Graves' disease is a rare disease affecting the thyroid gland and often the skin and eyes. This disorder is characterized by abnormal enlargement of the thyroid gland (goiter) and increased secretion of thyroid hormone (hyperthyroidism). Symptoms of Graves' disease may include fatigue, weight loss, an abnormal intolerance of heat, muscle weakness, and protrusion or bulging of the eyeballs from their sockets. The exact cause of Graves' disease is not known, although an imbalance in the immune system is thought to play a role.
Onset of the symptoms associated with Graves’ disease is usually gradual, often taking several weeks or months to develop. Symptoms may include behavioral changes such as nervousness, irritability, and restlessness and difficulty sleeping (insomnia). Additional symptoms include fatigue, weight loss, muscle weakness, an abnormal intolerance to heat, increased sweating, and a rapid heartbeat (tachycardia).
Graves’ disease is often associated with abnormalities affecting the eyes that are commonly referred to as Graves’ ophthalmopathy. These abnormalities include swelling of the tissues surrounding the eye that may cause the eye to protrude or bulge out of its protective socket (orbit). Affected individuals may also experience inflammation, redness and irritation of the eyes, and/or blurred or double vision.
In some cases, individuals with Graves’ disease develop a skin condition known as pretibial dermopathy or myxedema. This condition is characterized by the development of thickened, reddish skin on the front of shins. It is usually limited to the shins but, in some cases, may also occur on the feet.
Additional symptoms associated with Graves’ disease include heart palpitations, slight tremors of the hands and/or fingers, hair loss, brittle nails, exaggerated reflexes (hyperreflexia), increased appetite, and an increase in the frequency of bowel movements. Females with Graves’ disease may experience a decrease in the menstrual cycle. In some cases, Graves’ disease may progress to cause congestive heart failure or abnormal thinning and weakness of the bones (osteoporosis) that leaves them brittle and susceptible to repeated fractures.
The exact cause of Graves’ disease is not known. Several factors may contribute to the development of the disorder, including immunologic, genetic, environmental, and/or other factors.
Graves’ disease may be a disease of the autoimmune system. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. In Graves’ disease, antibodies mistakenly attack the thyroid gland, stimulating it to grow and produce an excess of thyroid hormone.
Researchers also theorize that affected individuals may carry genes for, or have a genetic susceptibility to, Graves’ disease. However, it is suspected that the disease gene(s) may not be expressed unless something in the environment triggers the disease (multifactorial). Environmental factors may include extreme emotional stress, infection, or pregnancy.
Researchers believe that a susceptibility gene for Graves’ disease may be located on the long arm (q) of chromosome 14 (14q31). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered. For example, “chromosome 14p31” refers to band 31 on the short arm of chromosome 14.
Some researchers also believe that a susceptibility gene for Graves’ disease may be located on the long arm (q) of chromosome 20 (20q11).
Symptoms of Graves’ disease are caused by overproduction of thyroid hormone by the thyroid gland, which leads to abnormally elevated levels of thyroid hormone in the body (thyrotoxicosis). The thyroid gland is a thin, butterfly-shaped organ located in front of the windpipe (trachea). In Graves’ disease, the thyroid gland is abnormally enlarged (goiter).
Graves’ disease is a rare condition that affects females more often than males. It usually occurs during middle age, but also affects children and adolescents. Graves’ disease occurs in almost any part of the world. According to one estimate, Graves’ disease occurs in less than one-fourth of 1 percent of the general population.
A 1987 survey of 924 individuals with hyperthyroidism from 17 thyroid centers in six European countries indicated that 60 percent of individuals with hyperthyroidism have Graves’ disease.
A diagnosis of Graves' disease is made based upon a detailed patient history, a thorough clinical evaluation, identification of characteristic findings, and specialized tests such as blood tests.
Treatment of Graves' disease in adults usually involves one of three methods. antithyroid drugs, use of radioactive iodine, or surgery. The specific form of treatment recommended may be based upon the age of an affected individual and the degree of the illness.
The least invasive method of treating Graves' disease is the use of drugs that reduce the release of thyroid hormone (antithyroid drugs). These drugs are especially preferred for the treatment of young children and pregnant women, individuals with mild cases of hyperthyroidism, or individuals in whom prompt control of hyperthyroidism is required. The two most common antithyroid drugs used to treat Graves' disease are propylthiouracil and methimazole. Antithyroid drugs may be used alone or in conjunction with replacement hormone therapy.
If antithyroid drugs prove unsuccessful, individuals with Graves' disease may be treated with radioactive iodine (radioiodine). Iodine is a highly active chemical element. Affected individuals will swallow a solution containing radioiodine, which will travel through the bloodstream and collect in the thyroid gland where it will damage and destroy thyroid tissue. This will result in a decrease in the amount of thyroid hormone that is produced. If thyroid hormone levels fall too low, hormone therapy to regain adequate levels of thyroid hormone may be necessary.
The surgical removal of part or most of the thyroid gland (thyroidectomy) as a method of treatment for Graves' disease is usually reserved for individuals in whom the other forms of treatment have not been successful. Hormone replacement therapy may be necessary to ensure the body has adequate thyroid hormone levels.
In addition to the three above-mentioned treatments, drugs that block thyroid hormone that is already circulating in the blood from performing its functions (betablockers) may be prescribed. Lifelong follow up and laboratory studies are necessary in many cases. In some cases, lifelong hormone replacement therapy may be necessary.
Mild cases of Graves' ophthalmopathy (eye abnormalities associated with Graves' disease) may be treated with sunglasses, ointments, artificial tears, and/or prisms that are attached to glasses. More serious cases of Graves' ophthalmopathy may be treated with corticosteroids, such as prednisone, to reduce the swelling of tissues surrounding the eyes. Orbital radiotherapy and orbital decompression surgery may also be necessary.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
Clinical trials are underway to study the myocardial 31-phosphate imaging in hyperthyroidism. Interested persons may wish to contact:
Paul W. Ladenson, M.D.
Division of Endocrinology and Metabolism
600 N. Wolfe St.
Baltimore, MD 21205
Clinical trials are underway to study the physiologic determinants of exercise capacity in hyperthyroidism. Interested persons may wish to contact:
School of Medicine
4566 Scott Ave., Campus Box 8113
St. Louis, MO 63110
Doctors at the Mayo Clinic are studying orbital radiotherapy as a possible treatment for symptoms of Graves’ disease that involve the eye. More studies are needed to determine the long-term safety and effectiveness of this treatment. For more information, contact:
200 First St. SW
Rochester, MN 55905
Researchers are studying the genetics of Graves’ disease and Hashimoto’s syndrome. For more information, contact Human Biological Data Interchange Thyroid Disease Resource at (800) 835-6751.
According to a recent study, therapies for Graves’ disease were less effective in men and younger individuals of both sexes. Long-term follow up and evaluation of these findings are necessary to determine their clinical significance in regard to Graves’ disease.
Researchers are studying the effects of radioactive iodine (RAI) as a potential treatment for children with Graves’ disease. In initial studies, RAI was effective in treating nearly all children with Graves’ disease. More research is necessary to determine the long-term safety and effectiveness of this potential treatment for the pediatric population with Graves’ disease.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
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