Assessment of the Influence of Thyroglobulin (Tg) Autoantibodies and Other Interfering Factors on the Use of Serum Tg as Tumor Marker in Differentiated Thyroid Carcinoma

Abstract

The purpose of the study was to examine the value of a commercial immunoradiometric (IRMA) method for measuring serum thyroglobulin as a tumor marker after treatment for differentiated thyroid carcinoma. A prospective analysis of consecutive serum samples from 53 patients was performed using the IRMA method and a traditional double antibody radioimmunoassay (RIA). The results were compared with those of 100 healthy control subjects and furthermore the method was validated by investigating sera from 24 patients with Hashimoto's thyroiditis positive for thyroglobulin autoantibodies. Finally, in vitro studies of the influence of thyroglobulin autoantibodies on the method were done. The IRMA method had an acceptable analytical precision and was more sensitive than the RIA. It was furthermore less sensitive to the presence of thyroglobulin autoantibodies but it was affected by them, and it showed less unspecific serum effect. Both methods had limitations as tumor marker when the patients had a thyroid remnant, when serum thyrotropin was not suppressed, and in cases of local recurrence. The highest predictive value was found in patients with distant metastases. Thus, in cases of only slightly elevated serum thyroglobulin, the strongest indication for recurrence is still an increasing serum thyroglobulin level within the same patient rather than a single value.

Antithyroglobulin antibodies in patients with differentiated thyroid carcinoma: methods of detection, interference with serum thyroglobulin measurement and clinical significance

“…The exogenous Tg recovery test has been proposed for the detection of TgAb interference (19,20), but, in agreement with other studies (6,9,10,13,14), we demonstrated here that normal recovery of Tg in serum containing TgAb does not exclude interference and this method should therefore not be used for the validation of Tg measurements. This divergence might be explained by differences in endogenous and exogenous Tg, the use of different isoforms with variable immunoreactivity in the preparation of the test (21), and TgAb heterogeneity (22).…”

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

“…In these patients, a rising Tg level indicates disease that is likely to become clinically apparent (281,283,301,(303)(304)(305). In this setting, routine surveillance is recommended with imaging and treatment determined by the degree of Tg elevation and its trend over time (see Fig.…”

“…TgAb are detected in up to 20%-25% of patients with DTC, primarily PTC, and they interfere with Tg measurements in a qualitative, quantitative, and method-dependent manner, rendering the Tg level uninterpretable (304,(306)(307)(308)(309)(310). Antibody interference with the most commonly used Tg immunometric assays always results in underestimation of Tg (i.e., a potentially false negative test), whereas interference with radioimmunoassay has the potential to cause either under-or overestimation of Tg, depending on the characteristics of the patient-specific TgAb and the radioimmunoassay reagents (307,310).…”

Analyses of the molecular forms of serum thyroglobulin from patients with Graves' disease, subacute thyroiditis or differentiated thyroid cancer by velocity sedimentation on sucrose gradient and Western blot

“…Anti-Tg autoantibodies (TgaAb) were detectable in 10 out of the 21 patients (see Table 1). In the selected sera with TgaAb, TgaAb did not seem to interfere in the Tg RIA insofar as serum dilutions yielded displacement curves parallel to the standard curve (20)(21)(22). Four serum samples were collected from patients with subacute thyroiditis diagnosed on clinical and serological grounds including elevated levels of circulating Tg (200-2900 ng/ml; mean: 1030 ng/ml).…”