Skip to main content
SpringerLink
Log in

Relationship between cigarette smoking and Graves’ ophthalmopathy

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Environmental triggers in the development of Graves’ disease (GD) have been suggested from the very first description of the disease. Since 1987 a number of studies from various countries, have assessed the risk for Graves’ ophthalmopathy (GO) associated with smoking, and found an odds-ratio of approximately 4 associated with smoking. Smokers have a higher risk for more advanced GO and a dose response relation is evident. Temporality is suggested by a few prospective studies, as is reversibility since former smokers had a lower risk of developing GO than current smokers, even with a comparable lifetime tobacco consumption. In view of the biological plausibility of the association (suggested mechanisms include tissue hypoxia, modulation of circulating pro- and anti-inflammatory cytokines and accentuation of fibroblast HLA-DR expression) it seems that the association is, indeed, causal. Treatment effect of GD/GO is also influenced by cigarette smoking. It is an independent risk factor for relapse of GD after antithyroid drug treatment. Furthermore, it attenuates the effect of orbital radiotherapy and high-dose systemic glucocorticoids in GO and causes a higher rate of progression of eye disease after radioiodine therapy.

The possibility of hindering GO or attenuating its course suggests that counselling on smoking cessation should be an integral part of the treatment of any patient with GD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bertelsen JB, Hegedüs L. Cigarette smoking and the thyroid. Thyroid 1994, 4: 327–31.

    Article  PubMed  CAS  Google Scholar 

  2. Bartalena L, Bogazzi F, Tanda ML, Manetti L, Dell’ Unto E, Martino E. Cigarette smoking and the thyroid. Eur J Endocrinol 1995, 133: 507–12.

    Article  PubMed  CAS  Google Scholar 

  3. Brix TH, Hegedüs L. Environmental factors in the pathogenesis of Graves’ disease. In: Dutton JJ, Haik BG eds. Thyroid Eye Disease. Diagnosis and treatment. New York: Marcel Dekker. 2002, 127–38.

    Chapter  Google Scholar 

  4. Vestergaard P. Smoking and thyroid disorders — a metaanalysis. Eur J Endocrinol 2002, 146: 153–61.

    Article  PubMed  CAS  Google Scholar 

  5. Bartalena L, Pinchera A, Marcocci C. Management of Graves’ ophthalmopathy: Reality and perspectives. Endocr Rev 2000, 21: 168–99.

    PubMed  CAS  Google Scholar 

  6. Brix TH, Kyvik KO, Hegedüs L. What is the evidence of genetic factors in the etiology of Graves’ disease? — a brief review. Thyroid 1998, 8: 627–34.

    Article  PubMed  CAS  Google Scholar 

  7. Brix TH, Kyvik KO, Christensen K, Hegedüs L. Evidence for a major role of heredity in Graves’ disease — a population based study of two Danish twin cohorts. J Clin Endocrinol Metab 2001, 86: 930–4.

    PubMed  CAS  Google Scholar 

  8. Vanderpump MPJ, Tunbridge VMG. The epidemiology of thyroid diseases. In: Braverman LE, Utiger RD eds. Werner and Ingbar’s The Thyroid: A fundamental and clinical text. Philadelphia: Lippincott-Raven, 2000, 467–74.

    Google Scholar 

  9. Hägg E, Asplund K. Is endocrine ophthalmopathy related to smoking? Br Med J 1987, 295: 634–5.

    Article  Google Scholar 

  10. Bartalena L, Martino E, Marcocci C, et al. More on smoking habits in Graves’ ophthalmopathy. J Endocrinol Invest 1989, 12: 733–7.

    Article  PubMed  CAS  Google Scholar 

  11. Berg G, Michanek A, Holmberg E, Nyström E. Clinical outcome of radioiodine treatment of hyperthyroidism: A follow-up study. J Intern Med 1996, 239: 165–71.

    Article  PubMed  CAS  Google Scholar 

  12. Chen YL, Chang TC, Chen CJ. Influence of smoking on Graves’ disease with or without ophthalmopathy and nontoxic nodular goiter in Taiwan. J Formosa Med Assoc 1994, 93: 40–4.

    CAS  Google Scholar 

  13. Prummel MF, Wiersinga WM. Smoking and risk of Graves’ disease. JAMA 1993, 269: 479–82.

    Article  PubMed  CAS  Google Scholar 

  14. Shine B, Fells P, Edwards OM, Weetman AP. Association between Graves’ ophthalmopathy and smoking. Lancet 1990, 335: 1261–4.

    Article  PubMed  CAS  Google Scholar 

  15. Winsa B, Mandahl A, Karlsson FA. Graves’ disease, endocrine ophthalmopathy and smoking. Acta Endocrinol (Copenh) 1993, 128: 156–60.

    CAS  Google Scholar 

  16. Yoshiuchi K, Kumano H, Nomura S, et al. Stressful life events and smoking were associated with Graves’ disease in women, but not in men. Psychosom Med 1998, 60: 182–5.

    PubMed  CAS  Google Scholar 

  17. Ericsson UB, Lindgärde F. Effects of cigarette smoking on thyroid function and the prevalence of goiter, thyrotoxicosis and autoimmune thyroiditis. J Intern Med 1991, 229: 67–71.

    Article  PubMed  CAS  Google Scholar 

  18. Brix TH, Hansen PS, Kyvik KO, Hegedüs L. Cigarette smoking and risk of clinically overt thyroid disease: A population based twin case-control study. Arch Intern Med 2000, 160: 661–6.

    Article  PubMed  CAS  Google Scholar 

  19. Vestergaard P, Rejnmark L, Weeke J. et al. Smoking as a risk factor for Graves’ disease, toxic nodular goiter, and primary idiopathic hypothyroidism. Thyroid 2002, 12: 69–75.

    Article  PubMed  Google Scholar 

  20. Nunery WR, Martin RT, Heinz GW, Gavin TJ. The association of cigarette smoking with clinical subtypes of ophthalmic Graves’ disease. Ophthal Plast Reconstr Surg 1993, 9: 77–82.

    Article  PubMed  CAS  Google Scholar 

  21. Balazs C, Stenszky V, Farid NR. Association between Graves’ ophthalmopathy and smoking. Lancet 1990, 336: 754.

    Article  PubMed  CAS  Google Scholar 

  22. Bartalena L, Bogazzi F, Tanda ML, et al. Cigarette smoking and treatment outcomes in Graves’ ophthalmopathy. Ann Intern Med 1998, 129: 632–5.

    Article  PubMed  CAS  Google Scholar 

  23. Pfeilschifter J, Ziegler R. Smoking and endocrine ophthalmopathy: Impact of smoking, severity and current vs. lifetime cigarette consumption. Clin Endocrinol (Oxf) 1996, 45: 477–81.

    Article  CAS  Google Scholar 

  24. Tallstedt L, Lundell G, Taube A. Graves’ ophthalmopathy and tobacco smoking. Acta Endocrinol (Copenh) 1993, 129: 147–50.

    CAS  Google Scholar 

  25. Tellez M, Cooper J, Edmonds C. Graves’ ophthalmopathy in relation to cigarette smoking and ethnic origin. Clin Endocrinol (Oxf) 1993, 36: 291–4.

    Article  Google Scholar 

  26. Weetman AP, Wiersinga WM. Current management of thyroid — associated ophthalmopathy in Europe. Results of an international survey. Clin Endocrinol (Oxf) 1998, 49: 21–8.

    Article  CAS  Google Scholar 

  27. Ludgate M, Baker G. Unlocking the immunological mechanisms of orbital inflammation in thyroid eye disease. Clin Exp Immunol 2002, 127: 193–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Glinoer D, de Nayer P, Bex M; Belgian Collaborative Study Group on Graves’ Disease. Effects of L-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves’ hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomised study. Eur J Endocrinol 2001, 144: 475–83.

    Article  PubMed  CAS  Google Scholar 

  29. Chowdhury TA, Dyer PH. Clinical, biochemical and immunological characteristics of relapses and non-relapses of thyroid thyrotoxicosis treated with anti-thyroid drugs. J Intern Med 1998, 244: 293–7.

    Article  PubMed  CAS  Google Scholar 

  30. Kimball LE, Kulinskaya E, Brown B, Johnston C, Farid NR. Does smoking increase relapse rates in Graves’ disease? J Endocrinol Invest 2002, 25: 152–7.

    Article  PubMed  CAS  Google Scholar 

  31. Prummel MF, Wiersinga WM, Mourits MP, Koorneef L, Berghout A, van der Gaag R. Effect of abnormal thyroid function on the severity of Graves’ ophthalmopathy. Arch Intern Med 1990, 150: 1098–101.

    Article  PubMed  CAS  Google Scholar 

  32. Prummel MF, Wiersinga W M, Mourits MP, Koornneef L, Berghout A, van der Gaag R. Amelioration of eye changes of Graves’ ophthalmopathy by achieving euthyroidism. Acta Endocrinol (Copenh) 1989, 121: 185–9.

    Google Scholar 

  33. Wiersinga WM. Preventing Graves’ ophthalmopathy. N Engl J Med 1998, 338: 121–2.

    Article  PubMed  CAS  Google Scholar 

  34. Keltner JL. Is Graves’ ophthalmopathy a preventable disease? Arch Ophtalmol 1998, 116: 1106–7.

    Article  CAS  Google Scholar 

  35. Bartalena L, Marcocci C, Pinchera A. Graves’ ophthalmopathy: A preventable disease? Eur J Endocrinol 2002, 146: 457–61

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Odense University Hospital, DK-5000, Odense, Denmark

    Laszlo Hegedüs (Ass. Prof. of Internal Medicine and Endocrinology) & T. H. Brix

  2. Department of Endocrinology and Metabolism, University Hospital, Aarhus, Denmark

    P. Vestergaard

Authors
  1. Laszlo Hegedüs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. H. Brix
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Vestergaard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laszlo Hegedüs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hegedüs, L., Brix, T.H. & Vestergaard, P. Relationship between cigarette smoking and Graves’ ophthalmopathy. J Endocrinol Invest 27, 265–271 (2004). https://doi.org/10.1007/BF03345276

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345276

Key-words

Search

Navigation