The studies of the pathogenesis of Graves' disease which have been reviewed deal especially with the mechanisms that produce overactivity of the thyroid gland (hyperthyroidism) and exophthalmos. Thyroid activity in Graves' disease is controlled by a protein (IgG) unrelated to TSH. This protein, known as long-acting thyroid stimulator (LATS), is found in the sera of most, if not all, patients with Graves' disease. By stimulating the thyroid gland, LATS causes hyperthyroidism in most cases but, if much of the thyroid tissue is destroyed by the disease process, the patient may be euthyroid or even hypothyroid despite a high titer of LATS. LATS may also play a role in causing exophthalmos. However, there is evidence which suggests that exophthalmos-producing substance (EPS), produced in the pituitary, has a primary role in causing the exophthalmos of Graves' disease. What initiates the abnormal production of LATS and EPS is not known.
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