Cigarette smoking has been reported to alter relapse rate in patients with Graves'
disease (GD). However, the predictive effect of smoking in GD patients after withdrawal
of antithyroid drug treatment (ATDT) is still controversial. A prospective multicenter
trial has previously identified smoking as an independent risk factor for relapse.
Based on this study, the present paper gives a more detailed analysis of the impact
of smoking on the long term course of GD after ATDT withdrawal. To this end, 86 smokers
and 177 non-smokers were followed during two years after ATDT cessation. At the end
of ATDT (visit 1) and four weeks later (visit 2) smokers had significant higher TSH
receptor antibody (TRAb) levels than non-smokers (10.0 IU/L±1.6; mean±SEM vs. 6.4
IU/L±0.9; 11.0 IU/L±1.8 vs. 6.8 IU/L±0.8, p<0.01, respectively). During follow-up,
Kaplan Meier analysis showed a significant higher relapse rate in smokers than non-smokers.
A subset of GD patients with high TRAb levels >10 IU/L had the highest risk to develop
relapse during follow-up. Among them, smokers more often relapsed than non-smokers
irrespective of TRAb levels, p<0.01. Thus, in smokers with TRAb levels >10 IU/L the
predictive values of a positive and negative test for relapse was 68% and 73%, respectively
(specificity 95%). In conclusion, we identified two effects by which smoking alters
the course of GD.
First, smoking is implicated to elevate TRAb levels and therefore increase the risk
for relapse during follow-up.
Second, smoking is an independent risk factor to worsen the clinical course of both,
GD patients with low and high immunological risk to experience relapse after a successful
outcome of ATDT. Thus, our data suggest that smoking has modifying immunological consequences
and an adverse impact on the course of GD after withdrawal of ATDT. Therefore, patients
should be encouraged to stop smoking.