Skip to main content
SpringerLink
Log in

Angeborene Hypothyreose

Congenital hypothyroidism

  • Leitthema
  • Published:
Monatsschrift Kinderheilkunde Aims and scope Submit manuscript

Zusammenfassung

Die Einführung des Neugeborenenscreenings zur Früherkennung der angeborenen Hypothyreose führte zu neuen Erkenntnissen hinsichtlich Pathogenese, Diagnostik und Therapie des Krankheitsbilds. Die Mehrzahl (80%) der Patienten weisen Entwicklungsdefekte der Schilddrüse auf, nur 15–20% einen Biosynthesedefekt. Für beide Entitäten wurden molekulargenetische Ursachen nachgewiesen. Eine frühe, in den ersten beiden Lebenswochen mit ausreichender Dosis (10–15 µg/kg/Tag) L-Thyroxin initiierte Substitutionstherapie führt in über 90% der Fälle zu einer normalisierten Entwicklung. Bei sehr schweren Hypothyreosen, Defekten von Transkriptionsfaktoren, die auch in der Entwicklung des ZNS bedeutsam sind, und bei nicht ausreichender Compliance kann die Entwicklung trotz früher Diagnose beeinträchtigt sein. Derzeit ist nicht geklärt, ob eine persistierende Thyreotropinerhöhung bei normalen peripheren Schilddrüsenhormonspiegeln behandlungsbedürftig ist.

Abstract

The introduction of newborn screening programs has led to new concepts regarding the pathogenesis, diagnosis and therapy of congenital hypothyroidism. The majority (80%) of patients display developmental defects of the thyroid gland, and only 15%–20% have defective thyroid hormone biosynthesis. Molecular genetic studies have revealed heritable defects of candidate genes for both entities. Early and adequate treatment (10–15 mg/kg/day) with L-thyroxine has led to normal development in more than 90% of patients. Developmental deficits or neurological problems are observed in patients with very severe congenital hypothyroidism, defects of transcription factors also involved in CNS development and who comply poorly with treatment. To date it is unclear which patients with hyperthyrotropinemia and normal peripheral thyroid hormone concentrations will benefit from L-thyroxine therapy.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Abramowicz MJ, Duprez L, Parma J et al. (1997) Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J Clin Invest 99: 3018

    Article  PubMed  CAS  Google Scholar 

  2. Ambrugger P, Stoeva I, Biebermann H et al. (2001) Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism. Eur J Endocrinol 145: 19–24

    Article  PubMed  CAS  Google Scholar 

  3. American Academy of Pediatrics (2006) Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 117: 2290–2303

    Article  Google Scholar 

  4. Bongers Schokking JJ, De Muinck Keizer-Schrama SMPF (2005) Influence of timing and dose of thyroid hormone replacement on mental, psychomotor and behavioral development in children with congenital hypothyroidism. J Pediatr 147: 768–772

    Article  CAS  Google Scholar 

  5. Brumm J, Pfeufer A, Biebermann H et al. (2002) Congenital central hypothyroidism due to a homozygous thyrotropin beta 313 delta T mutation is caused by a founder effect. J Clin Endocrinol Metab 87: 4811

    Article  PubMed  CAS  Google Scholar 

  6. Bundesausschuss der Ärzte und Krankenkassen (2005) Bekanntmachung eines Beschlusses des Gemeinsamen Bundesausschusses über eine Änderung der Richtlinien des Bundesausschusses der Ärzte und Krankenkassen über die Früherkennung von Krankheiten bei Kindern bis zur Vollendung des 6. Lebensjahres (Kinder-Richtlinien) zur Einführung des erweiterten Neugeborenen-Screenings. BAnz 60: 4833

    Google Scholar 

  7. Calaciura F, Mendorla G, Distefano M et al. (1995) Childhood IQ measurements in infants with transient congenital hypothyroidism. Clin Endocrinol (Oxf) 43: 473–477

    Google Scholar 

  8. Dubuis JM, Glorieux J, Richer F et al. (1996) Outcome of severe congenital hypothyroidism: closing the developmental gap with early high dose levothyroxine treatment. J Clin Endocrinol Metab 81: 222–227

    Article  PubMed  CAS  Google Scholar 

  9. Fisher DA (1987) Effectiveness of newborn screening programs for congenital hypothyroidism: prevalence of missed cases. Pediatr Clin North Am 34: 881

    PubMed  CAS  Google Scholar 

  10. Fisher DA, Schoen EJ, LaFranchi S et al. (2000) The hypothalamic-pituitary-thyroid negative feedback control axis in children with treated congenital hypothyroidism. J Clin Endocrinol Metab 85: 2722–2729

    Article  PubMed  CAS  Google Scholar 

  11. Grant DB (1994) Growth in early treated congenital hypothyroidism. Arch Dis Child 70: 464

    Article  PubMed  CAS  Google Scholar 

  12. Gruters A, Krude H, Biebermann H (2004) Molecular genetic defects in congenital hypothyroidism. Eur J Endocrinol 151: 39–44

    Article  Google Scholar 

  13. Hishinuma A, Fukata S, Kakudo K et al. (2005) High incidence of thyroid cancer in long-standing goiters with thyroglobulin mutations. Thyroid 15: 1079–1084

    Article  PubMed  CAS  Google Scholar 

  14. Kohler B, Schnabel D, Biebermann H et al. (1996) Transient congenital hypothyroidism and hyperthyrotropinemia: normal thyroid function and physical development at the ages of 6–14 years. J Clin Endocrinol Metab 81: 1563–1568

    Article  PubMed  CAS  Google Scholar 

  15. Krude H, Schütz B, Biebermann H et al. (2002) Choreoathetosis, hypothyroidism and pulmonary alterations due to human NKX2–1 haploinsufficiency. J Clin Invest 109: 475–480

    PubMed  CAS  Google Scholar 

  16. LaFranchi SH, Hanna CE, Krainz PL et al. (1985) Screening for congenital hypothyroidism with specimen collection at two time periods results of the northwest regional screening program. Pediatrics 76: 734

    PubMed  CAS  Google Scholar 

  17. Leger J, Marinovic D, Garel C et al. (2002) Thyroid developmental anomalies in first degree relatives of children with congenital hypothyroidism. J Clin Endocrinol Metab 87: 575

    Article  PubMed  CAS  Google Scholar 

  18. Moreno J, Klootwijk W, Van Toor H et al. (2008) Mutations in the iodotyrosine deiodinase gene and hypothyroidism. N Engl J Med 358: 1811–1818

    Article  PubMed  CAS  Google Scholar 

  19. Oerbeck B, K Sundet K, Kase B et al. (2005) Congenital hypothyroidism: no adverse effects of high dose thyroxine treatment on adult memory, attention and behaviour. Arch Dis Child 90: 132–137

    Article  PubMed  CAS  Google Scholar 

  20. Olivieri A, Stazi MA, Mastroiacovo P et al. (2002) A population based study on the frequency of additional congenital malformatons in infants with congenital hypothyroidism: data from the Italian registry for congenital hpothyroidism (1991–1998). J Clin Endocrinol Metab 87: 557–563

    Article  PubMed  CAS  Google Scholar 

  21. Pohlenz J, Refetoff S (1999) Mutations in the sodium/iodide symporter gene as a cause for iodide transport defects and congenital hypothyroidism. Biochemie 81: 469

    Article  CAS  Google Scholar 

  22. Selva K, Harper A, Downs A et al. (2005) Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH. J Pediatr 147: 775–782

    Article  PubMed  CAS  Google Scholar 

  23. Tonacchera M, Perri A, DeMarco G et al. (2004) Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism. J Clin Endocrinol Metab 89: 5787–5792

    Article  PubMed  CAS  Google Scholar 

  24. Tylek-Lemanska D, Kumorowicz-Kopiec M, Starzyk J (2005) Screening for congenital hypothyroidism: the value of retesting after four months in neonates with low or very low birth weight. J Med Screen 12: 166–169

    Article  PubMed  Google Scholar 

  25. Van der Sluijs Veer L, Kempers M, Last BF et al.T (2008) Quality of life, developmental milestones and self-esteem of young adults with congenital hypothyroidism diagnosed by neonatal screening. J Clin Endocrinol Metab 93: 2654–2661

    Article  CAS  Google Scholar 

  26. Van Tijn DA, De Vijlder JJM, Verbeeten B jr et al. (2005) Neonatal detection of congenital hypothyroidism of central origin. J Clin Endocrinol Metab 90: 3350–3354

    Article  CAS  Google Scholar 

  27. Van Trotsenburg ASP, Vulsma T, Van Rozenburg-Marres SL et al. (2005) The effect of thyroxine treatment started in the neonatal period on development and growth of two-year-old Down syndrome children: a randomized clinical trial. J Clin Endocrinol Metab 90: 3304–3311

    Article  CAS  Google Scholar 

  28. Van Wassenaer AG, Kok JH, Dekker FW et al. (1997) Thyroid function in very preterm infants influences of gestational age and disease. Pediatr Res 42: 604–609

    Article  Google Scholar 

  29. Vigone MC, Fugazzola L, Zamproni I et al. (2005) Persistent mild hypothyroidism associated with novel sequence variants of the DUOX2 gene in two siblings. Hum Mutat 26: 395

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Charité Centrum für Frauen-, Kinder- und Jugendmedizin, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Deutschland

    A. Grüters & H. Krude

Authors
  1. A. Grüters
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Krude
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Grüters.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grüters, A., Krude, H. Angeborene Hypothyreose. Monatsschr Kinderheilkd 156, 951–960 (2008). https://doi.org/10.1007/s00112-008-1738-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00112-008-1738-3

Schlüsselwörter

Keywords

Search

Navigation