Graves’ Disease and the Manifestations of Thyrotoxicosis

Graves' disease includes thyrotoxicosis, goiter, exophthalmos, and pretibial myxedema when fully expressed, but can occur with one or more of these features. Graves' disease is a disease of "autoimmunity", but the final cause of autoimmunity remains unclear. A strong hereditary tendency is present. Inheritance of HLA antigens DR3, DQ 2, and DQA1*0501 predispose to Graves' disease. The abnormal immune response is characterized by the presence of antibodies directed against thyroid tissue antigens, including antibodies that react with the thyrotrophin receptor by binding to the receptor. Some of these antibodies act as agonists and stimulate the thyroid. The best-known of the antibodies is the serum factor first reported as "LATS", now known as "TSAb".It has been reported in active Graves' disease that Tlymphocyte suppressor cell function is diminished and suppressor cell number is reduced. It is hypothesized that an abnormality in the control of autoimmune responses is present in this disease and leads to production of high levels of autoantibodies that may stimulate the thyroid or eventually cause thyroid damage and cell death. The thyroid gland is hyperfunctioning in Graves' disease. The pituitary response to TRH is also suppressed. The gland is unusually responsive to small doses of iodide, which both block further hormone synthesis and inhibit release of hormone from the gland. The incidence of Graves' disease is reported in recent studies to be 1 to 2 cases per 1,000 population per year in England. This rate is considerably higher than the rate of about 0.3 cases per 1,000 previously reported from this country. The frequency in women is much greater than it is in men. The classic features of thyrotoxicosis are nervousness, diminished sleep, tremulousness, tachycardia, increased appetite, weight loss, and increased perspiration and signs are goiter, occasionally with exophthalmos, and rarely with pretibial myxedema. Physical findings include fine skin and hair, tremulousness, a hyperactive heart, Plummer's nails, muscle weakness, accelerated reflex relaxation, occasional splenomegaly, and often peripheral edema. Autoimmune vitiligo or hives may coexist in patients with Graves' disease. The disease typically begins gradually in adult women and is progressive unless treated. Thyrotoxicosis can cause congestive heart failure. Mitral valve prolapse, atrial tachycardia and fibrillation are commonly caused by thyrotoxicosis.. Amenorrhea or anovulatory cycling is common in women, and fertility is reduced.Thyrotoxicosis in untreated cases leads to cardiovascular damage, bone loss and fractures, or inanition, and can be fatal. The long-term history also includes spontaneous remission in some cases and eventual spontaneous development of hypothyroidism, since autoimmune thyroiditis coexists and destroys the thyroid gland.