Download PDF
Kinder- und Jugendmedizin 2016; 16(04): 247-256
DOI: 10.1055/s-0037-1616331
Endokrinologie
Schattauer GmbH

Angeborene Hypothyreose

Congenital hypothyroidism
J. Hoppmann
1   Universitätsklinik und Poliklinik für Kinder und Jugendliche Leipzig, Pädiatrische Endokrinologie, Department für Frauen- und Kindermedizin
,
R. Pfäffle
1   Universitätsklinik und Poliklinik für Kinder und Jugendliche Leipzig, Pädiatrische Endokrinologie, Department für Frauen- und Kindermedizin
,
W. Kiess
1   Universitätsklinik und Poliklinik für Kinder und Jugendliche Leipzig, Pädiatrische Endokrinologie, Department für Frauen- und Kindermedizin
› Author Affiliations
Further Information

Publication History

Eingereicht am: 19 March 2016

angenommen am: 24 March 2016

Publication Date:
11 January 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die angeborene Hypothyreose ist mit einer Inzidenz von 1:3000–4000 Neugeborenen die häufigste angeborene endokrine Erkrankung. Die häufigsten Ursachen einer permanenten Hypothyreose sind Schilddrüsenentwicklungsstörungen und Schilddrüsenhormonsynthesedefekte. Seltener liegt eine zentrale Hypothyreose vor. Ursachen einer transienten Hypothyreose sind ein akuter Jodexzess, ein chronischer Jodmangel, mütterliche Schilddrüsenantikörper oder Thyreostatika. Bei einem TSH-Wert >15 mU/l im Neugeborenenscreening wird die Verdachtsdiagnose einer primären angeborenen Hypothyreose gestellt. Die Diagnose gilt als gesichert, wenn der TSH-Wert in der Konfirmationsdiagnostik oberhalb und der T4/fT4-Wert unterhalb des altersspezifischen Referenzbereichs liegen. Die diagnostische Abklärung umfasst eine ausführliche Anamnese, eingehende klinische Untersuchung, die Sonografie der Schilddrüse und ggf. die Bestimmung von Thyreoglobulin, Schilddrüsenantikörpern und Jodausscheidung sowie die genetische Diagnostik. Die Behandlung mit L-Thyroxin sollte so früh wie möglich in einer Dosierung von 10–15 µg/kg KG/Tag erfolgen. Nach Therapiebeginn müssen regelmäßige Therapiekontrollen durchgeführt werden, die neben der körperlichen Untersuchung die Bestimmung von TSH und T4/fT4 umfassen. Alle Kinder sollten im Verlauf regelmäßige audiologische Kontrollen und Entwicklungs- bzw. Intelligenztests erhalten. Durch eine frühzeitige Diagnostik und adäquate Therapie wird eine normale Entwicklung der Kinder ermöglicht.

Summary

With an incidence of 1:3000–4000 congenital hypothyroidism is the most common congenital endocrine disease. The most prevalent causes of permanent congenital hypothyroidism are thyroid dysgenesis and defects of thyroid hormone synthesis. Central hypothyroidism is less common. Causes of transient hypothyroidism are acute iodine excess, chronic iodine deficiency, maternal thyroid antibodies, or anti-thyroid drugs. Primary congenital hypothyroidism is suspected if the TSH level is >15 mU/l at newborn screening. The diagnosis is confirmed if the TSH level is above and the T4/fT4 level below the age-specific reference range at the confirmatory laboratory test. The diagnostic work-up includes a detailed medical history, an extensive clinical examination, thyroid ultrasound and potentially the determination of thyroglobulin, thyroid antibodies, and iodine excretion, as well as genetic diagnostics. Affected children should be treated with levothyroxine as early as possible at a dose of 10 to 15 µg/kg/day. Afterwards, regular follow-up investigations need to be conducted that include the clinical examination and determination of TSH and T4/fT4 levels. In the course of the treatment, all children should be subjected to regular hearing tests as well as development and intelligence tests. An early diagnosis and adequate therapy allow children to develop normally.

Schlüsselwörter

Angeborene Hypothyreose - konnatale Hypothyreose - kongenitale Hypothyreose - Neugeborenenscreening

Keywords

Congenital hypothyroidism - newborn screening
 

  • Literatur

  • 1 Alm J, Hagenfeldt L, Larsson A, Lundberg K. Incidence of congenital hypothyroidism: retrospective study of neonatal laboratory screening versus clinical symptoms as indicators leading to diagnosis. Br Med J (Clin Res Ed) 1984; 289: 1171-1175.
    CrossrefPubMedGoogle Scholar
  • 2 Alvarez M, Iglesias Fernandez C, Rodriguez Sanchez A. et al. Episodes of overtreatment during the first six months in children with congenital hypothyroidism and their relationships with sustained attention and inhibitory control at school age. Horm Res Paediatr 2010; 74: 114-120.
    CrossrefPubMedGoogle Scholar
  • 3 Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften. S2k-Leitlinie: Diagnostik, Therapie und Verlaufskontrolle der Primären angeborenen Hypothyreose. 2010 URL: http://www.awmf.org/uploads/tx_szleitli nien/027–017l_S2k_Primaere_Angeborene_Hypothyreose_2011-abgelaufen.pdf
    PubMedGoogle Scholar
  • 4 Beltrao CB, Juliano AG, Chammas MC. et al. Etiology of congenital hypothyroidism using thyroglobulin and ultrasound combination. Endocr J 2010; 57: 587-593.
    CrossrefPubMedGoogle Scholar
  • 5 Bess FH, Dodd-Murphy J, Parker RA. Children with minimal sensorineural hearing loss: prevalence, educational performance, and functional status. Ear Hear 1998; 19: 339-354.
    CrossrefPubMedGoogle Scholar
  • 6 Boileau P, Bain P, Rives S, Toublanc JE. Earlier onset of treatment or increment in LT4 dose in screened congenital hypothyroidism: which is the more important factor for IQ at 7 years?. Horm Res 2004; 61: 228-233.
    CrossrefPubMedGoogle Scholar
  • 7 Bongers-Schokking JJ, de Muinck Keizer-Schrama SM. Influence of timing and dose of thyroid hormone replacement on mental, psychomotor, and behavioral development in children with congenital hypothyroidism. J Pediatr 2005; 147: 768-774.
    CrossrefPubMedGoogle Scholar
  • 8 Bongers-Schokking JJ, Resing WC, de Rijke YB. et al. Cognitive development in congenital hypothyroidism: is overtreatment a greater threat than undertreatment?. J Clin Endocrinol Metab 2013; 98: 4499-4506.
    CrossrefPubMedGoogle Scholar
  • 9 Brown RS, Bellisario RL, Botero D. et al. Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies. J Clin Endocrinol Metab 1996; 81: 1147-1151.
    PubMedGoogle Scholar
  • 10 Bruno R, Aversa T, Catena M. et al. Even in the era of congenital hypothyroidism screening mild and subclinical sensorineural hearing loss remains a relatively common complication of severe congenital hypothyroidism. Hear Res 2015; 327: 43-47.
    CrossrefPubMedGoogle Scholar
  • 11 Bubuteishvili L, Garel C, Czernichow P, Léger J. Thyroid abnormalities by ultrasonography in neonates with congenital hypothyroidism. J Pediatr 2003; 34: 109-113.
    Google Scholar
  • 12 Bundesanzeiger Nr. 40, S. 1013 (Anlage 2 – Erweitertes Neugeborenen-Screening). 2011
    PubMedGoogle Scholar
  • 13 Deladoëy J, Ruel J, Giguère Y. et al. Is the incidence of congenital hypothyroidism really increasing? A 20-year retrospective population-based study in Québec. J Clin Endocrinol Metab 2011; 96: 2422-2429.
    CrossrefPubMedGoogle Scholar
  • 14 Delange F. Screening for congenital hypothyroidism used as an indicator of the degree of iodine deficiency and of its control. Thyroid 1998; 8: 1185-1192.
    CrossrefPubMedGoogle Scholar
  • 15 Delvecchio M, Salerno M, Vogone MC. et al. Levothyroxine requirement in congenital hypothyroidism: a 12-year longituinal study. Endocrine 2015; 50: 674-680.
    CrossrefPubMedGoogle Scholar
  • 16 Dimitropoulos A, Moliinari L, Etter K. et al. Children with congenital hypothyroidism: long-term intellectual outcome after early high-dose treatment. Pediatr Res 2009; 65: 242-248.
    CrossrefPubMedGoogle Scholar
  • 17 Dubuis JM, Glorieux J, Richer F. et al. Outcome of severe congenital hypothyroidism: closing the developmental gap with early high dose levothyroxine treatment. J Clin Endocrinol Metab 1996; 81: 222-227.
    PubMedGoogle Scholar
  • 18 Elmlinger MW, Kühnel W, Lambrecht HG, Ranke MB. Reference intervals from birth to adulthood for serum thyroxine (T4), triiodothyronine (T3), free T3, free T4, thyroxine binding globuline (TBG) and thyrotropin (TSH). Clin Chem Lab Med 2001; 39: 973-979.
    PubMedGoogle Scholar
  • 19 Filippi L, Pezzati M, Poggi C. et al. Dopamine versus dobutamine in very low birthweight infants: endocrine effect. Arch Dis Child Fetal Neonatal Ed 2007; 92: F367-F371.
    CrossrefPubMedGoogle Scholar
  • 20 Gaudino R, Garel C, Czernichow P. et al. Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: a regional cohort study. Clin Endocrinol (Oxf) 2005; 62: 444-448.
    CrossrefPubMedGoogle Scholar
  • 21 Grosse SD, Van Vliet G. Prevention of intellectual disability through screening for congenital hypothyroidism: how much and at what level?. Arch Dis Child 2011; 96: 374-379.
    CrossrefPubMedGoogle Scholar
  • 22 Grüters A, Krude H. Detection and treatment of congenital hypothyroidism. Nat Rev Endocrinol 2012; 8: 104-113.
    CrossrefPubMedGoogle Scholar
  • 23 Grüters A, Krude H. Update on the management of congenital hypothyroidism. Horm Res 2007; 68: 107-111.
    CrossrefPubMedGoogle Scholar
  • 24 Grüters A, l’Allemand D, Heidemann PH, Schürnbrand P. Incidence of iodine contamination in neonatal transient hyperthyrotropinemia. Eur J Pediatr 1983; 140: 299-300.
    CrossrefPubMedGoogle Scholar
  • 25 Hauri-Hohl A, Dusoczky N, Dimitropoulos A. et al. Impaired neuromotor outcome in school-age children with congenital hypothyroidism receiving early high-dose substitution treatment. Pediatr Res 2011; 70: 614-618.
    PubMedGoogle Scholar
  • 26 Huo K, Zhang Z, Zhao D. et al. Risk factors for neurodevelopmental deficits in congenital hypothyroidism after early substitution treatment. Endocr J 2011; 58: 355-361.
    CrossrefPubMedGoogle Scholar
  • 27 Klein AH, Meltzer S, Kenny FM. Improved prognosis in congenital hypothyroidism treated before age three months. J Pediatr 1972; 81: 912-915.
    CrossrefPubMedGoogle Scholar
  • 28 Léger J, Ecosse E, Roussey M. et al. 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 2011; 96: 1771-1782.
    CrossrefPubMedGoogle Scholar
  • 29 Léger J, Olivieri A, Donaldson M. et al. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab 2014; 99: 363-384.
    CrossrefPubMedGoogle Scholar
  • 30 Lichtenberger-Geslin L, Dos Santos S, Hassani Y. et al. 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: 3644-3652.
    CrossrefPubMedGoogle Scholar
  • 31 Mantovani G. Clinical review: Pseudohypoparathyroidism: diagnosis and treatment. J Clin Endocrinol Metab 2011; 96: 3020-3030.
    CrossrefPubMedGoogle Scholar
  • 32 Marinovic D, Garel C, Czernichow P, Léger J. Ultrasonographic assessment of the ectopic thyroid tissue in children with congenital hypothyroidism. Pediatr Radiol 2004; 34: 109-113.
    CrossrefPubMedGoogle Scholar
  • 33 Medeiros-Neto G, de Lacerda L, Wondiford FE. Familial congenital hypothyroidism by abnormal and bioactive TSH due to mutations in the betasubunit gene. Trends Endocrinol Metab 1997; 8: 15-20.
    CrossrefPubMedGoogle Scholar
  • 34 Mengreli C, Maniati-Christidi M, Kanaka-Gantenbein C. et al. Transient congenital hypothyroidism due to maternal autoimmune thyroid disease. Hormones (Athens) 2003; 2: 113-119.
    CrossrefPubMedGoogle Scholar
  • 35 Oerbeck B, Sundet K, Kase BF. et al. Congenital hypothyroidism: influence of disease severity and L-thyroxine treatment on intellectual, motor, and school-associated outcomes in young adults. Pediatrics 2003; 112: 923-930.
    CrossrefPubMedGoogle Scholar
  • 36 Ohnishi H, Sato H, Noda H. et al. Color doppler ultrasonography: diagnosis of ectopic thyroid gland in patients with congenital hypothyroidism caused by thyroid dysgenesis. J Clin Endocrinol Metab 2003; 88: 5145-5149.
    CrossrefPubMedGoogle Scholar
  • 37 Olivieri A, Stazi MA, Mastroiacovo P. et al. A population-based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: data from the Italian Registry for Congenital Hypothyroidism (1991–1998). J Clin Endocrinol Metab 2002; 87: 557-562.
    PubMedGoogle Scholar
  • 38 Parazzini M, Ravazzani P, Medaglini S. et al. Click-evoked otoacustic emissions recorded from untreated congenital hypothyroid newborns. Hear Res 2002; 166: 136-142.
    CrossrefPubMedGoogle Scholar
  • 39 Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis 2010; 17: 1-22.
    Google Scholar
  • 40 Re RN, Kourides IA, Ridgway EC. et al. The effect of glucocorticoid administration on human pituitary secretion of thyrotropin and prolactin. J Clin Endocrinol Metab 1976; 43: 338-346.
    CrossrefPubMedGoogle Scholar
  • 41 Rovet JF. Children with congenital hypothyroidism and their siblings: do they really differ?. Pediatrics 2005; 115: e52-e57.
    CrossrefPubMedGoogle Scholar
  • 42 Rovet JF, Ehrlich R. Psychoeducational outcome in children with early-treated congenital hypothyroidism. Pediatrics 2000; 105: 515-522.
    CrossrefPubMedGoogle Scholar
  • 43 Rovet J, Walker W, Bliss B. et al. Long-term sequelae of hearing impairment in congenital hypothyroidism. J Pediatr 1996; 128: 776-783.
    CrossrefPubMedGoogle Scholar
  • 44 Salerno M, Militerni R, Bravaccio C. et al. Effect of different starting doses of levothyroxine on growth and intellectual outcome at four years of age in congenital hypothyroidism. Thyroid 2002; 12: 45-52.
    CrossrefPubMedGoogle Scholar
  • 45 Schoen EJ, Clapp W, To TT, Fireman BH. The key role of newborn thyroid scintigraphy with isotopic iodide (123I) in defining and managing congenital hypothyroidism. Pediatrics 2004; 114: e683-e688.
    CrossrefPubMedGoogle Scholar
  • 46 Selva KA, Harper A, Downs A. et al. Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH. J Pediatr 2005; 147: 775-780.
    CrossrefPubMedGoogle Scholar
  • 47 Szinnai G. Clinical genetics of congenital hypothyroidism. Endocr Dev 2014; 26: 60-78.
    PubMedGoogle Scholar
  • 48 Targovnik HM, Citterio CE, Rivolta CM. Thyroglobulin gene mutations in congenital hypothyroidism. Horm Res Paediatr 2011; 75: 311-321.
    CrossrefPubMedGoogle Scholar
  • 49 Van Tijn DA, de Vijlder JJ, Verbeeten Jr B. et al. Neonatal detection of congenital hypothyroidism of central origin. J Clin Endocrinol Metab 2005; 90: 3350-3359.
    CrossrefPubMedGoogle Scholar
  • 50 Von Heppe JH, Krude H, L’Allemand D. et al. The use of L-T4 as liquid solution improves the practicability and individualized dosage in newborns and infants with congenital hypothyroidism. J Pediatr Endocrinol Metab 2004; 17: 967-974.
    CrossrefPubMedGoogle Scholar
  • 51 Woo HC, Lizarda A, Tucker R. et al. Congenital hypothyroidism with a delayed thyroid-stimulating hormone elevation in very premature infants: incidence and growth and developmental outcomes. J Pediatr 2011; 158: 538-542.
    CrossrefPubMedGoogle Scholar
  • 52 Zoeller RT, Rovet J. Timing of thyroid hormone action in the developing brain: clinical observatinos and experimental findings. J Neuroendocrinol 2004; 16: 809-818.
    CrossrefPubMedGoogle Scholar