Thyroglobulin, Tumor Marker, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Thyroglobulin (Tg) is a glycoprotein (660,000 MW) composed of 2,748 amino acids, which contains 8% to 10% carbohydrate and iodine. The amount of iodine varies with the dietary intake of the individual. Seventy percent of the Tg monomer is composed of repeat sequences.
Tg is present in the serum of normal individuals. It is secreted only by the thyroid gland and composes about 75% of the total protein of thyroid follicular colloid. The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are synthesized from tyrosine residues of Tg in the thyroid epithelial cell. T4 and T3 are released after Tg is endocytosed and proteolytically degraded in the thyrocyte. Tg itself is not biologically active.
Thyroid cancer is commonly treated by surgical removal of the thyroid gland, often followed by ablation of the thyroid remnant. Patients receive lifelong thyroid hormone replacement therapy. Traditionally, (131)iodine scanning is used to detect residual disease. More recently, this approach has been supplemented, and often supplanted, by measurement of serum Tg concentrations.
Serum Tg concentrations are very low or undetectable in athyrotic individuals. In the absence of a significant thyroid remnant, elevated or rising serum Tg levels are suspicious of recurrent or persistent disease. It is usually unnecessary to withhold thyroid hormone replacement prior to Tg testing. However, to optimize the ability to detect recurrent disease, thyroid replacement is often withheld prior to Tg testing, or recombinant thyrotropin is administered, particularly if the patient also is undergoing (131)iodine scanning. Thyroid-stimulating hormone increases Tg production and iodine uptake of any benign or malignant residual thyroid tissue.
Follow-up of patients with differentiated thyroid cancers after thyroidectomy and ablation
An aid in determining the presence of thyroid metastasis to lymph nodes
Thyroglobulin (Tg) antibody screening is performed to rule out interference in the Tg assay. Values <22 IU/mL are considered normal and unlikely to cause interference.
All of the following interpretative suggestions for serum Tg apply only to patients who do not have elevated serum Tg autoantibodies:
-The American Thyroid Association guidelines for the management of differentiated thyroid cancer suggest that athyrotic thyroid cancer patients (total thyroidectomy and radioiodine remnant ablation) should have unstimulated (on thyroxine [T4]) and stimulated (thyroid hormone withdrawal or recombinant human thyroid-stimulating hormone [TSH] stimulation) serum Tg concentrations < or =2 ng/mL. Patients with higher levels should be investigated for persistent or recurrent disease.
-Athyrotic thyroid cancer patients with unstimulated or stimulated serum Tg concentrations >10 ng/mL are likely to have evidence of persistent or recurrent disease.
-In athyrotic low-risk thyroid cancer patients, recent evidence suggests that serum Tg levels <0.1 ng/mL, combined with neck ultrasound, obviate the need for stimulated Tg testing.
-For patients with small thyroidal remnants there are currently no universally accepted cutoff levels for Tg. It has been suggested that Tg levels should not exceed approximately 0.5 ng/mL per gram of remnant tissue in patients with suppressed TSH (<0.3 mIU/L), or approximately 1 ng/mL if TSH is in the normal reference range (0.3-5 mIU/L).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The test is most sensitive for detection of thyroid cancer recurrence when patients are off thyroid replacement long enough to have an elevated thyroid-stimulating hormone (TSH) prior to drawing the specimen. This test also can be used to follow patients with normal TSH; however, thyroglobulin (Tg) values from specimens with high TSH should not be compared with values with normal TSH, because TSH stimulation changes the baseline determinations.
Thyroid autoantibodies may interfere with the measurement of Tg. All specimens are prescreened for antibodies and a comment appended to the report if they are present. Undetectable levels of Tg should be interpreted with caution if anti-Tg is present. A Tg antibody result of <22 IU/mL is unlikely to cause clinically significant Tg assay interference. It is recommended that the Tg result be reviewed for concordance with clinical presentation
Specimens with Tg concentrations >250,000 ng/mL may "hook" and appear to have markedly lower levels.
Anti-Tg values determined by different methodologies might vary significantly and cannot be directly compared with one another. Some patients might be antibody-positive by some methods and antibody-negative by others. Comparing anti-Tg antibodies values from different methods might lead to erroneous clinical interpretation.
In patients receiving therapy with high biotin doses (ie, >5 mg/day), no specimen should be drawn until at least 8 hours after the last biotin administration
Tg concentrations >2,000 ng/mL may lead to falsely elevated anti-Tg concentrations. In this case, anti-Tg concentrations may be unreliable.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
THYROGLOBULIN, TUMOR MARKER
> or =16 years: < or =33 ng/mL
Athyrotic individuals normally have human thyroglobulin values < or =2 ng/mL.
THYROGLOBULIN ANTIBODY SCREEN
Reference values apply to all ages.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Cooper DS, Doherty GM, Haugen BR, et al: American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2009;19:1167-1214
2. Smallridge RC, Meek SE, Morgan MA, et al: Monitoring thyroglobulin in a sensitive immunoassay has comparable sensitivity to recombinant human TSH- stimulated thyroglobulin in follow-up of thyroid cancer patients. J Clin Endocrinol Metab, 2007;92:82-87
3. Torrens JI, Burch HB: Serum Thyroglobulin measurement. Utility in Clinical Practice. Endocrinol Metab Clin North AM 2001 June;30(2):429-467
4. National Academy of Clinical Biochemistry: Laboratory Medicine Practice Guidelines. Edited by LM Demers, CA Spencer. Laboratory support for the diagnosis and monitoring of thyroid disease, Section D. Thyroid antibodies (TPOAb, TgAb, TRAb), pp 43-54, and Section E. Thyroglobulin (Tg), pp 55-65-reprinted in unchanged form in Thyroid 2003;13(1):45-56, 57-67