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Newborn screening strategies for congenital hypothyroidism: an update

  • Newborn Screening
  • Published:
Journal of Inherited Metabolic Disease

Abstract

It is the purpose of this article to briefly review the initial development and subsequent evolution of newborn screening programs to detect infants with congenital hypothyroidism (CH) and then to provide an update of the advantages and disadvantages of the main test strategies. Pilot programs began screening newborn populations in North America in the mid-1970s using either primary thyroxine (T4)-follow-up thyroid stimulating hormone (TSH) or primary TSH testing. Many programs in the United States and around the world continue to prefer a primary T4-follow-up TSH test strategy. This approach has the advantage of detecting infants with primary CH, as well as cases of hypopituitary hypothyroidism, by follow-up of infants with a T4 below an absolute cutoff or with a persistently low T4 level, necessitating a higher recall rate. With increasing assay sensitivity and specificity, several programs in the United States and worldwide have elected to switch to a primary TSH test strategy. This test strategy has the advantage of detecting primary CH and subclinical hypothyroidism and at a lower recall rate. Programs considering switching to a primary TSH test strategy need to develop age-related TSH cutoffs to maintain an acceptable recall rate. Both test strategies have the potential to detect infants with CH characterized by “delayed TSH rise,” but only if they collect a routine or discretionary second specimen, now recommended in low-birth-weight and acutely ill infants. Lastly, a lower TSH cutoff appears to be one of the explanations for the recently described increased incidence of CH.

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Abbreviations

CH:

Congenital hypothyroidism

DBS:

Dried blood spot

NNSGRC:

National Newborn Screening and Genetics Resource Center

SCH:

Subclinical hypothyroidism

T3:

Triiodothyronine

T4:

Thyroxine

TBG:

Thyroxine-binding globulin

TSH:

Thyroid stimulating hormone

References

  • Alm J, Hagenfeldt L, Larsson A, Lundberg K (1984) Incidence of congenital hypothyroidism: retrospective study of neonatal laboratory screening versus clinical symptoms as indicators leading to diagnosis. Br Med J 289:1171–1175

    Article  CAS  Google Scholar 

  • Chiesa A, Prieto L, Papendieck P, Gilligan G, Niremberg M, Gruneiro-Papendieck L (2009) Characterization of thyroid disorders found by primary congenital hypothyroidism (CH) neonatal screening: Something is changing? Revi Invest Clin 61(Suppl 1):30

    Google Scholar 

  • Corbetta C, Webert G, Cortinovis F et al (2009) A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol 71:739–745

    Article  CAS  Google Scholar 

  • Delange F, Camus M, Winkler M, Dodion J, Ermans AM (1977) Serum thyrotropin Determination on day 5 of life as screening procedure for congenital hypothyroidism. Arch Dis Child 52:89–96

    Article  CAS  PubMed  Google Scholar 

  • Dussault JH, Coulombe P, Laberge C et al (1975) Preliminary report on a mass screening program for neonatal hypothyroidism. J Pediatr 86:670–674

    Article  CAS  PubMed  Google Scholar 

  • Fisher DA, Dussault JH, Foley TP Jr et al (1979) Screening for congenital hypothyroidism: Results of screening one million North American infants. J Pediatr 94:700–705

    Article  CAS  PubMed  Google Scholar 

  • Fukushi M, Fujikura K, Hanai J, Yano K, Tamima T, Fujieda K (2009) Neonatal screening for congenital hypothyroidism by measurement of TSH and free T4. Rev Invest Clin 61(Suppl 1):30

    Google Scholar 

  • Hanna CE, Krainz PL, Skeels MR et al (1986) Detection of congenital hypopituitary hypothyroidism: ten-year experience in the Northwest Regional Screening Program. J Pediatr 109:959–964

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Hunter MK, Mandel SH, Sesser DE, et al. (1998) Follow-up of newborns with low thyroxine and non-elevated thyroid-stimulating hormone-screening concentrations: Results of the 20-year experience in the Northwest Regional Newborn Screening Program. 132:70–74.

  • Illig R, Torresani T, Sobradillo B (1977) Early detection of neonatal hypothyroidism by serial TSH determination in dried blood. Helv Paediatr Acta 32:289–297

    CAS  PubMed  Google Scholar 

  • Klein AG, Foley TP Jr (1975) Letter: Screening for hypothyroidism. J Pediatr 87:667–668

    Google Scholar 

  • Kohler B, Schnabel D, Biebermann H, Gruters A (1996) Transient congenital hypothyroidism and hyperthyrotropinemia: normal thyroid function and physical development at the ages of 6-14 years. J Clin Endocrinol Metab 81:1563–1567

    Article  CAS  PubMed  Google Scholar 

  • LaFranchi SH, Murphey WH, Foley TP Jr (1979) Neonatal hypothyroidism detected by the Northwest Regional Screening Program. Pediatrics 63:180–191

    CAS  PubMed  Google Scholar 

  • LaFranchi SH, Hanna CE, Krainz PL, Skeels MR, Miyahira RS, Sesser DE (1985) Screening for congenital hypothyroidism with specimen collection at two time periods: Results of the Northwest Regional Screening Program. Pediatrics 76:734–740

    CAS  PubMed  Google Scholar 

  • Lanting CI, van Tijn DA, Loeber JG, Vulsma T, de Vijlder JJ, Verkerk PH (2005) Clinical effectiveness and cost-effectiveness of the use of the thyroxine/thyroxine-binding globulin ratio to detect congenital hypothyroidism of thyroidal and central origin in a neonatal screening program. Pediatrics 116(1):168–73

    Article  PubMed  Google Scholar 

  • Mandel SJ, Hermos RJ, Larson CA, Prigozhin AB, Rojas DA, Mitchell ML (2000) Atypical Hypothyroidism and the very low birthweight infant. Thyroid 8:693–695

    Article  Google Scholar 

  • Maniatis AK, Taylor L, Letson GW, Bloch CA, Kappy MS, Zeitler P (2006) Congenital Hypothyroidism and the second newborn metabolic screening in Colorado, USA. J Pediatr Endocrinol Metab 19:31–38

    PubMed  Google Scholar 

  • Miyai K, Oura T, Kawashima M, et al. (1978) A new method of paired thyrotropin assay as a screening test for neonatal hypothyroidism. J Clin Endocrinol Metab 47:1028-1033

    Google Scholar 

  • National Newborn Screening and Genetics Resource Center (NNSGRC), 2009 National Newborn Screening Information System (http://genes-r-us.uthscsa.edu).

  • Ruiz de Ona C, Obregon MJ, Escobar del Rey F, Morreale de Escobar G (1988) Developmental changes in rat brain 5’-deiodinase and thyroid hormones during the fetal period: the effects of fetal hypothyroidism and maternal thyroid hormones. Pediatr Res 24:588–594

    CAS  PubMed  Google Scholar 

  • Vulsma T, Gons MH, deVijlder JJM (1989) Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis. N Engl J Med (321):13–16

  • Wiley V, Bijarnia S, Wikcken B (2009) Screening for hypothyroidism in very low birth weight babies. Rev Invest Clin 61(Suppl 1):31

    Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics (CDRCP), Division of Endocrinology, Oregon Health & Science University, 707 SW Gaines St., Portland, OR, 97219, USA

    Stephen H. LaFranchi

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  1. Stephen H. LaFranchi
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Correspondence to Stephen H. LaFranchi.

Additional information

Communicated by: Rodney Pollitt

References to electronic databases:

OMIM #218700, U.S. National Newborn Screening and Genetics Resource Center: http://genes-r-us.uthscsa.edu, United Kingdom UCL Institute of Child Health: http://www.ich.ucl.ac.uk/clinical_information/clinical_guidelines/cmg_guideline_00079

Competing interest: None declared.

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LaFranchi, S.H. Newborn screening strategies for congenital hypothyroidism: an update. J Inherit Metab Dis 33 (Suppl 2), 225–233 (2010). https://doi.org/10.1007/s10545-010-9062-1

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  • DOI: https://doi.org/10.1007/s10545-010-9062-1

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