Accurate Measurement of Thyroglobulin in the Presence of Interfering Antibodies [Utilization Spotlight]
Since 2012, we have been publishing a Utilization Spotlight in every issue of the Communiqué. Each Spotlight offers a quick view of utilization management best practices in action. This Spotlight is from May 2015.
Serum thyroglobulin (Tg) measurement is used as a follow-up test for patients with differentiated follicular cell-derived thyroid carcinoma after surgical removal of the thyroid. The Mayo Clinic Endocrine Laboratory has developed an assay that allows accurate quantification of Tg in patients with antithyroglobulin autoantibodies or heterophile antibodies.
Serum thyroglobulin (Tg) measurement is used as a follow-up test for patients with differentiated follicular cell-derived thyroid carcinoma after surgical removal of the thyroid. Because Tg is highly organ-specific, serum Tg concentrations should be undetectable, or very low, after the thyroid gland is removed.
Antithyroglobulin autoantibodies (TgAB) occur in up to 30 percent of thyroid cancer patients and can cause false-low serum thyroglobulin results in current immunometric assays; in competitive assays, they may cause false-high results. Heterophile antibodies (HAB) are capable of interacting with the antibodies used in immunoassays, usually resulting in false-high measurements. Depending on the assay and the patient population, this can lead to erroneously high results in 0.1 to 3.0 percent of patients.
Because of the possible erroneous results, various guidelines, including those from the National Academy of Clinical Biochemistry and the American Thyroid Association, stress that antithyroglobulin autoantibody measurement should be performed in all specimens tested for thyroglobulin. Failure to detect thyroglobulin antibody interference in the presence of an undetectable thyroglobulin concentration could greatly impact patient management as disease recurrence might go undiagnosed.
The Mayo Clinic Endocrine Laboratory has developed an assay that allows accurate quantification of Tg in patients with TgAB or HAB. Trypsin digestion of serum proteins, which cuts both antibodies and Tg into predictable fragments, will result in accurate quantification of Tg in specimens with antibody interferences through measurement of Tg-specific tryptic peptides by mass spectrometry. This assay may be ordered as part of the reflex strategy (HTGR/Thyroglobulin, Tumor Marker Reflex to LC-MS/MS or Immunoassay).
Testing begins with the analysis of thyroglobulin antibody by immunoassay. If the thyroglobulin antibody result is negative (<4.0 IU/mL), thyroglobulin testing will be performed by immunoassay. If the thyroglobulin antibody result is positive (≥4.0 IU/mL), thyroglobulin testing will be performed by mass spectrometry. The assay enables accurate measurement of serum thyroglobulin in patients with known or suspected antithyroglobulin autoantibodies or possible heterophile antibodies, and provides the most efficient and cost-effective way to ensure accurate quantitation of thyroglobulin in thyroglobulin antibody-positive patients.