title: Disturbance of the fetal thyroid hormone state has long-term consequences for treatment of thyroidal and central congenital hypothyroidism.
abstract: BACKGROUND
  During T(4) supplementation of patients with thyroidal (primary) congenital hypothyroidism (CH) TSH concentrations are frequently elevated despite free T(4) (FT(4)) concentrations being well within the reference range. To examine the thyroid's regulatory system, we analyzed thyroid function determinants in children with congenital and acquired thyroid disorders and in controls.
  
  
  METHODS
  Retrospectively, plasma FT(4), TSH, and T(3) concentrations were analyzed in T(4)-supplemented children aged 0.5-20.0 yr with thyroidal CH, central (secondary or tertiary) CH, or autoimmune thyroid disease and in control children with type 1 diabetes mellitus.
  
  
  RESULTS
  When TSH was within the reference range (0.4-4.0 mU/liter), mean FT(4) in thyroidal CH [1.65 ng/dl; 95% confidence interval (CI), 1.62-1.67] was significantly higher than in autoimmune thyroid disease (1.15 ng/dl; 95% CI, 1.11-1.19) and diabetes (1.08 ng/dl; 95% CI, 1.06-1.10). In central CH, when TSH was less than or equal to 0.02 mU/liter, mean FT(4) was 1.27 ng/dl (95% CI, 1.24-1.29). When FT(4) was within the reference range (0.78-1.79 ng/dl), 43% of the TSH measurements in thyroidal CH were more than 4.0 mU/liter, compared with 18% in autoimmune thyroid disease and 0% in type 1 diabetes mellitus; in central CH, 95% of TSH measurements were less than 0.4 mU/liter.
  
  
  CONCLUSIONS
  In T(4)-supplemented patients with thyroidal CH, when TSH concentrations are established within the reference range, FT(4) concentrations tend to be elevated, and vice versa. Because this phenomenon could not be observed in acquired thyroidal hypothyroidism, we hypothesize that a pre- and/or perinatal hypothyroid state shifts the setpoint of the thyroid's regulatory system. In central CH, when FT(4) concentrations are established within the reference range, the pituitary secretes only minute amounts of TSH. For monitoring T(4) supplementation, reference ranges for FT(4) and TSH should be adapted to the etiology of hypothyroidism.
authors.affiliation: Emma Children's Hospital Academic Medical Center, University of Amsterdam, Department of Pediatric Endocrinology, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. m.j.kempers@amc.uva.nl
authors.forename: M J E
authors.initials: MJ
authors.lastname: Kempers
authors.forename: A S P
authors.initials: AS
authors.lastname: van Trotsenburg
authors.forename: D A
authors.initials: DA
authors.lastname: van Tijn
authors.forename: E
authors.initials: E
authors.lastname: Bakker
authors.forename: B M
authors.initials: BM
authors.lastname: Wiedijk
authors.forename: E
authors.initials: E
authors.lastname: Endert
authors.forename: J J M
authors.initials: JJ
authors.lastname: de Vijlder
authors.forename: T
authors.initials: T
authors.lastname: Vulsma
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007037:Hypothyroidism / Q000097:blood; D007223:Infant; D012189:Retrospective Studies; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use; D014284:Triiodothyronine / Q000097:blood
chemical_list: D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine