Skip to main content

Advertisement

SpringerLink
Log in

Thyroid-specific changes following treatment with biological therapies in patients with rheumatic diseases

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Biological anti-rheumatic agents (BAA) may induce autoimmune phenomena. Evidence on thyroid-specific effects of these agents is relatively limited. We studied prospectively, over 3 years, 36 rheumatic patients treated with BAA (18 Infliximab and 18 Rituximab) and no prior exposure to biological therapies (group-1), with respect to their thyroid function, thyroid antibody titers, and thyroid ultrasonographic parameters, such as left inferior thyroid artery peak systolic velocity (ITA PSV), left thyroid lobe vascularity index (TL VI), and echogenicity. Twenty-eight rheumatic patients treated with disease-modifying anti-rheumatic drugs and/or glucocorticoids (group-2), 21 rheumatic patients not receiving any treatment (group-3), and 49 healthy individuals (group-4) were used for comparison. Thyroid function and autoantibody titers were not significantly altered at any stage irrespectively of the administered BAA, previously unknown autoimmune thyroid disease (AITD) status, and/or concomitant treatment with glucocorticoids. Left ITA PSV was significantly increased in group-1 patients (mean ± SD start: 25.5 ± 14.1 cm/s vs. end: 29.8 ± 11.1 cm/s, p = 0.038 and p < 0.001, respectively). Six group-1, 7 group-2, and 3 group-3 patients developed reduced thyroid echogenicity during follow-up (start: p = 0.003 and end: p < 0.001). Left ITA PSV, left TL VI, and echogenicity changes were not related to alterations in thyroid volume, thyrotropin hormone levels, and/or underlying AITD. Infliximab and Rituximab do not cause any alterations in thyroid function and/or autoimmunity, even in patients with previously undiagnosed AITD. Elevated left ITA PSV and reduced thyroid echogenicity may be early features signaling progression to AITD in patients treated with BAA.

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.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. K.G. Saag, G.G. Teng, N.M. Patkar, J. Anuntiyo, C. Finney, J.R. Curtis et al., American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 59, 762–784 (2008)

    Article  CAS  PubMed  Google Scholar 

  2. D. El Fassi, C.H. Nielsen, H.C. Hasselbalch, L. Hegedus et al., The rationale for B lymphocyte depletion in Graves’ disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option. Eur. J. Endocrinol. 154, 623–632 (2006)

    Article  PubMed  Google Scholar 

  3. W.J. Sandborn, S.B. Hanauer, Infliximab in the treatment of Crohn’s disease: a user’s guide for clinicians. Am. J. Gastroenterol. 97, 2962–2972 (2002)

    Article  CAS  PubMed  Google Scholar 

  4. M.P. Vanderpump, W.M. Tunbridge, J.M. French, D. Appleton, D. Bates, F. Clark et al., The incidence of thyroid disorders in the community. A twenty year follow-up of the Whickham survey. Clin. Endocrinol. 43, 55–68 (1995)

    Article  CAS  Google Scholar 

  5. R.D. Utiger, The pathogenesis of autoimmune thyroid disease. N. Engl. J. Med. 325, 278–279 (1991)

    Article  CAS  PubMed  Google Scholar 

  6. F. D´Arbonneau, S. Ansart, R. Le Berre, M. Dueymes, P. Youinou, Y.L. Pennec, Thyroid dysfunction in primary Sjogren’s syndrome: a long-term follow-up study. Arthritis Rheum. 49, 804–809 (2003)

    Article  Google Scholar 

  7. J.B. Shiroky, M. Cohen, M.L. Ballachey, C. Neville, Thyroid dysfunction in rheumatoid arthritis: a controlled prospective survey. Ann. Rheum. Dis. 52, 454–456 (1993)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. J.R. Garber, R.H. Cobin, H. Gharib, J.V. Hennessey, I. Klein, J.I. Mechanick et al., Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Pract. 18, 988–1028 (2012)

    Article  PubMed  Google Scholar 

  9. R. Gutekunst, W. Hafermann, T. Mansky, P.C. Scriba, Ultrasonography related to clinical and laboratory findings in lymphocytic thyroiditis. Acta Endocrinol. 121, 129–135 (1989)

    CAS  PubMed  Google Scholar 

  10. W. Raber, A. Gessl, P. Nowotny, H. Vierhapper, Thyroid ultrasound versus antithyroid peroxidase antibody determination: a cohort study of four hundred fifty-one subjects. Thyroid 12, 725–731 (2002)

    Article  PubMed  Google Scholar 

  11. O.M. Pedersen, N.P. Aardal, T.B. Larssen, J.E. Varhaug, O. Myking, H. Vik-Mo, The value of ultrasonography in predicting autoimmune thyroid disease. Thyroid 10, 251–259 (2000)

    Article  CAS  PubMed  Google Scholar 

  12. I. Banaka, G. Kaltsas, S. Antoniou, G. Kanakis, A. Zilos, C. Baltas et al., Prognostic value of vascularity index for the diagnosis of autoimmune thyroid disease. JBR-BTR 94, 185–190 (2011)

    CAS  PubMed  Google Scholar 

  13. I. Banaka, D. Thomas, G. Kaltsas, Value of the left inferior thyroid artery peak systolic velocity in diagnosing autoimmune thyroid disease. J. Ultrasound Med. 32, 1969–1978 (2013)

    Article  PubMed  Google Scholar 

  14. J.C. Mandac, S. Chaudhry, K.E. Sherman, Y. Tomer, The clinical and physiological spectrum of interferon-alpha induced thyroiditis: toward a new classification. Hepatology 43, 661–672 (2006)

    Article  CAS  PubMed  Google Scholar 

  15. A.J. Coles, M. Wing, S. Smith, F. Coraddu, S. Greer, C. Taylor, Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 354, 1691–1695 (1995)

    Article  Google Scholar 

  16. H.G. Raterman, A. Jamnitski, W.F. Lems, A.E. Voskuyl, B.A. Dijkmans, W.H. Bos, Improvement of thyroid function in hypothyroid patients with rheumatoid arthritis after 6 months of adalimumab treatment: a pilot study. J. Rheumatol. 38, 247–251 (2011)

    Article  CAS  PubMed  Google Scholar 

  17. C. Eriksson, S. Engstrand, K.G. Sundqvist, S. Rantapaa-Dahlqvist, Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNFα. Ann. Rheum. Dis. 64, 403–407 (2005)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. M. Kaklamanos, D. Thomas, D. Pikazis, S. Christaki, G. Kaltsas, The effect of rituximab in thyroid function and autoimmunity. Thyroid 23, 1044–1045 (2013)

    Article  CAS  PubMed  Google Scholar 

  19. F.C. Arnett, S.M. Edworthy, D.A. Bloch, D.J. McShane, J.F. Fries, N.S. Cooper et al., The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 31, 315–324 (1988)

    Article  CAS  PubMed  Google Scholar 

  20. E.M. Tan, A.S. Cohen, J.F. Fries, A.T. Masi, D.J. McShane, N.F. Rothfield et al., The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 25, 1271–1277 (1982)

    Article  CAS  PubMed  Google Scholar 

  21. C. Vitali, S. Bombardieri, R. Jonsson, H.M. Moutsopoulos, E.L. Alexander, S.E. Carsons et al., European Study Group on Classification Criteria for Sjogren’s Syndrome: classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann. Rheum. Dis. 61, 554–558 (2002)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Y. Murakami, J. Takamatsu, S. Sakane, K. Kuma, N. Ohsawa, Changes in thyroid volume in response to radioactive iodine for Graves’ hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome. J. Clin. Endocrinol. Metab. 81, 3257–3260 (1996)

    CAS  PubMed  Google Scholar 

  23. L. Wartofsky, K.D. Burman, Alterations in thyroid function in patients with systemic illness: the « Euthyroid Sick Syndrome». Endocr. Rev. 3, 164–217 (1982)

    Article  CAS  PubMed  Google Scholar 

  24. J. Levy, E.V. Barnett, N.S. MacDonald, J.R. Klinenberg, Altered immunoglobulin metabolism in systemic lupus erythematosus and rheumatoid arthritis. J. Clin. Invest. 49, 708–715 (1970)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. L.D. Xie, Y. Gao, M.R. Li, G.Z. Lu, X.H. Guo, Distribution of immunoglobulin G subclasses of anti-thyroid peroxidase antibody in sera from patients with Hashomoto’s thyroiditis with different thyroid functional status. Clin. Exp. Immunol. 154, 172–176 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. R. Jansson, P. Thompson, F. Clark, S. McLachlan, Association between thyroid microsomal antibodies of subclass IgG-1 and hypothyroidism in autoimmune postpartum thyroiditis. Clin. Exp. Immunol. 63, 80–86 (1986)

    PubMed Central  CAS  PubMed  Google Scholar 

  27. M. Salvi, G. Vannucchi, I. Campi, N. Currò, D. Dazzi, S. Simonetta, Treatment of Grave’s disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study. Eur. J. Endocrinol. 156, 33–40 (2007)

    Article  CAS  PubMed  Google Scholar 

  28. D. El Fassi, C. Nielsen, S. Bonnema, H. Hasselbalch, L. Hegedus, B lymphocyte depletion with the monoclonal antibody Rituximab in Grave’s disease: a controlled pilot study. J. Clin. Endocrinol. Metab. 92, 1769–1772 (2007)

    Article  PubMed  Google Scholar 

  29. Y. Nagayama, H. Mizuguchi, T. Hayakawa, M. Niwa, S.M. McLachlan, B. Rapoport et al., Prevention of autoantibody-mediated Graves’-like hyperthyroidism in mice with IL-4, a Th2 cytokine. J. Immunol. 170, 3522–3527 (2003)

    Article  CAS  PubMed  Google Scholar 

  30. A.P. Weetman, Autoimmune thyroid disease: propagation and progression. Eur. J. Endocrinol. 148, 1–9 (2003)

    Article  CAS  PubMed  Google Scholar 

  31. D. Kurosaka, K. Hirai, M. Nishioka, Y. Miyamoto, K. Yoshida, K. Noda et al., Clinical significance of serum levels of vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in patients with rheumatoid arthritis. J. Rheumatol. 37, 1121–1128 (2010)

    Article  CAS  PubMed  Google Scholar 

  32. E.M. Paleolog, Angiogenesis in rheumatoid arthritis. Arthritis Res. 4, 81–90 (2002)

    Article  Google Scholar 

  33. K. Sato, K. Yamazaki, K. Shizume, Y. Kanaji, T. Obara, K. Ohsumi et al., Stimulation by thyroid-stimulating hormone and Grave’s immunoglobulin G of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo. J. Clin. Invest. 96, 1295–1302 (1995)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. M. Iitaka, S. Miura, K. Yamanaka, S. Kawasaki, S. Kitahama, Y. Kawakami et al., Increased serum vascular endothelial growth factor levels and intrathyroidal vascular area in patients with Grave’s disease and Hashimotos’ thyroiditis. J. Clin. Endocrinol. Metab. 83, 3908–3912 (1998)

    CAS  PubMed  Google Scholar 

  35. A. Hauschild, H. Gogas, A. Tarhini, M.R. Middleton, A. Testori, B. Dreno et al., Practical guidelines for the management of interferon-α-2b side effects in patients receiving adjuvant treatment for melanoma. Cancer 112, 982–994 (2008)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Prof. Moutsopoulos HM for his contribution in reviewing this work.

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research work reported.

Author information

Authors and Affiliations

  1. Endocrine Unit, Department of Pathophysiology, National and Kapodistrian University of Athens, 75 Mikras Asias St, 11527, Athens, Greece

    Michail Kaklamanos, Dimitrios Thomas & Gregory Kaltsas

  2. Rheumatology Unit, Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece

    Dimitrios Pikazis

Authors
  1. Michail Kaklamanos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dimitrios Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dimitrios Pikazis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gregory Kaltsas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michail Kaklamanos.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaklamanos, M., Thomas, D., Pikazis, D. et al. Thyroid-specific changes following treatment with biological therapies in patients with rheumatic diseases. Endocrine 50, 146–153 (2015). https://doi.org/10.1007/s12020-015-0551-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-015-0551-8

Keywords

Search

Navigation