Assessment of sensitive thyrotropin assays for an expanded role in thyroid function testing: Proposed criteria for analytic performance and clinical utility

Assays capable of detecting subnormal serum TSH concentrations can permit the prediction of response to TRH and the detection of hyperthyroidism. Five performance criteria for evaluating the eligibility of TSH assays for these new roles are proposed. Criterion 1 requires a less than 1% overlap between the variation of the lower normal value and the assay detection limit. Criteria 2 and 3 require subnormal basal TSH values in 95% of patients with subnormal TRH response, and detectable basal TSH values in 95% of patients with normal TRH responses. Criteria 4 and 5 require undetectable TSH values in 95% of hyperthyroid patients and detectable TSH values in 95% of clinically euthyroid subjects. Evaluation of 20 published studies using commercial reagents showed that only 5 assays met criterion 1; most reports did not provide adequate information for evaluation. We evaluated 2 sensitive assays by assessment of sera from 149 normal subjects and 893 patients. Substantial differences were found; only assay B met all performance criteria. With assay B, serum TSH levels were normal in 86%, increased in 7%, undetectable in 4%, and subnormal in 3% of 454 patients undergoing a screening T₄ measurement. Sensitive TSH assays fulfilling our criteria may be useful as front-line thyroid function tests.