Relationship between cigarette smoking and Graves' ophthalmopathy.

Environmental triggers in the development of Graves' disease (GD) have been suggested from the very first description of the disease. Since 1987 a number of studies from various countries, have assessed the risk for Graves' ophthalmopathy (GO) associated with smoking, and found an odds-ratio of approximately 4 associated with smoking. Smokers have a higher risk for more advanced GO and a dose response relation is evident. Temporality is suggested by a few prospective studies, as is reversibility since former smokers had a lower risk of developing GO than current smokers, even with a comparable lifetime tobacco consumption. In view of the biological plausibility of the association (suggested mechanisms include tissue hypoxia, modulation of circulating pro- and anti-inflammatory cytokines and accentuation of fibroblast HLA-DR expression) it seems that the association is, indeed, causal. Treatment effect of GD/GO is also influenced by cigarette smoking. It is an independent risk factor for relapse of GD after antithyroid drug treatment. Furthermore, it attenuates the effect of orbital radiotherapy and high-dose systemic glucocorticoids in GO and causes a higher rate of progression of eye disease after radioiodine therapy. The possibility of hindering GO or attenuating its course suggests that counselling on smoking cessation should be an integral part of the treatment of any patient with GD.