Thyroglobulin

Thyroglobulin is a homodimeric glycoprotein with a molecular weight of 660 kDa. It is produced by the thyroid gland whereby it functions as a substrate to produce the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Thyroglobulin is found in the serum as a by product of thyroid hormone synthesis and secretion.

In healthy individuals, serum thyroglobulin levels are low. However, the concentration of this protein has been shown to be elevated in benign conditions of the thyroid, for example, Graves’ disease and thyroiditis, as well malignant thyroid diseases such as differentiated thyroid cancer (DTC). As serum thyroglobulin levels may be increased in other diseases of the thyroid, measurement of thyroglobulin is not indicated for the diagnosis of DTC. However, its measurement is recommended for the monitoring of residual, recurrent or metastatic disease in patients with DTC following treatment with thyroidectomy and/or ablative doses of radioiodine. Successfully, treated post thyroidectomy patients should have an undetectable serum thyroglobulin level as, theoretically, the thyroid gland has been completely removed. Therefore, any measurable or rising serum thyroglobulin potentially indicates residual or recurrent disease.

Thyroglobulin antibodies (TgAb) are present in approximately 25% of patients with DTC and 10% of the general population. Thyroglobulin antibodies most commonly cause negative interference in immunometric assays, but can also cause positive interference. For this reason, TgAb should be measured on all samples requesting thyroglobulin to aid interpretation. In cases where anti-thyroglobulin antibodies are raised, an alternative method should be used to measure thyroglobulin, along with clinical correlation and TgAb trend.

For UHB patients, an Abbott Alinity immunometric assay (TgIMA) is the front line test for thyroglobulin and anti-thyroglobulin antibody testing. For samples with positive TgAb (>4.11 IU/mL), thyroglobulin by mass spectrometry (THYGMS) is then reflexed on. 

External users may request the full testing pathway used for internal UHB patients (TgIMA and TgAb, with THYGMS added if antibody positive), or they may request only the THYGMS assay. Please make it clear on the request form which assay(s) are required. To aid with interpretation, we kindly ask that results for thyroglobulin and anti-thyroglobulin by immunoassay are provided on the request form.

The thyroglobulin mass spectrometry assay (THYGMS) uses SISCAPA technology to remove the interference from TgAb (as the serum is digested and a specific thyroglobulin peptide is measured). We have shown that there is no in-vitro interference from TgAb. The THYGMS assay has a clinical specificity of 100% and clinical sensitivity of approximately 30% (this is similar to data reported in the literature - ranges between 25 to 60%).