Perspectives in pharmacological management of Graves' hyperthyroidism and orbitopathy

Drugs currently used for Graves' hyperthyroidism (thionamides) or for the major extrathyroidal expression of Graves' disease, Graves' orbitopathy (systemic glucocorticoids with or without orbital radiotherapy), have limited effects on the autoimmune processes underpinning these disorders. Thionamides show a high rate of treatment failure and at least 30% of patients with Graves' orbitopathy are eventually dissatisfied with treatment outcome. Progress in our understanding of the autoimmune basis of Graves' hyperthyroidism and orbitopathy made it possible, similar to other autoimmune disorders, to envision the use of novel immunomodulating drugs. Among the currently available biologic agents, the CD20(+) B-cell-depleting agent, rituximab, and TNF-alpha inhibitors are the drugs that have the highest chance of finding a place in the treatment of Graves' hyperthyroidism and orbitopathy, although randomized, controlled clinical trials are warranted to support their use.