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Incidence of radiation-induced Graves’ disease in patients treated with radioiodine for thyroid autonomy before and after introduction of a high-sensitivity TSH receptor antibody assay

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Abstract

Autoimmune hyperthyroidism may occur several months after radioiodine therapy (RIT) for functional thyroid autonomy. Exacerbation of pre-existing subclinical Graves’ disease (GD) has been held responsible for this phenomenon. Determination of TSH receptor antibody using solubilised porcine epithelial cell membranes is insensitive and may have failed to diagnose GD in these patients before RIT. Following the introduction of a more sensitive assay, using the human TSH receptor as an antigen, it has been expected that the incidence of radiation-induced GD after RIT for functional thyroid autonomy will be reduced. In a first group of 1,428 patients treated between November 1993 and March 1997 (group I) we used the porcine TRAb assay to exclude GD, while in a second group comprising 1,408 patients treated between January 2000 and December 2001 (group II), GD was excluded using the human TRAb assay. A matched control group of 231 patients was derived from group II. In group I a total of 15 (1.05%) patients developed obvious or suspected radiation-induced GD, while in group II 17 (1.2%) did so; the interval until development of GD was 8.4 and 8.8 months, respectively, after RIT. Serum anti-thyroid peroxidase levels before RIT were elevated in 36.4% of group I patients and 47.1% of group II patients, but in only 5.6% of the control group. Other non-specific signs of mild immunopathy of the thyroid were seen retrospectively in 73.3%, 64.7% and 16.0% of the patients in these three groups, respectively. In conclusion, the introduction of a high-sensitivity TRAb assay did not reduce the incidence of autoimmune hyperthyroidism occurring late after RIT for functional thyroid autonomy, but mild immunopathy of the thyroid is seen more frequently in these patients and seems to be a predisposing factor in the development of radiation-induced GD.

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References

  1. Chiovato L, Santini F, Vitti P, Bendinelli G, Pinchera A. Appearance of thyroid stimulating antibody and Graves’ disease after radioiodine therapy for toxic nodular goitre. J Clin Endocrinol 1994; 40:803–806.

    CAS  Google Scholar 

  2. Nygaard B, Knudsen JH, Hegedues L, Veje A, Hansen JEM. Thyrotropin receptor antibodies and Graves’ disease, a side effect of131I treatment in patients with non toxic-goiter. J Clin Endocrinol Metab 1997; 82:2926–2930.

    Article  CAS  PubMed  Google Scholar 

  3. Hirsch C, Spyra J, Langhammer R, Laubenbacher C, Senekowitsch-Schmidtke R, Schwaiger M. Zum Auftreten einer Immunhyperthyreose nach Radioiodtherapie von Schilddrüsenautonomien. Med Klin 1997; 92:130–137.

    CAS  PubMed  Google Scholar 

  4. Dunkelmann S, Rudolph F, Prillwitz A, Groth P, Schuemichen C. Paradoxical effects of radioiodine therapy in functional thyroid autonomy and mild immunothyropathy. Nuklearmedizin 1998; 37:17–22.

    Google Scholar 

  5. Nygaard B, Faber J, Veje A, Hegedus L, Hansen JM. Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by131I therapy. Thyroid 1999; 9:477–481.

    CAS  PubMed  Google Scholar 

  6. Soule J, Mayfield R. Graves’ disease after131I therapy for toxic nodule. Thyroid 2001; 10:91–92.

    Article  Google Scholar 

  7. Wallaschofski H, Orda C, Georgi P, Paschke R. Distinction between autoimmune and non-autoimmune hyperthyroidism by determination of TSH-receptor antibodies in patients with the initial diagnosis of toxic multinodular goiter. Horm Metab Res 2001; 33:504–507.

    Article  CAS  PubMed  Google Scholar 

  8. Wallaschofski H, Muller D, Georgi P, Paschke R. Induction of TSH-receptor antibodies in patients with toxic multinodular goitre by radioiodine treatment. Horm Metab Res 2002; 34:36–39.

    Article  CAS  PubMed  Google Scholar 

  9. Costagliola S, Morgenthaler NG, Hoermann R, Badenhoop K, Struck J, Freitag D, Poertl S, Weglohmer W, Hollidt JM, Quadbeck B, Dumont JE, Schumm-Draeger PM, Bergmann A, Mann K, Vassart G, Usadel KH. Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves’ disease. J Clin Endocrinol Metab 1999; 84:90–97.

    PubMed  Google Scholar 

  10. Pedersen I, Knudsen N, Perrild H, Ovesen L, Laurberg P. TSH-receptor antibody measurement for differentiation of hyperthyroidism in Graves’ disease and multinodular toxic goitre: a comparison of two competitive binding assays. Clin Endocrinol (Oxf) 2001; 55:381–390.

    Google Scholar 

  11. Meller J, Jauho A, Hüfner M, Gratz S, Becker W. Disseminated thyroid autonomy or Graves’ disease: reevaluation by a second generation TSH receptor antibody assay. Thyroid 2000; 10:1073–1079.

    CAS  PubMed  Google Scholar 

  12. Dunkelmann S, Endlicher D, Prillwitz A, Rudolph F, Groth P, Schuemichen C. Results of TcTUs-optimized radioiodine therapy of multifocal and disseminated functional thyroid autonomy. Nuklearmedizin 1999; 38:131–139.

    CAS  PubMed  Google Scholar 

  13. Brunn J, Block U, Ruf G, Bos I, Kunze WP, Scriba PC. Volumetry of the lobe of the thyroid gland by means of realtime sonography. Dtsch Med Wochenschr 1981; 106:1338–1340.

    CAS  PubMed  Google Scholar 

  14. DeGroot LJ. Radioiodine and immune system. Thyroid 1997; 7:259–264.

    PubMed  Google Scholar 

  15. Regalbuto C, Salamone S, Scollo C, Vigneri R, Pezzino V. Appearance of anti TSH-receptor antibodies and clinical Graves’ disease after radioiodine therapy for hyperfunctioning thyroid adenoma. J Endocrinol Invest 1999; 22:147–150.

    CAS  PubMed  Google Scholar 

  16. Davies TF. The thyroid immunology of the postpartum period. Thyroid 1999; 9:675–684.

    CAS  PubMed  Google Scholar 

  17. Ando T, Davies TF. Clinical review 160: postpartum autoimmune thyroid disease: the potential role of fetal microchimerism. J Clin Endocrinol Metab 2003; 88:2965–2971.

    Article  CAS  PubMed  Google Scholar 

  18. Pedersen OM, Bennedbaek FN, Hoir-Madsen M, Jacobsen BB, Hegedus L. The value of ultrasonography in predicting autoimmune thyroid disease. Thyroid 2000; 10:251–259.

    CAS  PubMed  Google Scholar 

  19. Hansen D, Bennedbaek FN, Hoir-Madson M, Hegedus L, Jacobsen BB. A prospective study of thyroid function, morphology and autoimmunity in young patients with type 1 diabetes. Eur J Endocrinol 2003; 148:245–251.

    CAS  PubMed  Google Scholar 

  20. Weetmann AP. Autoimmune thyroid disease: propagation and progression. Eur J Endocrinol 2003; 148:1–9.

    CAS  PubMed  Google Scholar 

  21. Sugenoya A, Kobayashi S, Kasuga Y, Masuda H, Fujimori M, Komatsu M, Takahashi S, Yokoyama S, Shimizu T, Yamada T. Evidence of intrathyroidal accumulation of TSH receptor antibody in Graves’ disease. Acta Endocrinol 1992; 126:416–418.

    CAS  PubMed  Google Scholar 

  22. Sakaguchi S, Ermak TH, Toda M, Berg LJ, Ho W, Fazekas de St Groth B, Perterson PA, Sakaguchi N, Davis MM. Induction of autoimmune disease in mice by germline alteration of the T cell receptor gene expression. J Immunol 1994; 152:1471–1484.

    CAS  PubMed  Google Scholar 

  23. Monzani F, Del Guerra P, Caraccio N, Casolaro A, Lippolis PV, Goletti O. Appearance of Graves’ disease after percutaneous ethanol injection for the treatment of hyperfunctioning thyroid adenoma. J Endocrinol Invest 1997; 20:294–298.

    CAS  PubMed  Google Scholar 

  24. Verde G. Graves’ disease after percutaneous ethanol injection for the treatment of autonomous thyroid adenoma. J Endocrinol Invest 1998; 21:334–335.

    CAS  PubMed  Google Scholar 

  25. Orsolon P, Lupi A, De Antoni Migliorati G, Vianello Dri A. Appearance of Graves’ disease following regression of autonomously functioning thyroid nodules. Two case reports. Minerva Endocrinol 1998; 23:53–56.

    CAS  PubMed  Google Scholar 

  26. Wallfish PG, Caplan D, Rosen IB. Postparathyroidectomy transient thyrotoxicosis. J Clin Endocrinol Metab 1992; 75:224–227.

    Article  PubMed  Google Scholar 

  27. Freeman JS, Ertel NH, McA’Nulty JA, Khan MY. Graves’ disease following resection of an autonomous solitary thyroid adenoma. J Med Soc N Y 1983; 80:444–446.

    CAS  Google Scholar 

  28. Bartalena L, Bogazzi F, Pecori F, Martino E. Graves’ disease occurring after subacute thyroiditis: report of a case and review of the literature. Thyroid 1996; 6:345–348.

    CAS  PubMed  Google Scholar 

  29. Bergoglio LM, Vilchez PE, Fatemi S, Spencer CA. TPOAb assay limitations may be responsible for the skew in the TSH upper reference limit. Proceedings of the Latin American Thyroid Society, Cordoba, Argentina 2003; A:123.

    Google Scholar 

  30. Hollowell JG, Staehling NW, Hannon WH, Flanders WD, Gunter EW, Spencer CA, Bravermann LE. Serum thyrotropin, thyroxine and thyroid antibodies in the United States population (1988-1994): NHANES II. J Clin Endocrinol Metab 2002; 87:489–499.

    Article  CAS  PubMed  Google Scholar 

  31. Pedersen IB, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Laurberg P. Thyroid peroxidase and thyroglobin autoantibodies in a large survey of populations with mild and moderate iodine deficiency. Clin Endocrinol (Oxf) 2002; 58:36–42.

    Google Scholar 

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Correspondence to Simone Dunkelmann.

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Dunkelmann, S., Wolf, R., Koch, A. et al. Incidence of radiation-induced Graves’ disease in patients treated with radioiodine for thyroid autonomy before and after introduction of a high-sensitivity TSH receptor antibody assay. Eur J Nucl Med Mol Imaging 31, 1428–1434 (2004). https://doi.org/10.1007/s00259-004-1519-8

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  • DOI: https://doi.org/10.1007/s00259-004-1519-8

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