title: High versus low dose of initial thyroid hormone replacement for congenital hypothyroidism.
abstract: BACKGROUND
  Congenital hypothyroidism (CHT) affects approximately one in 3000 to 4000 infants. CHT is one of the most common preventable causes of learning difficulties. Optimal management of CHT requires early diagnosis and prompt treatment to avoid abnormal neurodevelopmental outcome. One of the main issues in the management of CHT relates to the initial dose of levothyroxine to be used in order to achieve optimal results in terms of intellectual development. Currently, it remains unclear whether high dose thyroid hormone replacement is more effective than low dose in the treatment of CHT. Further research is required to determine an appropriate dose that improves mental and psychomotor developmental outcomes.
  
  
  OBJECTIVE
  To determine the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism.
  
  
  METHODS
  Randomised controlled trials were identified by searching The Cochrane Library, MEDLINE and EMBASE and reference lists of published papers.
  
  
  METHODS
  Randomised controlled clinical trials investigating the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism were included.
  
  
  METHODS
  Both authors independently selected trials, assessed risk of bias and extracted data.
  
  
  RESULTS
  The initial search identified 1014 records which identified 13 publications for further examination. After screening the full text of the 13 selected papers, only one study evaluating 47 babies finally met the inclusion criteria. Using the same cohort at two different time periods, the study investigated the effects of high versus low dose thyroid hormone replacement in relation to (1) time taken to achieve euthyroid status and (2) neurodevelopmental outcome. The study reported that a high dose is more effective in rising serum thyroxine and free thyroxine concentrations to the target range and earlier normalisation of thyroid stimulating hormone compared to a lower dose. Similarly, full scale intelligence quotient was noted to be significantly higher in children who received the high dose compared to the lower dose. However, the verbal intelligence quotient and performance intelligence quotient were similar in both groups. Growth and adverse effects were not reported in the included trial.
  
  
  CONCLUSIONS
  There is currently only one randomised controlled trial evaluating the effects of high versus low dose of initial thyroid hormone replacement for CHT. There is inadequate evidence to suggest that a high dose is more beneficial compared to a low dose initial thyroid hormone replacement in the treatment of CHT.
authors.affiliation: School of Reproductive and Developmental Medicine, University of Liverpool, 1st Floor, Liverpool Women's Hospital, Crown Street, Liverpool, Merseyside, UK, L8 7SS. ngszemay@yahoo.com
authors.forename: Sze May
authors.initials: SM
authors.lastname: Ng
authors.forename: Dhullipala
authors.initials: D
authors.lastname: Anand
authors.forename: Alan M
authors.initials: AM
authors.lastname: Weindling
mesh_terms: D003409:Congenital Hypothyroidism / Q000188:drug therapy*; D020249:Hormone Replacement Therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D013974:Thyroxine / Q000008:administration & dosage*
chemical_list: D013974:Thyroxine