Investigational drugs in early stage clinical trials for thyrotoxicosis with hyperthyroidism

ABSTRACT

Introduction: Thyrotoxicosis with hyperthyroidism is treated with these classical approaches (i) antithyroid drugs to blockade thyroid hormone release and normalize thyroid hormone production and (ii) destruction of the thyroid using radioiodine or surgical removal of the thyroid. The optimal medical therapy, especially for Graves´ disease, remains a subject of debate and there has been little progress in Graves’ disease therapeutics over the last decade.

Areas covered: Novel treatments of thyrotoxicosis with hyperthyroidism. This includes (i) small molecules such as synthetic thyroid hormone receptor antagonists and environmental molecules and (ii) molecules with interaction between thyroid stimulating hormone (TSH) receptor and TSH receptor antibodies such as M22, ANTAG3, org274179-0, 5C9, and K1-70. Other approaches to Graves´ disease treatment includes immunosuppressive treatment, glucocorticosteroids, rituximab, and intrathyroid injection of dexamethasone. Optimal iodine and selenium supplementation can also be considered.

Expert opinion: Clinical trials results suggest that novel thyroid treatments involving small molecule therapy, may predict a good future in Graves’ disease treatment; however, a greater understanding of these antagonists is needed. Other treatments comprising immunosuppressives have demonstrated a significant reduction of relapse of the disease, but are not recommended by international guidelines.

KEYWORDS:

• Thyroid stimulating hormone receptor antagonist
• antithyroid drugs
• Graves’ disease
• immunosuppressive treatment
• radioiodine
• thyroid receptor antagonists
• thyrotoxicosis
• hyperthyroidism
• thyroid stimulating hormone

Article highlights

• To analyze the flaws of classical approaches of thyrotoxicosis with hyperthyroidism treatment.

• To describe the optimal medical therapy, especially for Graves´ disease which remains a subject of debate.

• To consider small molecules such as synthetic and also environmental molecules as thyroid hormone receptor antagonists.

• To describe small molecules antagonist, synthesized by chemical modification, of thyroid stimulating hormone and thyroid stimulating hormone receptor antibodies

• To present other approaches to Graves´ disease treatment, especially immunosuppressive treatment, that can improve the outcome of the disease.

This box summarizes key points contained in the article.

Declaration of interest

The author have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.