Assessing the Measurement of Thyroglobulin in Patients with Differentiated Follicular Cell-Derived Thyroid Carcinoma


Measurement of serum thyroglobulin (Tg), a glycoprotein produced exclusively by thyroid tissue, is an essential component of the follow-up of patients with differentiated follicular cell-derived thyroid carcinoma. Given the organ-specificity of Tg, serum Tg concentrations can become undetectable, or very low, after the thyroid gland is removed for the treatment of thyroid cancer. The measurement of Tg is most commonly performed by immunoassays, but quantitation by immunoassays is affected by the presence of anti-thyroglobulin auto-antibodies (TgAb), which are present in 20 to 30 percent of patients with differentiated thyroid carcinoma.

The presence of TgAb may result in falsely low or high Tg results, depending on the immunoassay configuration. Furthermore, the TgAb presence alone is not a good predictor of the degree of interference to be expected.

Recently, mass spectrometry-based Tg quantification (Tg-MS) has emerged as a potential solution to provide accurate measurement. In these assays, a protein digestion step cleaves all proteins, including TgAb, thus eliminating them as interferences. Recent studies have shown that Tg-MS allows for the accurate quantitation of Tg in the presence of TgAb.

To establish the potential impact of Tg-MS on patient care, Mayo Clinic researchers performed a comprehensive analytical and clinical evaluation of immunoassays in well-characterized thyroid cancer patients. The study, published in the Journal of Clinical Endocrinology and Metabolism, allowed researchers to assess the performance of different Tg assays in the presence of TgAb, resulting in an improved understanding of the strengths and weaknesses of several widely used assays and interpretation of Tg measurements in TgAb patients.

Alicia Algeciras-Schimnich, Ph.D.
Alicia Algeciras-Schimnich, Ph.D.

“When we started the conceptualization of this study, we felt that we could address a number of analytical and clinical questions including the elucidation of the degree of interference of TgAb in Tg immunoassays and determination of the impact of Tg-MS assays in patient care by establishing the Tg-MS assays clinical sensitivity and specificity,” said Alicia Algeciras-Schimnich, Ph.D., Chair of the Division of Clinical Biochemistry at Mayo Clinic and author on the paper.

By working closely with the Mayo Clinic Endocrinology clinical practice, which treats a significant number of thyroid cancer patients, the team was able to identify almost 500 unique patients whomet the study inclusion criteria. The team also worked with external collaborators, as well as industry partners, to include as many Tg and TgAb immunoassays and Tg-MS assays as possible. Overall, the study evaluated the performance of 4 Tg immunometric assays, 2 Tg radioimmunoassays, and 2 Tg-MS assays.

In TgAb negative patients, all assays showed similar clinical and analytical performance. In TgAb positive patients, the immunometric assays always indicated underestimation of Tg when compared to the Tg-MS assays; however, the degree of underestimation varied between the immunoassays and ranged from 41 to 86 percent. On the other hand, the radioimmunoassays resulted in overestimation of Tg in TgAb positive patients containing low Tg concentrations.

Based on these results, in TgAb negative patients, the immunoassays should be the measurement method of choice. For TgAb positive patients, the use of Tg-MS would benefit up to 20 percent of patients where at least one of the immunoassays was unable to detect Tg.

“In TgAb positive patients, accurate Tg quantitation by Tg-MS will ensure the appropriate patient follow-up. However, the Tg-MS assays are not going to solve all problems in their current format,” said Dr. Algeciras-Schimnich. “Because of the suboptimal functional sensitivity of the current generation of Tg-MS assays, patients with persistent and/or recurrence disease with low Tg concentrations might be missed by the Tg-MS assays.”

Overall, the study answered several key analytical and clinical questions regarding the performance of Tg assays, which are relevant to the clinical practice.

“The study highlights the benefit of using Tg-MS in TgAb positive patients with an undetectable Tg by immunoassay. Improving the current Tg-MS assays’ analytical sensitivity will be imperative for more effective incorporation of this method in clinical practice,” added Dr. Algeciras-Schimnich.

Kelley Luedke (@kschrib)

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.