Graves' disease

Graves' disease is a form of tiroktoksikosis (hyperthyroidism) which is most frequently encountered in daily practice. Can occur at any age, often found in women than in men. Signs and symptoms of Graves' disease is the most easily recognizable is the goiter (diffuse hypertrophy and hyperplasia), thyrotoxicosis (thyroid gland hypersecretion / hyperthyroidism) and is often accompanied oftalmopati, and accompanied dermopati, though rarely. (1,2,3)
The pathogenesis of Graves' disease has so far not known. However, genetic and environmental factors thought to play a role in the mechanism is not certain the increased risk of suffering from Graves' disease. Based on the characteristics of the disease, Graves disease grouped into autoimmune diseases, such as the discovery of antibodies against TSH receptor (thyrotropin Stimulating Hormone - Receptor Antibody / TSHR-Ab) with varied levels. (1.2)
2.1 Definitions
Graves' disease (goiter difusa toksika) is the most common cause of hyperthyroidism is a disease that usually otonium characterized by the production of autoantibodies that have similar work TSH on the thyroid gland. Patients with Graves disease have the typical symptoms of hyperthyroidism and special additional symptoms are enlargement of the thyroid gland / goiter diffuse, oftamopati (eksoftalmus / bulging eyes) and sometimes with dermopati. (1,4,5,6)
2.2 Etiology
Graves' disease is one of the autoimmune disease, in which the cause is as yet known with certainty. This disease has a strong genetic predisposition, which 15% of patients have a close family relationship with the same disease. Approximately 50% of patients with Graves' disease family, was found thyroid autoantibodies in their blood. This disease was found 5 times more in women than in men, and can occur at any age. The incidence was highest in the age between 20 years to 40 years. (2.6)
2.3 Pathogenesis
At Graves disease, T lymphocytes undergo antigen stimulation of the thyroid gland which is located inside which will further stimulate B lymphocytes to synthesize antibodies against the antigen. Synthesized antibodies that will react with the TSH receptor in the thyroid cell membrane so that it will stimulate the growth and function of thyroid cells, known as TSH-R antibody. The presence of antibodies in the blood circulation is closely correlated with disease activity and relapse. Mechanisms of autoimmunity is an important factor in the pathogenesis of hyperthyroidism, oftalmopati, and dermopati in Graves' disease.
Until now there are 3 known major otoantigen the thyroid gland that thyroglobulin (Tg), thyroidal peroxidase (TPO) and TSH receptor (TSH-R). Besides, there is also a 64 kilodalton protein molecular weight on the surface of the cell membrane and cell-cell thyroid orbital alleged role in the process of change of orbital contents and Graves disease thyroid gland.
Thyroid cells have the ability to react with antigens on and when stimulated by the influence of cytokines (such as interferon gamma) to express the cell surface molecules class II (MHC class II, such as DR4) to present antigen to T lymphocytes
Figure 1: The pathogenesis of Graves' disease
Genetic factors play an important role in the autoimmune process, such as HLA-B8 and HLA-DR3 in Caucasian race, HLA-Bw46 and HLA-B5 in the Chinese race and HLA-B17 in blacks. Environmental factors also play a role in the pathogenesis of autoimmune thyroid disease such as Graves' disease. Viruses that infect human thyroid cells will stimulate DR4 expression on the surface of thyroid follicular cells, thought to be due to the influence of cytokines (especially interferon alfa). Gram-negative bacilli infections Yersinia enterocolitica, which causes chronic enterocolitis, allegedly had otoantigen cross-react with the thyroid gland. Antibodies against Yersinia enterocolitica shown to cross-react with TSH-R antibodies to thyroid cell membranes that can trigger acute episodes of Graves disease. High iodine intake can increase the levels of iodinated immunoglobulins that are more immunogenic thus increasing the tendency for the occurrence of autoimmune thyroid disease. Therapeutic dose of lithium is often used in the treatment of manic depressive psychosis, may also affect the function of suppressor T lymphocytes that can lead to autoimmune thyroid disease. Alleged stress factors can also trigger an acute episode of Graves' disease, but until now there is no strengthening the hypothesis that these allegations.
Graves oftalmopati occurrence involving cytotoxic lymphocytes (killer cells) and other cytotoxic antibodies that aroused as a result of antigen associated with thyroglobulin or TSH-R in fibroblasts, the muscles of the eyeball and thyroid tissue. Cytokines are formed from lymphocytes will cause inflammation and myositis orbital fibroblasts, causing swelling of the muscles of the eyeball, proptosis and diplopia.
Dermopati Graves (pretibial myxoedema) is also caused by cytokine stimulation in pretibial fibroblast tissue areas that will lead to the accumulation of glikosaminoglikans.
Various symptoms of thyrotoxicosis associated with catecholamine stimulation, such as takhikardi, tremor, and sweating a lot. Presence of hyperreactivity catecholamines, especially epinephrine allegedly caused by an increase in catecholamine receptors in the heart muscle. (2)
2.4 Clinical Overview
A. Symptoms and Signs
At Graves disease, there are two main groups namely tiroidal picture and ekstratiroidal that both may not appear. Tiroidal traits such as goiter due to thyroid gland hyperplasia and hyperthyroidism caused by excessive secretion of thyroid hormone. The symptoms of hyperthyroidism such as manifestations of hypermetabolism and excessive sympathetic activity. Patients complain of fatigue, trembling, can not stand the heat, sweat the more when hot, moist skin, weight loss despite increased appetite, palpitations, tachycardia, diarrhea, muscle atrophy and weakness srta. A manifestation ekstratiroidal oftalmopati and local infiltration of the skin that is usually confined to the lower limbs. Oftalmopati were found in 50% to 80% of patients characterized by bulging eyes, widened palpebral fissure, reduced blinking, lid lag (the delay in following eyelid eye movement) and the failure of convergence. (3) the classical clinical picture of Graves' disease include single tri hipertitoidisme, diffuse goiter and eksoftalmus. (5)
Vision changes (oftalmopati Graves), according to the American Thyroid Association are classified as follows (known by the acronym NOSPECS):
Class Description
0 No symptoms and signs
1 There is no sign of symptoms (such as upper lid retraction, stare, lid lag)
2 Changes in the soft tissues of the orbit
3 Proptosis (can be detected by Hertel exphthalmometer)
4 Involvement of the extra ocular muscles
5 Changes in the cornea (keratitis)
6 Blindness (optic nerve damage)
Class 1, the superior palpebral muscle spasm may accompany the initial state of Graves thyrotoxicosis that can heal spontaneously when circumstances tirotoksikosisnya adequately treated.
At 2-6 Class infiltrative process occurs in the muscles and orbital tissues.
Class 2 is characterized by inflammation of orbital soft tissues accompanied by periorbital edema, congestion and swelling of the conjunctiva (khemosis).
Class 3 is characterized by proptosis that can be detected by Hertel exophthalmometer.
At grade 4, a change in the muscles of the eyeball, especially in the form of infiltrative process musculus rectus inferior move that will cause hardship eyeball upwards. When the musculus rectus medialis, there will be difficulty in moving the eyeball laterally.
Class 5 is characterized by changes in the cornea (keratitis occurs).
Class 6 is characterized by optic nerve damage, which will cause blindness.
Graves Oftalmopati caused by infiltration of lymphocytes in the extraocular muscles accompanied by an acute inflammatory reaction. Eye cavity bounded by the bones of the orbit so that the swelling of the extraocular muscles would cause proptosis (protrusion) of the eyeball and muscle movement disorders eyeball, so it can happen diplopia. Enlargement of the muscles of the eyeball can be detected by a CT scan or MRI. Muscle swelling occurs when the posterior section, there will be emphasis optic nerve which will cause blindness.
In patients who were younger, were common clinical manifestations include palpitations, nervousness, fatigue, hiperkinesia, diarrhea, sweating a lot, can not stand the heat and prefer cold weather. In young women symptoms of Graves' disease can be either primary amenorrhea or infertility.
In children, an increase in the acceleration of growth and bone maturation process.
Whereas in patients with older age (> 60 years), clinical manifestations are particularly striking manifestation of cardiovascular and myopathy, characterized by palpitation, dyspnea d'effort, tremor, nervousness and weight loss. (1.2)
In neonates, clinical hyperthyroidism is a relatively rare disorder found, estimated the incidence was 1 in 25,000 pregnancies. Most patients are born to mothers who had active Graves' disease but may also occur in women with hypothyroidism or euthyroid state as autoimmune thyroiditis, radioactive iodine ablation treatment or because of surgery