Systemic Thyroid Dysfunction in Graves Disease

Abstract

Graves disease is an autoimmune disease characterized by the loss of immune tolerance to thyroid antigens and the resulting development of stimulating autoantibodies directed against thyrotropin [thyroid stimulating hormone (TSH)] receptors in the thyroid follicular cells, orbital fibroblasts and adipocytes, and the skin. These antibodies cause thyroid hormone overproduction by the thyroid follicular cells, leading to classic symptoms of hyperthyroidism. The activation of TSH receptors in local fibroblasts in the skin can lead to thyroid dermopathy, characterized by T-cell infiltration, local inflammation, and increased production of glycosaminoglycans leading to tissue swelling and hypertrophy. [1][2][3] The pathogenesis of Graves orbitopathy will be reviewed in a later chapter. ' DefinitionsThyrotoxicosis is a clinical state resulting from inappropriately high thyroid hormone levels and their action on target tissues. 2 Hyperthyroidism more specifically is a form of thyrotoxicosis that results from the inappropriate synthesis and secretion of thyroid hormone by the thyroid gland. The most common causes of hyperthyroidism in the United States are Graves disease, toxic multinodular goiter, and single toxic adenoma. 2 ' Clinical Presentation Upon presentation, patients can have signs and symptoms due to thyrotoxicosis, obstructive symptoms from a goiter such as dysphagia, and/or extrathyroidal manifestations of autoimmunity, as seen in orbitopathy and dermopathy. Thyroid hormone acts by binding to specific thyroid hormone receptors, modifying gene transcription in