Predictive factors for symptoms of thyroid ophthalmopathy development in patients after either radioiodine therapy or thyroidectomy

Authors: Z. Novák 1;  P. Hrdá1ihash2 ,2 ,2
Authors‘ workplace: Endokrinologický ústav, Praha, ředitel doc. MUDr. Vojtěch Hainer, CSc. 1;  Ústav imunologie a mikrobiologie 1. lékařské fakulty UK a VFN, Praha, přednosta doc. MUDr. Ivan Šterzl, CSc. 2
Published in: Vnitř Lék 2005; 51(6): 650-657
Category: Original Contributions


The aim of the study was to investigate whether patients with Graves-Basedow thyrotoxicosis developing into endocrine ophthalmopathy of diverse severity after treatment by radioiodine or total thyroidectomy are different in their pre-treatment parameters from Graves-Basedow patients without any signs of ophthalmopathy development. 42 patients were divided into 2 groups: a group of 26 patients treated by radioiodine and a group of 16 patients treated by thyroidectomy. All patients were without symptoms of ophthalmopathy and were examined clinically, on laboratory markers and by ultrasound of the thyroid and of the orbit. The patients were divided according to the orbit response after treatment into three groups: group 1 without symptoms of ophthalmopathy, group 2 with newly arisen symptoms of irritation and signs of ophthalmopathy activation, group 3 patients with diplopia. No difference was found among groups 1–3 of patients treated by radioiodine in the dosis and in the thyroid volume. In patients treated by thyroidectomy higher levels of anti thyroglobulin autoantibodies were found in joined groups 2 + 3 compared to group 1 (p = 0.044). In patients treated by radioiodine higher levels of anti TSH receptor antibodies were found in group 3 compared to the joined groups 1 + 2 (p = 0.033). In all patients (treated by radioiodine and thyroidectomy) were found higher levels of anti thyroglobulin antibodies in joined groups 2 + 3 compared to group 1 (p = 0.019), higher levels of anti TSH receptor antibodies in group 3 compared to joined groups 1 + 2 (p = 0.015) and increased thickness of the eye muscles in group 3 compared to joined groups 1 + 2 (p = 0.013). As predictive marker of ophthalmopathy anti thyroglobulin antibodies were found, elevated levels of anti TSH receptor antibodies and the sum of orbit muscle thickness served also for the prediction of the development of diplopia.

Key words:
Graves-Basedow thyrotoxicosis – endocrine ophthalmopathy – total thyroidectomy – radioiodine – autoantibodies


1. Asman P. Ophthalmological evulation in thyroid-associated ophthalmopathy. Acta Ophthalmol Scand 2003; 81: 437–448.

2. Bahn RS, Garrity JA, Gorman CA. Diagnosis and management of Grave’s ophthalmopathy. J Clin Endocrinol Metab 1990; 71: 559–563.

3. Bahn RS, Heufelder AE. Pathogenesis of Grave’s ophthalmopathy. N Engl J Med 1993; 329: 1468–1475.

4. Bartalena L, Marcocci C, Bogazzi F et al Relation between therapy for hyperthyroidism and the course of Grave’s ophthalmopathy. N Engl J Med 1998; 338: 73–78.

5. Bartalena L, Marcocci C, Gorman CA et al. Orbital radiotherapy for Grave’s ophthalmopathy: useful or useless? Safe or dangerous? J Endocrinol Invest 2003; 26: 5–16.

6. Burch, HB, Wartofsky L. Grave’s opthalmopathy: Current concepts regarding pathogenesis and management. Endocr Rev 1993; 14: 747–793.

7. Cambell RJ. Pathology of Grave’s opthalmopathy. In: Gorman CA, Waller RR, Dyer JA (eds). The eye and orbit in thyroid disesae. New York: Raven Press 1984: 25–31.

8. DeGroot LJ. Retro-orbital radiation and radioactive iodide ablation of the thyroid may be good for Grave’s ophthalmopathy. J Clin Endocrinol Metab 1995; 80: 339–340.

9. Dietlein M, Dederichs B, Wiegand A et al. Radioiodine therapy and thyroidassociated orbitopathy: risk factors and preventive effects of glucocorticoids. Exp Clin Endocrinol Diab 1999; 107: Suppl. 5: 190–194.

10. Dong Q, Ludgate M, Vassart G. Cloning and sequencing of a novel 64-kDa autoantigen recognized by patients with autoimmune thyroid disease. J Clin Endocrinol Metab 1991; 72: 1375–1381.

11. Gerding MN, Prummel MF, Kalmann R et al. The use of colour slides in the assessment of changes in soft-tissue involvement in Grave’s ophthalmopathy. J Endocrinol Invest 1998; 21: 459–462.

12. Gerding MN, Prummel MF, Wiersinga WM. Assessment of disease activity in Grave’s ophthalmopathy by orbital ultrasonography and clinical parameters. Clin Endocrinol (Oxf) 2000; 52: 641–646.

13. Gerding MN, van der Meer JW, Brovnink M et al. Association of thyrotrophin receptor antibodies with clinical features of Grave’s ophthalmopathy. Clin Endocrinol (Oxf.) 2000; 52: 267–277.

14. Gunji K, De Bellis A, Li AW et al. Cloning and charakterization of the novel thyroid and eye muscle shared protein G2s: autoantibodies against G2s are closely associated with ophthalmopathy in patients with Grave’s hyperthyroidism. J Clin Endocrinol Metab 2000; 85: 1341–1347.

15. Heufelder AE, Dutton CM, Sarkar G et al. Detection of TSH receptor RNA in cultured fibroblasts from patients with Grave’s ophthalmopathy and pretibial dermopathy. Thyroid 1993; 3: 297–300.

16. Heufelder AE, Spitzweg C. Pathogenesis of immunogentic hyperthyroidsm and endocrine orbitopathy. Internist 1998; 39: 599–606.

17. Heufelder AE, Joba W. Cellular immunity and orbital antigens in thyroid associated orbitopathy. Exp Clin Endocrinol Diabetes 1999; 107(Suppl 5): 152–157.

18. Heufelder AE. Pathogenesis of ophthalmopathy in autoimmune thyroid disease. Rev Endocr Metab Disord 2000; 1: 87–95.

19. Hiromatsu Y, Sato M, Inoue Y et al. Localization and clinical significance of thyrotropin receptor mRNA expression in orbital fat and eye muscle tissue from patients with thyroid-associated ophthalmopathy. Thyroid 1996; 6: 553–562.

20. Hsu SY, Chany CH, Su MY et al. Correlation between clinical activity score and thyroid autoantibodies in patients with thyroid ophthalmopathy. Kaohsiung J Med Sci 2000; 16: 533–538.

21. Jacobson DII, Gorman CA. Clinical review 13: Diagnosis and management of endocrine opthalmopathy. Med Clin North Am 1996; 69: 973–988.

22. Knudsen N, Bols B, Bülow I et al. Validation of ultrasonography of the thyroid gland for epidemiological purposes. Thyroid 1999; 9: 1069–1074.

23. Lind P. Strategies of radioiodine therapy for Grave’s disease. Eur J Nucl Med Mol Imaging 2002; 29(Suppl 2): 453–457.

24. Lisi S, Marino M, Pinchera A et al. Thyroglobulin in orbital tissues from patients with thyroid-associated ophthalmopathy: predominant localization in fibroadipose tissue. Thyroid 2002; 12: 351–360.

25. Marino M, Lisi S, Pinchera A et al. Glycosaminoglycans provide a binding site for thyroglobulin in orbital tissues of patients with thyroid-associated opthalmopathy. Thyroid 2003; 9: 851–859.

26. Noh JY, Hamada N, Inoue Y et al. Thyroid-stimulating antibody is related to Grave’s ophthalmopathy, but thyrotropin-binding inhibitor immunoglobulin is related to hyperthyroidism in patiens with Grave’s disease. Thyroid 2000; 10: 809–813.

27. Noth D, Gebauer M, Müller H et al. Grave’s ophthalmopathy natural history and treatment outcomes. Swiss Med Wkly 2001; 131: 603–609.

28. Prummel MF. Pathogenesis and clinical aspects of endocrine ophthalmopathy. Exp Clin Endocrinol Diabetes 1999; 107(Suppl 3): 75–78.

29. Ross PV, Koening RJ, Arscott P et al. Tissue specificity and serologic reactivity of an autoantigen associated with autoimmune thyroid disease. J Clin Endocrinol Metab 1993; 77: 433–438.

30. Schuppert F, Hiller WFA, Weinland G et al. Iodide, cytokines and TSH receptor expression in Grave’s disease. Exp Clin Endocrinol Diabetes 1996; 104 (Suppl 4): 68–74.

31. Shine B, Fells P, Edwards OM et al. Association between Grave’s opthalmopathy and smoking. Lancet 1990; 335: 1261–1264.

32. Váňa S, Němec J, Rezek P et al. Léčba endokrinní orbitopatie eliminací štítní žlázy. Vliv nezdařené eliminace, velkého pretibiálního myxedému a trvání hypotyreózy po eliminaci na dlouhodobé výsledky. Vnitř Lék 1998; 44: 387–390.

33. Volpe R. Immunology of the thyroid. In: Volpe R (ed). Autoimmune diseases of the endocrine system. Boca Raton: CRC Press, 1990: 73–240.

34. Wakelkamp IM, Gerding MN, van der Meer JW et al. Smoking and disease severity are independent determinants of serum adhesion molocule levels in Grave’s ophthalmopathy. Cln Exp Immunol 2002; 127: 316–320.

35. Werner SC. Modification of the Classification of the Eye Changes of Grave’s Disease: Recommendations of the Ad Hoc Committee of The American Thyroid Association. The Journal Clinical Endocrinology and Metabolism 1977; 44: 201–203.

36. Wiersinga WM, Bartalena L. Epidemiology and prevention of Grave’s ophthalmopathy. Thyroid 2002; 12: 855–860.

37. Wiersinga WM, Prummel MF. Grave’s ophthalmopathy: a rational approach to treatment. Trends Endocrinol Metab 2002; 13: 280–287.

38. Yamada M, Li AW, Wall JR. Thyroidassociated ophthalmopathy: clinical features, pathogenesis and management. Crit Rev Clin Lab Sci 2000; 37: 253–549.

Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue 6

2005 Issue 6

Most read in this issue
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account