Thyroglobulin and anti-thyroglobulin assays in thyroid cancer monitoring

To compare four methods for thyroglobulin (Tg) quantitation and three methods for detection and quantitation of thyroglobulin antibodies (Tg-Ab). We also wanted to explore the premise that thyroglobulin antibodies, as determined by commercially available assays, interfere with thyroglobulin assays in a predictable way.

Split sample method comparisons were run on all the methods for both the thyroglobulin and anti-thyroglobulin assays. In addition to this, samples from patients that had disseminated thyroid cancer but had low serum thyroglobulin concentrations and high thyroglobulin antibodies were further studied. These studies involved doing recovery studies (or antibody inhibition studies).

There was good agreement between methods for quantitation of thyroglobulin with slopes ranging from 0.77 to 1.23 although closer agreement was expected as the assays are all calibrated to the same reference standard (CRM 457). The situation for the thyroglobulin antibody assays is significantly worse, and the rate of antibody positivity ranged from 9-21% in this group of patients although there was agreement in only 6%. Different reference standards are used for the Tg-Ab assays we investigated. The Tg-Ab data did not lend itself to traditional linear regression analysis as the data showed wide scatter.

There is good agreement between the four thyroglobulin assays compared in this study. The linear regression analysis shows that there is proportional error present between the methods that is greater than 50%. This study is unable to demonstrate any difference in assay values based on the amount of anti-thyroglobulin present in the specimen. The agreement between different anti-thyroglobulin assays is very poor. This finding is very problematic since it makes it difficult to generalize any literature reports of interference. All the thyroglobulin assays appear to be suitable for monitoring patients with thyroid cancer, provided that the differences in calibration are taken into account. Differences in calibration between different assays need to be taken into account when changing assays. Conversely, the anti-thyroglobulin assays are virtually useless since there appears to be very little agreement between the three assays studied and no evidence of assay interference in the measurements of thyroglobulin.