title: [Establishment of composite reference intervals for thyroid-stimulating hormone and free thyroxine in determination of subclinical hypothyroidism].
abstract: OBJECTIVE
  To detect changes of thyroid stimulating hormone (TSH) with gender, age and levels of thyroid peroxidase antibodies (TPO-Ab) in patients with subclinical hypothyroidism, and to establish composite reference intervals for TSH and free thyroxine (FT4) in determination of subclinical hypothyroidism.
  
  
  METHODS
  From Oct. 2011 to July 2012, 7 964 healthy people (males: 4 789, females: 3 175) undergoing medical examinations were recruited. Their serum levels of TSH and FT4 were determined. Of those participants, 794 were also tested for TPO-Ab. The serum TSH and FT4 data were transformed into normal distributions, with outliers being eliminated and a correction for skewness (0. 909 and 0. 384, respectively) and kurtosis (2.605 and 1.947, respectively). The composite reference intervals were established according to the Mahalonobis distance formula.
  
  
  RESULTS
  Serum TSH increased with age and TPO-Ab. Using the conventional reference standards, 358 participants were identified with subclinical hypothyroidism, which included 230 at 41-70 years of age and 43 showing TPO-Ab positive. In contrast, using composite reference intervals, 301 participants were identified with subclinical hypothyroidism, which included 142 at 41-70 years of age and 25 showing TPO-Ab.
  
  
  CONCLUSIONS
  The conventional cutoff values for FT4 and TSH separately lead to overestimation of the prevalence of subclinical thyroid disease.
authors.forename: Liang
authors.initials: L
authors.lastname: Li-Bo
authors.forename: Lü
authors.initials: L
authors.lastname: Rui-Xue
authors.forename: Huang
authors.initials: H
authors.lastname: Heng-Jian
authors.forename: He
authors.initials: H
authors.lastname: He
authors.forename: An
authors.initials: A
authors.lastname: Zhen-Mei
authors.forename: Li
authors.initials: L
authors.lastname: Shuang-Qing
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*
chemical_list: D001323:Autoantibodies; C056626:thyroid microsomal antibodies; D013972:Thyrotropin; D013974:Thyroxine