Can we interpret serum thyroglobulin results?

Abstract

Thyroglobulin (Tg) is a tumour marker for differentiated thyroid cancer. Interpretation requires a knowledge of the current thyrotropin (TSH) concentration as secretion is TSH-dependent. While a raised serum Tg may be indicative of residual or recurrent thyroid cancer, trauma to the thyroid (e.g. surgical, biopsy or due to radioiodine treatment) also causes an increase. Tg may be measured when TSH is suppressed and also following recombinant TSH (rhTSH) stimulation. Interpretation of results in pregnancy and in children is discussed. Assay bias and interference by endogenous Tg antibodies (Abs) are the main confounders in the interpretation of results. Although there is an international standard for Tg, there are large differences in results and yet there are few assay-specific clinical decision limits. Patients should therefore be monitored with the same assay. Endogenous TgAbs may cause false-negative interference in immunometric assays and may cause false-positive results in radioimmunoassay. Although the measurement of TgAbs has been advocated for predicting interference, it is now clear that interference can still occur when TgAbs have not been detected, the effect being TgAb-assay-specific. Approaches to identifying those samples where there may be interference are discussed. The laboratory should have a protocol for the investigation of possible interferences and data on the bias of the Tg assay that they use. An appreciation of the clinical uses of the service is required as an understanding by endocrinologists, oncologists and endocrine surgeons of the analytical limitations of the service.

Factors associated with serum thyroglobulin in a Ukrainian cohort exposed to iodine-131 from the accident at the Chernobyl Nuclear Plant

“…The strong interference with serum Tg measurements at low ATg levels may be partially explained by ATg heterogeneity and the differing epitope binding specificities of the various anti-Tg antibodies (Madureira et al, 2008;Spencer and Lopresti, 2008). In addition, ATg interference leading to an underestimation of Tg levels is common with immunometric assays, and there appears to be no threshold concentration for ATg at which interference with Tg does not occur (Clark and Franklyn, 2012;Spencer et al, 2011;Spencer, 2000).…”

Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges

“…Furthermore, internal and external quality control programs, including samples at low and very low Tg concentrations, are of pivotal importance for checking the precision, reproducibility (internal quality control) and accuracy (e.g., lack of bias of analytical results) of assays to ensure optimal patient care. Laboratories providing Tg measurement are required to participate in a certified national or international program of quality assurance [41].…”

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

“…Several review articles have focused on Tg monitoring in patients with DTC (11,33,34) or the performance of different assays used for monitoring DTC (35,36). The evidence on the usefulness of Tg in patients with DTC is well established.…”