Evaluation and management of the child with hypothyroidism

  • Alexander K. C. LeungEmail author
  • Alexander A. C. Leung
Review Article



Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is, therefore, of utmost importance to optimize physical and neurodevelopmental outcomes.

Data sources

A PubMed search was completed in Clinical Queries using the key terms “hypothyroidism”.


Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment.


To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first 2 weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH < 5 mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism.


Dysgenesis Dyshormonogenesis Hashimoto thyroiditis Hypothyroidism Iodine deficiency Levothyroxine Mental retardation Stunted growth 


Author contributions

AKCL wrote the first draft of the manuscript, as well as a statement of whether an honorarium, grant, or other form of payment was given to anyone to produce the manuscript. AACL contributed to drafting and revising the manuscript. We have seen and approved the final version submitted for publication and take full responsibility for the manuscript.



Compliance with ethical standards

Ethical approval

Not required.

Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.


  1. 1.
    Diaz A, Lipman Diaz EG. Hypothyroidism. Pediatr Rev. 2014;35:336–7 (quiz 348–9).Google Scholar
  2. 2.
    Wassner AJ. Pediatric hypothyroidism: diagnosis and treatment. Paediatr Drugs. 2017;19:291–301.Google Scholar
  3. 3.
    Counts D, Varma SK. Hypothyroidism in children. Pediatr Rev. 2009;30:251–8.Google Scholar
  4. 4.
    Hashemipour M, Hovsepian S, Ansari A, Keikha M, Khalighinejad P, Niknam N. Screening of congenital hypothyroidism in preterm, low birth weight and very low birth weight neonates: a systematic review. Pediatr Neonatol. 2017;S1875–9572(17):30452–7.Google Scholar
  5. 5.
    Ross S. Disorders that cause hypothyroidism. In: Post TW, editor. UpToDate. Waltham. Accessed 8 Jan 2019.Google Scholar
  6. 6.
    Hanley P, Lord K, Bauer AJ. Thyroid disorders in children and adolescents: a review. JAMA Pediatr. 2016;170:1008–19.Google Scholar
  7. 7.
    Chan CL, Kappy MS. Thyroid screening/hypothyroidism. In: McMillan J, Barrett D, Boney C, editors. Clinical decision support: pediatrics. Wilmington: Decision Support in Medicine, LLC; 2015. Accessed 8 Jan 2019.
  8. 8.
    LaFranchi S. Clinical features and detection of congenital hypothyroidism. In: Post TW, editor. UpToDate. Waltham. Accessed 8 Jan 2019.Google Scholar
  9. 9.
    Kollati Y, Ambati RR, Reddy PN, Kumar NSS, Patel RK, Dirisala VR. Congenital hypothyroidism: facts, facets & therapy. Curr Pharm Des. 2017;23:2308–13.Google Scholar
  10. 10.
    Leung AK. Ectopic thyroid gland and thyroxine-binding globulin excess. Acta Paediatr Scand. 1986;75:872–4.Google Scholar
  11. 11.
    Leung AK, Wong AL, Robson WL. Ectopic thyroid gland simulating a thyroglossal duct cyst. Can J Surg. 1995;38:87–9.Google Scholar
  12. 12.
    Maciel LM, Kimura ET, Nogueira CR, Mazeto GM, Magalhães PK, Nascimento ML, et al. Congenital hypothyroidism: recommendations of the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism. Arq Bras Endocrinol Metabol. 2013;57:184–92.Google Scholar
  13. 13.
    Szinnai G. Clinical genetics of congenital hypothyroidism. Endocr Dev. 2014;26:60–78.Google Scholar
  14. 14.
    Aycan Z, Cangul H, Muzza M, Bas VN, Fugazzola L, Chatterjee VK, et al. Digenic DUOX1 and DUOX2 mutations in cases with congenital hypothyroidism. J Clin Endocrinol Metab. 2017;102:3085–90.Google Scholar
  15. 15.
    Sugisawa C, Higuchi S, Takagi M, Hasegawa Y, Taniyama M, Abe K, et al. Homozygous DUOXA2 mutation (p.Tyr138*) in a girl with congenital hypothyroidism and her apparently unaffected brother: case report and review of the literature. Endocr J. 2017;64:807–12.Google Scholar
  16. 16.
    Connelly KJ, Boston BA, Pearce EN, Sesser D, Snyder D, Braverman LE, et al. Congenital hypothyroidism caused by excess prenatal maternal iodine ingestion. J Pediatr. 2012;161:760–2.Google Scholar
  17. 17.
    Kurtoğlu S, Akın L, Akın MA, Çoban D. Iodine overload and severe hypothyroidism in two neonates. J Clin Res Pediatr Endocrinol. 2009;1:275–7.Google Scholar
  18. 18.
    Hasanbegovic E, Hasanbegovic S, Begic E. Hypothyroidism in pediatric population—Bosnian and Herzegovinian situation. Med Arch. 2017;71:62–5.Google Scholar
  19. 19.
    Saleh DS, Lawrence S, Geraghty MT, Gallego PH, McAssey K, Wherrett DK, et al. Prediction of congenital hypothyroidism based on initial screening thyroid-stimulating-hormone. BMC Pediatr. 2016;16:24.Google Scholar
  20. 20.
    Pimentel J, Chambers M, Shahid M, Chawla R, Kapadia C. Comorbidities of thyroid disease in children. Adv Pediatr. 2016;63:211–6.Google Scholar
  21. 21.
    Roberts HE, Moore CA, Fernhoff PM, Brown AL, Khoury MJ. Population study of congenital hypothyroidism and associated birth defects, Atlanta, 1979–1992. Am J Med Genet. 1997;71:29–32.Google Scholar
  22. 22.
    Hivnor C. Hypothroidism (cretinism). In: Heyman WR, Anderson BE, Hivnor C, et al. editors. Clinical decision support: dermatology. 2nd ed. Wilmington: Decision Support in Medicine, LLC; 2015. Accessed 8 Jan 2019.
  23. 23.
    Van Vliet G, Larroque B, Bubuteishvili L, Supernant K, Léger J, Association of Française pour le Dépistage et la Prévention des Handicaps de l’Enfant. Sex-specific impact of congenital hypothyroidism due to thyroid dysgenesis on skeletal maturation in term newborns. J Clin Endocrinol Metab. 2003;88:2009–13.Google Scholar
  24. 24.
    LaFranchi S. Treatment and prognosis of congenital hypothyroidism. In: Post TW, editor. UpToDate. Waltham. Accessed 8 Jan 2019.Google Scholar
  25. 25.
    Lichtenberger-Geslin L, Dos Santos S, Hassani Y, Ecosse E, Van Den Abbeele T, Léger J. Factors associated with hearing impairment in patients with congenital hypothyroidism treated since the neonatal period: a national population-based study. J Clin Endocrinol Metab. 2013;98:3644–52.Google Scholar
  26. 26.
    Leung AK, Shukla A, Akierman A. Neonatal hypoglycemia. J Singapore Paediatr Soc. 1988;30:77–82.Google Scholar
  27. 27.
    Baş VN, Ozgelen S, Cetinkaya S, Aycan Z. Diseases accompanying congenital hypothyroidism. J Pediatr Endocrinol Metab. 2014;27:485–9.Google Scholar
  28. 28.
    Leung AK. Wiedemann–Beckwith syndrome and hypothyroidism. Eur J Pediatr. 1985;144:295.Google Scholar
  29. 29.
    Leung AK, McArthur RG. Hypothyroidism with thyroxine-binding globulin excess. Pediatrics. 1989;83:147–8.Google Scholar
  30. 30.
    Jacob H, Peters C. Screening, diagnosis and management of congenital hypothyroidism: European Society for Paediatric Endocrinology Consensus Guideline. Arch Dis Childh Educ Pract. 2015;100:260–3.Google Scholar
  31. 31.
    Foley TP Jr. Hypothyroidism. Pediatr Rev. 2004;25:94–100.Google Scholar
  32. 32.
    Jonklaas J, Kahric-Janicic N, Soldin OP, Soldin SJ. Correlations of free thyroid hormones measured by tandem mass spectrometry and immunoassay with thyroid-stimulating hormone across 4 patient populations. Clin Chem. 2009;55:1380–8.Google Scholar
  33. 33.
    Williams JL, Paul DL, Bisset G 3rd. Thyroid disease in children: part 1: state-of-the-art imaging in pediatric hypothyroidism. Pediatr Radiol. 2013;43:1244–53.Google Scholar
  34. 34.
    Hashemipour M, Rostampour N, Nasry P, Hovsepian S, Basiratnia R, Hekmatnia A, et al. The role of ultrasonography in primary congenital hypothyroidism. J Res Med Sci. 2011;16:1122–8.Google Scholar
  35. 35.
    de Sedassari AA, de Souza LR, de Sedassari NA, de Borges MF, Palhares HM, de Andrade Neto GB. Sonographic evaluation of children with congenital hypothyroidism. Radiol Bras. 2015;48:220–4.Google Scholar
  36. 36.
    American Academy of Pediatrics, Rose SR, Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS, Public Health Committee, Lawson Wilkins Pediatric Endocrine Society, Foley T, Kaplowitz PB, Kaye CI, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006;117:2290–303.Google Scholar
  37. 37.
    Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the American thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24:1670–751.Google Scholar
  38. 38.
    Léger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, et al. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. Horm Res Paediatr. 2014;81:80–103.Google Scholar
  39. 39.
    Schoelwer MJ, Tu W, Zhou J, Eugster EA. Targeted levothyroxine therapy for treatment of congenital hypothyroidism. Endocr Pract. 2017;23:1067–71.Google Scholar
  40. 40.
    Carswell JM, Gordon JH, Popovsky E, Hale A, Brown RS. Generic and brand-name l-thyroxine are not bioequivalent for children with severe congenital hypothyroidism. J Clin Endocrinol Metab. 2013;98:610–7.Google Scholar
  41. 41.
    Lomenick JP, Wang L, Ampah SB, Saville BR, Greenwald FI. Generic levothyroxine compared with synthroid in young children with congenital hypothyroidism. J Clin Endocrinol Metab. 2013;98:653–8.Google Scholar
  42. 42.
    Bongers-Schokking JJ, Resing WC, de Rijke YB, de Ridder MA, de Muinck Keizer-Schrama SM. Cognitive development in congenital hypothyroidism: is overtreatment a greater threat than undertreatment? J Clin Endocrinol Metab. 2013;98:4499–506.Google Scholar
  43. 43.
    Rovet JF, Ehrlich RM, Sorbara DL. Effect of thyroid hormone level on temperament in infants with congenital hypothyroidism detected by screening of neonates. J Pediatr. 1989;114:63–8.Google Scholar
  44. 44.
    Rovet J, Alvarez M. Thyroid hormone and attention in congenital hypothyroidism. J Pediatr Endocrinol Metab. 1996;9:63–6.Google Scholar
  45. 45.
    Van Vliet G, Deladoëy J. Diagnosis, treatment and outcome of congenital hypothyroidism. Endocr Dev. 2014;26:50–9.Google Scholar
  46. 46.
    Heidari Z, Feizi A, Hashemipour M, Kelishadi R, Amini M. Growth development in children with congenital hypothyroidism: the effect of screening and treatment variables—a comprehensive longitudinal study. Endocrine. 2016;54:448–59.Google Scholar
  47. 47.
    Rahmani K, Yarahmadi S, Etemad K, Koosha A, Mehrabi Y, Aghang N, et al. Congenital hypothyroidism: optimal initial dosage and time of initiation of treatment: a systematic review. Int J Endocrinol Metab. 2016;14:e36080.Google Scholar
  48. 48.
    Seo MK, Yoon JS, So CH, Lee HS, Hwang JS. Intellectual development in preschool children with early treated congenital hypothyroidism. Ann Pediatr Endocrinol Metab. 2017;22:102–7.Google Scholar
  49. 49.
    Leung AK. Thyroiditis: a clinical update. J Singapore Paediatr Soc. 1987;29:63–7.Google Scholar
  50. 50.
    Leung AK. Hashimoto thyroiditis. In: Leung AK, editor. Common problems in ambulatory pediatrics: specific clinical problems, vol. 1. New York: Nova Science Publishers Inc; 2011. p. 135–9.Google Scholar
  51. 51.
    Vanderpump MP. Epidemiology of iodine deficiency. Minerva Med. 2017;108:116–23.Google Scholar
  52. 52.
    Nguyen CT, Braverman LE, Singer PA. Got rice? An unusual case of iodine-deficiency hypothyroidism. Thyroid. 2016;26:1338–9.Google Scholar
  53. 53.
    Booms S, Hill E, Kulhanek L, Vredeveld J, Gregg B. Iodine deficiency and hypothyroidism from voluntary diet restrictions in the US: case reports. Pediatrics. 2016;137:e20154003.Google Scholar
  54. 54.
    Brooks MJ, Post EM. Acquired hypothyroidism due to iodine deficiency in an American child. J Pediatr Endocrinol Metab. 2014;27:1233–5.Google Scholar
  55. 55.
    Golekoh MC, Cole CR, Jones NY. Severe hypothyroidism from iodine deficiency associated with parenteral nutrition. JPEN J Parenter Enteral Nutr. 2016;40:1191–3.Google Scholar
  56. 56.
    Shiga K, Kodama H, Kaga F, Izumi Y, Nakamoto N, Fujisawa C. Hypothyroidism caused by iodine deficiency and iodine levels in enteral formulas. Pediatr Int. 2011;53:501–4.Google Scholar
  57. 57.
    Clemens PC, Neumann RS. The Wolff–Chaikoff effect: hypothyroidism due to iodine application. Arch Dermatol. 1989;125:705.Google Scholar
  58. 58.
    Kotwal A, Kotwal J, Prakash R, Kotwal N. Does iodine excess lead to hypothyroidism? Evidence from a case–control study in India. Arch Med Res. 2015;46:490–4.Google Scholar
  59. 59.
    Shumer DE, Mehringer JE, Braverman LE, Dauber A. Acquired hypothyroidism in an infant related to excessive maternal iodine intake: food for thought. Endocr Pract. 2013;19:729–31.Google Scholar
  60. 60.
    LaFranchi S. Acquired hypothyroidism in childhood and adolescence. In: Post TW, editor. UpToDate. Waltham. Accessed 9 Jan 2019.Google Scholar
  61. 61.
    Bilen MA, Patel A, Hess KR, Munoz J, Busaidy NL, Wheler JJ, et al. Association between new-onset hypothyroidism and clinical response in patients treated with tyrosine kinase inhibitor therapy in phase I clinical trials. Cancer Chemother Pharmacol. 2016;78:167–71.Google Scholar
  62. 62.
    Husseni MA. The incidence of hypothyroidism following the radioactive iodine treatment of Graves’ disease and the predictive factors influencing its development. World J Nucl Med. 2016;15:30–7.Google Scholar
  63. 63.
    Naushad K, Prasanth, Ravishankar, Krishnakumar P. Acquired hypothyroidism in an adolescent boy following thyroid surgery. Indian J Pediatr. 2006;73:843.Google Scholar
  64. 64.
    Demirbilek H, Kandemir N, Gonc EN, Ozon A, Alikasifoglu A, Yordam N. Hashimoto’s thyroiditis in children and adolescents: a retrospective study on clinical, epidemiological and laboratory properties of the disease. J Clin Endocrinol Metab. 2007;20:1199–204.Google Scholar
  65. 65.
    Bindra A, Braunstein GD. Thyroiditis. Am Fam Physician. 2006;73:1769–76.Google Scholar
  66. 66.
    Takami HE, Kameyama K. Hashimoto’s thyroiditis. World J Surg. 2008;32:688–92.Google Scholar
  67. 67.
    Brenta G, Fretes O. Dyslipidemias and hypothyroidism. Pediatr Endocrinol Rev. 2014;11:390–9.Google Scholar
  68. 68.
    Chistiakov DA. Immunogenetics of Hashimoto’s thyroiditis. J Autoimmune Dis. 2005;2:1.Google Scholar
  69. 69.
    Doggui R, El Atia J. Iodine deficiency: physiological, clinical and epidemiological features, and pre-analytical considerations. Ann Endocrinol. 2015;76:59–66.Google Scholar
  70. 70.
    Gaitan E, Dunn JT. Epidemiology of iodine deficiency. Trends Endocrinol Metab. 1992;3:170–5.Google Scholar
  71. 71.
    Olivieri A, Radetti G, Medda E, Italian Study Group for Congenital Hypothyroidism. Incidence of congenital hypothyroidism in the Autonomous Province of Bolzano: benefit of increased iodine intake. J Endocrinol Invest. 2015;38:185–7.Google Scholar
  72. 72.
    Wächter W, Mvungi MG, Triebel E, van Thiel D, Marschner I, Wood WG, et al. Iodine deficiency, hypothyroidism, and endemic goitre in southern Tanzania. A survey showing the positive effects of iodised oil injections by TSH determination in dried blood spots. J Epidemiol Community Health. 1985;39:263–70.Google Scholar
  73. 73.
    Wormsbecker A, Clarson C. Acquired primary hypothyroidism: vaginal bleeding in a quiet child. CMAJ. 2010;182:588–90.Google Scholar
  74. 74.
    Cimbek EA, Şen Y, Yuca SA, Çam D, Gür C, Peru H. Kocher–Debré–Semelaigne syndrome with rhabdomyolysis and increased creatinine. J Pediatr Endocrinol Metab. 2015;28:1383–5.Google Scholar
  75. 75.
    Leung AK, Pacaud D. Diagnosis and management of galactorrhea. Am Fam Physician. 2004;70:543–50.Google Scholar
  76. 76.
    Brenta G, Vaisman M, Sgarbi JA, Bergoglio LM, Andrada NC, Bravo PP, et al. Clinical practice guidelines for the management of hypothyroidism. Arq Bras Endocrinol Metabol. 2013;57:265–91.Google Scholar
  77. 77.
    Moorefield WG Jr, Urbaniak JR, Ogden WS, Frank JL. Acquired hypothyroidism and slipped capital femoral epiphysis. Report of three cases. J Bone Joint Surg Am. 1976;58:705–8.Google Scholar
  78. 78.
    Moyer J, Jacks L, Hunter JD, Chan G. Slipped capital femoral epiphysis and associated hypothyroidism. A review of the literature with two classic case examples. J Pediatr Endocrinol Metab. 2016;29:427–34.Google Scholar
  79. 79.
    Leung AK. Carotenemia. Adv Pediatr. 1987;34:223–48.Google Scholar
  80. 80.
    Zhu Y, Qiu W, Deng M, Zhu X. Myxedema coma: a case report of pediatric emergency care. Medicine. 2017;96:e6952.Google Scholar
  81. 81.
    Leung AK. Familial “hashitoxic’ periodic paralysis. J R Soc Med. 1985;78:638–40.Google Scholar
  82. 82.
    Perlsteyn M, Deladoëy J, Van Vliet G. Similar age-dependent levothyroxine requirements of schoolchildren with congenital or acquired hypothyroidism. Eur J Pediatr. 2016;175:869–72.Google Scholar
  83. 83.
    Van Dop C, Conte FA, Koch TK, Clark SJ, Wilson-Davis SL, Grumbach MM. Pseudotumor cerebri associated with initiation of levothyroxine therapy for juvenile hypothyroidism. N Engl J Med. 1983;308:1076–80.Google Scholar
  84. 84.
    Schoenmakers N, Alatzoglou KS, Chatterjee VK, Dattani MT. Recent advances in central congenital hypothyroidism. J Endocrinol. 2015;227:R51–71.Google Scholar
  85. 85.
    Catli G, Abaci A, Büyükgebiz A, Bober E. Subclinical hypothyroidism in childhood and adolescense. J Pediatr Endocrinol Metab. 2014;27:1049–57.Google Scholar
  86. 86.
    Shriraam M, Sridhar M. Subclinical hypothyroidism in children. Indian Pediatr. 2014;51:889–95.Google Scholar
  87. 87.
    Salerno M, Capalbo D, Cerbone M, De Luca F. Subclinical hypothyroidism in childhood—current knowledge and open issues. Nat Rev Endocrinol. 2016;12:734–46.Google Scholar
  88. 88.
    Tng EL. The debate on treating subclinical hypothyroidism. Singapore Med J. 2016;57:539–45.Google Scholar
  89. 89.
    Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT. Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. J Clin Endocrinol Metab. 2005;90:581–5 (discussion 586–7).Google Scholar
  90. 90.
    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.Google Scholar
  91. 91.
    Leung AK. Euthyroid sick syndrome. Ann R Coll Physicians Surg Canada. 1987;20:245–8.Google Scholar
  92. 92.
    Nomura R, Miyai K, Kuge R, Okura T, Goto M, Hasegawa Y. Free T3 to free T4 ratio less than 2.0 suggests low T3 syndrome rather than central hypothyroidism from the age of two to eighteen years. Endocr J. 2017;64:213–9.Google Scholar
  93. 93.
    Leung AK, McArthur RG, Ross SA, McMillan DD, Sauve RS. Thyroxine-binding globulin deficiency in Beckwith syndrome. J Pediatr. 1979;95:752–4.Google Scholar

Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2019

Authors and Affiliations

  1. 1.Department of PediatricsThe University of Calgary, and The Alberta Children’s HospitalCalgaryCanada
  2. 2.Department of Medicine, The University of CalgaryCalgaryCanada

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