The Dilemma of How to Manage Graves’ Hyperthyroidism in Patients with Associated Orbitopathy

Introduction:  Fifty percent of hyperthyroid Graves’ patients have Graves’ orbitopathy (GO).  The severity varies; it can range from mild to moderately severe, and rarely, GO is sight-threatening. Management of GO is a debatable matter:  Should antithyroid drugs (ATDs), radioactive iodine (RAI) ablation, or thyroidectomy be the treatment of choice?

Methods:  A PubMed search was done to gather articles related to this topic published in the last 30 years.  Additionally, bibliographies of related citations and major textbooks were evaluated to look for other data.

Results:  In treating GO, it is crucial to quickly restore and then maintain euthyroidism.

While ATDs and thyroidectomy do not influence GO, RAI can cause a progression or new onset of GO.  This is particularly seen in smokers, but that risk may be reduced by oral steroid prophylaxis.

For mild orbitopathy patients, hyperthyroidism treatment can be chosen independently of GO.

However, for moderate-to-severe GO, the orbitopathy should be treated immediately.  There are no evidence-based recommendations for whether these moderate-to-severe cases should be treated for their hyperthyroidism with ATDs (conservative treatment) or RAI, thyroidectomy, or both (ablative treatments).  Instead, management is currently based on expert opinion.

More randomized clinical trials are needed to investigate new treatments such as biological agents (rituximab).  The may be able to counteract pathogenic mechanisms of both GO and hyperthyroidism.

Conclusions:  Personal experience and/or expert opinion currently guide the optimal treatment for hyperthyroid patients with moderate-to-severe and active GO.  Randomized clinical trials are needed.

Commentary by Christian Nasr MD

This article by expert Italian thyroidologists summarizes an extensive look at the relevant publications from the last 30 years. This was needed because of the lack of good prospective trials; GO is a rare disorder, and it is difficult to determine whether the progression occurred because of the rendered treatment or as a natural history of the disease.

There is no disagreement, however, regarding the clearly higher prevalence of the disorder in smokers and the fact that continued smoking increases the likelihood of progression. There is evidence, in this and other literature, that treating with radioactive iodine may worsen GO and that treating with different regimens of glucocorticoids may reduce that risk.