|Values are valid only on day of printing.|
As an adjunct in the diagnosis of autoimmune thyroid diseases: Hashimoto disease, postpartum thyroiditis, neonatal hypothyroidism, and Graves disease
Identification of potentially unreliable serum thyroglobulin measurements by immunoassay in the follow-up of patients with differentiated follicular-cell derived thyroid carcinomas (for this application order HTG2 / Thyroglobulin, Tumor Marker, Serum or HTGR / Thyroglobulin, Tumor Marker Reflex to LC-MS/MS or Immunoassay)
Thyroglobulin autoantibodies bind thyroglobulin (Tg), a major thyroid-specific protein. Tg plays a crucial role in thyroid hormone synthesis, storage, and release.
Tg is not secreted into the systemic circulation under normal circumstances. However, follicular destruction through inflammation (thyroiditis and autoimmune hypothyroidism), hemorrhage (nodular goiter), or rapid disordered growth of thyroid tissue, as may be observed in Graves disease or follicular cell-derived thyroid neoplasms, can result in leakage of Tg into the blood stream. This results in the formation of autoantibodies to Tg (anti-Tg) in some individuals. The same processes also may result in exposure of other "hidden" thyroid antigens to the immune system, resulting in the formation of autoantibodies to other thyroid antigens, in particular thyroid peroxidase (TPO) (anti-TPO). Since anti-Tg and anti-TPO autoantibodies are observed most frequently in autoimmune thyroiditis (Hashimoto disease), they were originally considered to be of possible pathogenic significance in this disorder. However, the consensus opinion today is that they are merely disease markers. It is felt that the presence of competent immune cells at the site of thyroid tissue destruction in autoimmune thyroiditis simply predisposes the patient to form autoantibodies to hidden thyroid antigens.
In individuals with autoimmune hypothyroidism, 30% to 50% will have detectable anti-Tg autoantibodies, while 50% to 90% will have detectable anti-TPO autoantibodies. In Graves disease, both types of autoantibodies are observed at approximately half these rates.
The presence of anti-Tg, which occurs in 15% to 30% of thyroid cancer patients, could result in misleading Tg results. In immunometric assays, the presence of thyroid antibody can lead to false-low measurement; whereas it might lead to false-high results in competitive assays.
Reference values apply to all ages.
Diagnosis of Autoimmune Thyroid Disease:
Measurements of antithyroid peroxidase (TPO) have higher sensitivity and equal specificity to antithyroglobulin (anti-Tg) measurements in the diagnosis of autoimmune thyroid disease. Anti-Tg levels should, therefore, only be measured if anti-TPO measurements are negative, but clinical suspicion of autoimmune thyroid disease is high. Detection of significant titers of anti-Tg or anti-TPO autoantibodies is supportive evidence for a diagnosis of Graves disease in patients with thyrotoxicosis. However, measurement of the pathogenic antithyroid-stimulating hormone (TSH) receptor antibodies by binding assay (THYRO / Thyrotropin Receptor Antibody, Serum) or bioassay (TSI / Thyroid-Stimulating Immunoglobulin [TSI], Serum) is the preferred method of confirming Graves disease in atypical cases and under special clinical circumstances.
Positive thyroid autoantibody levels in patients with high-normal or slightly elevated serum thyrotropin levels predict the future development of more profound hypothyroidism.
Patients with postpartum thyroiditis with persistently elevated thyroid autoantibody levels have an increased likelihood of permanent hypothyroidism.
In cases of neonatal hypothyroidism, the detection of anti-TPO or anti-Tg in the infant suggests transplacental antibody transfer, particularly if the mother has a history of autoimmune thyroiditis or detectable thyroid autoantibodies. The neonatal hypothyroidism is likely to be transient in these cases.
Thyroid Cancer Follow-up:
Following therapy of differentiated follicular-cell derived thyroid cancer, patients with no residual thyroid tissue and no persistent or recurrent cancer will have undetectable or very low serum Tg levels. Persistently elevated or rising serum Tg levels, either on or off thyroxine replacement therapy, suggest possible tumor persistence or recurrence. However, if a patient also has measurable anti-Tg autoantibody levels, the results of serum Tg measurements may be unreliable. Anti-Tg may result in both falsely-low and, less commonly, falsely high serum Tg measurements. Therefore, in anti-Tg-positive patients, serum Tg measurements should not be used as the sole measurement for thyroid cancer follow-up and should be interpreted with caution. A thyroglobulin antibody result of <4.0 IU/mL is unlikely to cause clinically significant thyroglobulin assay interference. It is recommended that the thyroglobulin result be reviewed for concordance with clinical presentation.
Antithyroglobulin (anti-Tg) and antithyroid peroxidase (anti-TPO) values determined by different methodologies might vary significantly and cannot be directly compared with one another. Some patients might show to be antibody-positive by some methods and antibody-negative by others. Comparing anti-Tg and anti-TPO values from different methods might lead to erroneous clinical interpretation.
1 Sapin P, d’Herbomez M, Gasser F, et al: Increased sensitivity of a new assay for anti-thyroglobulin antibody detection in patients with autoimmune thyroid disease. Clin Biochem 2003 Nov;36(8):611-616
2. Saravanan P, Dayan CM: Thyroid autoantibodies. Endocrinol Metab Clin North Am 2001 June;30(2):315-337
3. 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