Impact of smoking on the response to treatment of thyroid associated ophthalmopathy

Abstract

Background: In patients with Graves' disease, smoking considerably increases the incidence and severity of thyroid associated ophthalmopathy (TAO). The authors sought to determine if smoking also influences the course of TAO during treatment, and the efficacy of therapy. Methods: 41 smokers and 19 non-smokers with moderate untreated TAO were included in this prospective study. All patients were treated with steroids and, 6 weeks after the beginning of drug therapy, with orbital irradiation. Follow up was performed 1.5, 4.5, 7.5, and 12 months after the beginning of the study. Proptosis, clinical activity score (CAS), and motility were evaluated. The extent of smoking was derived from the concentration of the haemoglobin adduct N-2-hydroxyethylvaline (HEV), a parameter of long term smoking. Results: There was no difference in the clinical manifestations of TAO between smokers and non-smokers at the beginning of treatment. However, CAS decreased (p<0.05) and motility improved (p<0.02) significantly faster and to a greater extent in non-smokers than smokers. Inverse correlations between the CAS decrease and the HEV levels observed 4.5 and 7.5 months after the beginning of treatment and between the improvement of motility and the HEV levels after 1.5, 4.5, and 7.5 months indicated a dose dependence. Mean HEV levels did not vary much during the follow up period and were significantly different in smokers (mean 5.4 (SD 2.7) µg/l) and non-smokers (mean 1.8 (1.3) µg/l; p<0.01). Conclusion: Smoking influences the course of TAO during treatment in a dose dependent manner. The response to treatment is delayed and considerably poorer in smokers.

Relevance of TSH-receptor antibody levels in predicting disease course in Graves’ orbitopathy: comparison of the third-generation TBII assay and Mc4-TSI bioassay

“…By standardizing our steroid administration protocol, we were able to definitively demonstrate that the association of TRAb with GO course severity is independent of steroid use. Although it is well documented that smoking adversely affects the course of GO, [25][26][27] our results did not elucidate this relationship. This might be because there were only 27 smokers and only 39 patients with severe GO in our study.…”

“…Importantly, patients with higher initial levels of TRAb had a significantly higher risk of severe outcomes upon multiple logistic regression analysis. As GO pathogenesis remains incompletely understood and because there are few clues that are currently available to assist clinicians in estimating the course of GO, [23][24][25][26][27] identifying novel, objectively measurable risk factors that could predict severe GO outcomes are of important scientific and clinical benefit. In patients with high levels of TRAb, it would be reasonable to follow up with these patients and monitor the activity and severity more closely.…”

Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO

“…† Smoking increases the likelihood of progression of GO after radioiodine therapy for hyperthyroidism (25)(26)(27). † Some evidence suggests that smoking either delays or worsens the outcomes of treatments for GO (28,29). † There is some retrospective evidence that quitting smoking is associated with a better outcome of GO (19,21).…”

Pathogenesis of Graves Ophthalmopathy: Implications for Prediction, Prevention, and Treatment

“…Current or former smokers constitute 64% of Graves patients with GO, 48% of those without overt GO, and only 28% of healthy individuals. 25 In addition, smoking is highly associated with the development of more severe GO, 26 with the failure of immunosuppressive therapy, 27 and with aggravation of GO after radioiodine therapy for thyrotoxicosis. These effects do not appear to be related to behavioral changes associated with thyrotoxicosis or to differences in the age, gender, or educational background of smokers compared with nonsmokers.…”