Sampling Time Is Important but May Be Overlooked in Establishment and Use of Thyroid-Stimulating Hormone Reference Intervals

In the current debate on reference interval(s) for serum thyroid-stimulating hormone (TSH) concentrations, a lowering of the upper reference limit from ∼4.0 to 2.5, or even 2.0, mU/L has been proposed by the National Academy of Clinical Biochemistry (NABC) (1). This proposal is based in part on the observation that populations with the lowest prevalence of antithyroid antibodies have the lowest TSH upper limits. Other arguments for the lowering of the upper limit of the reference interval are related to the question of whether mild TSH increases have any clinical consequences. This question, however, illustrates the problem of mixing the concepts of ( a ) decision limits (e.g., discrimination values, cutoffs, action limits), which are based on the clinical consequences and treatment strategies and ( b ) reference intervals, which are based solely on biology and mathematics applied in an appropriate …