Graves Disease - A Comprehensive Review

Abstract

Graves Disease (GD) is an inflammatory disorder that often results in hyperthyroidism. GD is particularly prone to affecting women, African Americans, individuals with pre-existing autoimmune conditions, and first-degree relatives of those with GD. GD presents through a breakdown of immune tolerance against thyroid antigens. This occurs through a multifactorial autoimmune dysfunction of environmental and mainly genetic contribution. Hereditary predisposition accounts for 79% of the GD risk and increases susceptibility to dysfunction by environmental risk factors such as smoking, vitamin D deficiency, and stressful life events. GD is caused by a disruption of the thyroid gland on a molecular level. The disease is characterized by an overstimulation of the thyroid gland causing hyperthyroidism. This issue is caused by thyroid-stimulating immunoglobulin (TSI) synthesized by B cells. These immunoglobulins bind to the TSH receptors on the thyroid gland, activating it and producing an abundance of the thyroid hormones, levothyroxine (T4) and triiodothyronine (T3). The clinical presentation of GD encompasses a diverse array of signs and symptoms, from common manifestations such as palpitations, weight reduction, and exophthalmos, to less conventional presentations like cardiac complications and cholestatic hepatic injury. There are many methods of diagnosis that are used for GD including the gold standard, which tests for TSI and antibodies against the TSH receptor. Other methods include radioactive iodine uptake and CT scans that test for thyroid enlargement and are used to substitute radioactive iodine uptake tests for pregnant women. The three classical treatments for GD are antithyroid drugs, radioiodine treatment, and thyroidectomy. Additional treatments include corticosteroids which are used to decrease exophthalmos. Beta-adrenergic blockers are used for tachycardia, palpitations, and also blocking the peripheral conversion of T4 to T3. Immunotherapies, such as Mycophenolate mofetil and Azathioprine show promise as potential treatments are currently being investigated. This comprehensive review provides an up-to-date compact analysis of literature pertinent to the epidemiology, etiology, risk factors, genetics, pathophysiology, classifications, clinical presentation, diagnosis, and treatments of GD.