Non-thionamide antithyroid drug options in Graves’ hyperthyroidism

ABSTRACT

Introduction

The thionamide anti-thyroid drugs namely carbimazole, methimazole, and propylthiouracil, have been the predominant therapy modality for Graves’ hyperthyroidism for over 60 years. Although these agents have proven efficacy and favorable side-effect profiles, non-thionamide alternatives are occasionally indicated in patients who are intolerant or unresponsive to thionamides alone. This review examines the available non-thionamide drug options for the control of Graves’ hyperthyroidism and summarizes their clinical utility, efficacy, and limitations.

Areas covered

We reviewed existing literature on mechanisms, therapeutic utility, and side-effect profiles of non-thionamide anti-thyroid drugs. Established non-thionamide agents act on various phases of the synthesis, release, and metabolism of thyroid hormones and comprise historical agents such as iodine compounds and potassium perchlorate as well as drug repurposing candidates like lithium, glucocorticoids, beta-blockers, and cholestyramine. Novel experimental agents in development target key players in Graves’ disease pathogenesis including B-cell depletors (Rituximab), CD40 blockers (Iscalimab), TSH-receptor antagonists, blocking antibodies, and immune-modifying peptides.

Expert opinion

Non-thionamide anti-thyroid drugs are useful alternatives in Graves’ hyperthyroidism and more clinical trials are needed to establish their safety and long-term efficacy in hyperthyroidism control. Ultimately, the promise for a cure will lie in novel approaches that target the well-established immunopathogenesis of Graves’ disease.

KEYWORDS:

• Hyperthyroidism
• Graves’ disease
• Antithyroid drugs
• Carbimazole
• Methimazole
• Propylthiouracil
• non-thionamide agents

Article highlights

• Non-thionamide anti-thyroid drugs are occasionally indicated in patients with Graves’ hyperthyroidism either as adjunctive treatment in pre-surgical or severe cases, or in patients who are intolerant or unresponsive to thionamides.

• Iodine containing compounds, potassium perchlorate, lithium, glucocorticoids, beta-blockers, and cholestyramine, all act on various stages in the synthesis, release, and metabolism of thyroid hormones and have been used with varying efficacy in short term control of hyperthyroidism.

• Iodine compounds are used for rapid pre-operative control pending thyroidectomy while beta-blockers, glucocorticoids, cholestyramine, and lithium are used adjunctively for rapid control of hyperthyroidism in severe presentations.

• Glucocorticoids, cholestyramine, and potassium perchlorate have been used as adjunct therapy in amiodarone induced thyrotoxicosis while pre-therapeutic lithium has been shown to increase the effectiveness of radioactive iodine therapy.

• Novel therapeutic agents in various phases of drug design and development target key players in Graves’ disease pathogenesis including antibody producing B-cells and the TSH receptor antibody-receptor complex.

• Further clinical trials are needed to establish the safety and long-term efficacy of non-thionamide therapies in the control of hyperthyroidism. In particular, novel therapeutic approaches that address the immunopathogenesis of Graves’ disease hold promise for the future.

Additional information

Funding

This paper was not funded.