Determinants of the TSH reference range
There is controversy on the upper thyrotropin (TSH) reference level. Currently available studies are based on cross-sectional data leaving uncertainty about the prognostic significance of the upper TSH reference level. Studies establishing TSH reference values should be evaluated using strict quality criteria including population representativeness and sample size. In addition, not only subjects with known thyroid disorder, but also those with subclinical disorders including goiter and nodules should be excluded from the reference population.
The clinical value of TSH reference values depends on the study design. Reference values are only of diagnostic significance if analyzed from cross-sectional data, but they are of prognostic significance if established from longitudinal studies.