Ann Pediatr Endocrinol Metab.  2024 Oct;29(5):337-343. 10.6065/apem.2346204.102.

Predictors for thyroid dysfunction after discontinuation of levothyroxine in children and adolescents with Hashimoto thyroiditis

• Kim MJ
• Lee YJ
• Choe Y
• Shin CH
• Lee YA

• KMID: 2560468
• DOI: http://doi.org/10.6065/apem.2346204.102

Abstract

Purpose
Few data on the clinical course after levothyroxine (L-T4) discontinuation in pediatric patients with Hashimoto thyroiditis (HT) are available. We investigated outcomes and predictors for successful withdrawal from L-T4 among children with HT.
Methods
Among 168 patients diagnosed with HT between January 2000 and March 2021 at Seoul National University Children’s Hospital and in whom L-T4 therapy was initiated during childhood, we attempted to discontinue this therapy in 47, 3 boys and 44 girls. L-T4 was restarted when patients developed overt or subclinical hypothyroidism (thyroid-stimulating hormone [TSH] levels≥10 mIU/L) after L-T4 discontinuation.
Results
Median age at discontinuation was 15.4 years (12.7–18.4 years) with a median duration of L-T4 therapy of 47 months (20.3–80.3 months). During the median 30 months of follow-up (10.6–61.0 months) after L-T4 discontinuation, 33 (70.2%) developed thyroid dysfunction. Among these patients, 17 were eventually restarted on L-T4. TSH levels over 50 mIU/L at L-T4 initiation (hazard ratio, HR 3.5, P=0.002), age under 12 years at L-T4 discontinuation (HR 11.1, P=0.0001), and TSH levels higher than the upper 50% of normal (above 2.25 mIU/L in the present study) at L-T4 discontinuation (HR 2.7, P=0.014) were significantly predictive for overt hypothyroidism or subclinical hypothyroidism after L-T4 discontinuation. In addition, age under 12 years at L-T4 discontinuation was only predictive factor for restarting L-T4 medication (HR 4.3, P=0.012).
Conclusion
L-T4 discontinuation in pediatric patients with HT resulted in thyroid dysfunction in 70.2% of cases; 36.2% of patients who attempted discontinuation required resumption of L-T4. Older age and lower TSH levels at L-T4 discontinuation were advantageous for successful withdrawal.

Keyword

Hashimoto thyroiditis; Discontinuation of levothyroxine; Predictors; Child

Figure

• 

  Fig. 1. Flow chart of study selection in this study. L-T4, levothyroxine; HT, Hashimoto thyroiditis.

• 

  Fig. 2. Clinical outcomes after levothyroxine (L-T4) discontinuation. TSH, Thyroid- stimulating hormone; FT4, free T4.

• 

  Fig. 3. Event (thyroid dysfunction)-free survival after levothyroxine (L-T4) discontinuation. Approximately 39.8% and 31.5% of patients remained euthyroid at 12 and 24 months after L-T4 discontinuation, respectively.

Reference

References

1. Akamizu T, Amino N. Hashimoto’s thyroiditis. 2017 Jul 17. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

2. Penta L, Cofini M, Lanciotti L, Leonardi A, Principi N, Esposito S. Hashimoto's disease and thyroid cancer in children: are they associated? Front Endocrinol (Lausanne). 2018; 9:565.

3. Demirbilek H, Kandemir N, Gonc E, Ozon A, Alikasifoglu A. Assessment of thyroid function during the long course of Hashimoto's thyroiditis in children and adolescents. Clin Endocrinol. 2009; 71:451–4.

4. 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.

5. 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.

6. Kaplowitz PB. Subclinical hypothyroidism in children: normal variation or sign of a failing thyroid gland? Int J Pediatr Endocrinol. 2010; 2010:281453.

7. Lee YJ, Jung SY, Jung HW, Kim SY, Lee YA, Lee SY, et al. Unfavorable course of subclinical hypothyroidism in children with Hashimoto’s thyroiditis compared to those with isolated non-autoimmune hyperthyrotropinemia. J Korean Med Scie. 2017; 32:124.

8. 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.

9. Lee HS, Hwang JS. The natural course of Hashimoto's thyroiditis in children and adolescents. J Pediatr Endocrinol Metab. 2014; 27:807–12.

10. Radetti G, Salerno M, Guzzetti C, Cappa M, Corrias A, Cassio A, et al. Thyroid function in children and adolescents with Hashimoto's thyroiditis after l-thyroxine discontinuation. Endocr Connect. 2017; 6:206–12.

11. Burgos N, Toloza FJ, Singh Ospina NM, Brito JP, Salloum RG, Hassett LC, et al. Clinical outcomes after discontinuation of thyroid hormone replacement: a systematic review and meta-analysis. Thyroid. 2021; 31:740–51.

12. Jung KY, Kim H, Choi HS, An JH, Cho SW, Kim HJ, et al. Clinical factors predicting the successful discontinuation of hormone replacement therapy in patients diagnosed with primary hypothyroidism. PLoS One. 2020; 15:e0233596.

13. Takasu N, Komiya I, Asawa T, Nagasawa Y, Yamada T. Test for recovery from hypothyroidism during thyroxine therapy in Hashimoto's thyroiditis. Lancet. 1990; 336:1084–6.

14. Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014; 13:391–7.

15. Kim JH, Yun S, Hwang SS, Shim JO, Chae HW, Lee YJ, et al. The 2017 Korean National Growth Charts for children and adolescents: development, improvement, and prospects. Korean J Pediatr. 2018; 61:135–49.

16. Salerno M, Improda N, Capalbo D. Management of endocrine disease subclinical hypothyroidism in children. Eur J Endocrinol. 2020; 183:R13–28.