Prognosis
If left untreated, more serious complications could result, including birth defects in pregnancy, increased risk of a miscarriage, bone mineral loss and, in extreme cases, death. Graves disease is often accompanied by an increase in heart rate, which may lead to further heart complications, including loss of the normal heart rhythm (atrial fibrillation), which may lead to stroke. If the eyes are proptotic (bulging) enough that the lids do not close completely at night, dryness will occur – with the risk of a secondary corneal infection, which could lead to blindness. Pressure on the optic nerve behind the globe can lead to visual field defects and vision loss, as well. Prolonged untreated hyperthyroidism can lead to bone loss, which may resolve when treated. Epidemiology
Graves disease occurs in about 0.5% of people. Graves disease data has shown that the lifetime risk for women is around 3% and 0.5% for men. It occurs about 7.5 times more often in women than in men and often starts between the ages of 40 and 60. It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases). History
Graves disease owes its name to the Irish doctor Robert James Graves, who described a case of goiter with exophthalmos in 1835. Medical eponyms are often styled nonpossessively; thus Graves disease and Graves disease are variant stylings of the same term. The German Karl Adolph von Basedow independently reported the same constellation of symptoms in 1840.
Infectious trigger
Since Graves disease is an autoimmune disease which appears suddenly, often later in life, a viral or bacterial infection may trigger antibodies which cross-react with the human TSH receptor, a phenomenon known as antigenic mimicry.The bacterium Yersinia enterocolitica bears structural similarity with the human thyrotropin receptor and was hypothesized to contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals. In the 1990s, it was suggested that Y. enterocolitica may be associated with Graves disease. More recently, the role for Y. enterocolitica has been disputed.Epstein–Barr virus (EBV) is another potential trigger. Mechanism
Thyroid-stimulating immunoglobulins recognize and bind to the thyrotropin receptor (TSH receptor) which stimulates the secretion of thyroxine (T4) and triiodothyronine (T3). Thyroxine receptors in the pituitary gland are activated by the surplus hormone, suppressing additional release of TSH in a negative feedback loop. The result is very high levels of circulating thyroid hormones and a low TSH level. Pathophysiology
Graves disease is an autoimmune disorder, in which the body produces antibodies that are specific to a self-protein: the receptor for thyroid-stimulating hormone. (Antibodies to thyroglobulin and to the thyroid hormones T3 and T4 may also be produced.) These antibodies cause hyperthyroidism because they bind to the TSHr and chronically stimulate it. The TSHr is expressed on the thyroid follicular cells of the thyroid gland (the cells that produce thyroid hormone), and the result of chronic stimulation is an abnormally high production of T3 and T4.