Clinical Rheumatology

, Volume 36, Issue 5, pp 1071–1076 | Cite as

The clinical importance of the thyroid nodules during anti-tumor necrosis factor therapy in patients with axial spondyloarthritis

  • Rana Terlemez
  • Kenan Akgün
  • Deniz Palamar
  • Sinan Boz
  • Hidayet Sarı
Original Article


The clinical importance of the thyroid nodules in patients with axial spondyloarthritis (ax-SpA) rests with the need to exclude thyroid malignancy. The aim of this study is to assess the risk of thyroid malignancy in ax-SpA patients receiving anti-TNF therapy. From September 2015 until December 2015, 70 patients diagnosed with ax-SpA were included in the research. Forty of the patients had received anti-TNF therapy, and 30 of the patients were anti-TNF naive. All cases were screened for the presence of nodules in the thyroid gland with ultrasound. Of the patients that received anti-TNF therapy, 15 (37.5%); and of the anti-TNF naive patients, 11 (36.7%) had thyroid nodule(s). Four patients from the anti-TNF group underwent fine needle aspiration biopsy of the nodules, and two of them were diagnosed with papillary thyroid carcinoma. None of the nodules in anti-TNF naive patients required biopsy. When compared to the normal population, the standardized incidence ratio (SIR) was found to be increased in both male (SIR 2.03, 95% CI 1.9 to 18) and female (SIR 2.7, 95% CI 2.6 to 24) cases. It is not yet established whether the development of cancer during the treatment process is the effect of the treatment or if it is a part of the natural course of the disease or if it is coincidental. We saw a mild increase in thyroid malignancies in ax-SpA patients who received anti-TNF therapy. Therefore, we believe that the thyroid gland should also be taken into consideration while screening for malignancy before anti-TNF therapy.


Anti-TNF agent Axial spondyloarthritis Thyroid malignancy 


Compliance with ethical standards

All procedures performed in study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.




  1. 1.
    Wajant H (2009) The role of TNF in cancer. Springer, BerlinCrossRefGoogle Scholar
  2. 2.
    Carswell E, Old LJ, Kassel RL et al (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci 72:3666–3670CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Rink L, Kirchner H (1996) Recent progress in the tumor necrosis factor-α field. Int Arch Allergy Immunol 111:199–209CrossRefPubMedGoogle Scholar
  4. 4.
    Dixon WG, Watson KD, Lunt M et al (2010) Influence of anti–tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology biologics register. Arthrit Care Res 62:755–763CrossRefGoogle Scholar
  5. 5.
    Bongartz T, Sutton AJ, Sweeting MJ et al (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295:2275–2285CrossRefPubMedGoogle Scholar
  6. 6.
    Askling J, Fored CM, Brandt L et al (2005) Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists. Ann Rheum Dis 64:1421–1426CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Shacter E, Weitzman SA (2002) Chronic inflammation and cancer. Oncology 16:217–226PubMedGoogle Scholar
  8. 8.
    Mellemkjaer L, Linet MS, Gridley G (1996) Rheumatoid arthritis and cancer risk. Eur J Cancer 32:1753–1757CrossRefGoogle Scholar
  9. 9.
    Feltelius N, Ekbom A, Blomqvist P (2003) Cancer incidence among patients with ankylosing spondylitis in Sweden 1965–95: a population based cohort study. Ann Rheum Dis 62:1185–1188CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hundahl SA, Fleming ID, Fremgen AM et al (1998) A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the US, 1985-1995. Cancer 83:2638–2648CrossRefPubMedGoogle Scholar
  11. 11.
    Aschebrook-Kilfoy B, Schechter RB, Shih YC et al (2013) The clinical and economic burden of a sustained increase in thyroid cancer incidence. Cancer Epidem Biomar Prev 22:1252–1259CrossRefGoogle Scholar
  12. 12.
    Gültekin M, Güledal B. (2014) Cancer statistics Turkey. Ministry of Health, Public Health Agency of TurkeyGoogle Scholar
  13. 13.
    Pham T, Bachelez H, Berthelot JM et al (2011) TNF alpha antagonist therapy and safety monitoring. Joint Bone Spine 78:15–185CrossRefPubMedGoogle Scholar
  14. 14.
    Haugen BR, Alexander EK, Bible KC et al (2015) 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid 26:1–133Google Scholar
  15. 15.
    Ward MM, Deodhar A, Akl EA et al (2016) American College of Rheumatology/spondylitis Association of America/Spondyloarthritis research and treatment network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis & Rheumatology 68:282–298CrossRefGoogle Scholar
  16. 16.
    Neta G, Rajaraman P, Berrington de Gonzalez A (2013) A prospective study of medical diagnostic radiography and risk of thyroid cancer. Am J Epidemiol 177:800–809CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Simpson AK, Whang PG, Jonisch A et al (2008) The radiation exposure associated with cervical and lumbar spine radiographs. J Spinal Disord 21:409–412CrossRefGoogle Scholar
  18. 18.
    Rybicki F, Nawfel RD, Judy PF et al (2002) Skin and thyroid dosimetry in cervical spine screening: two methods for evaluation and a comparison between a helical CT and radiographic trauma series. Am J Roentg 179:933–937CrossRefGoogle Scholar
  19. 19.
    Fantò M, Peragallo MS, Pietrosanti M et al (2015) Risk of malignancy in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis under immunosuppressive therapy: a single-center experience. Inter Emerg Med 11:31–40CrossRefGoogle Scholar
  20. 20.
    Tarhan F, Oruk G, Niflioglu O et al (2013) Thyroid involvement in ankylosing spondylitis and relationship of thyroid dysfunction with anti-TNF α treatment. Rheumatol Int 33:853–857Google Scholar
  21. 21.
    Emmungil H, Erdogan M, Kalfa M et al (2014) Autoimmune thyroid disease in ankylosing spondylitis. Clin Rheumatol 33:955–961CrossRefPubMedGoogle Scholar
  22. 22.
    Pascart T, Ducoulombier V, Roquette D et al (2014) Autoimmune thyroid disorders during anti-TNF alpha therapy: coincidence, paradoxical event or marker of immunogenicity? Joint Bone Spine 81:369–370Google Scholar
  23. 23.
    Ilhanli I, Guder N (2015) Papillary thyroid carcinoma during Etanercept therapy in a patient with psoriatic arthritis. Sci J Clin Med 4:93–95CrossRefGoogle Scholar
  24. 24.
    Golmia R, Scheinberg M (2010) Infliximab use and sequential occurrence of autoantibodies and neoplasia in a patient with spondyloarthritis. Rev Bras Reumatol 50:723–726CrossRefPubMedGoogle Scholar
  25. 25.
    Westhovens I, Lories RJ, Westhovens R et al (2013) Anti-TNF therapy and malignancy in spondyloarthritis in the Leuven spondyloarthritis biologics cohort (BIOSPAR). Clin Exp Rheumatol 32:71–76 126 CrossRefPubMedGoogle Scholar
  26. 26.
    Nannini C, Cantini F, Niccoli L et al (2009) Single-center series and systematic review of randomized controlled trials of malignancies in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis receiving anti–tumor necrosis α therapy: is there a need for more comprehensive screening procedures? Arthrit Care Res 61:801–812CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2017

Authors and Affiliations

  • Rana Terlemez
    • 1
  • Kenan Akgün
    • 1
  • Deniz Palamar
    • 1
  • Sinan Boz
    • 2
  • Hidayet Sarı
    • 1
  1. 1.Cerrahpasa Medical Faculty, Physical Medicine and Rehabilitation, RheumatologyIstanbul UniversityIstanbulTurkey
  2. 2.Cerrahpasa Medical Faculty, RadiologyIstanbul UniversityIstanbulTurkey

Personalised recommendations