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.
Diagnosis
Graves disease may present clinically with one or more of these characteristic signs:
Rapid heartbeat (80%)
Diffuse palpable goiter with audible bruit (70%)
Tremor (40%)
Exophthalmos (protuberance of one or both eyes), periorbital edema (25%)
Fatigue (70%), weight loss (60%) with increased appetite in young people and poor appetite in the elderly, and other symptoms of hyperthyroidism/thyrotoxicosis
Heat intolerance (55%)
Tremulousness (55%)
Palpitations (50%)Two signs are truly diagnostic of Graves disease (i.e., not seen in other hyperthyroid conditions): exophthalmos and nonpitting edema (pretibial myxedema). Goiter is an enlarged thyroid gland and is of the diffuse type (i.e., spread throughout the gland). Diffuse goiter may be seen with other causes of hyperthyroidism, although Graves disease is the most common cause of diffuse goiter. A large goiter will be visible to the naked eye, but a small one (mild enlargement of the gland) may be detectable only by physical examination. Occasionally, goiter is not clinically detectable, but may be seen only with computed tomography or ultrasound examination of the thyroid. Another sign of Graves disease is hyperthyroidism; that is, overproduction of the thyroid hormones T3 and T4. Normal thyroid levels are also seen, and occasionally also hypothyroidism, which may assist in causing goiter (though it is not the cause of the Graves disease). Hyperthyroidism in Graves disease is confirmed, as with any other cause of hyperthyroidism, by measuring elevated blood levels of free (unbound) T3 and T4.Other useful laboratory measurements in Graves disease include thyroid-stimulating hormone (TSH, usually undetectable in Graves disease due to negative feedback from the elevated T3 and T4), and protein-bound iodine (elevated).