In graves disease the excessive secretion of thyroid hormone is accompanied by diffuse enlargement of the thyroid gland diffuse goitre. Graves disease, one of the autoimmune thyroid diseases, is caused by the production of igg autoantibodies directed against the thyrotropin receptor. In graves disease, the main autoantigen is the thyroidstimulating hormone tsh receptor tshr, which is expressed primarily in the thyroid but also in adipocytes, fibroblasts, bone cells, and a variety of additional sites 4,5. Graves disease is an autoimmune disorder in which the thyroid is activated by antibodies to the thyrotropin receptor. Aetiologicalfactors certain clinical associations are characteristic of this conditionit. Hashimotos thyroiditis ht and graves disease gd are two very common organspecific autoimmune diseases which are characterized by the presence of circulating thyroid antibodies and infiltration by autoreactive lymphocytes of the thyroid gland, and occasionally the orbit. Graves disease is a disease of autoimmunity, but the final cause of autoimmunity remains unclear. Fibroblasts residing within orbital tissues are thought to be targets of autoimmune attack in the disease. In addition to hyperthyroidism, clinical involvement of the eyes develops in 25% to 50% of individuals with graves disease. Prabhakar 1 department of microbiology and immunology b. With this disease, your immune system attacks the thyroid and causes it to make more thyroid hormone than your body needs. Pdf current concepts in the molecular pathogenesis of. The prevalence of graves disease is similar in white and asian people, and lower in black people.
Robert volpe, md 1995 the pathogenesis of graves disease. Hyperthyroidism in graves disease is due to the binding of stimulatory autoantibodies to the tsh receptor tshr on thyroid follicular cells. It is a form of idiopathic lymphocytic orbital inflammation, and although its pathogenesis is not completely understood, autoimmune activation of orbital fibroblasts, which in tao express the tsh receptor, is thought to play a central role. The common finding in ted that accounts for most of its clinical manifestations seems to be enlargement. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. At its core, stimulatory autoantibodies are directed at the thyroidstimulating hormone receptor tshr, resulting in dysregulated thyroid gland activity and growth. It is only in the atypical cases, or with coexisting disease, or in mild or early disease, that the diagnosis may be in.
The abnormal immune response is characterized by the presence of. Graves, md, circa 1830s, is an autoimmune disease characterized by hyperthyroidism due to circulating autoantibodies. Chapter 11diagnosis and treatment of graves disease. Most patients with hyperthyroidism have an enlarged thyroid gland goiter, but characteristics of the enlargement vary. Graves ophthalmopathy go is a medically incurable, chronic autoimmune process that affects the orbital tissues and is tightly linked with autoimmune thyroid diseases, most notably graves disease gd. Thyroid eye disease ted is a visionthreatening condition that is most commonly associated with graves disease gd. Ophthalmopathy is a potentially disfiguring and sightthreatening component of graves disease. Graves orbitopathy represents orbit involvement and is clinically relevant in about half of the patients with the graves disease. The underlying cause of graves disease is not known, but there is genetic susceptibility to the disease, and smoking is a risk factor, especially for graves ophthalmopathy. Intravenous glucocorticoid therapy for graves ophthalmopathy and. Pathogenesis the pathogenesis of graves disease is illustrated in fig.
It frequently results in and is the most common cause of hyperthyroidism. The article by hollingsworth and mabry that appears in this issue of the journal p 148 provides interesting and important supplemental information to the authors earlier article. Graves disease, also called toxic diffuse goitre or exophthalmic goitre, endocrine disorder that is the most common cause of hyperthyroidism excess secretion of thyroid hormone and thyrotoxicosis effects of excess thyroid hormone action in tissue. Researchers identify factor in pathogenesis of graves disease. Pdf role of the t and b lymphocytes in pathogenesis of. Ultimately, the hyperthyroidism manifested by patients affected by the disease is caused by the production of autoantibodies against the thyrotropin receptor tshr, which mimic the effects of the hormone on thyroid cells, thereby stimulating autonomous production of thyroxine and triiodothyronine. Thyroid hormones control how your body uses energy, so. Studies concerning the pathogenesis of graves disease and go have long been hampered by the lack of an animal model reproducing the salient clinical and biochemical characteristics of the disease.
Examples of thyroid disorders that give rise to hyperthyroidism include graves disease, plummer disease, and thyroiditis. Graves disease may be associated with antitpo antibodies but it is caused by antithyrotropin tsh receptor autoantibody that mimic tsh and stimulate hormone synthesis, secretion and thyroid growth. Although it has often been referred to as graves ophthalmopathy, or simply thyroid eye disease ted, it is primarily a disease of the orbit and is better termed graves orbitopathy. The diagnosis of graves disease is usually easily made. Prevalence and natural history of graves orbitopathy in a large series of patients with newly diagnosed graves hyperthyroidism seen at a single center. Difference between graves disease and hashimoto compare the. Further evidence of ongoing autoimmunity in graves disease is the elevation of icam1, and il6 and il8 cytokines seen in hyperthyroid patients 12. Inheritance of hla antigens dr3, dq 2, and dqa10501 predispose to graves disease. Nonautoimmune type ii reactions transfusion reactions abo incompatibility. It occurs more commonly amongst women, smokers and patients with other autoimmune diseases or a family history of thyroid autoimmunity manji et al. Graves disease is an autoimmune thyroid disorder with an unknown etiology. Dec 10, 2011 graves disease is a most common cause of hyperthyroidism in iodine sufficient areas. Hyperthyroidism, also called thyrotoxicosis, excess production of thyroid hormone by the thyroid gland.
Pathogenesis of graves ophthalmopathy springerlink. Thyroidassociated ophthalmopathy tao, or thyroid eye disease ted, is the most common extrathyroidal manifestation of graves disease. Graves disease is an autoimmune disease that leads to a generalized overactivity of the entire thyroid gland. Graves disease is an autoimmune disease that leads to a generalized overactivity of the entire thyroid gland hyperthyroidism.
Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional. It is about 150 years since the publication of the original descriptions of the disorder now termed graves disease. The hyperthyroidism and goitre of graves disease are caused by stimulation of the thyroid by tsh receptor antibodies. It is the most common cause of hyperthyroidism in the united states. Parrys disease would recognize parrys priority over graves but his first description is generally recognized. Current perspective on the pathogenesis of graves disease.
Graves disease, also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. Pathogenesis and treatment represent the viewpoints of many prominent clinicians and investigators working in the field. Pathogenesis and therapy of neonatal graves disease jama. Epidemiology of graves orbitopathy go and relationship with thyroid disease. Most patients with hyperthyroidism have an enlarged thyroid gland, but the characteristics of the enlargement vary. Graves disease gd is a very common autoimmune disorder of the thyroid in. Graves disease is caused by thyroid stimulating immunoglobulin tsi, also known as thyroid stimulating. Pathogenesis of the hyperthyroidism of gravess disease article pdf available in british medical journal 15441. Although some patients with go experience only mild. Yicheng qi, huan zheng, nan liu, ting guo, wei zhu, shu wang, bin cui and guang ning, genetic association between gene polymorphisms and the pathogenesis of graves disease in the han chinese population, clinical endocrinology, 84, 2, 265270, 2015. Graves disease the journal of clinical endocrinology. Request pdf current perspective on the pathogenesis of graves disease and ophthalmopathy graves disease gd is a very common autoimmune. Ocular involvement is probably due to the presence of autoantibodies in the orbital tissues, regardless of the control state of thyroid. The abnormally increased thyroid activity that is characteristic of graves disease is caused by immunoglobulins which specifically interact with the thyroid cell and stimulate it.
Associated orbitopathy occurs in around 25% of cases and is usually mild. This further implicates igf1r in the pathogenesis of patients with graves disease. Graves disease is often used to denote this condition of exophthalmos and hyperthyroidism. The pathogenesis of tao remains enigmatic as do the connections between. Graves disease gd is an autoimmune disorder responsible for 6090% of thyrotoxicosis, with an incidence of 1 to 2 cases per population per year in england. However, as a useful model was developed recently in which naive balbc mice were inoculated with splenocytes primed with either a tshr fusion. In graves disease, b cells play a vital role as they are the source of pathognomonic activating autoantibodies trab against thyroidstimulatin g hormone receptor. It is 4 to 9 times more common in women than in men.
The disease affects about five in every 10,000 people in the united states. Graves, md, circa 1830s, is an autoimmune disease characterized by hyperthyroidism due to circulating. The hyperthyroidism and goitre of graves disease are caused by stimulation of the thyroid by tsh receptor anti. Although the concept of infection of the thyroid gland leading to altered antigen expression and autoimmunity has appeal, little firm evidence for this mechanism in the pathogenesis of graves disease exists. It is named after robert graves, an irish physician, who described this form of hyperthyroidism about 150 years ago. It is also possible that some viruses are specifically implicated in the pathogenesis of graves disease or hashimoto thyroiditis which combines goitre and autoimmunity. Graves disease symptoms, diagnosis and treatment bmj. Current perspective on the pathogenesis of graves disease and. The intrathyroidism of the viral genome of a polyomavirus, the bk virus, has recently been reported in patients with goitre or cancer. In addition to hyperthyroidism, 2550% of individuals with graves disease have clinical involvement of the eyes known as graves ophthalmopathy go2.
Hyperthyroidism endocrine and metabolic disorders merck. Although the mechanism underlying the thyroid gland dysfunction in gd is now relatively wellcharacterized, the pathophysiology of ted is only beginning to be elucidated. Pdf pathogenesis of the hyperthyroidism of gravess disease. The thyroid is a small, butterflyshaped gland in the front of your neck. Taking a novel angle, peter gergely here examines the role of different types of leucocytes across a spectrum of autoimmune diseases, combin.
Another characteristic of the disease is spontaneous remission of hyperthyroidism, which occurs in 30 to 40 percent of patients. Graves disease gd is a very common autoimmune disorder of the thyroid in which stimulatory antibodies bind to the thyrotropin receptor. Closely associated with gd is the ocular condition known as thyroidassociated ophthalmopathy tao. Graves disease is a relatively common disorder occurring primarily in women with an incidence of 1 populationyear 1.
Sisti e, coco b, menconi f, leo m, rocchi r, latrofa f, et al. Medicare coverage of routine screening for thyroid dysfunction. Graves disease is the most common autoimmune disease, affecting 0. The pathogenesis of autoimmune disease peter gergely the mechanisms of autoimmune pathology are normally described on a disease by disease basis. Introduction graves ophthalmopathy go, an autoimmune condition associated with graves disease gd, occursat a prevalence of nearly 40% in patients diagnosed. Side by side comparison graves disease vs hashimoto in tabular form 6. It is clinically evident in 25 to 50 percent of patients with graves hyperthyroidism and occurs occa. Anticardiolipin antibodies are present in increased incidence in patients with autoimmune thyroid disease, including graves disease. The hyperthyroidism that develops is one of many somatic and psychiatric manif.
Autoimmune diseases sle lupus nephritis, rheumatoid arthritis drug reactions allergies to penicillin and sulfonamides. Graves ophthalmopathy go, an autoimmune condition associated with graves disease gd, occurs at a prevalence of nearly 40% in patients diagnosed with gd. Graves disease occurs when your immune system attacks your thyroid gland, causing it to enlarge and make too much thyroid hormone a condition called hyperthyroidism. What is the pathogenesis of hyperthyroidism in graves disease. Graves disease is the most common cause of hyperthyroidism, with an annual incidence of 20 to. Examples of thyroid disorders that give rise to hyperthyroidism include diffuse goitre graves disease, toxic multinodular goitre plummer disease, and thyroid inflammation. Graves disease is an autoimmune thyroid condition associated with hyperthyroidism. Involvement of polyomaviruses in the pathogenesis of. The pathogenesis of graves disease is illustrated in fig. Epidemiology and prevention of graves ophthalmopathy. Hashimotos thyroiditis ht and graves disease gd are two very common organspecific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Most commonly affects middle aged women with female to male ratio of 4.
One normal immune system response is the production of antibodies designed to target a specific virus, bacterium or other foreign substance. Graves disease autoimmune process in which antibodies stimulate the tsh receptor leading to. The pathogenesis of infiltrative ophthalmopathy responsible for the exophthalmos in graves disease is poorly understood but may result from immunoglobulins directed to the tsh receptors in the orbital fibroblasts and fat that result in release of proinflammatory cytokines, inflammation, and accumulation of glycosaminoglycans. Graves disease is caused by a malfunction in the bodys diseasefighting immune system, although the exact reason why this happens is still unknown. Graves disease, the most common cause of hyperthyroidism, can lead to severe swelling around the eye sockets. Current perspective on the pathogenesis of graves disease and ophthalmopathy bellur s. The editors are grateful for their contributions which cover an unusually comprehensive compendium of subjects relating to the disease. Graves disease is an autoimmune condition of the thyroid. It is characterized by diffuse goitre and hyperthyroidism. Pdf on jan 1, 2018, irene campi and others published graves. The role of oxidative stress on the pathogenesis of graves. Graves disease is an autoimmune disorder that causes hyperthyroidism, or overactive thyroid. Graves disease gd is a common autoimmune condition.
The clinical manifestations of graves ophthalmopathy go stem from a combination of increased orbital fat and extraocular muscle volume within the orbital space. In graves disease, the main autoantigen is the thyroidstimulating hormone tsh receptor tshr, which is expressed primarily in the thyroid but is also expressed in adipocytes, fibroblasts, and a variety of additional sites and appears to be closely aligned with the insulinlike glucose factor 1 igf1 receptor. Hyperthyroidism, excess production of thyroid hormone by the thyroid gland. The pathogenesis of graves disease endocrine practice.
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