Antithyroid Drugs for Graves' Disease and Hyperthyroidism

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Antithyroid drugs — also called thioamides — are one of the three conventional treatments available for hyperthyroidism, an overactive thyroid. The other treatments are radioactive iodine (RAI) and thyroid surgery (thyroidectomy).

Hyperthyroidism is most often caused by autoimmune Graves’ disease, multinodular goiter, or toxic adenoma (a benign tumor or “hot” nodule) in your thyroid. The common symptoms of hyperthyroidism include an elevated heart rate and blood pressure, anxiety, insomnia, weight loss, diarrhea, and muscle weakness.

In the United States, two antithyroid drugs — methimazole (brand name Tapazole) and propylthiouracil (PTU) — are used to treat hyperthyroidism. Outside the U.S., carbimazole (brand name Neo-Mercazole) — a drug similar to methimazole — is also used.

Doctors typically prescribe antithyroid drugs as short-term or first-line hyperthyroidism treatment in a number of situations:

  • When you have mild or subclinical hyperthyroidism
  • When you have acute hyperthyroidism, in preparation for RAI or surgery
  • When you are hyperthyroid due to multinodular goiter or toxic adenoma, not Graves’ disease
  • When you are pregnant, or you are breastfeeding and want to continue nursing
  • When you are unable to follow required safety regulations after RAI treatment
  • When you have mild thyroid eye disease

How antithyroid drugs work

Antithyroid drugs treat your overactive thyroid by blocking the gland’s ability to use iodine to produce thyroid hormones, including thyroxine (T4) and triiodothyronine (T3).  Antithyroid drugs do not, however, remove excess thyroid hormone from your bloodstream, so it can take a number of weeks before an antithyroid drug affects your hyperthyroidism and related symptoms.

Methimazole

The preferred drug in the U.S. is methimazole, sometimes called thiamazole. There are several generic versions of methimazole available, and the brand name in the U.S. is Tapazole.

Methimazole is preferred for several reasons:

  • Methimazole poses less risk of liver damage than PTU
  • Methimazole is more concentrated and faster-acting than PTU
  • Methimazole can be taken once a day, while PTU needs to be taken several times a day to be effective

Because of a slight increase in birth defects, methimazole is not used during the first trimester of pregnancy, when PTU is substituted.

Methimazole usually takes around six weeks to lower your thyroid levels to normal.

Propylthiouracil (PTU)

Propylthiouracil (PTU) is an antithyroid drug that is less commonly used, for several reasons:

  • PTU does not work as rapidly as methimazole to resolve hyperthyroidism
  • PTU has more side effects than methimazole
  • PTU poses a greater risk of causing liver damage
  • PTU is short-acting and requires multiple doses per day to control hyperthyroidism

PTU is only recommended in several situations:

  • When RAI and surgery are not an option, and you are having serious side effects from methimazole
  • When you are experiencing severe and life-threatening thyroid storm, and not responding to methimazole
  • When you need an antithyroid drug during the first trimester of pregnancy. PTU has a lower risk of causing birth defects during the first trimester compared to methimazole. In most cases, doctors recommend switching back to methimazole after the first trimester of pregnancy.

There is no brand name PTU in the U.S., but several manufacturers make generic PTU.

Starting an antithyroid drug

It is important to take your antithyroid drug as directed by your doctor, and not to miss any doses.

Keep in mind that after starting an antithyroid drug, it can take from two to eight weeks to reduce your thyroid levels to normal. During this period, your doctor will test your thyroid levels, and adjust your dosage as needed, until your hyperthyroidism is reversed and thyroid levels are normalized.

Testing is usually repeated and dosage adjusted if needed every one to two months.

Remission

When you are taking antithyroid drugs you may experience a remission — usually after one to two years on the medication — as your thyroid hormone and antibody levels return to the reference range. Approximately 30 percent of people with Graves' disease and hyperthyroidism go into remission on antithyroid drug treatment.

To assess for a remission, your doctor may periodically check your TSH-receptor antibodies (TRAb) in addition to testing your thyroid stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) levels. If your TRAb levels are low, this can be a sign of remission, and your doctor may slowly reduce — and eventually stop — your antithyroid drug treatment.

If you stop taking antithyroid drugs, you should have blood tests one or two months later, and then regularly over the next year. If your levels remain stable for a year, your chance of a recurrence drops to approximately 10 percent.

Antithyroid drugs when breastfeeding

If you are breastfeeding, most experts agree that you can safely take methimazole. Ideally, you should breastfeed before taking your medication, to help reduce your baby's exposure to any residual drug. Research shows, however, that when you are on the correct dosage of methimazole, the amount that passes into your breast milk is minimal and does not pose a risk to your baby. You should have frequent testing, however, to ensure that you remain on the correct dose of methimazole.

Note that PTU, because of the risk of liver damage, is not recommended while breastfeeding.

Minor side effects of antithyroid drugs

As many as 15 percent of people have a minor negative reaction to or side effects from taking antithyroid drugs, including:

  • Allergic reactions
  • Skin rash, hives
  • Itchy skin
  • Hair loss
  • Pain and swelling in your joints
  • Abdominal pain or nausea

If you have any of these reactions, you should notify your doctor right away.

If you cannot tolerate antithyroid drugs, you will need to consider radioiodine treatment or surgery for your hyperthyroidism treatment.

Serious side effects and complications from antithyroid drugs

There are several rare but very serious conditions that can result from taking antithyroid drugs.

Agranulocytosis: A very small subset of patients on antithyroid drugs develop agranulocytosis, a potentially life-threatening complication. When you develop agranulocytosis, your body is unable to fight off infections. Agranulocytosis can develop when taking both methimazole and PTU but is more likely with PTU.

You are at greater risk of agranulocytosis:

  • In the first three months of treatment
  • If you are over 60
  • If you are taking higher doses of an antithyroid drug

If you develop any signs of infection while taking antithyroid drugs — especially a sore throat or a fever — you need to see your doctor immediately. Your doctor should order a differential white blood cell (WBC) test to identify the possible onset of agranulocytosis before it becomes life-threatening.

The treatment for agranulocytosis is to stop taking antithyroid drugs, and it usually resolves within a week of stopping antithyroid treatment.

Liver damage: Liver damage is a rare but potentially life-threatening risk of antithyroid drug treatment, typically occurring during the first three months of treatment. PTU is more likely to cause liver damage than methimazole, however. The symptoms include:

  • Jaundice (yellowing of your skin or eyes)
  • Dark urine
  • Light stools
  • Abdominal pain
  • Nausea
  • Loss of appetite

If you have any of these symptoms while taking an antithyroid drug, contact your doctor immediately.

Aplastic anemia: With aplastic anemia, your bone marrow becomes unable to make enough blood cells. Symptoms include:

  • Nausea
  • Skin rashes
  • Fatigue
  • Shortness of breath
  • Chest pain
  • Dizziness
  • Headaches
  • Pale skin
  • Weakness
  • Rapid heart rate, chest pain, and irregular heart rhythms
  • Easy bruising and bleeding
  • Bleeding that's difficult to stop
  • Nosebleeds, bleeding gums, bloody stool, or heavy menstrual bleeding

If you have any of these symptoms while taking an antithyroid drug, contact your doctor immediately.

Vasculitis: Antithyroid drugs can cause vasculitis, an inflammation of your blood vessels. The symptoms of vasculitis include:

  • Rashes, especially a purple-red raised rash
  • Joint aches and pains
  • Fever
  • Headache
  • Fatigue
  • Weight loss
  • Night sweats
  • Numbness or weakness

If you have any of these symptoms while taking an antithyroid drug, contact your doctor immediately.

See more helpful articles:

How to Effectively Take Thyroid Medication

The Risks for and Symptoms of Hyperthyroidism

The Causes of Hyperthyroidism

How Hyperthyroidism is Diagnosed

Sources:

Glatstein, MD, Miguel Marcelo et. al. "Pharmacologic treatment of hyperthyroidism during lactation," Canadian Family Physician. 2009 Aug; 55(8): 797–798. PMCID: PMC2726094. Online abstract.

Karras, Spiros and Krassas, Gerasimos "Breastfeeding and Antithyroid Drugs: A View from Within." Eur Thyroid J. 2012 Apr; 1(1): 30–33. Online abstract.