Antithyroid Drugs to Treat Graves' Disease and Hyperthyroidism

Pharmacist giving prescription to customer
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Antithyroid drugs -- also referred to as thionamides -- are medications that treat an overactive thyroid (hyperthyroidism) by blocking the thyroid gland's ability to produce thyroid hormone. In the treatment of an overactive thyroid (which most commonly results from the autoimmune condition Graves' disease), it is critical to slow down the gland's excess production of thyroid hormones, especially the hormones thyroxine (T4) and triiodothyronine (T3).

In addition to treating hyperthyroidism resulting from Graves' disease, antithyroid drugs may also be used to treat hyperthyroidism associated with toxic multinodular goiter, thyrotoxicosis, or a toxic adenoma ("hot nodule"). Antithyroid drugs are sometimes used to treat women with hyperthyroidism during pregnancy as well.

Antithyroid drugs work by making it more difficult for the body to use iodine, thereby blocking the formation of thyroid hormones in the gland.

Antithyroid drugs are one of the key treatments for hyperthyroidism and Graves' disease. The other treatments include radioactive iodine (RAI) ablation and surgical removal of all or part of the thyroid gland.

In some cases, physicians prescribe antithyroid drugs as a long-term treatment for Graves' disease/hyperthyroidism. Some studies have estimated that approximately 30 percent of Graves' disease patients will have a remission after prolonged treatment with antithyroid drugs.

Some physicians only recommend antithyroid drug treatment for a short time, followed by more permanent treatments such as thyroid surgery or RAI.

What Are the Types of Antithyroid Drugs?

Two antithyroid drugs are currently available in the United States: methimazole and propylthiouracil (which is usually abbreviated as PTU).

In Europe and Asia, another antithyroid drug, carbimazole, is also available.

Methimazole: Methimazole prevents the thyroid from using iodine to produce thyroid hormone. Methimazole is sometimes also called thiamazole and is used around the world. It is generally taken once per day. It is available under the brand name Tapazole in the US, and also as a generic from various manufacturers.

Propylthiouracil (PTU): PTU acts by preventing the thyroid from using iodine to produce thyroid hormone, and also inhibits T4 from being converted into T3. It has a short-acting timespan, and must be taken two to three times per the day to effectively lower thyroid hormone levels. Only generic PTU is available; there are no brand names of PTU marketed in the US, and a number of manufacturers produce generic PTU.

Carbimazole: Carbimazole metabolizes to methimazole in the body. Like methimazole, carbimazole inhibits the thyroid's ability to produce thyroid hormone. The most well-known brand of carbimazole is Neomercazole.

Carbimazole is quite similar in action to methimazole.

In the United States, methimazole is considered the preferred antithyroid drug in most situations.

How Should Antithyroid Drugs Be Taken?

Antithyroid drugs work best when you can keep a constant amount in your bloodstream. To maintain that constant level, it's important to take your antithyroid drug dose at the proper times, and if you are taking more than one pill a day, evenly space your doses. Generally, methimazole is taken once a day (or twice a day for those on larger doses), and PTU is taken 3 to 4 times per day, or every 6 to 8 hours.

How Quickly Do Antithyroid Drugs Work?

It's important to note that antithyroid drugs do not block the effects of thyroid hormone that was made by the gland before starting the drug. So generally, even after you begin taking an antithyroid drug, your thyroid will continue to release the hormone it has already formed, causing continued hyperthyroidism symptoms. It can take as many as six to eight weeks, therefore, for elevated thyroid hormones to begin to normalize, and symptoms of hyperthyroidism to subside.

Effectiveness of Antithyroid Drugs

An estimated 25 to 50% of patients go into remission when taking an antithyroid drug for at least six months to a year. This is most likely if...

  • You have mild or subclinical hyperthyroidism.
  • Your goiter (thyroid enlargement) is small or minimal.
  • You are not a smoker.
  • You do not have high levels of blocking antibodies.
  • You are not a child, teen or young adult .
  • You do not have ophthalmopathy.

People who have more serious hyperthyroidism, a large goiter, smoke, have high levels of blocking antibodies, ophthalmopathy, and/or are a child, teenager or young adult have less of a chance of permanent remission on antithyroid drug therapy.

Some studies have shown that remission rates are higher when you take antithyroid drugs for more than 18 to 24 months versus 6 to 12 months, but the findings are still controversial.

While some 30 to 40 percent of patients treated with antithyroid drugs remain in remission 10 years after they stop their drug treatment, an estimated half of the patients who have a remission will also have a recurrence.

Why is Methimazole Generally the Preferred Antithyroid Drug in the U.S.?

In the United States, as of 2010, methimazole is considered the preferred antithyroid drug in most cases.

In April 2010, the US Food and Drug Administration (FDA) added a "black box" warning to the label for propylthiouracil.

What Warnings and Interactions Are Associated With Antithyroid Drugs?

Always check with your doctor or pharmacist regarding interactions between any medications you are prescribed.

There are, however, several key potential interactions associated with antithyroid drugs of particular note, including:

  • Anticoagulants (oral): Oral anticoagulant medications may be made my effective potentiated by methimazole.
  • Beta-blockers: For some patients, their dose of beta-blockers may need to be reduced when a patient's thyroid function returns to normal after antithyroid drug treatment.
  • Digitalis glycosides: Dosages of digitalis glycoside medication may need to be decreased when a patient's thyroid function returns to normal after antithyroid drug treatment.
  • Theophylline: Antithyroid drug treatment may reduce the dosage requirement for the asthma medicine theophylline.

Antithyroid Drug Guidelines for Thyroid Patients

If you are pregnant or plan to become pregnant, you should discuss this with your doctor before you start antithyroid drug treatment.

If you become pregnant while taking antithyroid drugs, call your doctor immediately.

Before you have any medical tests or surgical procedures, including dental surgery, inform your doctor that you are taking antithyroid medication.

If you are taking antithyroid drugs, advise your practitioner if any of the following signs or symptoms of liver injury occur, including: fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising or yellowing of the eyes or skin, nausea, a yellowing of the skin or eyes, light-colored stools or dark urine.

In addition to liver issues, a rare but reported risk of antithyroid drugs is agranulocytosis, a condition where the bone marrow suddenly stops making white blood cells, which increases your risk of serious, even life-threatening infection, bleeding, anemia and other significant conditions. Any of the following potential symptoms should be reported immediately to your physician: fever, chills, sore throat, hoarseness, sore mouth, sores in the mouth, coughing, painful urination, shortness of breath, swelling of feet or lower legs, swollen lymph nodes, swollen salivary glands, difficult urination, blood in your urine, unusual bleeding, unusual bruising, red spots on the skin, severe skin rash, nosebleeds, black stools, bloody stools, unusual tiredness, unusual weakness or any feeling of significant discomfort, illness or weakness.

Your doctor will test your white blood cell count, and if there are signs of potential agranulocytosis, the doctor will have you stop the antithyroid drug immediately because you are at risk of a blood infection.

Most patients recover from agranulocytosis if the antithyroid drug is stopped and antibiotic therapy is started.

Agranulocytosis is rare, but those most at risk are those at the beginning of treatment, those over 40, those taking PTU, and those on a methimazole dose of 40 mg or more. To protect yourself, insist on a baseline white blood count before you start treatment. You may want to push for the doctor to run a white blood count every time your blood is taken to check thyroid function, particularly early on in your treatment.

Can You Take Antithyroid Drugs While Pregnant?

When a woman is hyperthyroid while pregnant, treatment options are limited. Radioactive iodine (RAI) is not an option to treat Graves' disease or hyperthyroidism at any point during pregnancy, due to the risk the radiation poses to the fetus. Surgery to remove an overactive thyroid is typically only performed during the second trimester of pregnancy, as surgery increases the risk of miscarriage when performed in the first trimester, and increases the risk of premature delivery when performed during the third trimester.

Babies of mothers taking antithyroid drugs have a higher risk of goiter, hypothyroidism, or even cretinism (a severe result of hypothyroidism that can cause mental retardation). That means that both PTU and methimazole are in the FDA's Category D during pregnancy, meaning that they pose a risk to a fetus, but the benefit may outweigh the risk. The risk of untreated hyperthyroidism for both mother and baby, for example, is considered greater than the risk of taking a low dose of antithyroid medication, and so antithyroid drugs are used -- very carefully -- in pregnancy.

Typically, doctors will recommend the smallest possible dose that will control the condition.

Methimazole more easily crosses the placental membranes, and methimazole is associated with a higher risk of fetal side effects -- including birth defects in the scalp -- if taken during the first trimester of pregnancy. These scalp defects have not been seen in babies of mothers who took PTU, so PTU is the recommended drug during the first trimester of pregnancy. Methimazole is typically recommended for second and third trimester treatment.

Can You Take Antithyroid Drugs While Breastfeeding?

Breastfeeding while on antithyroid drugs is controversial. Some physicians say that it is safe, but have preferred PTU over methimazole, since methimazole crosses into breast milk more easily. Other practitioners have concerns about the use of any of these drugs during breastfeeding. Patients should discuss this with their physician as the medication and dosage level may have an effect on the doctor's recommendations regarding breastfeeding.

Before you start antithyroid drugs, talk to your doctor about any history of liver problems, such as hepatitis or jaundice, as they can affect your ability to process antithyroid drugs safely, and your risk of side effects can be greater.

Also be sure to tell your doctor if you have or have ever had any blood disease, such as decreased white blood cell (known as leukopenia), decreased platelets (thrombocytopenia), or aplastic anemia.

Sources

Daily Med, U.S. Food and Drug Administration medication Database.

FDA Drug Safety Communication: New Boxed Warning on severe liver injury with propylthiouracil, April 21, 2010.

Mandel, Susan J. and David S. Cooper. "The Use of Antithyroid Drugs in Pregnancy and Lactation." The Journal of Clinical Endocrinology & Metabolism. Vol. 86, No. 6 2354-2359. 

"Graves' Disease and the Manifestations of Thyrotoxicosis," Thyroid Manager Online Textbook.

"Hyperthyroidism Management with Antithyroid Drugs," Thyroid Manager Online Textbook.

Ross, Douglas MD, "Patient information: Antithyroid drugs," UpToDate. Last updated: November 13, 2009

With thanks to Leslie Blumenberg for her research support for this article

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