Smoking Increases Graves’ Disease Severity and Relapse Risk: Study

Graves' disease is an autoimmune disease that results in hyperthyroidism due to the action of antibodies that stimulate the thyroid-stimulating hormone receptor. The clinical manifestations of the disease include weight loss, palpitations, tremors, and heat intolerance, and can also cause Graves' orbitopathy, which is a debilitating eye disease that involves inflammation and tissue remodeling in the orbit.

The study was carried out as an observational cohort study in a secondary-level endocrinology service in the United Kingdom. The study included all consecutive adult patients with diagnosed Graves' disease using standard biochemical and clinical criteria. The diagnosis was based on suppressed levels of thyroid-stimulating hormone, increased levels of thyroid hormones, and the presence of antibodies to the thyroid-stimulating hormone receptor or increased uptake in the thyroid gland.

A total of 991 patients were included in the study, and the study found that 663 patients completed the follow-up period after the discontinuation of antithyroid drug treatment and were eligible to be evaluated for relapse at one year. In addition, the study found that 712 patients were included in the relapse analysis.

Key findings:

• The observational cohort study consisted of 991 patients with newly diagnosed GD.

• Among these patients, 27% were current smokers.

• Current smokers had higher TRAb levels at the time of diagnosis compared to nonsmokers.

• This difference was significant because the median TRAb level was 7.8 IU/L compared to 6.6 IU/L in nonsmokers. This difference was significant (P = 0.002).

• In addition, smoking was related to Graves’ orbitopathy with an odds ratio of 1.76 and 95% CI 1.17 to 2.64.

• Moreover, the study showed a dose-response association because each increase of 10 cigarettes/day was related to a 34% increased risk of orbitopathy and a 60% increased risk of relapse during the 12 months following withdrawal of antithyroid drugs.

• In the study, 663 out of 991 patients completed at least 12 months of follow-up.

• In addition, 712 patients contributed to the long-term relapse study.

• Using time-dependent models, the study showed the highest relapse risk shortly after withdrawal of antithyroid drugs.

• Specifically, the study showed a hazard ratio of 1.24 at 6 months in current smokers. Mediation analysis showed that TRAb was responsible for only 7% of the association between smoking and relapse risk.

Smoking has been associated with increased autoimmune activity, a higher incidence of Graves’ orbitopathy, and a higher rate of relapse after antithyroid drug treatment in a dose-response relationship. Smokers tend to show increased TRAb at presentation as well as after stopping antithyroid drug treatment, and the dose of cigarette exposure increases the risk of complications and relapse. However, it has also been noted that smokers who stop smoking show a risk profile comparable to those who do not smoke, suggesting that this might be a potential target to improve the outcome of Graves’ disease.

Reference:

Sarah Forbes, May Loo, Su Ann Tee, Kathryn Stewart, Jonathan Vernazza, Lauren Carroll, Nicholas Vennart, Peter Bartholomew, Kilimangalam Narayanan, Vasileios Tsatlidis, Salman Razvi, Cigarette smoking exposure and clinical outcomes in Graves' disease, The Journal of Clinical Endocrinology & Metabolism, 2026;, dgag061, https://doi.org/10.1210/clinem/dgag061