Skip to main content
SpringerLink
Log in

Long-term outcome of treatments for Graves disease in the children and adolescent population

  • Meta- Analysis
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Background

Several studies were conducted over the years to find a significant association between non-surgical therapies such as Antithyroid Drug (ATD) Therapy and Radio-iodo therapy (RIT) with Graves’ disease (GD) remission and relapse. However, these investigations did not have a specific focus on the age category of children and adolescents. Hence, this Research is performed to assess the association of non-surgical therapy (ATD and RIT) with Graves’ disease (GD) remission and relapse in the children and adolescent population.

Design

A systematic review and meta-analysis of observational studies and clinical trials were carried out.

Methods

A systematic search of PubMed, EMBASE, and SCOPUS from their inception till April 2022 was performed for studies stating an association between ATD therapy and GD remission and relapse in participants 1–17 years old. The random-effects model was used in the meta-analysis to provide a pooled proportion of both primary outcomes. The quality and each study were assessed using the Newcastle Ottawa Scale (NOS).

Result

From 6195 studies searched from the databases, only 16 relevant articles remained after a detailed evaluation. These studies, having a total of 2557 patients aged 5–17 years, were involved in the analysis with a pooled estimate showing a significant association of ATD therapy with GD remission (Estimate: 0.400, 95% Confidence interval: 0.265–0.535; I^2 = 98.16%) and with GD relapse (Estimate: 0.359, 95% Confidence interval: 0.257–0.461; I^2 = 98.26%). Subgroup analyses were conducted to assess the remission rate of different therapies suggesting that antithyroid drugs play a significant role in the remission of the patients. All included studies were classified as moderate quality.

Conclusion

Following meta-analysis suggested that the ATD used in the analysis is effective in remitting GD in the children and adolescents population. Nevertheless, long-term RIT therapy and thyroidectomy leads to hypothyroidism. Still, large-sample, and high-quality studies targeting ATDs’ use in children and adolescents with long-term surveillance of prognosis are needed.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. L. Bartalena, Diagnosis and management of Graves disease: a global overview. Nat. Rev. Endocrinol. 9(12), 724–734 (2013)

    Article  CAS  PubMed  Google Scholar 

  2. T.J. Smith, L. Hegedüs, Graves’ disease. N. Engl. J. Med. 375(16), 1552–1565 (2016)

    Article  PubMed  Google Scholar 

  3. J. Léger, I. Oliver, D. Rodrigue, A.S. Lambert, R. Coutant, Graves’ disease in children. Ann. Endocrinol. 79(6), 647–655 (2018)

    Article  Google Scholar 

  4. W. Yu, N. Wu, L. Li, J. Wang, H. OuYang, H. Shen, Side effects of ptu and mmi in the treatment of hyperthyroidism: a systematic review and meta-analysis. Endocr. Pr. J. Am. Coll. Endocrinol. Am. Assoc. Clin. Endocrinol. 26(2), 207–217 (2020)

    Google Scholar 

  5. P.N. Taylor, B. Vaidya, Side effects of anti-thyroid drugs and their impact on the choice of treatment for thyrotoxicosis in pregnancy. Eur. Thyroid J. 1(3), 176–185 (2012). https://doi.org/10.1159/000342920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. The EQUATOR Network. https://www.equator-network.org/reporting-guidelines/prisma/

  7. Estimating the mean and variance from the median, range, and the size of a sample. BMC Medical Res Methodol. 2022. https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/1471-2288-5-13

  8. B.M. Lippe, E.M. Landaw, S.A. Kaplan, Hyperthyroidism in children treated with long term medical therapy: twenty-five percent remission every two years. J. Clin. Endocrinol. Metab. 64(6), 1241–1245 (1987)

    Article  CAS  PubMed  Google Scholar 

  9. H. Ohye, A. Minagawa, J.Y. Noh, K. Mukasa, Y. Kunii, N. Watanabe et al. Antithyroid drug treatment for graves’ disease in children: a long-term retrospective study at a single institution. Thyroid J. Am. Thyroid Assoc. 24(2), 200–207 (2014)

    Article  CAS  Google Scholar 

  10. F. Azizi, M. Takyar, E. Madreseh, A. Amouzegar, Long-term methimazole therapy in juvenile Graves’ disease: a randomized trial. Pediatrics 143(5), e20183034 (2019)

    Article  PubMed  Google Scholar 

  11. T. Mizokami, K. Hamada, T. Maruta, K. Higashi, J. Tajiri, Long-term outcomes of radioiodine therapy for Juvenile Graves disease with emphasis on subsequently detected thyroid nodules: a single institution experience from Japan. Endocr Pract 26(7), 729–737 (2020)

    Article  PubMed  Google Scholar 

  12. R. Barrio, M. López-Capapé, I. Martinez-Badás, A. Carrillo, J.C. Moreno, M. Alonso, Graves’ disease in children and adolescents: response to long-term treatment. Acta Paediatr. Oslo Nor. 1992 94(11), 1583–1589 (2005)

    Google Scholar 

  13. H. Sato, M. Minagawa, N. Sasaki, S. Sugihara, I. Kazukawa, K. Minamitani et al. Comparison of methimazole and propylthiouracil in the management of children and adolescents with Graves’ disease: efficacy and adverse reactions during initial treatment and long-term outcome. J. Pediatr. Endocrinol. Metab. JPEM 24(5–6), 257–263 (2011)

    CAS  PubMed  Google Scholar 

  14. F. Kaguelidou, J.C. Carel, J. Léger, Graves’ disease in childhood: advances in management with antithyroid drug therapy. Horm. Res 71(6), 310–317 (2009)

    CAS  PubMed  Google Scholar 

  15. A.T. Bossowski, V. Reddy, L.A. Perry, L.B. Johnston, K. Banerjee, J.C. Blair et al. Clinical and endocrine features and long-term outcome of Graves’ disease in early childhood. J. Endocrinol. Invest 30(5), 388–392 (2007)

    Article  CAS  PubMed  Google Scholar 

  16. E. Bayramoğlu, S. Elmaogulları, E. Sagsak, Z. Aycan, Evaluation of long-term follow-up and methimazole therapy outcomes of pediatric Graves’ disease: a single-center experience. J. Pediatr. Endocrinol. Metab. JPEM 32(4), 341–346 (2019)

    Article  PubMed  Google Scholar 

  17. T.D. Cheetham, P. Wraight, I.A. Hughes, N.D. Barnes, Radioiodine treatment of Graves’ disease in young people. Horm. Res 49(6), 258–262 (1998)

    CAS  PubMed  Google Scholar 

  18. A.N. Cury, V.T. Meira, O. Monte, M. Marone, N.M. Scalissi, C. Kochi et al. Clinical experience with radioactive iodine in the treatment of childhood and adolescent Graves’ disease. Endocr. Connect 2(1), 32–37 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  19. Y.T. Chiang, W.H. Ting, C.Y. Huang, S.K. Huang, C.I. Chan, B.W. Cheng et al. Long-term outcomes of graves disease in children treated with anti-thyroid drugs. Pediatr. Neonatol. 61(3), 311–317 (2020)

    Article  PubMed  Google Scholar 

  20. N. Nakatake, S. Fukata, J. Tajiri, Prediction of post-treatment hypothyroidism using changes in thyroid volume after radioactive iodine therapy in adolescent patients with Graves’ disease. Int J. Pediatr. Endocrinol. 2011(1), 14 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  21. S. Rabon, A.M. Burton, P.C. White, Graves’ disease in children: long-term outcomes of medical therapy. Clin. Endocrinol. 85(4), 632–635 (2016)

    Article  CAS  Google Scholar 

  22. O. Marques, A. Antunes, M.J. Oliveira, Treatment of Graves’ disease in children: the Portuguese experience. Endocrinol. Diabetes Nutr. 65(3), 143–149 (2018)

    Article  Google Scholar 

  23. Ottawa Hospital Research Institute. 2022. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

  24. J.R. Reid, S.F. Wheeler, Hyperthyroidism: diagnosis and treatment. Am. Fam. Physician 72(4), 623–630 (2005)

    PubMed  Google Scholar 

  25. S. De Leo, S.Y. Lee, L.E. Braverman, Hyperthyroidism. Lancet Lond. Engl. 388(10047), 906–918 (2016)

    Article  Google Scholar 

  26. V. Sundaresh, J.P. Brito, Z. Wang, L.J. Prokop, M.N. Stan, M.H. Murad et al. Comparative effectiveness of therapies for Graves’ hyperthyroidism: a systematic review and network meta-analysis. J. Clin. Endocrinol. Metab. 98(9), 3671–3677 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. C.F. Mooij, T.D. Cheetham, F.A. Verburg, A. Eckstein, S.H. Pearce, J. Léger et al. 2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease. Eur. Thyroid J. 11(1), e210073 (2022)

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine and Surgery, Dow University of Health and Sciences, Karachi, Pakistan

    Mohammad Jawwad, Syed Arsalan Ahmed, Syed Muhammad Mehdi Zaidi, Syed Ashad Ahmed Fatmi, Muhammad Hasan Ashraf, Shozab Naeem & Muhammad Shuraim Chola

Authors
  1. Mohammad Jawwad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Syed Arsalan Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Syed Muhammad Mehdi Zaidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Syed Ashad Ahmed Fatmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Muhammad Hasan Ashraf
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shozab Naeem
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Muhammad Shuraim Chola
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Jawwad.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jawwad, M., Ahmed, S.A., Zaidi, S.M.M. et al. Long-term outcome of treatments for Graves disease in the children and adolescent population. Endocrine 81, 223–230 (2023). https://doi.org/10.1007/s12020-023-03371-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-023-03371-1

Keywords

Search

Navigation