Skip to main content
SpringerLink
Log in

The inhibitory effect of large doses of methimazole on iodine induced lymphocytic thyroiditis and serum anti-thyroglobulin antibody titers in BB/Wor rats

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

Abstract

The BB/Wor rat spontaneously develops autoimmune insulin dependent diabetes mellitus and lymphocytic thyroiditis (LT). Excess iodine ingestion enhances and low iodine diet decreases the incidence of LT in this rat model but does not affect the incidence of diabetes mellitus. The administration of a low dose of methimazole (MMI; 870 ng/gm bw ip daily) from 30–90 days of age had no significant effect on thyroid function or on the incidence of iodine induced LT and serum anti-thyroglobulin (Tg) antibodies measured by an ELISA assay. A large dose of MMI (0.05% in the drinking water) induced goiter and hypothyroidism. In addition, the incidence of LT was markedly attenuated (76% vs 6%, p < 0.001) and reduced titers of serum anti-Tg antibodies (0.59 ± 0.1 OD vs 0.08 ± 0.01, p < 0.001) were observed. This inhibitory effect of MMI on the occurrence of iodine induced LT in the BB/Wor rat may be due to the lower antigenicity of the poorly iodinated Tg secondary to MMI therapy and/or to an immunosuppressant effect of MMI itself.

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. Pinchera A., Liberti P., Martino E., Fenzi G.F., Grasso L., Rovis L., Baschieri L., Doria G. Effects of anti-thyroid drug therapy on the long acting thyroid stimulator and the antithyroglobulin antibodies. J. Clin. Endocrinol. Metab. 29: 231, 1969.

    Article  PubMed  CAS  Google Scholar 

  2. Teng C.S., Yeung R.T.T. Changes in thyroid-stimulating antibody activity in Graves’ disease treated with anti-thyroid drug and its relationship to relapse: A prospective study. J. Clin. Endocrinol. Metab. 50: 144, 1980.

    Article  PubMed  CAS  Google Scholar 

  3. Fenzi G.F., Hashizume K., Roudeboush C.P., DeGroot L.J. Changes in thyroid stimulating immunoglobulins during antithyroid drug therapy. J. Clin. Endocrinol. Metab. 48: 572, 1980.

    Article  Google Scholar 

  4. McGregor A.M., Petersen M.M., McLachlan S.M., Rooke P., Smith B.R., Hall R. Carbimazole and the autoimmune response in Graves’ disease. N. Engl.J. Med. 303: 302, 1980.

    Article  PubMed  CAS  Google Scholar 

  5. Karlsson F.A., Dahlberg P.A. Thyroid stimulating antibodies (TSAb) in patients with Graves’ disease undergoing antithyroid drug treatment. Indicators of activity of disease. Clin. Endocrinol. (Oxf.) 14: 579, 1981.

    Article  CAS  Google Scholar 

  6. McGregor A.M., Ibbertson H.K., Smith B.R., Hall R. Carbimazole and autoantibody synthesis in Hashimoto’s thyroiditis. Br. Med. J. 288: 518, 1984.

    Article  Google Scholar 

  7. Wilson R., McKillop J.H., Chopra M., Thompson J.A. The effect of antithyroid drugs on B and T cell activity in vitro. Clin. Endocrinol. (Oxf.) 28: 389, 1988.

    Article  CAS  Google Scholar 

  8. Weetman A.P., McGregor A.M., Hall R. Evidence for an effect of antithyroid drugs on the natural history of Graves’ disease. Clin. Endocrinol. (Oxf.) 21: 163, 1984.

    Article  CAS  Google Scholar 

  9. Codaccioni J.L., Orgiazzi J., Blanc P., Pugeat M., Roulier R., Carayon P. Lasting remissions in patients treated for Graves’ hyperthyroidism with propranolol alone: A pattern of spontaneous evolution of the disease. J. Clin. Endocrinol. Metab. 67: 656, 1988.

    Article  PubMed  CAS  Google Scholar 

  10. Totterman T.M., Karlsson F.A., Bengtsson M., Mendel-Hartvig I. Induction of circulating activated suppressor-like T cells by methimazole therapy for Graves’ disease. N. Engl. J. Med. 316: 15, 1987.

    Article  PubMed  CAS  Google Scholar 

  11. Ludgate M.E., McGregor A.M., Weetman A.P., Ratonachaiyavong S., Lazarus J.H., Hall R., Middleton G.W. Analysis of T cell subsets in Graves’ disease: alterations associated with carbimazole. Br. Med. J. 288: 526, 1984.

    Article  CAS  Google Scholar 

  12. Volpe R., Karlsson A., Jansson R., Dahlberg P.A. Evidence that antithyroid drugs induce remissions in Graves’ disease by modulating thyroid cellular activity. Clin. Endocrinol. (Oxf.) 25: 453, 1986.

    Article  CAS  Google Scholar 

  13. McGregor A.M., Rees-Smith B., Hall R., Petersen M.M., Miller M., Dewitz P.J. Prediction of relapse in hyperthyroid Graves’ disease. Lancet 1: 1101, 1980.

    Article  PubMed  CAS  Google Scholar 

  14. Volpe R. Autoimmune thyroid disease. In: Volpe R. (Ed.), Autoimmunity and endocrine disease. Marcel Dekker, New York, 1985, p. 109.

    Google Scholar 

  15. Davies T.F., Weiss I., Gruber M.A. Influence of methimazole on murine thyroiditis. J. Clin. Invest. 73: 367, 1984.

    Google Scholar 

  16. Rennie D.P., McGregor A.M., Keast D., Weetman A.P., Foord S.M., Dieguez C., Williams E.D., Hall R. The influence of methimazole on thyroglobin-induced autoimmune thyroiditis in the rat. Endocrinology 112: 326, 1983.

    Article  PubMed  CAS  Google Scholar 

  17. Allen E.M., Rajatanavin R., Nogimori T., Cushing G., Ingbar S.H., Braverman L. The effect of methimazole on the development of spontaneous lymphocytic thyroiditis in the diabetesprone BB/Wor rat. Am. J. Med. Sci. 292: 167, 1986.

    Article  Google Scholar 

  18. Romaldini J.H., Bromberg N., Werner M.C. Comparison of effects of high and low dose regimens of antithyroid drugs in the management of Graves’ hyperthyroidism. J. Clin. Endocrinol. Metab. 57: 563, 1983.

    Article  PubMed  CAS  Google Scholar 

  19. Allen E.M., Appel M.C., Braverman L.E. The effect of iodide ingestion on the development of spontaneous lymphocytic thyroiditis in the diabetesprone BB/W rat. Endocrinology 118: 1972, 1986.

    Google Scholar 

  20. Solomon B.L., Euaul J.E., Burman K.D., Wartofsky L. Remission rates with antithyroid drug therapy: Continuing influence of iodine intake. Ann. Intern. Med. 107: 510, 1987.

    Article  PubMed  CAS  Google Scholar 

  21. Azizi F. Environmental iodine intake affects the response to methimazole in patients with diffuse toxic goiter. J. Clin. Endocrinol. Metab. 61: 374, 1987.

    Article  Google Scholar 

  22. Czarnocka B., Ruf J., Ferrand M., Carayon P., Lis-sitzky S. Purification of the human thyroid peroxidase and its identification as the microsomal antigen involved in autoimmune thyroid diseases. FEBS. Lett. 190: 147, 1985.

    Article  PubMed  CAS  Google Scholar 

  23. Engler H., Taurog A., Luthy C., Dorris M.L. Reversible and irreversible inhibition of thyroid peroxidase-catalyzed iodination by thioureylene drugs. Endocrinology 112: 190, 1983.

    Article  Google Scholar 

  24. Shiroozu A., Taurog H., Engler H., Dorris M.L. Mechanism of action of thyroureylene antithyroid drugs in the rat: Possible inactivation of thyroid peroxidase by propylthiouracil. Endocrinology 113: 362, 1983.

    Article  PubMed  CAS  Google Scholar 

  25. Sundick R.S., Herdegen D.M., Brown T.R., Bagchi N. The incorporation of dietary iodine into thyroglobulin increases its immunogenicity. Endocrinology 120: 2078, 1987.

    Article  PubMed  CAS  Google Scholar 

  26. Champion B.R., Rayner D.C., Byfield P.G.H., Page K.R., Yo Chan C.T., Roitt I.M. Critical role of iodination for T cell recognition of thyroglobulin in experimental murine autoimmunity. J.Immunol. 139: 3665, 1987.

    PubMed  CAS  Google Scholar 

  27. Nunez J., Pommier J. Formation of thyroid hormones. Vitam. Horm. 39: 175, 1982.

    Article  PubMed  CAS  Google Scholar 

  28. Weetman A.P., Gunn C., Hall R., McGregor A.M. The accumulation of [35S] methimazole by monocytes and macrophages. Acta Endocrinol. (Kbh.) 107: 366, 1984.

    CAS  Google Scholar 

  29. Weetman A.P., Holt E., Campbell A.K., Hall R., McGregor A.M. Methimazole and generation of oxygen radicals by monocytes: Potential role in immunosuppression. Br. Med. J. 208: 518, 1984.

    Article  Google Scholar 

  30. Taylor J.J., Wilson R.L., Kendall-Taylor P. Evidence for direct interactions between methimazole and free radicals. FEBS. Lett. 176: 337, 1984.

    Article  CAS  Google Scholar 

  31. Reinhardt W., Paul T.L., Allen E.M., Alex S., Yang Y.N., Appel M.C., Braverman L.E. Effect of L-thyroxine administration on the incidence of iodine induced and spontaneous lymphocytic thyroiditis in the BB/Wor rat. Endocrinology 122: 1179, 1988.

    Article  PubMed  CAS  Google Scholar 

  32. Woda B.A., Like A.A., Padden C., McFadden M. Deficiency of phenotypic cytotoxic-suppressor T lymphocytes in the BB/W rat. J. Immunol. 136: 856, 1986.

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. W. Reinhardt

    Present address: Division of Endocrinology, Universitaetsklinikum, 43 Essen, FRG

Authors and Affiliations

  1. Departments of Medicine and Pathology, University of Massachusetts Medical School, Worcester, MA, 01655, USA

    W. Reinhardt, M. C. Appel, S. Alex, Y. N. Yang & L. E. Braverman M.D.

Authors
  1. W. Reinhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. C. Appel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Alex
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. N. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. E. Braverman M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by Grants DK 18919, DK 30657 and DK 41090, NIDDK, NIH, Bethesda, MD and Deutsche Forschungsgemeinschaft.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reinhardt, W., Appel, M.C., Alex, S. et al. The inhibitory effect of large doses of methimazole on iodine induced lymphocytic thyroiditis and serum anti-thyroglobulin antibody titers in BB/Wor rats. J Endocrinol Invest 12, 559–563 (1989). https://doi.org/10.1007/BF03350760

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03350760

Keywords

Search

Navigation