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T4 but not T3 administration is associated with increased recurrence of Graves’ disease after successful medical therapy

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Abstract

TSH has been incriminated in Graves’ disease for increasing the production of antibodies against TSH receptor (TRAb). It has been, therefore, suggested that T4 administration after successful antithyroid drug (ATD) treatment may indirectly decrease the production of TRAb and, therefore, the frequency of recurrence of hyperthyroidism. To study the role of T4 and T3 on the recurrence rate of Graves’ disease 108 patients with Graves’ disease (22 males, age: 49.8±14.3 yr, mean±SD, and 86 females, age: 41.7±12 yr) were followed-up for 24 months after successful treatment with ATD (carbimazole). During the follow-up period, patients daily received either 100 μg T4 or 25 μg T3 or placebo after random and double-blinded assignment into three groups. They were evaluated trimonthly up to 12 months and at 24 months. Plasma TRAb levels were measured at the beginning and at 12 months. At 12 months of the follow-up period, 14 out of 33 (42.4%), 6 out of 38 (15.8%), and 9 out of 37 (24.3%) patients receiving T4, T3 and placebo, respectively, recurred. Recurrence rate of T4-treated patients was statistically higher than that of the T3-treated patients or controls (p<0.05). At the beginning of the follow-up period patients who were going to recur had significantly higher TRAb levels and goiter weight than patients who were not (p<0.05). At 24 months of the follow-up period, from the patients who did not drop out of the study, none out of 11 (0%), 2 out of 19 (10.5%) and 1 out of 12 (8.3%) receiving T4, T3 and placebo, respectively, recurred. We conclude that T4 administration after successful ATD treatment of Graves’ disease is associated with increased recurrence of hyperthyroidism as compared to the T3 or placebo administration. High TRAb levels and goiter weight at the end of ATD treatment may hint at recurrence.

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References

  1. Astwood E.B. Treatment of hyperthyroidism with thiourea and thiouracil. J.A.M.A. 1943, 122: 78–81.

    Article  CAS  Google Scholar 

  2. Wartofsky L., Glinoer D., Solomon B, et al. Differences and similarities in the diagnosis and treatment of Graves’ disease in Europe, Japan and the United States. Thyroid 1991, 1: 129–135.

    Article  CAS  PubMed  Google Scholar 

  3. Hedley A.J., Young R.E., Jones S.J., Alexander W.D., Bewsher P.D., Scottish Automated Follow-Up Register Group. Antithyroid drugs in the treatment of hyperthyroidism of Graves’ disease: long-term follow-up of 434 patients. Clin. Endocrinol. (Oxf.) 1989, 31: 209–218.

    Article  CAS  Google Scholar 

  4. Schleusener H., Schwander J., Fischer C., et al. Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves’ disease. Acta Endocrinol. (Copenh.) 1989, 120: 689–701.

    CAS  Google Scholar 

  5. Törring O., Tallstedt L., Wallin G., et al. Graves’ hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine — a prospective randomized study. J. Clin. Endocrinol. Metab. 1996, 81: 2986–2993.

    PubMed  Google Scholar 

  6. Mastorakos G., Doufas A.G., Mantzos J., Koutras D.A. Long-term follow-up of 202 patients with Graves’ disease treated medically. Thyroidology 1997, 9: 71–80.

    Google Scholar 

  7. Hashizume K., DeGroot L.J. Release of thyrotropin receptor from thyroid plasma membranes: effect of hydrocortisone, propanolol, and adenosine 3′,5′-monophosphate. Endocrinology 1980, 106: 1463–1468.

    Article  CAS  PubMed  Google Scholar 

  8. Hashizume K., Ichikawa K., Sakurai K., et al. Administration of thyroxine in treated Graves’ disease: effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism. N. Engl. J. Med. 1991, 324: 947–953.

    Article  CAS  PubMed  Google Scholar 

  9. Hashizume K., Ichikawa K., Nishii Y., et al. Effects of administration of thyroxine on the risk of postpartum recurrence of hyperthyroid Graves’ disease. J. Clin. Endocrinol. Metab. 1992, 75: 6–10.

    CAS  PubMed  Google Scholar 

  10. Doufas A.G., Mastorakos G., Mantzos J., Koutras D.A. Recurrence of Graves’ disease is independent of thyroxine administration after medical therapy. Thyroid 1995, 5 (Suppl. 1): S70.

    Google Scholar 

  11. McIver B., Rae P., Beckett G., Wilkinson E., Gold A., Toft A. Lack of effect of thyroxine in patients with Graves’ hyperthyroidism who are treated with an antithyroid drug. N. Engl. J. Med. 1996, 334: 220–224.

    Article  CAS  PubMed  Google Scholar 

  12. Pfeilschifter J., Ziegler R. Suppression of serum thyrotropin with thyroxine in patients with Graves’ disease: effects on recurrence of hyperthyroidism and thyroid volume. Eur. J. Endocrinol. 1997, 136: 81–86.

    Article  CAS  PubMed  Google Scholar 

  13. Rittmaster R.S., Abbot E.C., Douglas R., et al. Effect of methimazole, with or without L-thyroxine, on remission rates in Graves’ disease. J. Clin. Endocrinol. Metab. 1998, 83: 814–818.

    CAS  PubMed  Google Scholar 

  14. Mantzos J.D., Yialouris P.P. A simple and reproducible method for the estimation of triiodothyronine uptake (thyroxine binding index) using a new adsorbent. Clin. Biochem. 1982, 15: 76–79.

    Article  CAS  PubMed  Google Scholar 

  15. Statistica software for Windows. Copyright © 1984-1994 by StatSoft, Inc., Tulsa, Oklahoma.

  16. Doufas A.G., Mastorakos G., Chatziioannou S., et al. The predominant form of non-toxic goiter in Greece is now autoimmune thyroiditis. Eur. J. Endocrinol. 1999, 140: 505–511.

    Article  CAS  PubMed  Google Scholar 

  17. Lucas A., Salinas I., Rius F., et al. Medical therapy of Graves disease: does thyroxine prevent recurrence of hyperthyroidism? J. Clin. Endocrinol. Metab. 1997, 82: 2410–2413.

    CAS  PubMed  Google Scholar 

  18. Garcia-Mayor R.V., Paramo C., Luna Cano R., Perez Mendez L.F., Galofre J.C., Andrade A. Antithyroid drug and Graves’ hyperthyroidism. Significance of treatment duration and TRAb determination on lasting remission. J Endocrinol. Invest. 1992, 15: 815–820.

    Article  CAS  PubMed  Google Scholar 

  19. Vitti P., Rago T., Chiovato L., et al. Clinical features of patients with Graves’ disease undergoing remission after antithyroid drug treatment. Thyroid 1997, 7: 369–375.

    Article  CAS  PubMed  Google Scholar 

  20. Feldt-Rasmussen U., Schleusener H., Carayon P. Metaanalysis evaluation of the impact of thyrotropin receptor antibodies on long term remission after medical therapy of Graves’ disease. J. Clin. Endocrinol. Metab. 1994, 78: 98–102.

    CAS  PubMed  Google Scholar 

  21. Rink T., Holle L.H., Schroth H.J., Garth H. Individual outcome monitoring of TSH receptor antibody level for predicting the prognosis of Graves’ disease. Nuklearmedizin 1998, 37: 90–94.

    CAS  PubMed  Google Scholar 

  22. Keck F.S., Loos U. Peripheral autoregulation of thyromimetic activity in man. Horm. Metab. Res. 1988, 20: 110–114.

    Article  CAS  PubMed  Google Scholar 

  23. Glinoer D., de Nayer P., Bex M. 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 randomized study. Eur. J. Endocrinol. 2001, 144: 475–483.

    Article  CAS  PubMed  Google Scholar 

  24. Bartalena L. Smoking and Graves’ disease. J. Endocrinol. Invest. 2002, 25: 402.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Therapeutics, Alexandra and Evgenidion Hospitals, Athens University, Endocrine Unit, 3 Neofytou VAMVA, 10674, Athens, Greece

    G. Mastorakos MD, A. G. Doufas, E. Mantzos, J. Mantzos & D. A. Koutras

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  1. G. Mastorakos MD
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  2. A. G. Doufas
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  3. E. Mantzos
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  4. J. Mantzos
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  5. D. A. Koutras
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Correspondence to G. Mastorakos MD.

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Mastorakos, G., Doufas, A.G., Mantzos, E. et al. T4 but not T3 administration is associated with increased recurrence of Graves’ disease after successful medical therapy. J Endocrinol Invest 26, 979–984 (2003). https://doi.org/10.1007/BF03348195

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