Cigarette Smoking Exposure and Clinical Outcomes in Graves' Disease.

Abstract

Smoking is a recognised 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. Observational cohort study. Single-centre secondary-care endocrinology service 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. 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. Baseline TRAb and thyroid hormone levels, symptom score, presence of orbitopathy, ATD duration, and relapse at 12 months and long term, defined as recurrent biochemical hyperthyroidism with elevated TRAb after ATD withdrawal. 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 non-smokers, p=0.002) 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 non-smokers, supporting cessation or reduction as a meaningful intervention to improve GD outcomes.