Levothyroxine use and thyroid gland volumes in children with autoimmune thyroiditis: a systematic review and meta-analysis
Abstract
Background Autoimmune thyroiditis may manifest as overt hypothyroidism, subclinical hypothyroidism, euthyroidism, or hyperthyroidism in children. Although there is no consensus on treating euthyroidism and autoimmune thyroiditis in children, some studies have demonstrated the efficacy of levothyroxine in reducing thyroid volume, improving thyroid function, and stabilizing the immunological process.
Objective To determine the effect of levothyroxine on thyroid gland volume changes, thyroid function, and thyroid antibodies in euthyroid children with autoimmune thyroiditis.
Methods We performed a literature search of electronic databases (the Cochrane Library, MEDLINE, EBSCO, ProQuest, clinicaltrials.gov, and other sources, as well as a non-electronic search (searching journals and conference proceedings by hand) to identify studies of euthyroid children with autoimmune thyroiditis published by August 2018. Only English-language articles were included in the search (electronic and non-electronic). Randomized controlled trials that compared levothyroxine with a control (placebo or no treatment) in euthyroid children with autoimmune thyroiditis were selected. The outcome measures were thyroid volume changes, thyroid function, and thyroid antibody levels in euthyroid children with autoimmune thyroiditis. Two authors independently extracted the data, assessed the risk of bias, and analyzed the pooled data from the included studies using a random effects model. The same authors performed a sensitivity analysis.
Results We identified 57 studies. Of these, three studies, involving 97 subjects (51 subjects in an intervention group and 46 subjects in the control group) were selected for inclusion in a systematic review/meta-analysis. The meta-analysis revealed a significant difference in mean thyroid volume changes between the two groups (-1.10 SDs; 95%CI -1.56 to -0.64; P<0.0001; I2=6%). The mean difference in the thyroid-stimulating hormone (TSH) change of the two groups was -1.82 mU/L (95%CI -3.52 to -0.11; I2=87%; P=0.04). The standardized mean difference in free thyroxine (fT4) change of the two groups was 0.82 pmol/L (95%CI -1.14 to 2.78; I2=89%; P=0.41).
Conclusion In euthyroid children with autoimmune thyroiditis, levothyroxine treatment reduces the thyroid volume better. The TSH level change in the intervention group is better than those in the control group. Levothyroxine treatment did not significantly improve free T4.
References
2. Cappa M, Bizzarri C, Crea F. Autoimmune thyroid diseases in children. J Thyroid Res. 2010;2011:675703.
3. Iddah MA, Macharia BN. Autoimmune thyroid disorders. ISRN Endocrinol. 2013;2013:509764.
4. Pyzik A, Grywalska E, Matyjaszek-Matuszek B, Rolinski J. Immune disorders in Hashimoto’s thyroiditis: what do we know so far? J Immunol Res. 2015;2015:979167.
5. Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13:391-7.
6. Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med. 1996;335:99-107.
7. Gopalakrishnan S, Chugh PK, Chhillar M, Ambardar VK, Sahoo M, Sankar R. Goitrous autoimmune thyroiditis in a pediatric population: a longitudinal study. Pediatrics. 2008;122:e670-4.
8. Wasniewska M, Corrias A, Salerno M, Mussa A, Capalbo D, Messina MF, et al. Thyroid function patterns at Hashimoto’s thyroiditis presentation in childhood and adolescence are mainly conditioned by patients’ age. Horm Res Paediatr. 2012;78:232–6.
9. Akamizu T, Amino N, DeGroot LJ. Hashimoto’s thyroiditis. 2012. Available from: http://www.thyroidmanager.org/chapter/hashimotos-thyroiditis/.
10. Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014;3:76-94.
11. Pearce SHS, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, et al. 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J. 2013;2:215-28.
12. Aksoy DY, Kerimoglu U, Okur H, Canpinar H, Karaagaoglu E, Yetgin S, et al. Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto’s thyroiditis. Endocr J. 2005;52:337-43.
13. Gupta MK, Chiang T, Deodhar SD. Effect of thyroxine on immune response in C57B1/6J mice. Acta Endocrinol (Copenh). 1983;103:76–80.
14. Hegedüs L, Hansen JM, Feldt-Rasmussen U, Hansen BM, Høier-Madsen M. Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto’s thyroiditis. Clin Endocrinol. 1991;35:235-8.
15. Kordonouri O, Klinghammer A, Lang EB, Gruters-Klieslich A, Grabert M, Holl RW. Thyroid autoimmunity in children and adolescents with type 1 diabetes: a multicenter survey. Diabetes Care. 2002;25:1346-50.
16. Korzeniowska K, Jarosz-Chobot P, Szypowska A, Ramotowska A, Fendler W, Kalina-Faska B, et al. L-thyroxine stabilizes autoimmune inflammatory process in euthyroid nongoitrous children with Hashimoto’s thyroiditis and type 1 diabetes mellitus. J Clin Res Pediatr Endocrinol; 2013;5:240-4.
17. Padberg S, Heller K, Usadel KH, Schumm-Draeger PM. One-year prophylactic treatment of euthyroid Hashimoto’s thyroiditis patients with levothyroxine: is there a benefit? Thyroid. 2001;11:249-55.
18. Svensson J, Ericsson U, Nilsson P, Olsson C, Jonsson B, Lindberg B, et al. Levothyroxine treatment reduces thyroid size in children and adolescents with chronic autoimmune thyroiditis. J Clin Endocrinol Metab. 2006;91:1729-34.
19. Utiger RD. Commentary: Thyroxine therapy improves immunological abnormalities but does not alter thyroid size in euthyroid patients with Hashimoto’s disease. Clin Thyroidol. 2001;13:38. Available from: http://www.thyroid.org/
20. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100.
21. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
22. Deeks JJ, Higgins JP, Altman DG. Analysing data and undertaking meta-analyses. In: Higgins JP, Green S, editors. Cochrane handbook for systematic reviews of interventions. Hoboken: Wiley-Blackwell; 2011. p. 243-96.
23. Karges B, Muche R, Knerr I, Ertelt W, Wiesel T, Hub R, et al. Levothyroxine in euthyroid autoimmune thyroiditis and type 1 diabetes: a randomized, controlled trial. J Clin Endocrinol Metab. 2007;92:1647-52.
24. Dörr HG, Bettendorf M, Binder G, Karges B, Kneppo C, Schmidt H, et al. Levothyroxine treatment of euthyroid children with autoimmune Hashimoto thyroiditis: results of a multicenter, randomized, controlled trial. Horm Res Paediatr. 2015;84:266-74.
25. Scarpa V, Kousta E, Tertipi A, Vakaki M, Fotinou A, Petrou V, et al. Treatment with thyroxine reduces thyroid volume in euthyroid children and adolescents with chronic autoimmune thyroiditis. Horm Res Paediatr. 2010;73:61-7.
26. Özen S, Berk O, ?im?ek DG, Darcan S. Clinical course of Hashimoto’s thyroiditis and effects of levothyroxine therapy on the clinical course of the disease in children and adolescents. J Clin Res Pediatr Endocrinol. 2011;3:192-7.
27. Radetti G, Maselli M, Buzi F, Corrias A, Mussa A, Cambiaso P, et al. The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto’s thyroiditis and isolated hyperthyrotropinaemia: a 3-year follow-up. Clin Endocrinol. 2012;76:394-8.
28. Watt T, Groenvold M, Rasmussen AK, Bonnema SJ, Hegedüs L, Bjorner JB, et al. Quality of life in patients with benign thyroid disorders. A review. Eur J Endocrinol. 2006;154:501-10.
29. Bianchi GP, Zaccheroni V, Solaroli E, Vescini F, Cerutti R, Zoli M, et al. Health-related quality of life in patients with thyroid disorders. Qual Life Res. 2004;13:45-5.
30. Prummel MF, Wiersinga WM. Thyroid peroxidase autoantibodies in euthyroid subjects. Best Practice Res Clin Endocrinol Metab. 2005;19:1-15.
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Accepted 2019-08-01
Published 2019-08-01
