Skip to main content
Log in

Changes of circulating thyroid autoantibody levels during and after therapy with methimazole in patients with Graves’ disease

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

Abstract

The changes occurring in the levels of circulating thyroid microsomal antibody (M-Ab) and antithyroglobulin antibody (Tg-Ab) during antithyroid drug therapy were studied in 32 patients receiving methimazole for Graves’ disease. M-Ab was determined by competitive binding radioassay and Tg-Ab by a sandwich radiometric method. Before treatment 25 subjects (78.1%) had abnormally elevated (≥ 75 U/ml) M-Ab levels. A more than 30% reduction of M-Ab concentration with respect to the pretreatment value was found in 16 (64.0%) of these patients within the first 3–5 months of therapy, in 23 (92.0%) within 8–11 months and in 21 (84.0%) at the end of treatment (16–18 months). No change was found in the 7 patients with initial M-Ab levels < 75 U/ml. The reduction of M-Ab was more pronounced in the patients with good control of thyrotoxicosis than in those who were still hyperthyroid or were rendered hypothyroid during treatment. Twenty-three patients were followed after completion of the course of methimazole therapy, and 13 of them showed relapse of hyperthyroidism. A significant rise of M-Ab with respect to the values observed at the end of treatment occurred in all relapsing patients who had abnormally elevated M-Ab levels before therapy. With one exception, no M-Ab increase was found in the 10 nonrelapsing patients. However, no difference between relapsing and nonrelapsing patients was observed when the M-Ab changes occurring during treatment were considered. A similar trend during and after withdrawal of therapy was noted for Tg-Ab but, because of the relatively small percentage of positive subjects (25%), the results were less conclusive. The present data indicate that methimazole treatment induces a fall of thyroid antibodies in patients with Graves’ disease, and that relapse of hyperthyroidism is associated with an increase of these antibodies. However, the antibody changes occurring during treatment showed no prognostic value in predicting the outcome of therapy.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Volpé R. The pathogenesis of Graves’ disease: an overview. Glin. Endocrinol. Metab. 7: 3, 1978.?

    Article  Google Scholar 

  2. McKenzie J.M., Zakarija M., Sato A. Humoral immunity in Graves’ disease. Clin. Endocrinol. Metab. 7: 31, 1978.

    Article  PubMed  CAS  Google Scholar 

  3. Pinchera A., Fenzi G.F. Endocrine autoimmune diseases. In: De Groot L.J. (Ed.), Endocrinology. Grune and Stratton, New York, 1979, p. 2063.

    Google Scholar 

  4. Pinchera A., Mariotti S., Vitti P., Tosi M., Grasso L., Pacini F., Buti R., Baschieri L. Interference of serum thyroglobulin in the radioassay forserum antithyroglobulin antibodies. J. Clin. Endocrinol. Metab. 45: 1077, 1977.

    Article  PubMed  CAS  Google Scholar 

  5. Mariotti S., Pinchera A., Vitti P., Chiovato L., Marcocci C., Urbano C., Tosi M., Bhieri L. Comparison of radioassty and haemoagglutination methods for anti-thyroid microsomal antibodies. Clin. Exp. Immunol. 34: 118, 1978.

    PubMed Central  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Mukhtar E.D., Smith B.R., Pyle G.A., Hall R., Vice P. Relation of thyroid-stimulating immunoglobulins to thyroid function and effects of surgery, radioiodine and antithyroid drugs. Lancet 1: 713, 1975.

    Article  PubMed  CAS  Google Scholar 

  8. Davies T.F., Evered D.C., Smith B.R., Yeo P.P.B., Clark F., Hall R. Value of thyroid-stimulating-antibody determinations in predicting short-term thyrotoxic relapse in Graves disease. Lancet 1: 1181, 1977.

    Article  PubMed  CAS  Google Scholar 

  9. Schleusener H., Finke R., Kotulla P., Wenzel K.W., Mein-hold H., Roedler H.D. Determination of thyroid stimulating immunoglobulins (TSI) during the course of Graves’ disease. A reliable indicator for remission and persistence of this disease? J. Endocrinol. Invest. 7: 155, 1978.

    Article  Google Scholar 

  10. Schleusener H., Kotulla P., Finke R., Sorje H., Meinhold H., Adlkofer F., Wenzel K.W. Relationship between thyroid status and Graves’ diseasespecific immunoglobulins. J. Clin. Endocrinol. Metab. 47: 379, 1978.

    Article  PubMed  CAS  Google Scholar 

  11. O’Donnel J., Trokoudes K., Silverberg J., Row V., Volpe R. Thyrotropin displacement activity of serum immunoglobulins from patients with Graves’ disease. J. Clin. Endocrinol. Metab. 46: 770, 1978.

    Article  Google Scholar 

  12. Fenzi G.F., Hashizume K., Roudeboush C.P., DeGroot L.J. Changes in thyroid-stimulating immunoglobulins during antithyroid therapy. J. Clin. Endocrinol. Metab. 48: 572, 1979.

    Article  PubMed  CAS  Google Scholar 

  13. Kuzuya N., Chiu S.C., Ikeda H., Uchimura H., Ito K., Nagataki S.Correlation between thyroid stimulators and 3, 5, 3’-triiodothyronine suppressibility in patients during treatment with thionamide drugs: comparison of assays by thyroid-stimulating and thyrotropin-displacing activities. J. Clin. Endocrinol. Metab. 48: 706, 1979.

    Article  PubMed  CAS  Google Scholar 

  14. Teng C.S., Yeung R.T.T. Changes in thyroid-stimulating antibody in Graves’ disease treated with antithyroid drugs and its relationship to relapse: a prospective study. J. Clin. Endocrinol. Metab. 50: 144, 1980.

    Article  PubMed  CAS  Google Scholar 

  15. 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 

  16. Zakarija M., McKenzie J.M., Banovac K. Clinical significance of assay of thyroid-stimulating antibody in Graves’ disease. Ann. Intern. Med. 93: 28, 1980.

    Article  PubMed  CAS  Google Scholar 

  17. Beck K., Nistrup Madsen S. Influence of treatment with radioiodine and propylthiouracil on thyroid stimulating immunoglobulins in Graves’ disease. Clin. Endocrinol. (Oxf.) 13: 417, 1980.

    Article  Google Scholar 

  18. Pinchera A., Fenzi G.F., Bartalena L., Chiovato L., Marcocci C., Toccafondi R., Rotella C.M., Aterini S., Zonefrati R. Thyroid cell-surface and thyroid-stimulating antibodies in patients with thyroid autoimmune disorders. In: Stockgit J.R., Nagataki S. (Eds.), Thyroid Research VIII. Australian Academy of Sciences, Canberra, 1980, p. 707.

    Google Scholar 

  19. Kilpatrick J.A. Changes in LATS and other thyroid autoantibody levels with therapy. NZ J. Med. 80: 495, 1974.

    CAS  Google Scholar 

  20. Anderson J.W., McConahey W.M., Alarcon-Segovia D., Emslander R.F., Wakim K.G. Diagnostic value of thyroid antibodies. J. Clin. Endocrinol. Metab. 29: 937, 1967.

    Article  Google Scholar 

  21. Hjort T., Birk Lauridsen U., Persson I. Thyroid antibodies and thyroglobulin-like products in serum during antithyroid therapy. Acta Med. Scand. 188: 431, 1970.

    Article  PubMed  CAS  Google Scholar 

  22. Wilkin J., Swanson Beck J., Gunn A., Al Moussah M., Isles T.E., Crooks J. Autoantibodies in thyrotoxicosis: a quantitative study of their behavior in relation to the course of treatment. J. Endocrinol. Invest. 3: 5, 1980.

    Article  PubMed  CAS  Google Scholar 

  23. Buchanan W.W., Koutras D.A., Crooks J., Alexander W.D., Brass W., Anderson J.R., Goudie R.B., Gray K.G. The clinical significance of the complement-fixation testin thyrotoxicosis. J. Endocrinol. 24: 115, 1962.

    Article  PubMed  CAS  Google Scholar 

  24. Bonnyns M., Vanhaelst L. Relationship between the long-acting thyroid stimulator and the thyroid microsomal antibody. J. Endocrinol. 43:125, 1969.

    Article  PubMed  CAS  Google Scholar 

  25. Pinchera A., Fenzi G.F., Bartalena L., Chiovato L., Marcocci C., Pacini F. Thyroid antigens involved in autoimmune thyroid diseases. In: Klein E., Horster F.A. (Eds.), Autoimmunity in thyroid diseases. Schattauer Verlag, Stuttgart, 1979, p. 49.

    Google Scholar 

  26. Marcocci C., Bartalena L., Chiovato L., Fenzi G.F., Macchia E., Malasoma M., Mammoli C., Miccoli P., Monzani F., Pinchera A. Variations of thyroid autoantibodies in Graves’ patients during long-term antithyroid drugs therapy. In: Pinchera A., Doniach D., Fenzi G.F., Baschieri L. (Eds.), Autoimmune aspects of endocrine disorders. Academic Press, London, 1980, p. 179.

    Google Scholar 

  27. Mori T., Fischer J., Kriss J.P. Studies of an in vivo binding reaction between thyroid microsomes and Long-Acting Thyroid Stimulator globulin (LATS): 1. Development of solid-state competitive binding radioassay methods for measurement of antimicro-somal and antithyroglobulin antibodies. J. Clin. Endocrinol. Metab. 31: 119, 1970.

    Article  PubMed  CAS  Google Scholar 

  28. Bayer M.F., Kriss J.P. A solid phase, sandwich-type radioimmunoassay for antithyroglobulin; elimination of false positive results and semiquahtitative measurement of antithyroglobulin in the presence of elevated thyroglobulin. J. Clin. Endocrinol. Metab. 49: 565, 1979.

    Article  PubMed  CAS  Google Scholar 

  29. Fulthorpe A.J., Roitt I.M., Doniach D., Couchman K. A stable sheep-cell preparation for detecting thyroglobulin autoantibodies and its clinical application. J.Clin. Pathol. 14: 654, 1961.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Fabris N. Immunodepression in thyroid-deprived animals. Clin. Exp. Immunol. 15: 601, 1973.

    PubMed Central  PubMed  CAS  Google Scholar 

  31. Wall J.R., Ryan E.A. Effect of experimental hyper and hypothyroidism on immune reactivity. In: Stockigt J.R., Nagataki S. (Eds.), Thyroid Research VIII. Australian Academy of Sciences, Canberra, 1980, p. 781.

    Google Scholar 

  32. Wall J.R., Joyner D.M., Ryan E.A., Wren S.F.G. Effect of experimental hyperthyroidism and hypothyroidism on B and T lymphocyte reactivity to bacterial, fungal and tissue antigens. In: Pinchera A., Doniach D., Fenzi G.F., Baschieri L. (Eds.), Autoimmune aspects of endocrine disorders. Academic Press, London, 1980, p. 215

    Google Scholar 

  33. Pinchera A., Rovis L., Davoli C., Grasso L., Baschieri L. LATS and Graves’ disease; clinical and radioimmunological studies. In: Mattar E., DeBrong-Mattar G., James V.T.H. (Eds.), Recent advances in endocrinology. Excerpta Medica, Amsterdam, 1971, p. 91.

    Google Scholar 

  34. Monaco F., Santolamazza C., De Ros I., Andreoli M. Effects of propythiouracil and methylmercaptoimidazole on thyroglobulin synthesis. Acta Endocrinol. (Kbh.) 93: 32, 1980.

    CAS  Google Scholar 

  35. Uller R.P., Van Herle A.J. Effect of therapy on serum thyroglobulin levels in patientswith Graves’ disease. J. Clin. Endocrinol. Metab. 46: 747, 1978.

    Article  PubMed  CAS  Google Scholar 

  36. Mariotti S., Kaplan E.L., Medof M.E., DeGroot L.J. Circulating thyroid antigen-antibody immune complexes. In: Stockigt J.R., Nagataki S. (Eds.), Thyroid Research VIII. Australian Academy of Sciences, Canberra, 1980, p. 696.

    Google Scholar 

  37. Cano P.O., Chertman H.H., Jerry L.H., McKenzie J.M. Circulating immune complexes in Graves’ disease. Endocr. Res. Commun. 3: 307, 1976.

    Article  PubMed  CAS  Google Scholar 

  38. Brohee D., Delespesse G., Debisschop M.J., Bonnyns M. Circulating immune complexes in various thyroid diseases. Clin. Exp. Immunol. 36: 379, 1979.

    PubMed Central  PubMed  CAS  Google Scholar 

  39. Hopf U., Hutteroth T.H., Kotulla P. Demonstration of circulating immune complexes in Graves’ disease by the Raji cell technique and their relation to different thyroid autoantibodies. Horm. Metab. Res. 11: 622, 1979.

    Article  PubMed  CAS  Google Scholar 

  40. Van Der Heide D., Daha M.R., Bolk J.H., Bussemaker J.K., De Bruin T.W.A., Goslings B.M., Van Es L.A., Querido A. Circulating immune complexes and thyroid-stimulating immunoglobulins before, during and after antithyroid drug therapy in patients with Graves’ disease. Lance 1: 28, 1980.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marcocci, C., Chiovato, L., Mariotti, S. et al. Changes of circulating thyroid autoantibody levels during and after therapy with methimazole in patients with Graves’ disease. J Endocrinol Invest 5, 13–19 (1982). https://doi.org/10.1007/BF03350476

Download citation

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03350476

Key-words

Navigation