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Home , Thyroid disease

Graves’ Disease

National Endocrine and Metabolic Diseases Information Service

What is Graves’ disease? Graves’ disease, also known as toxic Pituitary diffuse goiter, is the most common cause gland of in the United States. U.S. Department of Health and Hyperthyroidism is a disorder that occurs Human Services when the gland makes more thyroid hormone than the body needs. NATIONAL INSTITUTES OF HEALTH The Thyroid The thyroid is a 2-inch-long, butterfly-shaped gland in the front of the neck below the TSH , or voice box. The thyroid makes two , (T3) and thyroxine (T4). T3 is made from T4 and is the more active hormone, directly affecting Thyroid the tissues. Thyroid hormones circulate throughout the body in the bloodstream and act on virtually every tissue and cell in the body. T3-T4 Thyroid hormones affect metabolism, brain development, breathing, heart and

nervous system functions, body temperature, The thyroid’s production of thyroid hormones—T3 muscle strength, skin dryness, menstrual and T4—is regulated by thyroid-stimulating hormone cycles, weight, and cholesterol levels. (TSH), which is made by the . Hyperthyroidism causes many of the body’s functions to speed up. Thyroid hormone production is regulated by What are the symptoms of another hormone called thyroid-stimulating hormone (TSH), which is made by the Graves’ disease? pituitary gland in the brain. When thyroid People with Graves’ disease may have hormone levels in the blood are low, the common symptoms of hyperthyroidism pituitary releases more TSH. When thyroid such as hormone levels are high, the pituitary • nervousness or irritability responds by decreasing TSH production. • or muscle weakness Autoimmune Disorder • heat intolerance Graves’ disease is an autoimmune disorder. Normally, the immune system protects • trouble sleeping the body from infection by identifying and • hand destroying bacteria, viruses, and other • rapid and irregular heartbeat potentially harmful foreign substances. But in autoimmune diseases, the immune system • frequent bowel movements or attacks the body’s own cells and organs. • With Graves’ disease, the immune system • goiter, which is an enlarged thyroid that makes an antibody called thyroid-stimulating may cause the neck to look swollen and immunoglobulin (TSI)—sometimes called can interfere with normal breathing and TSH receptor antibody—that attaches swallowing to thyroid cells. TSI mimics TSH and stimulates the thyroid to make too much A small number of people with Graves’ thyroid hormone. Sometimes the TSI disease also experience thickening and antibody instead blocks thyroid hormone reddening of the skin on their shins. This production, leading to conflicting symptoms usually painless problem is called pretibial that may make correct diagnosis more or Graves’ dermopathy. difficult. In addition, the eyes of people with Graves’ disease may appear enlarged because their eyelids are retracted—seem pulled back into the eye sockets—and their eyes bulge out from the eye sockets. This condition is called Graves’ ophthalmopathy (GO).

2 Graves’ Disease Who is likely to develop What is Graves’ Graves’ disease? ophthalmopathy? Scientists cannot predict who will develop Graves’ ophthalmopathy is a condition Graves’ disease. However, factors such associated with Graves’ disease that as age, sex, heredity, and emotional and occurs when cells from the immune environmental stress are likely involved. system attack the muscles and other Graves’ disease usually occurs in people tissues around the eyes. younger than age 40 and is seven to eight 1 The result is inflammation and a times more common in women than men. buildup of tissue and fat behind the eye Women are most often affected between socket, causing the eyeballs to bulge out. ages 30 and 60. And a person’s chance of Rarely, inflammation is severe enough developing Graves’ disease increases if other to compress the optic nerve that leads to family members have the disease. the eye, causing vision loss. Researchers have not been able to find a Other GO symptoms are specific gene that causes the disease to be passed from parent to child. While scientists • dry, gritty, and irritated eyes know some people inherit an immune system • puffy eyelids that can make antibodies against healthy cells, predicting who will be affected is • double vision difficult. • light sensitivity People with other autoimmune diseases have • pressure or pain in the eyes an increased chance of developing Graves’ disease. Conditions associated with Graves’

• trouble moving the eyes disease include type 1 diabetes, rheumatoid About 25 to 30 percent of people with arthritis, and vitiligo—a disorder in which Graves’ disease develop mild GO, and some parts of the skin are not pigmented. 2 to 5 percent develop severe GO.1 This eye condition usually lasts 1 to 2 years and often improves on its own. GO can occur before, at the same time as, or after other symptoms of hyperthyroidism develop and may even occur in people whose thyroid function is normal. Smoking makes GO worse.

1Yeung SJ, Habra MA, Chiu AC. Graves’ disease. emedicine website. www.emedicine. medscape.com/article/120619-overview. Updated 2010. Accessed December 10, 2011.

3 Graves’ Disease How is Graves’ disease TSI test. providers may also recommend the TSI test, although this test diagnosed? usually isn’t necessary to diagnose Graves’ Health care providers can sometimes disease. This test, also called a TSH antibody diagnose Graves’ disease based only on a test, measures the level of TSI in the blood. physical examination and a medical history. Most people with Graves’ disease have this Blood tests and other diagnostic tests, such antibody, but people whose hyperthyroidism as the following, then confirm the diagnosis. is caused by other conditions do not. TSH test. The ultrasensitive TSH test is More information about testing for thyroid usually the first test performed. This test problems is provided by the National detects even tiny amounts of TSH in the Endocrine and Metabolic Diseases blood and is the most accurate measure of Information Service (NEMDIS) in the fact thyroid activity available. sheet, , available at www.endocrine.niddk.nih.gov. T3 and T4 test. Another blood test used to diagnose Graves’ disease measures T3 and T4 levels. In making a diagnosis, health care How is Graves’ disease providers look for below-normal levels of treated? TSH, normal to elevated levels of T4, and elevated levels of T . People with Graves’ disease have three 3 treatment options: radioiodine therapy, Because the combination of low TSH and medications, and thyroid . high T3 and T4 can occur with other thyroid Radioiodine therapy is the most common problems, health care providers may order treatment for Graves’ disease in the United other tests to finalize the diagnosis. The States. Graves’ disease is often diagnosed following two tests use small, safe doses of and treated by an endocrinologist—a doctor radioactive because the thyroid uses who specializes in the body’s hormone- iodine to make thyroid hormone. secreting glands. Radioactive iodine uptake test. This test Radioiodine Therapy measures the amount of iodine the thyroid collects from the bloodstream. High levels of In radioiodine therapy, patients take iodine uptake can indicate Graves’ disease. radioactive iodine-131 by mouth. Because the thyroid gland collects iodine to Thyroid scan. This scan shows how and make thyroid hormone, it will collect the where iodine is distributed in the thyroid. radioactive iodine from the bloodstream in With Graves’ disease the entire thyroid is the same way. Iodine-131—stronger than involved, so the iodine shows up throughout the radioactive iodine used in diagnostic the gland. Other causes of hyperthyroidism tests—gradually destroys the cells that make such as nodules—small lumps in the up the thyroid gland but does not affect gland—show a different pattern of iodine other body tissues. distribution.

4 Graves’ Disease Many health care providers use a large Medications enough dose of iodine-131 to shut down the Beta blockers. Health care providers thyroid completely, but some prefer smaller may prescribe a medication called a beta doses to try to bring hormone production blocker to reduce many of the symptoms into the normal range. More than one round of hyperthyroidism, such as tremors, rapid of radioiodine therapy may be needed. heartbeat, and nervousness. But beta Results take time and people undergoing this blockers do not stop thyroid hormone treatment may not notice improvement in production. symptoms for several weeks or months. Antithyroid medications. Health care People with GO should talk with a health providers sometimes prescribe antithyroid care provider about any risks associated medications as the only treatment for with radioactive iodine treatments. Several Graves’ disease. Antithyroid medications studies suggest radioiodine therapy interfere with thyroid hormone production can worsen GO in some people. Other but don’t usually have permanent results. treatments, such as prescription steroids, Use of these medications requires frequent may prevent this complication. monitoring by a health care provider. Although iodine-131 is not known to cause More often, antithyroid medications are birth defects or infertility, radioiodine used to pretreat patients before surgery or therapy is not used in pregnant women or radioiodine therapy, or they are used as women who are breastfeeding. Radioactive supplemental treatment after radioiodine iodine can be harmful to the fetus’ thyroid therapy. and can be passed from mother to child Antithyroid medications can cause side in breast milk. Experts recommend that effects in some people, including women wait a year after treatment before becoming pregnant. • allergic reactions such as rashes and itching Almost everyone who receives radioactive iodine treatment eventually develops • a decrease in the number of white blood , which occurs when the cells in the body, which can lower a thyroid does not make enough thyroid person’s resistance to infection hormone. People with hypothyroidism must • liver failure, in rare cases take synthetic thyroid hormone, a medication that replaces their natural thyroid hormone.

5 Graves’ Disease Another antithyroid medication, Stop your antithyroid medication and (PTU), is available for call your health care provider right away women in this stage of pregnancy or for if you develop any of the following while women who are allergic to or intolerant of taking antithyroid medications: methimazole and have no other treatment options. Health care providers may prescribe • fatigue PTU for the first trimester of pregnancy and • weakness switch to methimazole for the second and third trimesters. • vague abdominal pain Some women are able to stop taking

• loss of appetite antithyroid medications in the last 4 to • skin rash or itching 8 weeks of pregnancy due to the remission of hyperthyroidism that occurs during • easy bruising pregnancy. However, these women should • yellowing of the skin or whites of continue to be monitored for recurrence of the eyes, called thyroid problems following delivery. • persistent sore throat Studies have shown that mothers taking • fever antithyroid medications may safely breastfeed. However, they should take only moderate doses, less than 10−20 milligrams daily, of the antithyroid medication In the United States, health care providers methimazole. Doses should be divided and prescribe the antithyroid medication taken after feedings, and the infants should 2 methimazole (Tapazole, Northyx) for most be monitored for side effects. types of hyperthyroidism. Women requiring higher doses of Antithyroid medications and pregnancy. the antithyroid medication to control Because pregnant and breastfeeding women hyperthyroidism should not breastfeed. cannot receive radioiodine therapy, they are usually treated with an antithyroid medication instead. However, experts agree that women in their first trimester of pregnancy should probably not take methimazole due to the rare occurrence of damage to the fetus.

2Ogunyemi DA. Autoimmune thyroid disease and pregnancy. emedicine website. http://emedicine. medscape.com/article/261913-overview. Updated March 12, 2012. Accessed April 10, 2012. 6 Graves’ Disease Thyroid Surgery Eye Care Surgery is the least-used option for treating The eye problems associated with Graves’ Graves’ disease. Sometimes surgery may be disease may not improve following thyroid used to treat treatment, so the two problems are often treated separately. • pregnant women who cannot tolerate antithyroid medications Eye drops can relieve dry, gritty, irritated eyes—the most common of the milder • people suspected of having thyroid symptoms. If pain and swelling occur, health cancer, though Graves’ disease does not care providers may prescribe a steroid such cause cancer as prednisone. Other medications that • people for whom other forms of suppress the immune response may also treatment are not successful provide relief. Before surgery, the health care provider Special lenses for glasses can help with light may prescribe antithyroid medications sensitivity and double vision. People with to temporarily bring a patient’s thyroid eye symptoms may be advised to sleep with hormone levels into the normal range. This their head elevated to reduce eyelid swelling. presurgical treatment prevents a condition If the eyelids do not fully close, taping them called —a sudden, severe shut at night can help prevent dry eyes. worsening of symptoms—that can occur when hyperthyroid patients have general In more severe cases, external radiation anesthesia. may be applied to the eyes to reduce inflammation. Like other types of radiation When surgery is used, many health care treatment, the benefits are not immediate; providers recommend the entire thyroid most people feel relief from symptoms 1 to be removed to eliminate the chance that 2 months after treatment. hyperthyroidism will return. If the entire thyroid is removed, lifelong thyroid hormone Surgery may be used to improve bulging medication is necessary. of the eyes and correct the vision changes caused by pressure on the optic nerve. A Although uncommon, certain problems can procedure called orbital decompression occur in thyroid surgery. The parathyroid makes the eye socket bigger and gives the glands can be damaged because they are eye room to sink back to a more normal located very close to the thyroid. These position. Eyelid surgery can return retracted glands help control calcium and phosphorous eyelids to their normal position. levels in the body. Damage to the laryngeal nerve, also located close to the thyroid, can lead to voice changes or breathing problems. But when surgery is performed by an experienced surgeon, less than 1 percent of patients have permanent complications.1 People who need help finding a surgeon can contact one of the organizations listed under “For More Information.”

7 Graves’ Disease Can treatment for Graves’ Dietary Supplements disease affect pregnancy? Iodine is an essential mineral for the thyroid. Treatment for Graves’ disease can sometimes However, people with autoimmune thyroid affect pregnancy. After treatment with disease may be sensitive to harmful side surgery or radioactive iodine, TSI antibodies effects from iodine. Taking iodine drops or can still be present in the blood, even when eating foods containing large amounts of thyroid levels are normal. If a pregnant iodine—such as seaweed, dulse, or kelp— woman has received either of these may cause or worsen hyperthyroidism. More treatments prior to becoming pregnant, the information about iodine is provided by the antibodies she produces may travel across National Library of Medicine in the fact Iodine in diet, www.nlm. the placenta to the baby’s bloodstream and sheet, available at nih.gov/medlineplus. stimulate the fetal thyroid. A pregnant woman who has been treated Women need more iodine when they are with surgery or radioactive iodine should pregnant—about 250 micrograms a day— inform her health care provider so her because the baby gets iodine from the baby can be monitored for thyroid-related mother’s diet. In the United States, about problems later in the pregnancy. Pregnant 7 percent of pregnant women may not women may safely be treated with antithyroid get enough iodine in their diet or through 3 Choosing iodized salt— medications. prenatal vitamins. salt supplemented with iodine—over plain For more information about pregnancy and salt and prenatal vitamins containing iodine antithyroid medications, see “Medications” will ensure this need is met. under the section titled “How is Graves’ To help ensure coordinated and safe care, disease treated?” More information about people should discuss their use of dietary pregnancy and thyroid disease is provided by supplements, such as iodine, with their health the NEMDIS in the fact sheet, Pregnancy and care provider. Tips for talking with health Thyroid Disease, available at www.endocrine. niddk.nih.gov. care providers are available at the National Center for Complementary and Alternative Medicine’s Time to Talk campaign at www. Eating, Diet, and Nutrition nccam.nih.gov. Experts recommend that people eat a balanced diet to obtain most nutrients. More information about diet and nutrition is provided by the National Agricultural Library available at www.nutrition.gov.

3Zimmerman MB. in pregnancy and the effects of maternal iodine supplementation on the offspring: a review. American Journal of Clinical Nutrition. 2009;89(2):668S–672S. 8 Graves’ Disease Hope through Research Points to Remember The National Institute of Diabetes and • Graves’ disease is the most Digestive and Kidney Diseases (NIDDK) common cause of hyperthyroidism conducts and supports research into many in the United States. kinds of disorders, including Graves’ disease. Researchers throughout the United • In Graves’ disease, the immune States and the world are working to better system stimulates the thyroid understand, prevent, and treat this disease. gland to make too much thyroid hormone. National Institutes of Health (NIH)-supported scientists are investigating • Common symptoms of the natural history, clinical presentation, hyperthyroidism include and genetics of thyroid function disorders nervousness or irritability, to further understand thyroid diseases. fatigue or muscle weakness, heat Scientists continue to study treatment intolerance, trouble sleeping, options for Graves’ disease and GO. hand tremors, rapid and irregular heartbeat, frequent bowel The following federally funded research movements or diarrhea, weight studies and clinical trials are currently under loss, and goiter. way: • People with Graves’ disease may • Evaluation of Patients With Thyroid also have bulging eyes, a condition Disorders, funded under NIH clinical called Graves’ ophthalmopathy trial number NCT00001159 (GO). • Trial of Rituximab for Graves’ • Graves’ disease is most often Ophthalmopathy, funded under NIH treated with radioiodine therapy, clinical trial number NCT00595335 which gradually destroys the cells • Phase II Randomized Controlled Study that make up the thyroid gland. of Sequential Orbital Radiotherapy for Antithyroid medications and Graves’ Ophthalmopathy, funded under surgery to remove the thyroid are NIH clinical trial number NCT00004660 sometimes used. Participants in clinical trials can play a more

• The eye problems associated active role in their own health care, gain with Graves’ disease may require access to new research treatments before separate treatment. they are widely available, and help others • A pregnant woman who has been by contributing to medical research. For treated with surgery or radioactive information about current studies, visit www. iodine prior to becoming pregnant ClinicalTrials.gov. should inform her health care provider so her baby can be monitored for thyroid-related problems later in the pregnancy.

9 Graves’ Disease For More Information The Endocrine Society 8401 Connecticut Avenue, Suite 900 American Academy of Otolaryngology— Chevy Chase, MD 20815 Head and Neck Surgery Phone: 1–888–363–6274 1650 Diagonal Road or 301–941–0200 Alexandria, VA 22314–2857 Fax: 301–941–0259 Phone: 703–836–4444 Email: [email protected] Internet: www.entnet.org Internet: www.endo-society.org American Association of Clinical Graves’ Disease and Thyroid Foundation Endocrinologists P.O. Box 2793 245 Riverside Avenue, Suite 200 Rancho Santa Fe, CA 92067 Jacksonville, FL 32202 Phone: 1–877–643–3123 Phone: 904–353–7878 Fax: 1–877–643–3123 Fax: 904–353–8185 Email: [email protected] Internet: www.aace.com Internet: www.gdatf.org American Thyroid Association The Hormone Foundation 6066 Leesburg Pike, Suite 550 8401 Connecticut Avenue, Suite 900 Falls Church, VA 22041 Chevy Chase, MD 20815–5817 Phone: 1–800–THYROID (1–800–849–7643) Phone: 1–800–HORMONE (1–800–467–6663) or 703–998–8890 Fax: 301–941–0259 Fax: 703–998–8893 Email: [email protected] Internet: www.thyroid.org Internet: www.hormone.org

10 Graves’ Disease Acknowledgments Publications produced by the NIDDK are carefully reviewed by both NIDDK scientists and outside experts. This publication was originally reviewed by Lewis Braverman, M.D., Boston University School of Medicine and Boston Medical Center; Leonard Wartofsky, M.D., M.A.C.P., Washington Hospital Center; Nicholas J. Sarlis, M.D., NIDDK; Nabeel Babar, M.D., NIDDK; and the National Eye Institute, NIH.

11 Graves’ Disease You may also find additional information about this National Endocrine topic by visiting MedlinePlus at www.medlineplus.gov. and Metabolic Diseases This publication may contain information about medications. When prepared, this publication Information Service included the most current information available. For updates or for questions about any medications, 6 Information Way contact the U.S. Food and Drug Administration toll- Bethesda, MD 20892–3569 free at 1–888–INFO–FDA (1–888–463–6332) or visit Phone: 1–888–828–0904 www.fda.gov. Consult your health care provider for more information. TTY: 1–866–569–1162 Fax: 703–738–4929 Email: [email protected] The U.S. Government does not endorse or favor any Internet: www.endocrine.niddk.nih.gov specific commercial product or company. Trade, proprietary, or company names appearing in this The National Endocrine and Metabolic document are used only because they are considered Diseases Information Service is an necessary in the context of the information provided. information dissemination service of the If a product is not mentioned, the omission does not mean or imply that the product is unsatisfactory. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health, which is part of the U.S. Department of Health and Human Services. The NIDDK conducts and supports biomedical research. As a public service, the NIDDK has established information services to increase knowledge and understanding about health and disease among patients, health professionals, and the public.

This publication is not copyrighted. The NIDDK encourages users of this publication to duplicate and distribute as many copies as desired. This publication is available at www.endocrine.niddk.nih.gov.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health

NIH Publication No. 12–6217 July 2012

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