Cigarette smoking exposure and clinical outcomes in Graves' disease

Smoking is a recognized risk factor for Graves' disease (GD), but its quantitative relationship with disease severity, autoimmunity, and relapse after antithyroid drug (ATD) therapy is unclear.

To evaluate the dose-dependent association between smoking exposure and key clinical outcomes in GD.

This was a single-center observational cohort study conducted in a secondary-care endocrinology unit in the United Kingdom. Consecutive adults with newly diagnosed GD confirmed by suppressed TSH, elevated thyroid hormones, and positive TRAb or diffusely increased scintigraphic uptake were analysed. All 991 eligible patients were included in baseline analyses; 663 completed ≥12 months follow-up after ATD cessation, and 712 contributed to long-term relapse analyses. The main outcome measures were baseline TRAb levels, presence of orbitopathy, and relapse at 12 months and long term, defined as recurrent biochemical hyperthyroidism with elevated TRAb after ATD withdrawal. Other outcomes included additional biochemical, scintigraphic and clinical measures. Exposures were smoking status (non-, ex-, current smoker) and cigarettes/day.

Current smokers (27%) had higher TRAb levels at diagnosis (median 7.8 vs 6.6 IU/L in nonsmokers, P = .002) and increased odds of orbitopathy (OR 1.76, 95% CI 1.17-2.64). Each 10 cigarettes/day conferred a 34% (95% CI 10-79%) higher odds of orbitopathy and 60% higher 12-month relapse risk. Smokers also had higher TRAb at ATD cessation. In time-dependent Cox models, excess relapse risk among current smokers was greatest early after ATD withdrawal (HR 1.24 at 6 months) and diminished by 2 years. TRAb mediated only 7% of the smoking-relapse association.

Smoking is associated with greater autoimmune activity, higher orbitopathy risk, and increased relapse in a dose-dependent manner. Ex-smokers have risks comparable with nonsmokers, supporting cessation or reduction as a meaningful intervention to improve GD outcomes.