agranulocytosis — Agranulocytosis is characterized by a decrease in the production of white blood cells. This condition is extremely serious, but affects only one out of every 200 to 500 people who take an antithyroid drug. Elderly people taking PTU and very high doses of MMI may be more susceptible to this side effect.

Agranulocytosis is more likely to occur within the first three months of starting treatment with an antithyroid drug. If you develop a sore throat, fever, or other signs or symptoms of infection, you should stop your medication and immediately contact your healthcare provider. Serious and potentially life threatening infections, or even death, can occur before agranulocytosis resolves. However, once the antithyroid drug is stopped, agranulocytosis usually resolves within a few days.

• Other — There are three other very rare complications of antithyroid drugs: liver damage (more common with PTU), aplastic anemia (failure of the bone marrow to produce blood cells), and vasculitis (inflammation of blood vessels associated with PTU).

The risk of liver damage has become an important concern, particularly in children. For this reason, PTU is being used less often. Your clinician will discuss these with you before you start your medication. Although all of these are rare, your clinician will discuss the warning signs with you before you start your medication.

MONITORING THYROID HORMONES DURING TREATMENT

During treatment, your blood thyroid hormone levels will be monitored periodically. Antithyroid drugs typically reduce levels of both T3 and T4, but levels of T3 may take longer to return to normal. TSH levels usually take the longest to return to normal.

About 30 percent of people who take an antithyroid drug for one to two years will have prolonged remission of Graves' disease. It is not known if the antithyroid drug plays an active role in this remission or if it simply controls thyroid hormone levels until Graves' disease resolves on its own.

Checking for remission and recurrence — No test can reliably predict remission of Graves' disease. While imperfect, the measurement of TSH-receptor antibodies is widely used in Europe to determine if a person is in remission; this test may be used in the future in the United States.

Usually, after one to two years of treatment, clinicians recommend discontinuing the antithyroid drug. Blood tests are usually performed two to three weeks after stopping the antithyroid drug. The blood tests are periodically repeated over six months to determine if hormone levels remain stable or increase over time (called a recurrence).

A person is said to have a recurrence if the TSH level is lower than normal. This can occur within 10 days of stopping antithyroid drug treatment, or it can occur several years later. If levels of T3, T4, and TSH remain normal for six months, the prognosis is good; relapse after this time occurs in only 8 to 10 percent of people.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Hyperthyroidism
Patient information: Thyroid nodules

Professional Level Information:
Beta blockers in the treatment of hyperthyroidism
Cardiovascular effects of hyperthyroidism
Clinical manifestations and diagnosis of hyperthyroidism in children and adolescents
Diagnosis and treatment of hyperthyroidism during pregnancy
Diagnosis of hyperthyroidism
Disorders that cause hyperthyroidism
Neurologic manifestations of hyperthyroidism and Graves' disease
Overview of the clinical manifestations of hyperthyroidism in adults
Radioiodine in the treatment of hyperthyroidism
Subclinical hyperthyroidism
Surgery in the treatment of hyperthyroidism
Thionamides in the treatment of Graves' disease
Treatment of Graves' hyperthyroidism
Pharmacology and toxicity of thionamides
Patient information: Thyroid nodules

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• The American Thyroid Association

      (www.thyroid.org)

• Thyroid Foundation of Canada

      (www.thyroid.ca)

• The Hormone Foundation

      (www.hormone.org/public/thyroid.cfm, available in English and Spanish)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Thyroid Conditions Forum

      (http://thyroid.about.com/forum)

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