Performance characteristics of 5 automated thyroglobulin autoantibody and thyroid peroxidase autoantibody assays

Abstract

Background

Measurement of thyroid peroxidase autoantibodies (TPOAb) is useful in diagnosing patients with autoimmune thyroid disease. Measurement of thyroglobulin autoantibodies (TgAb) is used to detect potential interferences with thyroglobulin immunoassays and in limited situations for the diagnosis of autoimmune thyroid disease.

Methods

The limit of detection, imprecision, reference interval, method comparison and diagnostic concordance for the ADVIA Centaur, ARCHITECT i2000, AxSYM, Immulite 2000, Modular E170 (TPOAb only), and UniCel DxI 800 (TgAb only) methods were evaluated. The Advantage was used as the comparison method.

Results

Total imprecision ranged from 2.6% to 14.9% for TgAb and 2.1% to 15.8% for TPOAb. Passing–Bablok slopes ranged from 0.51 to 10.4 (TgAb) and 1.05 to 7.12 (TPOAb) with correlation coefficients of 0.48 to 0.82 (TgAb) and 0.66 to 0.78 (TPOAb). Assay cutoffs were adjusted using a common set of reference interval samples. Concordance with the Advantage assay using the new cutoffs was found to be improved and ranged from 68.5% to 84.7% (TgAb) and 77.5% to 84.7% (TPOAb).

Conclusions

Although all assays generally performed well, assay concordance for a negative or positive result ranged from 54.2 to 84.7%. Quantitative agreement between methods was generally poor and methods could not be used interchangeably. Additional standardization efforts are required to improve inter-method agreement.

Introduction

The measurement of autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) are useful in identifying patients with autoimmune thyroid disease [1]. In iodine sufficient areas it is usually not necessary or cost-effective to measure both TgAb and TPOAb, since TPOAb-negative patients with detectable TgAb rarely display thyroid dysfunction [2]. TPOAb measurements may also be useful as a risk factor for thyroid dysfunction during therapy with certain drugs, hypothyroidism in Down's syndrome, thyroid dysfunction during pregnancy, and post-partum thyroiditis [2]. TgAb measurements are recommended for all samples prior to thyroglobulin analysis because even low TgAb titers may have unpredictable effects on thyroglobulin results [2]. TgAb measurements may also be useful in patients with nodular goiter and in monitoring iodine therapy for endemic goiter in iodine deficient areas [2]. Several quantitative, automated immunoassays for the detection of TgAb and TPOAb in patient sera have been developed. Due to the known variability and poor standardization among methods, the National Academy of Clinical Biochemistry (NACB) has noted the importance of assessing the analytical and clinical performance of commercially available thyroid autoantibody assays [2]. As part of this assessment, the NACB has recommended criteria for establishing reference intervals for thyroid autoantibody assays comprised of young, biochemically euthyroid male subjects, with no goiter and no family history of autoimmune thyroid disease because females are more likely to have undiagnosed thyroid disease. A review of the literature found a limited group of method comparison studies, yet failed to identify a comprehensive study evaluating the performance characteristics of each method [3], [4], [5]. Therefore, we conducted experiments evaluating the performance characteristics of 5 automated TgAb and TPOAb assays.