Antithyroglobulin 

Updated: Nov 24, 2015
  • Author: Ricardo Cardona, MD; Chief Editor: Eric B Staros, MD  more...
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Reference Range

Thyroglobulin is a protein found in thyroid cells. Antithyroglobulin antibody testing is used in the evaluation for thyroid problems.

Antithyroglobulin is not normally found in the blood stream. However, 10-20% of healthy individuals have detectable antithyroglobulin levels.

The reference range value for antithyroglobulin is less than 116 IU/mL.

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Interpretation

The following conditions are associated with elevated antithyroglobulin levels:

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Collection and Panels

Collection details are as follows:

  • Specimen type - Blood serum; serum gel is acceptable
  • Container - Red-top tube (see image below)
    Red Top Vacutainer tube. Image courtesy of Wikimed Red Top Vacutainer tube. Image courtesy of Wikimedia Commons.
  • Collection method - Venipuncture
  • Specimen volume - 1 mL
  • Panel - Both thyroglobulin and antithyroglobulin are usually included in the thyroglobulin tumor marker panel
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Background

Description

The 3 types of thyroid autoantigens that generate antibodies in autoimmune thyroid disease (Graves disease or Hashimoto thyroiditis) are thyroglobulin, thyroid microsomal antigen, and the thyrotropin receptor.

Conditions associated with thyroglobulin antibody include Hashimoto thyroiditis, Graves disease, myxedema, adenomatous hyperplasia, thyroid carcinoma, rheumatoid arthritis (RA), chronic urticaria, systemic lupus erythematosus (SLE), autoimmune hemolytic anemia, Sjögren syndrome, and type 1 diabetes. Serum antibodies to thyroglobulin are present in 10-20% of healthy individuals. Pregnant women and family members of those with a history of autoimmune thyroiditis can also have positive thyroglobulin antibody.

The autoantigen thyroglobulin is an iodine-containing glycoprotein of high molecular weight that is secreted into the colloid of follicle cells of the thyroid gland. Thyroglobulin, a prohormone, contains the iodinated tyrosine moieties that form the active hormones thyroxine (T4) and triiodothyronine (T3) after combining with the amino acid tyrosine. Thyroid hormones are essential for most metabolic process in the human body. Healthy individuals may have values of up to 30 ng/mL (45 pmol/L).

Thyroglobulin is specific to the thyroid follicle. Its presence in a tissue biopsy sample provides proof of thyroid origin. In addition, testing for thyroglobulin is of great importance regarding metastatic, recurrent, or residual disease in patients with a previous diagnosis of differentiated thyroid cancer. [1]

Up to 10% of the general population and 20% of individuals with differentiated thyroid cancer have detectable antithyroglobulin antibodies, which represents a challenge because thyroglobulin values obtained in the presence of antithyroglobulin antibodies may not be clinically reliable. Hence, most laboratories do not release results for thyroglobulin in the presence of antithyroglobulin antibodies.

Indications/Applications

Several clinical indications exist for measuring thyroglobulin antibodies.

Monitoring differentiated thyroid cancer

In patients with differentiated thyroid cancer (particularly papillary or follicular thyroid cancer), important information about the presence or absence of residual, recurrent, or metastatic disease can be obtained using serum thyroglobulin measurements. Thyroglobulin antibodies are present in up to 20% of patients with differentiated thyroid cancer, and this can interfere with the thyroglobulin assay, rendering it unreliable for monitoring differentiated thyroid cancer.

The significance of thyroglobulin antibody values after surgical and radioiodine ablation for differentiated thyroid cancer is unclear, but a persistence of thyroglobulin antibodies indicates possible residual thyroid tissue and an increased risk of recurrence. [2, 3, 4] Another cause of persistent thyroglobulin antibodies (even up to 20 years in some individuals without detectable differentiated thyroid cancer) is coexistent autoimmune thyroid disease. [1]

Hashimoto thyroiditis

Hashimoto thyroiditis is an autoimmune disease in which the thyroid gland is attacked by autoantibodies. Thyroglobulin antibody is 1 of 2 types of antithyroid antibodies described in Hashimoto thyroiditis. Antimicrosomal (now termed antithyroid peroxidase [anti-TPO] antibodies) antibody is the other antibody, and it is highly specific for autoimmune thyroiditis. Antithyroglobulin can lead to the destruction of the thyroid gland. However, they are not as specific for autoimmune thyroid disease. Their presence in the absence of antimicrosomal antibody is not sufficient to establish the diagnosis.

One study examined 2030 consecutive patients who had both antimicrosomal and antithyroglobulin antibodies to determine if they had Hashimoto thyroiditis. Positive results for antimicrosomal antibodies were obtained in 99% of all patients, but only 36% of patients were positive for antithyroglobulin. These results suggest that performing both tests is costlier and does not offer any diagnostic advantage. Therefore, thyroglobulin antibody testing is not recommended for the diagnosis of Hashimoto thyroiditis. [5, 6]

Chronic urticaria

Thyroid autoantibodies reportedly can be found in 10-33% of patients with chronic urticaria, but the frequency of thyroid autoantibodies in the general population is approximately 3-6%. Urticaria is also reported more frequently in patients with Hashimoto thyroiditis.

In some cases of chronic urticaria, the mechanism of thyroid autoantibodies is thought to involve the formation of immune complexes, activation of complement, and/or initiation of the release of proinflammatory mediators. [7, 8]

Considerations

Thyroglobulin antibody binds to circulating thyroglobulin and interferes with the accuracy of thyroglobulin assays (ie, immunometric assay, radioimmunoassay [RIA]), which causes the immunometric assay to yield falsely low values. [9] Low titers of thyroglobulin antibody also cause problems, especially at low thyroglobulin levels. Conversely, RIAs tend to report falsely high thyroglobulin values in the presence of thyroglobulin antibodies.

This difference occurs because immunometric assays measure only unbound (free) thyroglobulin, but RIAs measure unbound and thyroglobulin antibody–bound thyroglobulin. Thus, an RIA can still detect thyroglobulin, but it often overestimates the level when thyroglobulin antibody is present. Therefore, some authorities recommend using a thyroglobulin RIA when thyroglobulin antibody is present, because a low value is likely to be the true value, but a high value can represent an overestimate of the true thyroglobulin level.

A thyroglobulin “recover” is offered by some laboratories that use immunometric assays, in order to determine if thyroglobulin antibody is causing interference. With this method, thyroglobulin is measured before and after the sample is spiked with a known quantity of thyroglobulin. If a satisfactory quantity of the spiked thyroglobulin is detected, then thyroglobulin antibody is not considered to have interfered and a thyroglobulin value is reported. Conversely, if the spiked value is unsatisfactory, thyroglobulin antibody is suggested and no thyroglobulin value is reported.

Thyroglobulin antibody interference is very important; thus, all thyroglobulin assays must include a thyroglobulin antibody measurement. Newly detected thyroglobulin antibody in a patient who had differentiated thyroid cancer previously could signal recurrence of the cancer. [3] Additionally, an increase or persistence of thyroglobulin antibody levels in a patient with differentiated thyroid cancer without autoimmune thyroid disease may be a surrogate tumor marker. A suggested explanation for this is that unlike the immunometric assay, the RIA detects both unbound (free) thyroglobulin and bound thyroglobulin (complexed to antithyroglobulin antibodies). Therefore, the reported thyroglobulin value may be higher than the actual unbound circulating serum thyroglobulin value, but it is much less likely to be a falsely low value. [9, 10, 11]

Because of the differences between RIA and immunometric assay results, some experts recommend that in the presence of antithyroglobulin antibodies, RIAs should be used to measure the serum thyroglobulin (understanding the possibility of obtaining a falsely high result), with the assumption that a low value is likely to be the true value and reflect the clinical situation. This approach appears to be valid, but RIAs are not widely available and their results still need to be interpreted with caution.

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