Skip to main content
SpringerLink
Log in

Neonatal Screening for Congenital Hypothyroidism: What It Has Taught us About Thyroid and Brain Development

  • Chapter
Thyroid Diseases in Childhood

Abstract

Congenital hypothyroidism (CH) is a relatively common disorder with a prevalence of 1 in 2,500 live births [1]. CH is characterized by a significant deficiency of thyroid hormones starting in the perinatal period, which can lead to severe intellectual disabilities if left untreated but which was only recognized clinically at a median age of 9 months [2]. Therefore, biochemical screening for CH is now routinely performed at 2 days of life, enabling the initiation of thyroid hormone therapy during the second week of life, if required. The implementation, since the 1970s [3], of a universal newborn screening (NBS) for CH has prevented severe intellectual disability in numerous patients [4, 5]. This tremendous success might suggest that the “problem of CH has been solved” and that it now suffices to refine the screening procedure to “diagnose” all possible cases, even the most benign. This belief leads to the following misperceptions:

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Deladoey J, Ruel J, Giguere Y, Van Vliet G (2011) Is the incidence of congenital hypothyroidism really increasing? A 20-year retrospective population-based study in Quebec. J Clin Endocrinol Metab 96:2422–2429

    Article  CAS  PubMed  Google Scholar 

  2. Wolter R, Noel P, De Cock P, Craen M, Ernould C, Malvaux P, Verstaeten F, Simons J, Mertens S, Van Broeck N, Vanderschueren-Lodeweyckx M (1979) Neuropsychological study in treated thyroid dysgenesis. Acta Paediatr Scand Suppl 277:41–46

    Article  CAS  PubMed  Google Scholar 

  3. Dussault JH, Laberge C (1973) Thyroxine (T4) determination by radioimmunological method in dried blood eluate: new diagnostic method of neonatal hypothyroidism? Union Med Can 102:2062–2064

    CAS  PubMed  Google Scholar 

  4. Grosse SD, Van Vliet G (2011) Prevention of intellectual disability through screening for congenital hypothyroidism: how much and at what level? Arch Dis Child 96:374–379

    Article  PubMed  Google Scholar 

  5. Boyle CA, Bocchini JA Jr, Kelly J (2014) Reflections on 50 years of newborn screening. Pediatrics 133:961–963

    Article  PubMed Central  PubMed  Google Scholar 

  6. Rastogi MV, LaFranchi SH (2010) Congenital hypothyroidism. Orphanet J Rare Dis 5:17

    Article  PubMed Central  PubMed  Google Scholar 

  7. Harris KB, Pass KA (2007) Increase in congenital hypothyroidism in New York State and in the United States. Mol Genet Metab 91:268–277

    Article  CAS  PubMed  Google Scholar 

  8. Schoen EJ, Clapp W, To TT, Fireman BH (2004) The key role of newborn thyroid scintigraphy with isotopic iodide (123I) in defining and managing congenital hypothyroidism. Pediatrics 114:e683–e688

    Article  PubMed  Google Scholar 

  9. Lucas-Herald A, Jones J, Attaie M, Maroo S, Neumann D, Bradley T, Hermanns P, Pohlenz J, Donaldson M (2014) Diagnostic and predictive value of ultrasound and isotope thyroid scanning, alone and in combination, in infants referred with thyroid-stimulating hormone elevation on newborn screening. J Pediatr 164:846–854

    Article  PubMed  Google Scholar 

  10. Maquet E, Costagliola S, Parma J, Christophe-Hobertus C, Oligny LL, Fournet JC, Robitaille Y, Vuissoz JM, Payot A, Laberge S, Vassart G, Van Vliet G, Deladoey J (2009) Lethal respiratory failure and mild primary hypothyroidism in a term girl with a de novo heterozygous mutation in the TITF1/NKX2.1 gene. J Clin Endocrinol Metab 94:197–203

    Article  CAS  PubMed  Google Scholar 

  11. Carre A, Szinnai G, Castanet M, Sura-Trueba S, Tron E, Broutin-L’Hermite I, Barat P, Goizet C, Lacombe D, Moutard ML, Raybaud C, Raynaud-Ravni C, Romana S, Ythier H, Leger J, Polak M (2009) Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. Hum Mol Genet 18:2266–2276

    Article  CAS  PubMed  Google Scholar 

  12. Calebiro D, Gelmini G, Cordella D, Bonomi M, Winkler F, Biebermann H, de Marco A, Marelli F, Libri DV, Antonica F, Vigone MC, Cappa M, Mian C, Sartorio A, Beck-Peccoz P, Radetti G, Weber G, Persani L (2012) Frequent TSH receptor genetic alterations with variable signaling impairment in a large series of children with nonautoimmune isolated hyperthyrotropinemia. J Clin Endocrinol Metab 97:E156–E160

    Article  CAS  PubMed  Google Scholar 

  13. Lucas-Herald A, Bradley T, Hermanns P, Jones J, Attaie M, Thompson E, Pohlenz J, Donaldson M (2013) Novel heterozygous thyrotropin receptor mutation presenting with neonatal hyperthyrotropinaemia, mild thyroid hypoplasia and absent uptake on radioisotope scan. J Pediatr Endocrinol Metab 26:583–586

    Article  CAS  PubMed  Google Scholar 

  14. Leger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, Polak M, Butler G, Espe Pes Slep Jspe Apeg Appes I, Congenital Hypothyroidism Consensus Conference G (2014) European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab 99:363–384

    Google Scholar 

  15. Van Vliet G, Grosse SD (2011) The continuing health burden of congenital hypothyroidism in the era of neonatal screening. J Clin Endocrinol Metab 96:1671–1673

    Article  PubMed  Google Scholar 

  16. Nebesio TD, McKenna MP, Nabhan ZM, Eugster EA (2010) Newborn screening results in children with central hypothyroidism. J Pediatr 156:990–993

    Article  PubMed  Google Scholar 

  17. Kempers MJ, Lanting CI, van Heijst AF, van Trotsenburg AS, Wiedijk BM, de Vijlder JJ, Vulsma T (2006) Neonatal screening for congenital hypothyroidism based on thyroxine, thyrotropin, and thyroxine-binding globulin measurement: potentials and pitfalls. J Clin Endocrinol Metab 91:3370–3376

    Article  CAS  PubMed  Google Scholar 

  18. Fagman H, Nilsson M (2010) Morphogenesis of the thyroid gland. Mol Cell Endocrinol 323:35–54

    Article  CAS  PubMed  Google Scholar 

  19. Szinnai G (2014) Genetics of normal and abnormal thyroid development in humans. Best Pract Res Clin Endocrinol Metab 28:133–150

    Article  CAS  PubMed  Google Scholar 

  20. Stoppa-Vaucher S, Van Vliet G, Deladoey J (2011) Variation by ethnicity in the prevalence of congenital hypothyroidism due to thyroid dysgenesis. Thyroid 21:13–18

    Article  PubMed Central  PubMed  Google Scholar 

  21. Albert BB, Cutfield WS, Webster D, Carll J, Derraik JG, Jefferies C, Gunn AJ, Hofman PL (2012) Etiology of increasing incidence of congenital hypothyroidism in New Zealand from 1993–2010. J Clin Endocrinol Metab 97:3155–3160

    Article  CAS  PubMed  Google Scholar 

  22. Sack J, Kletter G, Amado O, Akstein E (1985) Screening for neonatal hypothyroidism in Israel during a 4-year period. Isr J Med Sci 21:485–489

    CAS  PubMed  Google Scholar 

  23. Corbetta C, Weber G, Cortinovis F, Calebiro D, Passoni A, Vigone MC, Beck-Peccoz P, Chiumello G, Persani L (2009) A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol (Oxf) 71:739–745

    Article  CAS  Google Scholar 

  24. Deladoey J, Belanger N, Van Vliet G (2007) Random variability in congenital hypothyroidism from thyroid dysgenesis over 16 years in Quebec. J Clin Endocrinol Metab 92:3158–3161

    Article  CAS  PubMed  Google Scholar 

  25. Baccarelli A, Giacomini SM, Corbetta C, Landi MT, Bonzini M, Consonni D, Grillo P, Patterson DG, Pesatori AC, Bertazzi PA (2008) Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin. PLoS Med 5, e161

    Article  PubMed Central  PubMed  Google Scholar 

  26. Bongers-Schokking JJ, de Muinck Keizer-Schrama SM (2005) Influence of timing and dose of thyroid hormone replacement on mental, psychomotor, and behavioral development in children with congenital hypothyroidism. J Pediatr 147:768–774

    Article  CAS  PubMed  Google Scholar 

  27. Deladoey J, Van Vliet G (2014) The changing epidemiology of congenital hypothyroidism: fact or artifact? Expert Rev Endocrinol Metab 9:387–395

    Article  CAS  Google Scholar 

  28. Kemper AR, Ouyang L, Grosse SD (2010) Discontinuation of thyroid hormone treatment among children in the United States with congenital hypothyroidism: findings from health insurance claims data. BMC Pediatr 10:9

    Article  PubMed Central  PubMed  Google Scholar 

  29. Stoppa-Vaucher S, Lapointe A, Turpin S, Rydlewski C, Vassart G, Deladoey J (2010) Ectopic thyroid gland causing dysphonia: imaging and molecular studies. J Clin Endocrinol Metab 95:4509–4510

    Article  CAS  PubMed  Google Scholar 

  30. Deladoey J, Van Vliet G (2013) Treating congenital hypothyroidism – which levothyroxine? Nature reviews. Endocrinology 9:257–258

    CAS  PubMed  Google Scholar 

  31. Simoneau-Roy J, Marti S, Deal C, Huot C, Robaey P, Van Vliet G (2004) Cognition and behavior at school entry in children with congenital hypothyroidism treated early with high-dose levothyroxine. J Pediatr 144:747–752

    Article  CAS  PubMed  Google Scholar 

  32. Selva KA, Harper A, Downs A, Blasco PA, Lafranchi SH (2005) Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH. J Pediatr 147:775–780

    Article  CAS  PubMed  Google Scholar 

  33. Ng SM, Anand D, Weindling AM (2009) High versus low dose of initial thyroid hormone replacement for congenital hypothyroidism. Cochrane Database Syst Rev CD006972

    Google Scholar 

  34. Carswell JM, Gordon JH, Popovsky E, Hale A, Brown RS (2013) Generic and brand-name L-thyroxine are not bioequivalent for children with severe congenital hypothyroidism. J Clin Endocrinol Metab 98:610–617

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Lomenick JP, Wang L, Ampah SB, Saville BR, Greenwald FI (2013) Generic levothyroxine compared with synthroid in young children with congenital hypothyroidism. J Clin Endocrinol Metab 98:653–658

    Article  CAS  PubMed  Google Scholar 

  36. Lichtenberger-Geslin L, Dos Santos S, Hassani Y, Ecosse E, Van Den Abbeele T, Leger J (2013) Factors associated with hearing impairment in patients with congenital hypothyroidism treated since the neonatal period: a national population-based study. J Clin Endocrinol Metab 98:3644–3652

    Article  CAS  PubMed  Google Scholar 

  37. Dimitropoulos A, Molinari L, Etter K, Torresani T, Lang-Muritano M, Jenni OG, Largo RH, Latal B (2009) Children with congenital hypothyroidism: long-term intellectual outcome after early high-dose treatment. Pediatr Res 65:242–248

    Article  CAS  PubMed  Google Scholar 

  38. Grosse SD, Matte TD, Schwartz J, Jackson RJ (2002) Economic gains resulting from the reduction in children’s exposure to lead in the United States. Environ Health Perspect 110:563–569

    Article  PubMed Central  PubMed  Google Scholar 

  39. Leger J, Ecosse E, Roussey M, Lanoe JL, Larroque B (2011) Subtle health impairment and socioeducational attainment in young adult patients with congenital hypothyroidism diagnosed by neonatal screening: a longitudinal population-based cohort study. J Clin Endocrinol Metab 96:1771–1782

    Article  CAS  PubMed  Google Scholar 

  40. Hauri-Hohl A, Dusoczky N, Dimitropoulos A, Leuchter RH, Molinari L, Caflisch J, Jenni OG, Latal B (2011) Impaired neuromotor outcome in school-age children with congenital hypothyroidism receiving early high-dose substitution treatment. Pediatr Res 70:614–618

    Article  CAS  PubMed  Google Scholar 

  41. Azar-Kolakez A, Ecosse E, Dos Santos S, Leger J (2013) All-cause and disease-specific mortality and morbidity in patients with congenital hypothyroidism treated since the neonatal period: a national population-based study. J Clin Endocrinol Metab 98:785–793

    Article  CAS  PubMed  Google Scholar 

  42. Hoste C, Rigutto S, Van Vliet G, Miot F, De Deken X (2010) Compound heterozygosity for a novel hemizygous missense mutation and a partial deletion affecting the catalytic core of the H2O2-generating enzyme DUOX2 associated with transient congenital hypothyroidism. Hum Mutat 31:E1304–E1319

    Article  CAS  PubMed  Google Scholar 

  43. Castanet M, Lyonnet S, Bonaiti-Pellie C, Polak M, Czernichow P, Leger J (2000) Familial forms of thyroid dysgenesis among infants with congenital hypothyroidism. N Engl J Med 343:441–442

    Article  CAS  PubMed  Google Scholar 

  44. Perry R, Heinrichs C, Bourdoux P, Khoury K, Szots F, Dussault JH, Vassart G, Van Vliet G (2002) Discordance of monozygotic twins for thyroid dysgenesis: implications for screening and for molecular pathophysiology. J Clin Endocrinol Metab 87:4072–4077

    Article  CAS  PubMed  Google Scholar 

  45. Narumi S, Muroya K, Asakura Y, Adachi M, Hasegawa T (2010) Transcription factor mutations and congenital hypothyroidism: systematic genetic screening of a population-based cohort of Japanese patients. J Clin Endocrinol Metab 95:1981–1985

    Article  CAS  PubMed  Google Scholar 

  46. Castanet M, Sura-Trueba S, Chauty A, Carre A, de Roux N, Heath S, Leger J, Lyonnet S, Czernichow P, Polak M (2005) Linkage and mutational analysis of familial thyroid dysgenesis demonstrate genetic heterogeneity implicating novel genes. Eur J Hum Genet 13:232–239

    Article  CAS  PubMed  Google Scholar 

  47. Dentice M, Cordeddu V, Rosica A, Ferrara AM, Santarpia L, Salvatore D, Chiovato L, Perri A, Moschini L, Fazzini C, Olivieri A, Costa P, Stoppioni V, Baserga M, De Felice M, Sorcini M, Fenzi G, Di Lauro R, Tartaglia M, Macchia PE (2006) Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis. J Clin Endocrinol Metab 91:1428–1433

    Article  CAS  PubMed  Google Scholar 

  48. Lu XY, Phung MT, Shaw CA, Pham K, Neil SE, Patel A, Sahoo T, Bacino CA, Stankiewicz P, Kang SH, Lalani S, Chinault AC, Lupski JR, Cheung SW, Beaudet al (2008) Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis. Pediatrics 122:1310–1318

    Google Scholar 

  49. Thorwarth A, Mueller I, Biebermann H, Ropers HH, Grueters A, Krude H, Ullmann R (2010) Screening chromosomal aberrations by array comparative genomic hybridization in 80 patients with congenital hypothyroidism and thyroid dysgenesis. J Clin Endocrinol Metab 95:3446–3452

    Article  CAS  PubMed  Google Scholar 

  50. Opitz R, Maquet E, Huisken J, Antonica F, Trubiroha A, Pottier G, Janssens V, Costagliola S (2012) Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development. Dev Biol 372:203–216

    Article  CAS  PubMed  Google Scholar 

  51. Opitz R, Hitz MP, Vandernoot I, Trubiroha A, Abu-Khudir R, Samuels M, Desilets V, Costagliola S, Andelfinger G, Deladoey J (2015) Functional zebrafish studies based on human genotyping point to netrin-1 as a link between aberrant cardiovascular development and thyroid dysgenesis. Endocrinology 156:377–388

    Google Scholar 

  52. Bongers-Schokking JJ, Resing WC, de Rijke YB, de Ridder MA, de Muinck Keizer-Schrama SM (2013) Cognitive development in congenital hypothyroidism: is overtreatment a greater threat than undertreatment? J Clin Endocrinol Metab 98:4499–4506

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Endocrinology Service and Research Center, Sainte-Justine Hospital, 3175 Côte Sainte-Catherine, Montréal, QC, H3T 1C5, Canada

    Johnny Deladoëy MD, PhD & Guy Van Vliet

  2. Department of Pediatrics, University of Montreal, Montreal, QC, H3T 1C5, Canada

    Johnny Deladoëy MD, PhD & Guy Van Vliet

  3. Quebec Neonatal Blood Screening Program, CHU de Québec, Montreal, QC, Canada

    Yves Giguère

  4. Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec City, QC, G1K 7P4, Canada

    Yves Giguère

Authors
  1. Johnny Deladoëy MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guy Van Vliet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yves Giguère
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Johnny Deladoëy MD, PhD .

Editor information

Editors and Affiliations

  1. Novara, Italy

    Gianni Bona

  2. Messina, Italy

    Filippo De Luca

  3. Division of Pediatrics, Piedemonte Hospital, Novara, Italy

    Alice Monzani

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Deladoëy, J., Van Vliet, G., Giguère, Y. (2015). Neonatal Screening for Congenital Hypothyroidism: What It Has Taught us About Thyroid and Brain Development. In: Bona, G., De Luca, F., Monzani, A. (eds) Thyroid Diseases in Childhood. Springer, Cham. https://doi.org/10.1007/978-3-319-19213-0_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-19213-0_4

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-19212-3

  • Online ISBN: 978-3-319-19213-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation