title: Early thyroxine treatment in Down syndrome and thyroid function later in life.
abstract: OBJECTIVE
  The hypothalamus-pituitary-thyroid (HPT) axis set point develops during the fetal period and first two years of life. We hypothesized that thyroxine treatment during these first two years, in the context of a randomized controlled trial (RCT) in children with Down syndrome, may have influenced the HPT axis set point and may also have influenced the development of Down syndrome-associated autoimmune thyroiditis.
  
  
  METHODS
  We included 123 children with Down syndrome 8.7 years after the end of an RCT comparing thyroxine treatment vs placebo and performed thyroid function tests and thyroid ultrasound. We analyzed TSH and FT4 concentrations in the subgroup of 71 children who were currently not on thyroid medication and had no evidence of autoimmune thyroiditis.
  
  
  RESULTS
  TSH concentrations did not differ, but FT4 was significantly higher in the thyroxine-treated group than that in the placebo group (14.1 vs 13.0 pmol/L;P= 0.02). There was an increase in anti-TPO positivity, from 1% at age 12 months to 6% at age 24 months and 25% at age 10.7 years with a greater percentage of children with anti-TPO positivity in the placebo group (32%) compared with the thyroxine-treated group (18.5%) (P= 0.12). Thyroid volume at age 10.7 years (mean: 3.4 mL; range: 0.5-7.5 mL) was significantly lower (P< 0.01) compared with reference values (5.5 mL; range: 3-9 mL) and was similar in the thyroxine and placebo group.
  
  
  CONCLUSIONS
  Thyroxine treatment during the first two years of life led to a mild increase in FT4 almost 9 years later on and may point to an interesting new mechanism influencing the maturing HPT axis set point. Furthermore, there was a trend toward less development of thyroid autoimmunity in the thyroxine treatment group, suggesting a protective effect of the early thyroxine treatment. Lastly, thyroid volume was low possibly reflecting Down-specific thyroid hypoplasia.
authors.affiliation: Department of Pediatric Endocrinology.
authors.forename: Nitash
authors.initials: N
authors.lastname: Zwaveling-Soonawala
authors.affiliation: Department of Pediatric Endocrinology.
authors.forename: M Emma
authors.initials: ME
authors.lastname: Witteveen
authors.affiliation: Psychosocial DepartmentEmma Children's Hospital.
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Marchal
authors.affiliation: Department of Pediatric Endocrinology.
authors.forename: Femke C C
authors.initials: FCC
authors.lastname: Klouwer
authors.affiliation: Department of Pediatric Endocrinology.
authors.forename: Nadine A
authors.initials: NA
authors.lastname: Ikelaar
authors.affiliation: Departments of Radiology.
authors.forename: Anne M J B
authors.initials: AMJB
authors.lastname: Smets
authors.affiliation: Departments of Radiology.
authors.forename: Rick R
authors.initials: RR
authors.lastname: van Rijn
authors.affiliation: Departments of Clinical ChemistryLaboratory of Endocrinology.
authors.forename: Erik
authors.initials: E
authors.lastname: Endert
authors.affiliation: Endocrinology and MetabolismAcademic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Pediatric Endocrinology.
authors.forename: A S Paul
authors.initials: ASP
authors.lastname: van Trotsenburg
mesh_terms: D000328:Adult; D000367:Age Factors; D002648:Child; D004314:Down Syndrome / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D013960:Thyroid Function Tests / Q000639:trends; D013961:Thyroid Gland / Q000187:drug effects* / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage* / Q000097:blood; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D013972:Thyrotropin; D013974:Thyroxine