Differentiated thyroid cancer: Role of serum thyroglobulin
- R Michael Tuttle, MD
R Michael Tuttle, MD
- Professor of Medicine
- Memorial Sloan Kettering Cancer Center
- Section Editors
- David S Cooper, MD
David S Cooper, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Pituitary Disease; Thyroid Disease
- Professor of Medicine and International Health
- Johns Hopkins University School of Medicine
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
Thyroglobulin (Tg) is a storage form of thyroxine (T4) and triiodothyronine (T3). It is synthesized only by thyroid follicular cells and released into serum along with the thyroid hormones. Given the cellular specificity of Tg, its detection in biopsy specimens provides proof of the thyroid origin of the tissue. In addition, measurements of serum Tg provide important information about the presence or absence of residual, recurrent, or metastatic disease in patients with differentiated thyroid cancer. This topic review will describe the methods for measuring serum Tg and the use of serum Tg measurements in patients with differentiated thyroid cancer. Other aspects of the management of thyroid cancer are reviewed separately. (See "Differentiated thyroid cancer: Overview of management".)
Testing of serum thyroglobulin (Tg) should be done using a sensitive assay, ideally using the same assay for each sample.
Methodology — Serum Tg is now generally measured by two-antibody "sandwich" immunometric assays (the antigen is sandwiched between the two antibodies) in which the capture antibody is bound to a solid support and the detection antibody is labeled with either an isotopic (immunoradiometric assay, IRMA) or non-isotopic (usually immunochemiluminescent assay, ICMA) marker. The values in normal subjects in most laboratories range from 1 to approximately 30 ng/mL. These immunometric assays are quicker, readily automated, and have greater sensitivity (0.1 to 1 ng/mL) than most radioimmunoassays .
Interassay variation — We recommend that serial Tg measurements in thyroid cancer patients be done using the same assay.
Despite a trend toward assay standardization, serum Tg values obtained with different assays cannot be directly compared, as interassay variability remains substantial [2-4]. The variability in assay results is due to [1,5-7]:
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- THYROGLOBULIN ASSAY
- Interassay variation
- Intraassay variation
- Functional sensitivity
- Hook effect
- Heterophilic antibodies
- Thyroglobulin mRNA
- THYROGLOBULIN ANTIBODIES
- Impact on Tg assay
- Surrogate tumor marker
- CLINICAL APPLICATION
- Marker of persistent disease
- Detecting recurrent thyroid cancer
- Predictor of clinical outcomes
- SUMMARY AND RECOMMENDATIONS