71 - Graves Disease

Abstract

Graves disease (GD) is a systemic autoimmune disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T-cells into the thyroid and thyrotropin receptor (TSH-R)–expressing tissues. Stimulatory autoantibodies (Abs) in GD activate the TSH-R, leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. A genetic basis for susceptibility to GD has been demonstrated based on familial clustering of both the disease and thyroid Abs, high sibling recurrence risk, and association of the condition with numerous genomic variants. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R–Ab, enlarged, hypervascular (Doppler flow on neck ultrasound) thyroid gland, Graves orbitopathy (GO), and often a family history of autoimmune disorders. TSH-R–Ab in general, and stimulating TSH-R–Ab in particular, are the serologically sensitive and specific biomarkers for GD. TSH-R–Ab offers accurate and rapid diagnosis of GD and are most helpful in the differential diagnosis of thyrotoxicosis. The hyperthyroidism of GD is treated by reducing thyroid hormone synthesis with the use of antithyroid drugs (ATDs) or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy (TX). Although not optimal, ATDs are the favored first-line treatment worldwide for newly diagnosed GD. Patients are medically treated for 12 to 18 months with methimazole (MMI) as the preferred drug. In children with GD, a 36-month course of MMI is recommended. Patients with persistently high TSH-R–Ab at 18 months can opt for therapy with RAI or TX or continue MMI treatment. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term, low-dose MMI is a valuable and safe alternative. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. TX should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in GD patients with active/severe GO, and steroid prophylaxis is warranted in GD patients with mild/active GO receiving RAI. In conclusion, a clear trend towards serological diagnosis (TSH-R–Ab) and medical treatment of GD has emerged.