What is the root cause of Graves disease?

Graves’ disease is an autoimmune condition that causes your thyroid to become hyperactive -- work harder than it needs to. It is one of the most common thyroid problems and the leading cause of hyperthyroidism, a condition in which the thyroid gland produces too many hormones. It was named after the man who first described it in the early 19th century, Sir Robert Graves.

The thyroid gland is a small butterfly-shaped gland that sits in the front of your neck and releases hormones that help regulate your metabolism. When you have Graves’ disease, your immune system attacks your thyroid, causing it to overproduce those hormones, which causes a number of problems in different parts of your body. It usually affects people between the ages of 30 and 50 and is more common in women.

Once the disorder has been correctly diagnosed, it is quite easy to treat. In some cases, Graves' disease goes into remission or disappears completely after several months or years. Left untreated, however, it can lead to serious complications -- even death.

Hormones secreted by the thyroid gland control metabolism, or the speed at which the body converts food into energy. Metabolism is directly linked to the amount of hormones that circulate in the bloodstream. If, for some reason, the thyroid gland secretes too much of these hormones, the body's metabolism kicks into high gear, causing a pounding heart, sweating, trembling, and weight loss.

Normally, the thyroid gets its production orders through another chemical called thyroid-stimulating hormone (TSH), released by the pituitary gland in the brain. But in Graves' disease, a malfunction in the body's immune system releases abnormal antibodies that act like TSH. Spurred by these false signals to produce, the thyroid's hormone factories work overtime and overproduce.

Exactly why the immune system begins to produce these troublesome antibodies isn’t clear. Heredity and other characteristics seem to play a role. Studies show, for example, that if one identical twin contracts Graves' disease, there is a 20% likelihood that the other twin will get it too. Also, women are more likely than men to develop the disease. And smokers who develop Graves' disease are more prone to eye problems than nonsmokers with the disease. No single gene causes Graves’ disease. It is thought to be triggered by both genetics and environmental factors.

The most common symptoms of Graves’ are symptoms of hyperthyroidism, which include:

Eye complications

A small percentage of all Graves' patients will develop a condition called thyroid eye disease in which your eye muscles and tissues become swollen. This can cause exophthalmos -- your eyeballs protrude from their sockets -- and is considered a hallmark of Graves' disease, even though it’s rare. But having this complication doesn’t have anything to do with how severe your Graves’ disease is. In fact, it isn't clear whether such eye complications stem from Graves' disease itself or from a totally separate, but closely linked, disorder. If you have developed thyroid eye diease, your eyes may ache and feel dry and irritated. Protruding eyeballs are prone to excessive tearing and redness, partly because the eyelids can’t protect them as well.

In severe cases of exophthalmos, which are rare, swollen eye muscles can put tremendous pressure on the optic nerve, possibly leading to partial blindness. Eye muscles weakened by long periods of inflammation can lose their ability to control movement, resulting in double vision.

Skin complications

Some people with Graves’ may develop a rare skin condition known as pretibial myxedema or Graves’ dermopathy. It is a lumpy reddish thickening of the skin on the shins. It is usually painless and is not serious. Like exophthalmos this condition does not necessarily begin with the onset of Graves' and doesn’t have to do with how severe your disease is.

If you have symptoms or signs of the complications of Graves’ disease, your doctor will probably ask you if you have a family history of the condition and order one or more of the following tests:

A blood test to check your levels of thyroid stimulating hormone (TSH) and other thyroid hormones. With Graves’ disease your TSH levels are usually suppressed and your other hormones are elevated.
Lab tests to look for the antibodies that cause Graves’s disease. If you don’t have them, that’s a sign that your hyperthyroidism is caused by something else.
A radioactive iodine uptake test that uses small doses of radioactive iodine to watch how much of it is taken up into your thyroid from your bloodstream. Your body normally uses iodine to make thyroid hormones, so if it takes in a lot of the radioactive iodine it is a sign that it is working harder than it needs to.
A thyroid scan to see where the radioactive iodine travels in your thyroid gland. If it goes all over your thyroid, that suggests you have Graves’ disease, because with other causes of hypothyroidism, only some parts of the gland are involved.

There are two goals in the treatment for Graves’ disease. One is to stop your thyroid gland from overproducing thyroid hormone. The other is to stop the increased levels of thyroid hormone from causing problems in your body. There are a number of treatment options to achieve one or both of these goals.

Radioactive iodine therapy

With this treatment, you take another form of radioactive iodine by mouth than what is used in the test to diagnose Graves’ disease. The iodine gets into your thyroid and the radiation kills some of the cells in your thyroid that are overproducing thyroid hormones. It’s possible that this treatment could make any eye problems you have from Graves’ disease temporarily worse and it’s also likely it will lead to a lower production of thyroid hormone than is healthy. If that happens, your low thyroid can be treated. Because this treatment uses radiation, it’s not used on pregnant or breastfeeding women.

Medications

Anti-thyroid medications make your thyroid produce less thyroid hormone. They aren’t permanent treatments but can be used for long periods of time and sometimes help even after you’ve stopped treatment. They’re usually the treatment of choice for pregnant or breastfeeding women who can’t be exposed to radiation. They’re also sometimes used in combination with radioactive iodine therapy.
Beta blockersare medications typically used to reduce blood pressure, and they can help rapidly relieve some of the symptoms of hyperthyroidism including shaking, rapid heartbeat, and anxiety.

Surgery is a less common treatment for Graves’ disease but may be a good choice if you have a goiter or you’re pregnant and can’t take anti-thyroid medications. During surgery, some or all of your thyroid gland is removed. After surgery, you may need to take a daily thyroid medication for the rest of your life.

Although the symptoms can cause discomfort, Graves' disease generally has no long-term adverse health consequences if you get prompt and proper medical care.

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What is hyperthyroidism?

Hyperthyroidism, also called overactive thyroid, is when the thyroid gland makes more thyroid hormones than your body needs. The thyroid is a small, butterfly-shaped gland in the front of your neck. Thyroid hormones control the way the body uses energy, so they affect nearly every organ in your body, even the way your heart beats. With too much thyroid hormone, many of your body’s functions speed up.

The thyroid is a small gland in your neck that makes thyroid hormones.

How common is hyperthyroidism?

About 1 out of 100 Americans ages 12 years and older have hyperthyroidism.1

Who is more likely to develop hyperthyroidism?

Hyperthyroidism is more common in women and people older than 60.2 You are more likely to have hyperthyroidism if you

Is hyperthyroidism during pregnancy a problem?

Mild hyperthyroidism during pregnancy is usually not a problem. But severe hyperthyroidism during pregnancy, when untreated, can affect both the mother and the baby. If you have hyperthyroidism and plan to get pregnant or become pregnant, work with your doctor to get the disease under control.

Be sure your hyperthyroidism is under control before becoming pregnant.

What are the complications of hyperthyroidism?

Untreated, hyperthyroidism can cause serious health problems, including

an irregular heartbeat that can lead to blood clots, stroke, heart failure, and other heart-related problems
an eye disease called Graves’ ophthalmopathy
thinning bones, osteoporosis, and muscle problems
menstrual cycle and fertility issues

What are the symptoms of hyperthyroidism?

Symptoms of hyperthyroidism can vary from person to person and may include4

weight loss despite an increased appetite
rapid or irregular heartbeat
nervousness, irritability, trouble sleeping, fatigue
shaky hands, muscle weakness
sweating or trouble tolerating heat
frequent bowel movements
an enlargement in the neck, called a goiter

In older adults, hyperthyroidism is sometimes mistaken for depression or dementia. Older adults may have different symptoms, such as loss of appetite or withdrawal from people, than younger adults with hyperthyroidism. You may want to ask your doctor about hyperthyroidism if you or your loved one shows these symptoms.

What causes hyperthyroidism?

Hyperthyroidism has several causes, including

Graves’ disease

Graves’ disease, the most common cause of hyperthyroidism, is an autoimmune disorder. With this disease, your immune system attacks the thyroid and causes it to make too much thyroid hormone.

Overactive thyroid nodules

Overactive thyroid nodules, or lumps in your thyroid, are common and usually not cancerous. However, one or more nodules may become overactive and produce too much thyroid hormone. Overactive nodules are found most often in older adults.

Thyroiditis

Thyroiditis is inflammation of your thyroid gland. Some types of thyroiditis can cause thyroid hormone to leak out of your thyroid gland into your bloodstream. As a result, you may develop symptoms of hyperthyroidism.

The types of thyroiditis that can cause hyperthyroidism include

subacute thyroiditis, which involves a painfully inflamed and enlarged thyroid.
postpartum thyroiditis, which can develop after a woman gives birth.
painless thyroiditis, which is similar to postpartum thyroiditis, but occurs in the absence of pregnancy. Your thyroid may be enlarged. Experts think painless thyroiditis is probably an autoimmune condition.

Thyroiditis can also cause symptoms of hypothyroidism, or underactive thyroid. In some cases, after your thyroid is overactive for a period of time, it may become underactive.

Too much iodine

Your thyroid uses iodine to make thyroid hormone. How much iodine you consume affects how much thyroid hormone your thyroid makes. In some people, consuming large amounts of iodine may cause the thyroid to make too much thyroid hormone.

Some cough syrups and medicines, including some heart medicines, may contain a lot of iodine. Seaweed and seaweed-based supplements also contain a lot of iodine.

Too much thyroid hormone medicine

Some people who take thyroid hormone medicine for hypothyroidism may take too much. If you take thyroid hormone medicine, see your doctor at least once a year to have your thyroid hormone levels checked. You may need to adjust your dose if your doctor finds your thyroid hormone level is too high.

Some other medicines may also interact with thyroid hormone medicine and raise hormone levels. If you take thyroid hormone medicine, ask your doctor about interactions when starting new medicines.

Noncancerous tumor

In some rare cases, a noncancerous tumor of the pituitary gland, located at the base of the brain, can cause hyperthyroidism.

How do doctors diagnose hyperthyroidism?

Your doctor will take a medical history and perform a physical exam. A hyperthyroidism diagnosis can’t be based on symptoms alone because many of its symptoms are the same as those of other diseases. That’s why your doctor may use several thyroid blood tests and imaging tests to confirm the diagnosis and find its cause.

Because hyperthyroidism can cause fertility problems, women who have trouble getting pregnant often get tested for thyroid problems.

A blood test might confirm a diagnosis of hyperthyroidism.

How do doctors treat hyperthyroidism?

Your doctor will treat your hyperthyroidism to bring your thyroid hormone levels back to normal. Treating the disease will prevent long-term health problems, and it will relieve uncomfortable symptoms. No single treatment works for everyone.

Your treatment depends on what’s causing your hyperthyroidism and how severe it is. When recommending a treatment, your doctor will consider

your age
possible allergies to or side effects of the medicines
other conditions, such as pregnancy or heart disease
whether you have access to an experienced thyroid surgeon

Treatment options

Hyperthyroidism is usually treated with medicines, radioiodine therapy, or thyroid surgery.

Beta-blockers. Beta-blockers are drugs that block the action of substances, such as adrenaline, on nerve cells. They cause blood vessels to relax and widen.

Pros
- They can reduce symptoms—such as tremors, rapid heartbeat, and nervousness—until other treatments start working.
- They can make you feel better within hours.
Cons
- They don’t stop thyroid hormone production.

Antithyroid medicines. Antithyroid therapy is the simplest way to treat hyperthyroidism. Methimazole is used most often. Propylthiouracil is often used for women during the first 3 months of pregnancy because methimazole can, on rare occasions, harm the fetus.

Pros
- They cause the thyroid to make less thyroid hormone.
- Some patients’ symptoms from Graves’ disease may go away temporarily after taking antithyroid drugs.
Cons
- Antithyroid medicines can cause side effects, including
  - allergic reactions, such as rashes and itching
  - a decrease in the number of white blood cells in your body, which can lower resistance to infection
  - liver failure, in rare cases
- Antithyroid medicines
  - don’t provide a permanent cure, but they may allow symptoms to go away temporarily in the case of Graves’ disease
  - may take several weeks or months for thyroid hormone levels to move into the normal range
  - take about 1–2 years of total average treatment time, but can continue for many years
  - are not used to treat hyperthyroidism caused by thyroiditis

Seek care right away

Call your doctor right away if you have any of the following symptoms

fatigue or weakness
dull pain in your abdomen
loss of appetite
skin rash, itching, or easy bruising
yellowing of your skin or whites of your eyes, called jaundice
constant sore throat
fever, chills, or constant sore throat

Antithyroid therapy is the easiest way to treat hyperthyroidism.

Radioiodine therapy is a common and effective treatment. You can take radioactive iodine-131 by mouth as a capsule or liquid.

Pros
- Radioiodine therapy slowly destroys the cells of the thyroid gland that produce thyroid hormone.
- Radioiodine therapy does not affect other body tissues.
Cons
- You might need more than one treatment to bring thyroid hormone levels into the normal range, but beta-blockers can control symptoms between treatments.
- Radioiodine therapy isn’t used for women who are pregnant or breastfeeding. It can harm the fetus’ thyroid and can be passed from mother to child in breast milk.

Almost everyone who gets radioiodine therapy later develops hypothyroidism. But hypothyroidism is easier to treat than hyperthyroidism by using a daily thyroid hormone medicine, and it causes fewer long-term health problems.

Taking radioactive iodine-131 is a common and effective treatment.

Surgery to remove part or most of the thyroid gland is used less often to treat hyperthyroidism. Sometimes doctors use surgery to treat people with large goiters or pregnant women who cannot take antithyroid medicines.

Pros
- When part of the thyroid is removed, your thyroid hormone levels may return to normal.
Cons
- Thyroid surgery requires general anesthesia, which can cause a condition called thyroid storm—a sudden, severe worsening of symptoms. Taking antithyroid medicines before surgery can help prevent this problem.

When part of your thyroid is removed, you may develop hypothyroidism after surgery and need to take thyroid hormone medicine. If your whole thyroid is removed, you will need to take thyroid hormone medicine for life. After surgery, your doctor will continue to check your thyroid hormone levels.

In some cases, doctors use surgery to remove part or most of the thyroid gland.

Researchers are looking into new ways to treat hyperthyroidism. An example is radiofrequency ablation (RFA), a new approach to treating thyroid nodules that cause hyperthyroidism.5,6 RFA is used mainly in cases where medicines or surgery won’t help, and is not yet widely available.

How does eating, diet, and nutrition affect hyperthyroidism?

Your thyroid uses iodine to make thyroid hormones. If you have Graves’ disease or another autoimmune thyroid disorder, you may be sensitive to harmful side effects from iodine. Eating foods that have large amounts of iodine—such as kelp, dulse, or other kinds of seaweed—may cause or worsen hyperthyroidism. Taking iodine supplements can have the same effect. Talk with members of your health care team about

what foods to limit or avoid
any iodine supplements you take
any cough syrups or multivitamins you take because they may contain iodine

Clinical Trials for Hyperthyroidism

The NIDDK conducts and supports clinical trials in many diseases and conditions, including endocrine diseases. The trials look to find new ways to prevent, detect, or treat disease and improve quality of life.

What are clinical trials for hyperthyroidism?

Clinical trials—and other types of clinical studies—are part of medical research and involve people like you. When you volunteer to take part in a clinical study, you help doctors and researchers learn more about disease and improve health care for people in the future.

Researchers are studying many aspects of hyperthyroidism, such as its natural history, clinical presentation, and genetics.

Find out if clinical studies are right for you.

Watch a video of NIDDK Director Dr. Griffin P. Rodgers explaining the importance of participating in clinical trials.

What clinical studies for hyperthyroidism are looking for participants?

You can view a filtered list of clinical studies on hyperthyroidism that are open and recruiting at www.ClinicalTrials.gov. You can expand or narrow the list to include clinical studies from industry, universities, and individuals; however, the NIH does not review these studies and cannot ensure they are safe. Always talk with your health care provider before you participate in a clinical study.

References

[1] De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016;388(10047):906–918. doi:10.1016/S0140-6736(16)00278-6

[2] Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343–1421. doi:10.1089/thy.2016.0229

[3] Sawicka-Gutaj N, Gutaj P, Sowiński J, et al. Influence of cigarette smoking on thyroid gland—an update. Endokrynologia Polska. 2014;65(1):54–62. doi: 10.5603/EP.2014.0008

[4] Mathew P, Rawla P. Hyperthyroidism. In: StatPearls [Internet]. StatPearls Publishing. Updated November 21, 2020. Accessed April 29 2021. www.ncbi.nlm.nih.gov/books/NBK537053

[5] Muhammad H, Santhanam P, Russell JO, Kuo JH. RFA and benign thyroid nodules: review of the current literature. Laryngoscope Investigative Otolaryngology. 2021;6(1):155–165. Published January 9, 2021. doi:10.1002/lio2.517

[6] Patel KN, Yip L, Lubitz CC, et al. Executive summary of the American Association of Endocrine Surgeons guidelines for the definitive surgical management of thyroid disease in adults. Annals of Surgery. 2020;271(3):399–410. doi:10.1097/SLA.0000000000003735

This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.

The NIDDK would like to thank:
Thanh D. Hoang, D.O., FACP, FACE, CAPTAIN (select), Walter Reed National Military Medical Center