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INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS

Year 2025, Volume: 88 Issue: 4, 305 - 311, 30.10.2025
https://doi.org/10.26650/IUITFD.1654427

Abstract

Objective: Autoimmune thyroiditis (AIT) is a common endocrine disorder in paediatrics. Although genetic and environmental factors contribute to its development, infectious agents have also been considered as triggers. This study examined the potential role of Epstein–Barr virus (EBV), cytomegalovirus (CMV), parvovirus B19, human immunodeficiency virus (HIV), hepatitis C virus (HCV), and toxoplasma gondii in paediatric AIT.

Material and Methods: Forty nine patients (aged 1–18 years) who presented to the Paediatric Infectious Diseases and Paediatric Endocrinology outpatient clinics and were diagnosed with AIT within the previous six months were included in the study. Viral serology was routinely performed during the evaluation for lymphadenopathy in the Paediatric Infectious Diseases clinic. The diagnosis of AIT was based on positive thyroid autoantibodies (antiTG, anti TPO, and TSI), with or without thyroid dysfunction, and ultrasound f indings suggestive of thyroiditis. Clinical and laboratory data were retrospectively analysed using SPSS version 22.

Results: The median age was 13.1 years (IQR: 4.6). Of the patients, 14.3% (n=7) were male and 85.7% (n=42) were female. Four patients had Graves’ disease, and the rest had Hashimoto’s thyroiditis. Treatment was required in 53.1% (n=26). Parvovirus IgM was positive in three patients, EBV VCA IgM in four, and both in one. No significant differences in antiTPO or antiTG levels were found between the seropositive and seronegative patients. No cases had HIV or HCV, and 97% tested negative for Toxoplasma gondii antibodies.

Conclusion: Parvovirus B19 and EBV may contribute to AIT pathogenesis, but larger studies are needed to confirm these findings.

References

  • Ralli M, Angeletti D, Fiore M, D'Aguanno V, Lambiase A, Artico M, et al. Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Autoimmun Rev 2020;19(10):102649. google scholar
  • Fallahi P, Ferrari SM, Vita R, Benvenga S, Antonelli A. The role of human parvovirus B19 and hepatitis C virus in the development of thyroid disorders. Rev Endocr Metab Disord 2016;17(4):529-35. google scholar
  • Vejlgaard TB, Nielsen OB. Subacute thyroiditis in Parvovirus B19 infection. Ugeskr Laeger 1994;156(41):6039-40. google scholar
  • Desailloud R, Hober D. Viruses and thyroiditis: An update. Virol J 2009;6:5. google scholar
  • Mori K, Munakata Y, Saito T, Tani J, Nakagawa Y, Hoshikawa S, et al. Intrathyroidal persistence of human parvovirus B19 DNA in a patient with Hashimoto's thyroiditis. J Infect 2007;55(2):29-31. google scholar
  • Lehmann HW, Lutterbüse N, Plentz A, Akkurt I, Albers N, Hauffa BP, et al. Association of parvovirus B19 infection and Hashimoto's thyroiditis in children. Viral Immunol 2008;21(3):379-83. google scholar
  • Radon K, Dressel H, Windstetter D, Reichert J, Schmid M, Nowak D. Toxoplasma gondii infection, atopy and autoimmune disease. Eur J Med Res 2003;8(4):147-53. google scholar
  • Wasserman EE, Nelson K, Rose NR, Rhode C, Pillion JP, Seaberg E, et al. Infection and thyroid autoimmunity: A seroepidemiologic study of TPOaAb. Autoimmunity 2009;42(5):439-46. google scholar
  • Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44(235):291-303. google scholar
  • Neyzi O, Bundak R, Gökçay G, Günöz H, Furman A, Darendeliler F, et al. Reference values for weight, height, head circumference, and Body Mass Index in Turkish children. J Clin Res Pediatr Endocrinol 2015;7(4):280-93. google scholar
  • Chiovato L, Lapi P, Fiore E, Tonacchera M, Pinchera A. Thyroid autoimmunity and female gender. J Endocrinol Invest 1993;16(5):384-91. google scholar
  • Ansar Ahmed S, Penhale WJ, Talal N. Sex hormones, immune responses, and autoim- mune diseases. Mechanisms of sex hormone action. Am J Pathol 1985;121(3):531-51. google scholar
  • Ozcelik T, Uz E, Akyerli CB, Bagislar S, Mustafa CA, Gursoy A, et al. Evidence from autoimmune thyroiditis of skewed X- chromosome inactivation in female predisposition to autoimmunity. Eur J Hum Genet 2006;14(6):791-7. google scholar
  • de Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child. 2009;94(1):33-7. google scholar
  • Demirbilek H, Kandemir N, Gonc EN, Ozon A, Alikasifoglu A, Yordam N. Hashimoto’s thyroiditis in children and adolescents: a retrospective study on clinical, epidemiological and laboratory properties of the disease. J Pediatr Endocrinol Metab 2007;20(11):1199-1205 google scholar
  • Durak C, Yavas Abalı Z, Köksal MO, Beka H, Ağaçfidan A, Oğuz F, et al. The role of Parvovirus-B19 in autoimmune thyroiditis in adolescent children. Online Turk J Health Sci 2022;7(3):493-8. google scholar
  • Seishima M, Shibuya Y, Suzuki S. Hyperthyroidism associated with human parvovirus B19 infection. Clin Exp Dermatol 2009;34(7):439-40. google scholar
  • Janegova A, Janega P, Rychly B, Kuracinova K, Babal P.The role of Epstein- Barr virus infection in the development of autoimmune thyroid diseases. Endokrynol Pol 2015;66(2):132-6. google scholar
  • Thomas D, Karachaliou F, Kallergi K, Vlachopapadopoulou E, Antonaki G, Chatzimarkou F, et al. Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease. Endocrine 2008;33(2):171-5. google scholar
  • Khoury EL, Pereira L, Greenspan FS. Induction of HLA-DR expression on thyroid follicular cells by cytomegalovirus infection in vitro. Evidence for a dual mechanism of induction. Am J Pathol 1991;138(5):1209-23. google scholar
  • Shapira Y, Agmon-Levin N, Selmi C, Petríková J, Barzilai O, Ram M, et al. Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun 2012;39(1-2):112-6. google scholar
  • Alvarado-Esquivel C, Ramos-Nevarez A, Guido-Arreola CA, Cerrillo-Soto SM, Pérez-Álamos AR, Estrada-Martínez S, et al. Association between toxoplasma gondii infection and thyroid dysfunction: a case-control seroprevalence study. BMC Infect Dis 2019;19(1):826. google scholar
  • Hammerstad SS, Blackard JT, Lombardi A, Owen, RP, Concepcion E, Yi Z, et al. Hepatitis C virus infection of human thyrocytes: Metabolic, hormonal, and immunological implications. J Clin Endocrinol Metab 2019;105(4):1157-68. google scholar

ÇOCUKLAR VE ERGENLERDE OTOİMMÜN TİROİDİTİN PATOGENEZİNDE ENFEKSİYÖZ ETKENLERİN TETİKLEYİCİ ROLÜNÜN ARAŞTIRILMASI

Year 2025, Volume: 88 Issue: 4, 305 - 311, 30.10.2025
https://doi.org/10.26650/IUITFD.1654427

Abstract

Amaç: Otoimmün tiroidit (AIT), pediatrik endokrinolojide yaygın görülen bir hastalıktır. Genetik ve çevresel faktörlerin yanı sıra enfeksiyöz ajanların da hastalığın gelişiminde rol oynayabileceği öne sürülmüştür. Bu çalışma, EpsteinBarr virüsü (EBV), sitomegalovirüs (CMV), Parvovirüs B19, HIV, HCV ve Toxoplasma gondii’nin pediatrik AIT’deki potansiyel rolünü incelemektedir.

Gereç ve Yöntemler: Önceki altı ay içinde otoimmün tiroidit (AIT) tanısı almış, Çocuk Endokrinoloji ve Çocuk Enfeksiyon Hastalıkları polikliniklerine başvuran 1–18 yaş aralığındaki 49 hasta çalışmaya dahil edildi. Viral seroloji, Çocuk Enfeksiyon Hastalıkları polikliniğinde lenfadenopati değerlendirmesi sırasında rutin olarak yapılmıştı. AIT tanısı, tiroid fonksiyon bozukluğu olsun ya da olmasın, pozitif tiroid otoantikorları (antiTG, antiTPO ve/veya TSI) ve/veya tiroidite işaret eden ultrasonografi bulgularına (heterojenite veya psödonodüler görünüm) dayanılarak konuldu. Klinik ve laboratuvar verileri retrospektif olarak toplanarak SPSS sürüm 22 kullanılarak analiz edildi.

Bulgular: Hastaların medyan yaşı 13,1 yıl (IQR: 4,6) idi. Hastaların %14,3’ü (n=7) erkek, %85,7’si (n=42) kızdı. Dört hastada Graves hastalığı, geri kalanında Hashimoto tiroiditi vardı. Hastaların %53,1’i (n=26) tedavi gerektirdi. Üç hastada Parvovirüs IgM, dört hastada EBV VCA IgM ve bir hastada her ikisi de pozitif bulundu. Seropozitif ve seronegatif hastalar arasında antiTPO veya anti TG seviyeleri açısından anlamlı fark saptanmadı. Hiçbir hastada HIV veya HCV saptanmazken, hastaların %97’si Toxoplasma gondii antikorları açısından negatifti.

Sonuç: Parvovirüs B19 ve EBV, AIT patogenezine katkıda bulunabilir, ancak bu bulguların doğrulanması için daha geniş çaplı çalış malara ihtiyaç vardır.

References

  • Ralli M, Angeletti D, Fiore M, D'Aguanno V, Lambiase A, Artico M, et al. Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Autoimmun Rev 2020;19(10):102649. google scholar
  • Fallahi P, Ferrari SM, Vita R, Benvenga S, Antonelli A. The role of human parvovirus B19 and hepatitis C virus in the development of thyroid disorders. Rev Endocr Metab Disord 2016;17(4):529-35. google scholar
  • Vejlgaard TB, Nielsen OB. Subacute thyroiditis in Parvovirus B19 infection. Ugeskr Laeger 1994;156(41):6039-40. google scholar
  • Desailloud R, Hober D. Viruses and thyroiditis: An update. Virol J 2009;6:5. google scholar
  • Mori K, Munakata Y, Saito T, Tani J, Nakagawa Y, Hoshikawa S, et al. Intrathyroidal persistence of human parvovirus B19 DNA in a patient with Hashimoto's thyroiditis. J Infect 2007;55(2):29-31. google scholar
  • Lehmann HW, Lutterbüse N, Plentz A, Akkurt I, Albers N, Hauffa BP, et al. Association of parvovirus B19 infection and Hashimoto's thyroiditis in children. Viral Immunol 2008;21(3):379-83. google scholar
  • Radon K, Dressel H, Windstetter D, Reichert J, Schmid M, Nowak D. Toxoplasma gondii infection, atopy and autoimmune disease. Eur J Med Res 2003;8(4):147-53. google scholar
  • Wasserman EE, Nelson K, Rose NR, Rhode C, Pillion JP, Seaberg E, et al. Infection and thyroid autoimmunity: A seroepidemiologic study of TPOaAb. Autoimmunity 2009;42(5):439-46. google scholar
  • Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44(235):291-303. google scholar
  • Neyzi O, Bundak R, Gökçay G, Günöz H, Furman A, Darendeliler F, et al. Reference values for weight, height, head circumference, and Body Mass Index in Turkish children. J Clin Res Pediatr Endocrinol 2015;7(4):280-93. google scholar
  • Chiovato L, Lapi P, Fiore E, Tonacchera M, Pinchera A. Thyroid autoimmunity and female gender. J Endocrinol Invest 1993;16(5):384-91. google scholar
  • Ansar Ahmed S, Penhale WJ, Talal N. Sex hormones, immune responses, and autoim- mune diseases. Mechanisms of sex hormone action. Am J Pathol 1985;121(3):531-51. google scholar
  • Ozcelik T, Uz E, Akyerli CB, Bagislar S, Mustafa CA, Gursoy A, et al. Evidence from autoimmune thyroiditis of skewed X- chromosome inactivation in female predisposition to autoimmunity. Eur J Hum Genet 2006;14(6):791-7. google scholar
  • de Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child. 2009;94(1):33-7. google scholar
  • Demirbilek H, Kandemir N, Gonc EN, Ozon A, Alikasifoglu A, Yordam N. Hashimoto’s thyroiditis in children and adolescents: a retrospective study on clinical, epidemiological and laboratory properties of the disease. J Pediatr Endocrinol Metab 2007;20(11):1199-1205 google scholar
  • Durak C, Yavas Abalı Z, Köksal MO, Beka H, Ağaçfidan A, Oğuz F, et al. The role of Parvovirus-B19 in autoimmune thyroiditis in adolescent children. Online Turk J Health Sci 2022;7(3):493-8. google scholar
  • Seishima M, Shibuya Y, Suzuki S. Hyperthyroidism associated with human parvovirus B19 infection. Clin Exp Dermatol 2009;34(7):439-40. google scholar
  • Janegova A, Janega P, Rychly B, Kuracinova K, Babal P.The role of Epstein- Barr virus infection in the development of autoimmune thyroid diseases. Endokrynol Pol 2015;66(2):132-6. google scholar
  • Thomas D, Karachaliou F, Kallergi K, Vlachopapadopoulou E, Antonaki G, Chatzimarkou F, et al. Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease. Endocrine 2008;33(2):171-5. google scholar
  • Khoury EL, Pereira L, Greenspan FS. Induction of HLA-DR expression on thyroid follicular cells by cytomegalovirus infection in vitro. Evidence for a dual mechanism of induction. Am J Pathol 1991;138(5):1209-23. google scholar
  • Shapira Y, Agmon-Levin N, Selmi C, Petríková J, Barzilai O, Ram M, et al. Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun 2012;39(1-2):112-6. google scholar
  • Alvarado-Esquivel C, Ramos-Nevarez A, Guido-Arreola CA, Cerrillo-Soto SM, Pérez-Álamos AR, Estrada-Martínez S, et al. Association between toxoplasma gondii infection and thyroid dysfunction: a case-control seroprevalence study. BMC Infect Dis 2019;19(1):826. google scholar
  • Hammerstad SS, Blackard JT, Lombardi A, Owen, RP, Concepcion E, Yi Z, et al. Hepatitis C virus infection of human thyrocytes: Metabolic, hormonal, and immunological implications. J Clin Endocrinol Metab 2019;105(4):1157-68. google scholar
There are 23 citations in total.

Details

Primary Language English
Subjects Pediatric Endocrinology
Journal Section RESEARCH
Authors

Esin Karakılıç Özturan 0000-0002-8842-1752

Ceren Çetin 0000-0001-6423-7523

Ayşe Karaaslan 0000-0003-4289-3321

Yasemin Akın 0000-0002-7618-7778

Publication Date October 30, 2025
Submission Date March 10, 2025
Acceptance Date July 18, 2025
Published in Issue Year 2025 Volume: 88 Issue: 4

Cite

APA Karakılıç Özturan, E., Çetin, C., Karaaslan, A., Akın, Y. (2025). INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS. Journal of Istanbul Faculty of Medicine, 88(4), 305-311. https://doi.org/10.26650/IUITFD.1654427
AMA Karakılıç Özturan E, Çetin C, Karaaslan A, Akın Y. INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS. İst Tıp Fak Derg. October 2025;88(4):305-311. doi:10.26650/IUITFD.1654427
Chicago Karakılıç Özturan, Esin, Ceren Çetin, Ayşe Karaaslan, and Yasemin Akın. “INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS”. Journal of Istanbul Faculty of Medicine 88, no. 4 (October 2025): 305-11. https://doi.org/10.26650/IUITFD.1654427.
EndNote Karakılıç Özturan E, Çetin C, Karaaslan A, Akın Y (October 1, 2025) INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS. Journal of Istanbul Faculty of Medicine 88 4 305–311.
IEEE E. Karakılıç Özturan, C. Çetin, A. Karaaslan, and Y. Akın, “INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS”, İst Tıp Fak Derg, vol. 88, no. 4, pp. 305–311, 2025, doi: 10.26650/IUITFD.1654427.
ISNAD Karakılıç Özturan, Esin et al. “INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS”. Journal of Istanbul Faculty of Medicine 88/4 (October2025), 305-311. https://doi.org/10.26650/IUITFD.1654427.
JAMA Karakılıç Özturan E, Çetin C, Karaaslan A, Akın Y. INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS. İst Tıp Fak Derg. 2025;88:305–311.
MLA Karakılıç Özturan, Esin et al. “INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS”. Journal of Istanbul Faculty of Medicine, vol. 88, no. 4, 2025, pp. 305-11, doi:10.26650/IUITFD.1654427.
Vancouver Karakılıç Özturan E, Çetin C, Karaaslan A, Akın Y. INVESTIGATION OF THE TRIGGERING ROLE OF INFECTIOUS AGENTS IN THE PATHOGENESIS OF AUTOIMMUNE THYROIDITIS IN CHILDREN AND ADOLESCENTS. İst Tıp Fak Derg. 2025;88(4):305-11.

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