Utility of third generation thyrotropin assays in thyroid function testing

Determination of thyrotropin (TSH) by sensitive immunometric assays is curr ently judged as the most sensitive and also most cost-effective first-line approach to thyroid function testing. Further improvement of assay sensitiv ity has led to the description of third generation TSH assays with a functi onal sensitivity in the range of 0.01 to 0.02 mU/1. In the present study, w e analyzed interassay precision profiles of a commercially available third generation assay (ACS:180 TSH-3) and documented the critical role of the ti me span used for the assessment of a method's functional sensitivity. By us ing a standardized approach with five serum pools measured in 30 different runs across a 6-week period, functional sensitivity was calculated as 0.015 mU/1. The TSH concentrations measured by two different third generation as says (ACS:180 TSH-3 and Elecsys TSH) in samples from healthy blood donors w ere highly correlated (r = 0.76, n = 252). In some samples, however, discor dant results were obtained. Euthyroid reference intervals were determined a s 0.30-3.68 mU/l for the ACS:180 TSH-3 assay and as 0.36-3.64 mU/l for the Elecsys TSH assay. Reevaluation of reference intervals including only TPOAb or TgAb negative samples resulted in almost the same reference ranges. Mea suring TSH concentrations in various patient populations, third generation assay turned out to be advantageous in the following clinical situations. ( a) In patients with mildly suppressed but well detectable TSH concentration s due to functional thyroid autonomy (0.03-0.3 mU/l), overt hyperthyroidism can be excluded by third generation TSH measurement alone without the need of additional thyroid hormone measurements; (b) in patients receiving long term suppressive T4 treatment after thyroidectomy for differentiated thyro id cancer, measurement of basal TSH by third generation assays allow accura te monitoring of hormone therapy without the need for TRH testing; (c) in m ost patients with severe nonthyroidal illnesses and decreased TSH levels, T SH concentrations measured by third generation assays are only moderately s uppressed and can be clearly discriminated from undetectable levels in over t hyperthyroidism. In conclusion, the use of third generation TSH assays is recommended in specialized clinical laboratories frequently analyzing samp les taken in one of those clinical situations.