[Establishment of composite reference intervals for thyroid-stimulating hormone and free thyroxine in determination of subclinical hypothyroidism].

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.

Conclusion: The conventional cutoff values for FT4 and TSH separately lead to overestimation of the prevalence of subclinical thyroid disease.