Nonthionamide Drugs for the Treatment of Hyperthyroidism: From Present to Future

Abstract

Hyperthyroidism is a common endocrine disease. Although thionamide antithyroid drugs are the cornerstone of hyperthyroidism treatment, some patients cannot tolerate this drug class because of its serious side effects including agranulocytosis, hepatotoxicity, and vasculitis. Therefore, nonthionamide antithyroid drugs (NTADs) still have an important role in controlling hyperthyroidism in clinical practice. Furthermore, some situations such as thyroid storm or preoperative preparation require a rapid decrease in thyroid hormone by combination treatment with multiple classes of antithyroid drugs. NTADs include iodine-containing compounds, lithium carbonate, perchlorate, glucocorticoid, and cholestyramine. In this narrative review, we summarize the mechanisms of action, indications, dosages, and side effects of currently used NTADs for the treatment of hyperthyroidism. In addition, we also describe the state-of-the-art in future drugs under development including rituximab, small-molecule ligands (SMLs), and monoclonal antibodies with a thyroid-stimulating hormone receptor (TSHR) antagonist effect.

Figure 1

Mechanism of nonthionamide antithyroid drugs. Iodine-containing compounds mainly inhibit thyroid hormone release and transiently inhibit organification. Lithium also inhibits thyroid hormone release and may inhibit thyroid hormone synthesis. Perchlorate inhibits active iodide uptake by competitively binding with NIS. Glucocorticoid inhibits peripheral T4 to T3 conversion and may inhibit thyroid hormone secretion. MAbs act at the ectodomain of the TSH receptor while SMLs act at the transmembrane domain of the TSH receptor. MAbs: monoclonal antibodies; NIS: sodium iodide symporter; SMLs: small-molecule ligands; Tg: thyroglobulin; TSHR: thyroid-stimulating hormone receptor.