title: Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect.
abstract: OBJECTIVE
  To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment.
  
  
  METHODS
  A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language.
  
  
  METHODS
  First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland.
  
  
  METHODS
  361 children with congenital hypothyroidism given early treatment and 315 control children.
  
  
  METHODS
  Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence.
  
  
  RESULTS
  There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1-173 days), average thyroxine dose (12-76 micrograms in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5.
  
  
  CONCLUSIONS
  Despite early treatment in congenital hypothyroidism the disease severity has a threshold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education.
authors.affiliation: MRC Register for Children with Congenital Hypothyrodism, Institute of Child Health, London.
authors.forename: S L
authors.initials: SL
authors.lastname: Tillotson
authors.forename: P W
authors.initials: PW
authors.lastname: Fuggle
authors.forename: I
authors.initials: I
authors.lastname: Smith
authors.forename: A E
authors.initials: AE
authors.lastname: Ades
authors.forename: D B
authors.initials: DB
authors.lastname: Grant
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D003409:Congenital Hypothyroidism; D004739:England / Q000453:epidemiology; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000523:psychology; D007223:Infant; D007231:Infant, Newborn; D007360:Intelligence; D016015:Logistic Models; D015997:Neonatal Screening; D009660:Northern Ireland / Q000453:epidemiology; D012923:Social Class; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014852:Wales / Q000453:epidemiology
chemical_list: D013974:Thyroxine