Graves' Disease

Graves' Disease

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Graves' Disease is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Basedow Disease
  • Exophthalmic Goiter
  • Parry Disease
  • Graves' hyperthyroidism

Disorder Subdivisions

  • None

General Discussion

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.

Symptoms

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.

Causes

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).

Affected Populations

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.

Standard Therapies

Diagnosis

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

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.

Investigational Therapies

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

Blalock 904

600 N. Wolfe St.

Baltimore, MD 21205

(301) 955-3663



Clinical trials are underway to study the physiologic determinants of exercise capacity in hyperthyroidism. Interested persons may wish to contact:



Wade Martin

Washington University

School of Medicine

4566 Scott Ave., Campus Box 8113

St. Louis, MO 63110

(314) 362-2392



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:



Nancy Stanley

Mayo Clinic

200 First St. SW

Rochester, MN 55905

(507) 284-4738



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

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:275000; Last Update:12/3/99.



JOURNAL ARTICLES

Nebesio TD, et al. Time course to hypothyroidism after fixed-dose radioablation therapy of Graves' disease in children. J Pediatr. 2002;141:99-103.



Allahabadia A, et al. Age and gender predict the outcome of treatment for Graves' hyperthyroidism. J Clin Endocrinol Metab. 2000;85:1038-42.



Bartalena L, et al. Management of Graves' ophthalmopathy: reality and perspectives. Endocr Rev. 2000;21:168-99.



Tomer Y, et al. A new disease-susceptibility locus maps to chromosome 20q11.2. International Consortium for the Genetics of Autoimmune Thyroid Disease. Am J Hum Genet. 1998;63:1749-56.



Gorman CA, et al. Therapy for hyperthyroidism and graves' ophthalmopathy. New Engl J Med. 1998;338:1546-47.



Bartalena L, et al. Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. New Engl J Med. 1998;338:73-78.



Tomer Y, et al. Mapping of a major susceptibility locus for Graves' disease (GD-1) to chromosome 14q31. J Clin Endocrinol Metab. 1997;82:1645-48.



McIver B. Lack of effect of thyroxine in patients with Graves' hyperthyroidism who are treated with an antithyroid drug. New Engl J Med. 1996;334:220-24.



Wiersinga WM. Immunosuppression of Graves' hyperthyroidism -- still an elusive goal. New Eng J Med. 1996;334:265-66.



Hashizume K, et al. Administration of thyroxine in treated Graves' disease: effects on the level of antibodies to thyroid-stimulation hormone receptors and on the risk of reoccurrence of hyperthyroidism. New Eng J Med. 1991;324:947-53.



Ladenson PW. Treatment for Graves' disease: telling the thyroid to rest. New Eng J Med. 1991;324:989-90.



McFarland KF, et al. Graves' disease. Manifestations and therapeutic options. Postgrad Med. 1988;83:275-82.



Nomura K, et al. High serum progesterone in hyperthyroid men with Graves' disease. J Clin Endocrinol Metab. 1988;66:230-32.



Falk SA, et al. Graves' disease associated with histologic Hashimoto's thyroiditis. Otolaryngol Head Neck Surg. 1985;93:86-91.

Resources

Graves' Disease & Thyroid Foundation

P. O. Box 2793

Rancho Santa Fe, CA 92067

Tel: (877)643-3123

Fax: (877)643-3123

Tel: (877)643-3123

Email: info@gdatf.org

Internet: http://www.gdatf.org/



American Autoimmune Related Diseases Association, Inc.

22100 Gratiot Ave.

Eastpointe, MI 48021

Tel: (586)776-3900

Fax: (586)776-3903

Tel: (800)598-4668

Email: aarda@aarda.org

Internet: http://www.aarda.org/



Thyroid Foundation of Canada

263 MCG Building

Labrosse Ave

Pointe-Claire

QC, H9R 1A3

Canada

Fax: 5146309815

Tel: 8002678822

Internet: http://www.thyroid.ca



Hormone Health Network

8401 Connecticut Avenue

Suite 900

Chevy Chase, MD 20815-5817

Fax: (310)941-0259

Tel: (800)467-6663

Email: hormone@endo-society.org

Internet: http://www.hormone.org/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Autoimmune Information Network, Inc.

PO Box 4121

Brick, NJ 08723

Fax: (732)543-7285

Email: autoimmunehelp@aol.com



European Society for Immunodeficiencies

1-3 rue de Chantepoulet

Geneva, CH 1211

Switzerland

Tel: 410229080484

Fax: 41229069140

Email: esid@kenes.com

Internet: http://www.esid.org



AutoImmunity Community

Email: moderator@autoimmunitycommunity.org

Internet: http://www.autoimmunitycommunity.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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