Graves' disease is a condition that affects the function of the thyroid, which is a butterfly-shaped gland in the lower neck. The thyroid makes hormones that help regulate a wide variety of critical body functions. For example, thyroid hormones influence growth and development, body temperature, heart rate, menstrual cycles, and weight. In people with Graves' disease, the thyroid is overactive and makes more hormones than the body needs. The condition usually appears in mid-adulthood, although it may occur at any age.

Excess thyroid hormones can cause a variety of signs and symptoms. These include nervousness or anxiety, extreme tiredness (fatigue), a rapid and irregular heartbeat, hand tremors, frequent bowel movements or diarrhea, increased sweating and difficulty tolerating hot conditions, trouble sleeping, and weight loss in spite of an increased appetite. Affected women may have menstrual irregularities, such as an unusually light menstrual flow and infrequent periods. Some people with Graves' disease develop an enlargement of the thyroid called a goiter. Depending on its size, the enlarged thyroid can cause the neck to look swollen and may interfere with breathing and swallowing.

Between 25 and 50 percent of people with Graves' disease have eye abnormalities, which are known as Graves' ophthalmopathy. These eye problems can include swelling and inflammation, redness, dryness, puffy eyelids, and a gritty sensation like having sand or dirt in the eyes. Some people develop bulging of the eyes caused by inflammation of tissues behind the eyeball and "pulling back" (retraction) of the eyelids. Rarely, affected individuals have more serious eye problems, such as pain, double vision, and pinching (compression) of the optic nerve connecting the eye and the brain, which can cause vision loss.

A small percentage of people with Graves' disease develop a skin abnormality called pretibial myxedema or Graves' dermopathy. This abnormality causes the skin on the front of the lower legs and the tops of the feet to become thick, lumpy, and red. It is not usually painful.

Graves' disease affects about 1 in 200 people. The disease occurs more often in women than in men, which may be related to hormonal factors. Graves' disease is the most common cause of thyroid overactivity (hyperthyroidism) in the United States.

Graves' disease is thought to result from a combination of genetic and environmental factors. Some of these factors have been identified, but many remain unknown.

Graves' disease is classified as an autoimmune disorder, one of a large group of conditions that occur when the immune system attacks the body's own tissues and organs. In people with Graves' disease, the immune system creates a protein (antibody) called thyroid-stimulating immunoglobulin (TSI). TSI signals the thyroid to increase its production of hormones abnormally. The resulting overactivity of the thyroid causes many of the signs and symptoms of Graves' disease. Studies suggest that immune system abnormalities also underlie Graves' ophthalmopathy and pretibial myxedema.

People with Graves' disease have an increased risk of developing other autoimmune disorders, including rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, Addison disease, celiac disease, type 1 diabetes, and vitiligo.

Variations in many genes have been studied as possible risk factors for Graves' disease. Some of these genes are part of a family called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Other genes that have been associated with Graves' disease help regulate the immune system or are involved in normal thyroid function. Most of the genetic variations that have been discovered are thought to have a small impact on a person's overall risk of developing this condition.

Other, nongenetic factors are also believed to play a role in Graves' disease. These factors may trigger the condition in people who are at risk, although the mechanism is unclear. Potential triggers include changes in sex hormones (particularly in women), viral or bacterial infections, certain medications, and having too much or too little iodine (a substance critical for thyroid hormone production). Smoking increases the risk of eye problems and is associated with more severe eye abnormalities in people with Graves disease.

Genetic Testing Information

• Genetic Testing Registry: Graves disease, susceptibility to, 1

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• GRAVES DISEASE; GRD
• GRAVES DISEASE, SUSCEPTIBILITY TO, X-LINKED 1
• GRAVES DISEASE, SUSCEPTIBILITY TO, 2

Scientific Articles on PubMed

• PubMed

• Eschler DC, Hasham A, Tomer Y. Cutting edge: the etiology of autoimmune thyroid diseases. Clin Rev Allergy Immunol. 2011 Oct;41(2):190-7. doi: 10.1007/s12016-010-8245-8. Citation on PubMed or Free article on PubMed Central
• Hasham A, Tomer Y. Genetic and epigenetic mechanisms in thyroid autoimmunity. Immunol Res. 2012 Dec;54(1-3):204-13. doi: 10.1007/s12026-012-8302-x. Citation on PubMed or Free article on PubMed Central
• Jacobson EM, Huber A, Tomer Y. The HLA gene complex in thyroid autoimmunity: from epidemiology to etiology. J Autoimmun. 2008 Feb-Mar;30(1-2):58-62. doi: 10.1016/j.jaut.2007.11.010. Epub 2008 Jan 4. Citation on PubMed or Free article on PubMed Central
• National Institute of Diabetes and Digestive and Kidney Diseases
• Simmonds MJ, Gough SC. The search for the genetic contribution to autoimmune thyroid disease: the never ending story? Brief Funct Genomics. 2011 Mar;10(2):77-90. doi: 10.1093/bfgp/elq036. Citation on PubMed
• Tomer Y. Genetic susceptibility to autoimmune thyroid disease: past, present, and future. Thyroid. 2010 Jul;20(7):715-25. doi: 10.1089/thy.2010.1644. Citation on PubMed or Free article on PubMed Central