Home Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM)
Article
Licensed
Unlicensed Requires Authentication

Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM)

  • Feneli Karachaliou EMAIL logo , Nikitas Skarakis , Evangelia Bountouvi , Theodora Spyropoulou , Eleni Tsintzou , Aristofania Simatou and Vassiliki Papaevangelou
Published/Copyright: November 12, 2020
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 33 Issue 12

Abstract

Objectives

Treatment of children with Hashimoto thyroiditis (HT) and particularly of those with coexistent diabetes mellitus type 1 (TIDM) and normal/mildly elevated serum TSH is controversial. The aim of the study was to evaluate the natural course of HT in children with TIDM compared with children with no other coexistent autoimmunity and investigate for possible predictive factors of thyroid function deterioration.

Methods

Data from 96 children with HT, 32 with T1DM (23 girls, nine boys) mean (sd) age: 10.6 (2.3) years, and 64 age and sex-matched without T1DΜ (46 girls, 18 boys), mean (sd) age: 10.2 (2.9) years were evaluated retrospectively. They all had fT4 and TSH values within normal ranges and available data for at least three years’ follow-up.

Results

During the follow-up period, 11 children (34.4%) with TIDM exhibited subclinical hypothyroidism and two children (6.2%) progressed to overt hypothyroidism compared to 12 (18.8%) and two (3.1%) among children without TIDM, respectively. Among children with HT, a higher percentage (40.6%) of children with T1DM progressed to subclinical or overt hypothyroidism, compared with children (21.9%) with similar characteristics but without TIDM or other coexistent autoimmunity.

Conclusions

The annual conversion rate from euthyroidism to hypothyroidism in children with T1DM was significantly higher compared to sex and age-matched children without TIDM. Prospective randomized trials are needed to support the view of an earlier intervention therapy even in milder degrees of thyroid failure in these children.

Keywords: children; Hashimoto thyroiditis; treatment; type 1 diabetes
Corresponding author: Feneli Karachaliou, PhD, Pediatric Endocrinologist, Unit of Pediatric Endocrinology and Diabetes, 3rd University Pediatric Clinic,Attikon Hospital, 1 Rimini Rd, Chaidari, Athens, Greece, Phone:+30 6936205474; +30 2105832046, Fax: +30 2105832229, E-mail:

  1. Research funding: This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

  2. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Competing interests: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies, is in accordance with the tenets of the Helsinki Declaration (as revised in 2013).

References

1. Elizabeth, N, Pearce, MD, Alan, P, Farwell, MD, Lewis, E, Braverman, MD. Thyroiditis. N Engl J Med 2003;348:2646–55. https://doi.org/10.1056/NEJMra021194.Search in Google Scholar PubMed

2. Kaloumenou, I, Mastorakos, G, Alevizaki, M, Duntas, LH, Mantzou, E, Ladopoulos, C, et al.. Thyroid volume and echo structure in schoolchildren living in an iodine-replete area: relation to age, pubertal stage, and body mass index. Thyroid 2008;18:747–54. https://doi.org/10.1089/thy.2007.0370.Search in Google Scholar PubMed

3. Hunter, I, Greene, SA, MacDonald, TM, Morris, AD. Prevalence and aetiology of hypothyroidism in the young. Arch Dis Child 2000;83:207–10. https://doi.org/10.1136/adc.83.3.207.Search in Google Scholar PubMed PubMed Central

4. 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;94:33–7. https://doi.org/10.1136/adc.2007.134841.Search in Google Scholar PubMed

5. Skarpa, V, Kappaousta, E, Tertipi, A, Anyfandakis, K, Vakaki, M, Dolianiti, M, et al.. Epidemiological characteristics of children with autoimmune thyroid disease. Hormones (Basel) 2011;10:207–14. https://doi.org/10.14310/horm.2002.1310.Search in Google Scholar PubMed

6. De Luca, F, Santucci, S, Corica, D, Pitrolo, E, Romeo, M, Aversa, T. Hashimoto’s thyroiditis in childhood: presentation modes and evolution over time. Ital J Pediatr 2013;39:8. https://doi.org/10.1186/1824-7288-39-8.Search in Google Scholar PubMed PubMed Central

7. Zak, T, Noczyńska, A, Wasikowa, R, Zaleska-Dorobisz, U, Golenko, A. Chronic autoimmune thyroid disease in children and adolescents in the years 1999–2004 in Lower Silesia. Poland 2005;4:45–8. https://doi.org/10.14310/horm.2002.11142.Search in Google Scholar PubMed

8. Zen, S, Berk, O, Simsek, 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. https://doi.org/10.4274/jcrpe.425.Search in Google Scholar PubMed PubMed Central

9. 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. https://doi.org/10.1159/000343815.Search in Google Scholar PubMed

10. Chaudhary, V, Bano, S. Thyroid ultrasound. Indian J Endocrinol Metab 2013;17:219–27. https://doi.org/10.4103/2230-8210.109667.Search in Google Scholar PubMed PubMed Central

11. Radetti, G, Paganini, C, Gentili, L, Bernasconi, S, Betterle, C, Borkenstein, M, et al.. Frequency of Hashimoto’s thyroiditis in children with type 1 diabetes mellitus. Acta Diabetol 1995;32:121–4. https://doi.org/10.1007/bf00569570.Search in Google Scholar

12. Holl, RW, Bohm, B, Loos, U, Grabert, M, Heinze, E, Homoki, J. Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Effect of age, gender and HLA type. Horm Res 1999;52:113–8. https://doi.org/10.1159/000023446.Search in Google Scholar PubMed

13. Kordonouri, O, Klinghammer, A, Lang, EB, Gruters-Kieslich, A, Grabert, M, Holl, RW. Thyroid autoimmunity in children and adolescents with type 1 diabetes: a multicenter survey. Diabetes Care 2002;25:1346–50. https://doi.org/10.2337/diacare.25.8.1346.Search in Google Scholar PubMed

14. Radetti, G, Gottardi, E, Bona, G, Corrias, A, Salardi, S, Loche, S. The natural history of euthyroid Hashimoto’s thyroiditis in children. J Pediatr 2006;149:827–32. https://doi.org/10.1016/j.jpeds.2006.08.045.Search in Google Scholar PubMed

15. Aversa, T, Corrias, A, Salerno, M, Tessaris, D, Di Mase, R, Valenzise, M, et al.. Five year prospective evaluation of thyroid function test evolution in children with Hashimoto’s thyroiditis presenting with either euthyroidism or subclinical hypothyroidism. Thyroid 2016;26:1450–6. https://doi.org/10.1089/thy.2016.0080.Search in Google Scholar PubMed

16. Kordonouri, O, Hartmann, R, Wilms, M, Deiss, D, Gruters-Kieslichet, A. Natural course of autoimmune thyroiditis in type 1 diabetes: association with gender, age, diabetes duration and puberty. Arch Dis Child 2005;90:411–4. https://doi.org/10.1136/adc.2004.056424.Search in Google Scholar PubMed PubMed Central

17. Orzan, A, Novaca, C, Mihua, M, Ionescu Tirgoviste, C, Balgradean, M. Type 1 diabetes and thyroid autoimmunity in children. MAEDICA – J Clin Med 2016;11:308–12. PMID: 28828047.Search in Google Scholar

18. Franzese, A, Buono, P, Mascolo, M, Leo, AL, Valerio, G. Thyroid autoimmunity starting during the course of type 1 diabetes denotes a subgroup of children with more severe diabetes. Diabetes Care 2000;23:1201–2. https://doi.org/10.2337/diacare.23.8.1201.Search in Google Scholar PubMed

19. Mohn, A, Di Michele, S, Di Luzio, R, Tumini, S, Chiarelli, F. The effect of subclinical hypothyroidism on metabolic control in children and adolescents with Type 1diabetes mellitus. Diabet Med 2002;19:70–3. https://doi.org/10.1046/j.1464-5491.2002.00635.x.Search in Google Scholar PubMed

20. Kakleas, K, Paschali, E, Kefalas, N, Fotinou, A, Kanariou, M, Karayianni, C, et al.. Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Ups J Med Sci 2009;114:214–20. https://doi.org/10.3109/03009730903276381.Search in Google Scholar PubMed PubMed Central

21. Zimmermann, MB, Hess, SY, Molinari, L, De Benoist, B, Delange, F, Braverman, L, et al.. New reference values for thyroid volume by ultrasound in iodine-sufficient school children: a World Health Organization/Nutrition for Health and development iodine deficiency study group report. Am J Clin Nutr 2004;79:231–7. https://doi.org/10.1093/ajcn/79.2.231.Search in Google Scholar PubMed

22. Vanderpump, MP, Tunbridge, WM. Epidemiology and prevention of clinical and subclinical hypothyroidism. Thyroid 2002;12:839–47. https://doi.org/10.1089/105072502761016458.Search in Google Scholar PubMed

23. Moore, DC. Natural course of “subclinical” hypothyroidism in childhood and adolescence. Arch Pediatr Adolesc Med 1996;150:293–7. https://doi.org/10.1001/archpedi.1996.02170280063012.Search in Google Scholar PubMed

24. Jaruratanasirikul, S, Leethanaporn, K, Khuntigij, P, Sriplung, H. The clinical course of Hashimoto’s thyroiditis in children and adolescents: 6-year longitudinal follow-up. J Pediatr Endocrinol Metab 2001;14:177–84. https://doi.org/10.1515/jpem.2001.14.2.177.Search in Google Scholar PubMed

25. Bona, G, Prodam, F, Monzani, A. Subclinical hypothyroidism in children: natural history and when to treat. J Clin Res Pediatr Endocrinol 2013;5:23–8. https://doi.org/10.4274/jcrpe.851.Search in Google Scholar PubMed PubMed Central

26. Surks, M, Ortiz, E, Daniels, GH, Sawin, CT, Col, NF, Cobin, RH, et al.. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. J Am Med Assoc 2004;291:228–38. https://doi.org/10.1001/jama.291.2.228.Search in Google Scholar PubMed

27. Rákosníková, V, Zahradníková, M, Zikmund, J, Průhová, S, Lebl, J. Normal course of autoimmune thyroid disease in diabetic children. Cas Lek Cesk 2003;142:235–9. PMID: 12841127.Search in Google Scholar

28. Yoshida, H, Amino, N, Yagawa, K, Uemura, K, Satoh, M, Miyai, K, et al.. Association of serum antithyroid antibodies with lymphocytic infiltration of the thyroid gland: studies of seventy autopsied cases. J Clin Endocrinol Metab 1978;46:859–62. https://doi.org/10.1210/jcem-46-6-859.Search in Google Scholar PubMed

29. Aversa, T, Valenzise, M, Corrias, A, Salerno, M, De Luca, F, Mussa, A, et al.. Underlying Hashimoto’s thyroiditis negatively affects the evolution of subclinical hypothyroidism in children irrespective of other concomitant risk factors. Thyroid 2015;25:183–7. https://doi.org/10.1089/thy.2014.0235.Search in Google Scholar PubMed

30. 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. Clin Res Pediatr Endocrinol 2013;5:240–4. https://doi.org/10.4274/Jcrpe.1136.Search in Google Scholar PubMed PubMed Central

31. 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. https://doi.org/10.1089/105072501750159651.Search in Google Scholar PubMed

32. Schmidt, M, Voell, M, Rahlff, I, Dietlein, M, Kobe, C, Faust, M, et al.. Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) treated with levothyroxine. Thyroid 2008;18:755–60. https://doi.org/10.1089/thy.2008.0008.Search in Google Scholar PubMed

33. Aksoy, DY, Kerimoglu, U, Okur, H, Canpinar, H, Karaağaoğlu, E, Yetgin, S, et al.. Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto’s thyroiditis. Endocr J 2005;52:337–43. https://doi.org/10.1507/endocrj.52.337.Search in Google Scholar PubMed

34. 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. https://doi.org/10.1111/j.1365-2265.1991.tb03528.x.Search in Google Scholar PubMed

35. Hayashi, Y, Tamai, H, Fukata, S, Hirota, Y, Katayama, S, Kuma, K, et al.. A long term clinical, immunological, and histological follow-up study of patients with goitrous chronic lymphocytic thyroiditis. J Clin Endocrinol Metab 1985;61:1172–8. https://doi.org/10.1210/jcem-61-6-1172.Search in Google Scholar PubMed

36. Gupta, MK, Chiang, T, Deodhar, SD. Effect of thyroxine on immune response in CD 57B1/6J mice. Acta Endocrinol 1983;103:76–80. https://doi.org/10.1530/acta.0.1030076.Search in Google Scholar PubMed

37. 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. https://doi.org/10.1111/j.1365-2265.2011.04251.x.Search in Google Scholar PubMed

38. Svensson, J, Ericsson, U-B, Nilsson, P, Olsson, C, Jonsson, B, Lindberg, B, et al.. Levothyoxine treatment reduces thyroid size in children and adolescents with chronic autoimmune thyroiditis. J Clin Endocrinol Metab 2006;91:1729–34. https://doi.org/10.1210/jc.2005-2400.Search in Google Scholar PubMed

39. KordonourI, O, Hartman, R, Riebel, T, Liesenkoetter K-P. Early treatment with L-thyroxine in children and adolescents with type 1 diabetes, positive thyroid antibodies, and thyroid gland enlargement. Pediatr Diabetes 2007;8:180–4. https://doi.org/10.1111/j.1399-5448.2007.00247.x.Search in Google Scholar PubMed

40. Romaldini, JH, Biancalana, MM, Figueiredo, DI, Farah, CS, Mathias, PC. Effect of L-thyroxine administration on antithyroid antibody levels, lipid profile, and thyroid volume inpatients with Hashimoto’s thyroiditis. Thyroid 1996;6:183–8. https://doi.org/10.1089/thy.1996.6.183.Search in Google Scholar PubMed

41. Crisafulli, G, Aversa, T, Zirilli, G, Battista Pajno, G, Corica, D, De Luca, F, et al.. Subclinical hypothyroidism in children: when a replacement hormonal treatment might Be advisable. Front Endocrinol 2019;10:109. https://doi.org/10.3389/fendo.2019.00109.Search in Google Scholar PubMed PubMed Central

42. Cerbone, M, Capalbo, D, Wasniewska, M, Mattace Raso, G, Alfano, S, Meli, R, et al.. Cardiovascular risk factors in children with long-standing untreated idiopathic subclinical hypothyroidism. J Clin Endocrinol Metab 2014;99:2697–703. https://doi.org/10.1210/jc.2014-1761.Search in Google Scholar PubMed

43. Cerbone, M, Capalbo, D, Wasniewska, M, Alfano, S, Mattace Raso, G, Oliviero, U, et al.. Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism. Eur J Endocrinol 2016;175:11–9. https://doi.org/10.1530/eje-15-0833.Search in Google Scholar

44. Nader, NS, Bahn, RS, Johnson, MD, Weaver, AL, Singh, R, Kumar, S. Relationships between thyroid function and lipid status or insulin resistance in a pediatric population. Thyroid 2010;20:1333–9. https://doi.org/10.1089/thy.2010.0180.Search in Google Scholar PubMed

45. Brown, RS. Euthyroid autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus: to treat or not to treat?. Pediatr Diabetes 2007;8:177–9. https://doi.org/10.1111/j.1399-5448.2007.00275.x.Search in Google Scholar PubMed

46. Chase, HP, Garg, SK, Cockerham, RS, Wilcox, WD, Walravens, PA. Thyroid hormone replacement and growth of children with subclinical hypothyroidism and diabetes. Diabet Med 1990;7:299–303. https://doi.org/10.1111/j.1464-5491.1990.tb01393.x.Search in Google Scholar PubMed

47. Spirkova, A, Dusatkova, P, Peckova, M, Kolouskova, S, Snajderova, M, Obermannova, M, et al.. Treated autoimmune thyroid disease is associated with a decreased quality of life among young persons with type 1 diabetes. Int J Endocrinol 2015;2015:185859. https://doi.org/10.1155/2015/185859.Search in Google Scholar PubMed PubMed Central

48. Deitiker, P, Atassi, MZ. MHC genes linked to autoimmune disease. CRI 2015;35:203–51. https://doi.org/10.1615/critrevimmunol.2015014510.Search in Google Scholar PubMed

Received: 2020-04-28
Accepted: 2020-09-21
Published Online: 2020-11-12
Published in Print: 2020-12-16

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Papillary thyroid carcinoma in children with Hashimoto’s thyroiditis – a review of the literature between 2000 and 2020
  4. Original Articles
  5. Tyrosine metabolism in health and disease: slow-release amino acids therapy improves tyrosine homeostasis in phenylketonuria
  6. Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM)
  7. Glycated hemoglobin variability and microvascular complications in patients with type 1 diabetes mellitus
  8. Delineation of the genetic and clinical spectrum, including candidate genes, of monogenic diabetes: a multicenter study in South Korea
  9. Can we use copeptin as a biomarker for masked hypertension or metabolic syndrome in obese children and adolescents?
  10. Relationship of acanthosis nigricans with metabolic syndrome in obese children
  11. Daily intake of macronutrients and energy in childhood and its association with cardiometabolic risk factors in Colombians
  12. The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): a systematic review and meta-analysis
  13. Growth in achondroplasia, from birth to adulthood, analysed by the JPA-2 model
  14. Short Communication
  15. Assessing disparities in barriers to attending pediatric diabetes camp
  16. Letter to the Editor
  17. Severity in pediatric type 1 diabetes mellitus debut during the COVID-19 pandemic
  18. Case Reports
  19. The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene
  20. Effect of recombinant human insulin-like growth factor 1 therapy in a child with 3-M syndrome-1 with CUL7 gene mutation
  21. A nonsense variant in FGFR1: a rare cause of combined pituitary hormone deficiency
  22. Treatment response to long term antiresorptive therapy in osteogenesis imperfecta type VI: does genotype matter?
https://doi.org/10.1515/jpem-2020-0222
Keywords for this article
children; Hashimoto thyroiditis; treatment; type 1 diabetes

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Papillary thyroid carcinoma in children with Hashimoto’s thyroiditis – a review of the literature between 2000 and 2020
  4. Original Articles
  5. Tyrosine metabolism in health and disease: slow-release amino acids therapy improves tyrosine homeostasis in phenylketonuria
  6. Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM)
  7. Glycated hemoglobin variability and microvascular complications in patients with type 1 diabetes mellitus
  8. Delineation of the genetic and clinical spectrum, including candidate genes, of monogenic diabetes: a multicenter study in South Korea
  9. Can we use copeptin as a biomarker for masked hypertension or metabolic syndrome in obese children and adolescents?
  10. Relationship of acanthosis nigricans with metabolic syndrome in obese children
  11. Daily intake of macronutrients and energy in childhood and its association with cardiometabolic risk factors in Colombians
  12. The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): a systematic review and meta-analysis
  13. Growth in achondroplasia, from birth to adulthood, analysed by the JPA-2 model
  14. Short Communication
  15. Assessing disparities in barriers to attending pediatric diabetes camp
  16. Letter to the Editor
  17. Severity in pediatric type 1 diabetes mellitus debut during the COVID-19 pandemic
  18. Case Reports
  19. The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene
  20. Effect of recombinant human insulin-like growth factor 1 therapy in a child with 3-M syndrome-1 with CUL7 gene mutation
  21. A nonsense variant in FGFR1: a rare cause of combined pituitary hormone deficiency
  22. Treatment response to long term antiresorptive therapy in osteogenesis imperfecta type VI: does genotype matter?
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 12.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2020-0222/html
Scroll to top button