Purpose

To evaluate the epidemiological evidence for a causal association between tobacco smoking and thyroid eye disease (TED).

Methods

Systematic review, including quality assessment, of published epidemiological studies and evaluation of the evidence using established causality criteria.

Results

Fourteen papers describing 15 studies were included. There was a positive association between smoking and TED in four case–control studies when compared with control patients with Graves’ disease but no ophthalmopathy (odds ratio (OR) 1.94–10.1) and in seven case–control studies in which control subjects did not have thyroid disease (OR 1.22–20.2). Two cohort studies examined the occurrence of new cases of TED; one study found an increased incidence of TED with smoking. Four cohort studies investigated progression or outcome of treatment in patients with established TED, three finding an association between smoking and poorer outcome. The quality of the studies was variable, but the association with smoking was strong in the most methodologically rigorous studies. Other evidence supporting a causal link was a consistent association across studies, a dose–response effect, a reduced risk of TED in ex-smokers, and a temporal relationship.

Conclusion

This systematic review provided strong evidence for a causal association between smoking and development of TED. Current-smokers were also more likely to experience disease progression or poorer outcome of treatment. Patients with Graves’ disease and the general public should be educated about the risk of smoking and TED. These findings suggest that patients with Graves’ disease or TED who are smokers should be given effective support to stop smoking.