Subclinical but significant? Updated review of pediatric hypothyroidism

Felicia Cooper; Gabriela Guadalupe Rios; Andrea Rivera-Sepulveda; Olivia DiLeonardo; Mauri Carakushansky; Shilpa Gurnurkar

doi:10.1515/jpem-2025-0105

Article

Subclinical but significant? Updated review of pediatric hypothyroidism

Felicia Cooper , Gabriela Guadalupe Rios , Andrea Rivera-Sepulveda , Olivia DiLeonardo , Mauri Carakushansky and Shilpa Gurnurkar

Published/Copyright: October 29, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 12

Abstract

Objectives

The aims of this review are to describe the rates of diagnosis of true thyroid disease (and subsequent treatment) in children with an elevated TSH referred to pediatric endocrinology, risk factors associated with elevated TSH secondary to thyroid disease, and TSH threshold level associated with thyroid disease.

Methods

To accomplish these aims, our team searched through four databases to curate 211 articles regarding TSH values in healthy children ages 1–18 years without an underlying risk for hypothyroidism.

Results

Five studies met our criteria and were analyzed to create the conclusions about rates of hypothyroidism requiring treatment (6.3–59 %), risk factors to developing hypothyroidism (TSH>10 mIU/L, goiter, and anti-thyroid antibodies), and high-risk TSH value (9.6 mIU/L when averaged among four studies).

Conclusions

The results are helpful in guiding practitioners about when to repeat TSH value before considering referral to endocrinology, when to refer, and when to anticipate the need of thyroid hormone replacement.

Keywords: subclinical hypothyroidism; pediatrics; elevated thyroid stimulating hormone; systematic review

Corresponding author: Felicia Cooper, MD, Pediatric Endocrinology Fellow, Department of Pediatrics, Nemours Children’s Health, Orlando, 6535 Nemours Parkway, 32827, FL, USA, E-mail: FeliciaCooper2020@gmail.com

Acknowledgments

The authors would like to acknowledge Amanda Scott for assistance in editing the article.

Research ethics: The local Institutional Review Board deemed the study exempt from review.
Informed consent: Not applicable.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. OD assisted in article extraction and upload. FC, GGR, ARS, and SG selected articles for analysis and extracted data from each. FC, GGR, ARS, SG, and MC composed and edited the manuscript.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflicts of interest.
Research funding: None declared.
Data availability: Data sharing is not applicable to this article as no new data were created or analyzed in this study.

References

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

2. Shriraam, M, Sridhar, M. Subclinical hypothyroidism in children. Indian Pediatr 2014;51:889–95. https://doi.org/10.1007/s13312-014-0522-9.Search in Google Scholar PubMed

3. Bayram, C, Valenti, L, Britt, H. Orders for thyroid function tests - changes over 10 years. Aust Fam Physician 2012;41:555.Search in Google Scholar

4. Thienpont, LM, Van Uytfanghe, K, Poppe, K, Velkeniers, B. Determination of free thyroid hormones. Best Pract Res Clin Endocrinol Metabol 2013;27:689–700. https://doi.org/10.1016/j.beem.2013.05.012.Search in Google Scholar PubMed

5. Rapa, A, Monzani, A, Moia, S, Vivenza, D, Bellone, S, Petri, A, et al.. Subclinical hypothyroidism in children and adolescents: a wide range of clinical, biochemical, and genetic factors involved. J Clin Endocrinol Metab 2009;94:2414–20. https://doi.org/10.1210/jc.2009-0375.Search in Google Scholar PubMed

6. Crisafulli, G, Aversa, T, Zirilli, G, Pajno, GB, 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

7. Monzani, A, Prodam, F, Rapa, A, Moia, S, Agarla, V, Bellone, S, et al.. Endocrine disorders in childhood and adolescence. Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review. Eur J Endocrinol 2012;168:R1–11. https://doi.org/10.1530/EJE-12-0656.Search in Google Scholar PubMed

8. Lahoti, A, Klein, J, Schumaker, T, Vuguin, P, Frank, G. Prevalence and determinants of true thyroid dysfunction among pediatric referrals for abnormal thyroid function tests. Glob Pediatr Health 2016;3. https://doi.org/10.1177/2333794X16646701.Search in Google Scholar PubMed PubMed Central

9. Álvarez Casaño, M, López Siguero, JP. Review of the natural course of subclinical hypothyroidism and study of its costs. Revisión de la evolución de los pacientes con hipertirotropinemia y estudio de costes. Endocrinol Diabetes Nutr 2019;66:550–4. https://doi.org/10.1016/j.endinu.2019.03.006.Search in Google Scholar PubMed

10. Gammons, S, Presley, BK, White, PC. Referrals for elevated thyroid stimulating hormone to pediatric endocrinologists. J Endocr Soc 2019;3:2032–40. https://doi.org/10.1210/js.2019-00244.Search in Google Scholar PubMed PubMed Central

11. Murillo-Vallés, M, Martinez, S, Aguilar-Riera, C, Garcia-Martin, MA, Bel-Comós, J, Ybern, MLG. Subclinical hypothyroidism in childhood, treatment or only follow-up? BMC Pediatr 2020;20:282. https://doi.org/10.1186/s12887-020-02177-8.Search in Google Scholar PubMed PubMed Central

12. Szeliga, K, Antosz, A, Skrzynska, K, Kalina-Faska, B, Gawlik, A. Subclinical hypothyroidism in children and adolescents as mild dysfunction of the thyroid gland: a single-center study. Subkliniczna niedoczynność tarczycy u dzieci i młodzieży jako łagodna dysfunkcja gruczołu tarczowego – badanie jednoośrodkowe. Pediatr Endocrinol Diabetes Metab 2023;29:97–103. https://doi.org/10.5114/pedm.2023.124266.Search in Google Scholar PubMed PubMed Central

13. Aoki, Y, Belin, RM, Clickner, R, Jeffries, R, Phillips, L, Mahaffey, KR. Serum TSH and total T4 in the United States population and their association with participant characteristics: National health and nutrition examination survey (NHANES 1999-2002). Thyroid 2007;17:1211–23. https://doi.org/10.1089/thy.2006.0235.Search in Google Scholar PubMed

14. 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

15. Xing, D, Liu, D, Li, R, Zhou, Q, Xu, J. Factors influencing the reference interval of thyroid-stimulating hormone in healthy adults: a systematic review and meta-analysis. Clin Endocrinol 2021;95:378–89. https://doi.org/10.1111/cen.14454.Search in Google Scholar PubMed PubMed Central

16. Gyuricsko, E. The “slightly” abnormal thyroid test: what is the pediatrician to do? Curr Probl Pediatr Adolesc Health Care 2020;50:100770. https://doi.org/10.1016/j.cppeds.2020.100770.Search in Google Scholar PubMed

17. Huang, SA. Hypothyroidism. In: Lifshitz, F, editor. Pediatric Endocrinology, Volume 2: Growth, Adrenal, Sexual, Thyroid, Calcium, and Fluid Balance Disorders. New York: Taylor & Francis Group; 2006:405–11 pp.Search in Google Scholar

18. Habib, A, Molayemat, M, Habib, A. Elevated serum TSH concentrations are associated with higher BMI Z-scores in southern Iranian children and adolescents. Thyroid Res 2020;13:9. https://doi.org/10.1186/s13044-020-00084-9.Search in Google Scholar PubMed PubMed Central

19. Hollowell, JG, Staehling, NW, Flanders, WD, Hannon, WH, Gunter, EW, Spencer, CA, et al.. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National health and nutrition examination survey (NHANES III). J Clin Endocrinol Metab 2002;87:489–99. https://doi.org/10.1210/jcem.87.2.8182.Search in Google Scholar PubMed

20. Rivkees, S, Bauer, AJ. Thyroid disorders in children and adolescents. In: Sperling, MA, editor. Sperling Pediatric Endocrinology, 5th ed. Philadelphia: Elsevier; 2020:395–424 pp.10.1016/B978-0-323-62520-3.00013-0Search in Google Scholar

21. Jaruratanasirikul, S, Leethanaporn, K, Khuntigij, P, Sriplung, H. The clinical course of Hashimoto’s thryoiditis in children and adolescents: 6 years 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

22. Pobłocki, J, Pańka, T, Szczuko, M, Telesiński, A, Syrenicz, A. Whether a gluten-free diet should be recommended in chronic autoimmune thyroiditis or not? A 12-month follow-up. J Clin Med 2021;10:3240. https://doi.org/10.3390/jcm10153240.Search in Google Scholar PubMed PubMed Central

23. Gharib, H, Tuttle, RM, Baskin, HJ, Fish, LH, Singer, PA, McDermott, MT, et al.. Consensus statement #1: subclinical thyroid dysfunction: a joint statement on management from the American association of clinical endocrinologists, the American thyroid association, and the endocrine society. Thyroid 2005;15:24–33. https://doi.org/10.1089/thy.2005.15.24.Search in Google Scholar PubMed

24. Han, X, Ding, S, Lu, J, Li, Y. Global, regional, and national burdens of common micronutrient deficiencies from 1990 to 2019: a secondary trend analysis based on the global burden of disease 2019 study. eClinicalMedicine 2022;44:101299. https://doi.org/10.1016/j.eclinm.2022.101299.Search in Google Scholar PubMed PubMed Central

Received: 2025-02-26

Accepted: 2025-09-30

Published Online: 2025-10-29

Published in Print: 2025-12-17

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Articles in the same Issue

https://doi.org/10.1515/jpem-2025-0105

Keywords for this article

subclinical hypothyroidism; pediatrics; elevated thyroid stimulating hormone; systematic review