Management of Graves’ hyperthyroidism: present and future

ABSTRACT

Introduction

Graves’ disease (GD) is an autoimmune disorder due to loss of tolerance to the thyrotropin receptor (TSHR) and ultimately caused by stimulatory TSHR antibodies (TSHR-Ab). GD may be associated with extrathyroidal manifestations, mainly Graves’ orbitopathy. Treatment of GD relies on antithyroid drugs (ATDs), radioactive iodine (RAI), thyroidectomy. The major ATD limitation is the high recurrence rate after treatment. The major drawback of RAI and thyroidectomy is the inevitable development of permanent hypothyroidism.

Areas covered

Original articles, clinical trials, systematic reviews, meta-analyses from 1980 to 2021 were searched using the following terms: Graves’ disease, management of Graves’ disease, antithyroid drugs, radioactive iodine, thyroidectomy, Graves’ orbitopathy, thyroid-eye disease.

Expert opinion

ATDs are the first-line treatment worldwide, are overall safe and usually given for 18–24 months, long-term treatment may decrease relapses. RAI is safe, although associated with a low risk of GO progression, particularly in smokers. Thyroidectomy requires skilled and high-volume surgeons. Patients play a central role in the choice of treatment within a shared decision-making process. Results from targeted therapies acting on different steps of the autoimmune process, including iscalimab, ATX-GD-59, rituximab, blocking TSHR-Ab, small molecules acting as antagonists of the TSHR, are preliminary or preclinical, but promising in medium-to-long perspective.

KEYWORDS:

• Graves’ disease
• hyperthyroidism
• antithyroid drugs
• methimazole
• propylthiouracil
• radioactive iodine
• thyroidectomy
• Graves’ orbitopathy
• rituximab
• iscalimab
• thyrotropin receptor
• K1-70

Article highlights

• Currently available treatments for hyperthyroidism are largely imperfect, because they are either associated with a high rate of relapsing hyperthyroidism (antithyroid drugs) or with the inevitable occurrence of permanent hypothyroidism and need for lifelong thyroid hormone replacement therapy;

• Antithyroid drugs are currently the first-line treatment worldwide. Consideration should be given to long-term (several-to-many years) ATD treatment, which seems to be associated with a higher rate of remission compared to the standard and recommended 18-24 months course;

• With the above limitations, selection of treatment modality should take into considerations particular situations (e.g. pregnancy, childhood, presence/absence of GO, elderly, cardiovascular comorbidities), but most importantly, should be the result of a shared decision-making process in which the patient is at the center of the scene;

• Results from targeted therapies acting on different steps of the autoimmune process are preliminary (iscalimab, ATX-GD-59, rituximab, TSH receptor-blocking antibodies), or preclinical (small molecules acting as antagonists of the TSH receptor), but promising in a medium-to-long perspective;

• Using targeted therapies, more impressive results have been made in the field of GO, but they need to be confirmed by further studies.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors have no funding to report.