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A Novel Mass Spectrometry–Based Assay for the Accurate Measurement of Thyroglobulin From Patient Samples Containing Antithyroglobulin Autoantibodies
  1. Nigel J. Clarke, PhD,
  2. Yanni Zhang, PhD,
  3. Richard E. Reitz, MD
  1. From the Quest Diagnostics Nichols Institute, Endocrinology Department, San Juan Capistrano, CA.
  1. Received September 21, 2012.
  2. Accepted for publication September 30, 2012.
  3. Reprints: Nigel J. Clarke, PhD, Quest Diagnostics Nichols Institute, Endocrinology Department, 33608 Ortega Hwy, San Juan Capistrano, CA 92675. E-mail: nigel.j.clarke{at}
  4. Clarke and Zhang contributed equally to this work


Thyroid cancer is the most common endocrine cancer in the United States. The primary treatment of thyroid cancer is partial or complete thyroidectomy in patients in whom the cancer is discovered preoperatively, and is often followed by radioactive iodine ablation. After the initial therapy, patients are followed up regularly, most commonly by measurement of serum thyroglobulin (Tg) levels and high-resolution neck ultrasound. As Tg is only produced within the thyroid gland, it has long been recognized as an excellent biomarker for the presence of residual disease after treatment. A number of immunoassays are in common use to measure serum Tg levels. Unfortunately, irrespective of which method is chosen, there is a major potential artifact, in that the presence of autoantibodies binding to Tg (ATG) may bias the results to the point where they are clinically unreliable.

This article describes a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the measurement of serum Tg after tryptic digestion of serum samples. The method is compared to Tg analyses using both a Food and Drug Administration–approved immunometric assay (IMA) and a well-respected, clinically used radioimmunoassay. In the absence of ATG, the new LC-MS/MS assay demonstrates equivalency compared to the IMA. However, in ATG-positive patients, the IMA Tg results are lower than the LC-MS/MS assay and the radioimmunoassay Tg results are typically higher. These studies demonstrate the accuracy and validity of the measurement of Tg by LC-MS/MS. This assay will permit the accurate determination of Tg levels even in patients with ATG.

Key Words
  • thyroid cancer
  • thyroglobulin
  • mass spectrometry

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