The dilemma of how to manage Graves' hyperthyroidism in patients with associated orbitopathy.

CONTEXT: Graves' orbitopathy (GO) is present in about 50% of patients with Graves' hyperthyroidism. It may range from mild to moderately severe and (rarely) to sight-threatening. Whether antithyroid drugs (ATDs), radioactive iodine (RAI), or thyroidectomy should be the treatment of choice in the presence of overt and active GO is a matter of debate.

EVIDENCE ACQUISITION: The major source of data acquisition included PubMed search strategies. Articles published in the last 30 yr were screened. Furthermore, the bibliographies of relevant citations and chapters of major textbooks were evaluated for any additional appropriate citation.

EVIDENCE SYNTHESIS: Prompt restoration and stable maintenance of euthyroidism is important for the course of GO. ATDs and thyroidectomy per se do not influence the natural history of GO. RAI can cause progression or de novo development of GO, particularly in smokers. This effect can be prevented by oral steroid prophylaxis. In patients with mild orbitopathy, the choice of thyroid treatment is largely independent of GO. Moderate-to-severe and active GO should be treated without delay. Whether in these patients, concomitant treatment of hyperthyroidism should be conservative (ATDs) or ablative (RAI, thyroidectomy, or both) is presently based on expert opinion rather than evidence. Emerging and potentially interesting biological agents, such as rituximab, counteracting pathogenic mechanisms of both hyperthyroidism and GO, need to be evaluated in randomized clinical trials.

CONCLUSIONS: The choice of the optimal treatment for hyperthyroidism in patients with moderate-to-severe and active GO remains unsettled and is mainly based on personal experience. Randomized clinical trials in this field are eagerly needed.