A complete thyroid function test report usually includes two parts: one is the indicators reflecting the functional status of the thyroid gland (TT3, TT4, FT3, FT4, TSH), and then the thyroid autoantibodies related to the cause (such as TRAb, TgAb, TPOAb, etc.). For the former, we are all familiar with them; for the latter, we often do not know much.
In clinical practice, people often ask: What is the significance of elevated or decreased antibody levels? Is the goal of treatment to correct the abnormal nail function or to turn the antibody negative? What are the clinical options for lowering antibody levels? We will discuss these questions below.
Types and significance of autoantibodies to the thyroid gland
Thyroid antibodies are immunoglobulins produced by autoimmune disorders that target certain components of the thyroid gland.
There are two main clinical categories.
(1) Antibodies directed against TSH receptors on the surface of thyroid cells
The former is associated with the development of autoimmune hyperthyroidism (i.e. Graves’ disease), while the latter is associated with autoimmune hypothyroidism (e.g. Hashimoto’s disease).
Clinical significance
1) TRAb is of great value in the diagnosis, treatment, and prognostic evaluation of Graves’ disease (toxic diffuse goiter).
If the TRAb (stimulating antibody, TSAb) becomes negative after the treatment of Graves’ disease, the possibility of recurrence after stopping the medication is low. The likelihood of relapse is low;
If the TRAb remains positive after drug treatment, the treatment is not effective and relapse is more likely after stopping the drug. It has been reported in the literature that for those who are still positive for TRAb after one year of antithyroid drug (ATD) treatment, the relapse rate is 90% within three years.
2) Testing TRAb in pregnant women with Graves’ disease can help predict neonatal hyperthyroidism; TRAb can pass through the placenta and stimulate the fetal thyroid gland, causing transient hyperthyroidism in newborns (incidence 1 to 2%).
3) It is useful for the diagnosis of Graves’ ophthalmopathy with normal nail function. In some clinical patients with proptosis, although the thyroid function is normal, TR-Ab is strongly positive, and this case can also be diagnosed as Graves’ ophthalmopathy.
4) TRAb can also be positive in patients with hypothyroidism and autoimmune thyroiditis, and testing for TRAb can be helpful in the etiological diagnosis of these diseases.
Indications
1) Differential diagnosis of hyperthyroidism;
2) Diagnosis and evaluation of Graves’ ophthalmopathy;
3) Follow-up of pregnant women with Graves’ disease (including newborns);
4) Follow-up of Graves’ disease treatment;
5) Evaluation of hypothyroidism in the presence of blocking antibodies;
(2) Antibodies against the contents of thyroid cells
These include thyroglobulin antibodies (Tg-Ab) and thyroid peroxidase antibodies (TPO-Ab), which are caused by damage to thyroid cells and the spillage of intracellular “thyroglobulin” and “peroxidase (a key enzyme in the synthesis of thyroid hormones)” into the bloodstream. It is the hallmark antibody of autoimmune thyroiditis and its elevated level indicates that the thyroid tissue is in an active state of immune inflammation.
TPO-Ab has the same clinical significance as TG-Ab, but TPO-Ab has better sensitivity and specificity than TGAb and is the preferred indicator for the diagnosis of thyroid autoimmune diseases. In order to increase the detection rate, a combination of both antibodies is usually used in clinical practice.
Clinical significance
1) Etiological diagnosis: These antibodies are the main basis for the diagnosis of autoimmune thyroid disease (AITD), with significant elevations (strong positivity) seen mainly in patients with chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis) and moderate elevations commonly seen in toxic diffuse goiter (i.e. Graves’ disease); they can also be used for the differential diagnosis of AITD and non-AITD, for example, primary hypothyroidism versus The former is positive for TPO-Ab and Tg-Ab, while the latter is negative.
2) Efficacy observation: After treatment, TPO-Ab and Tg-Ab turn negative or titer decreases in patients with Graves’ disease, indicating good efficacy; if the antibody continues to be positive and the titer is high, it means the effect is not good and the disease is easy to relapse after stopping the medication.
3) Prognosis judgment: elevated TPO-Ab and Tg-Ab suggest that patients are at increased risk of hypothyroidism in the future. For example, persistent positive TPO-Ab and Tg-Ab in pregnant women indicates a higher risk of “postpartum thyroiditis” and “infantile hypothyroidism”.
4) TgAb can also be used as a monitoring indicator for differentiated thyroid cancer (TDC). Under normal circumstances, the TgAb level of differentiated thyroid cancer patients will gradually decrease after radical surgery and turn negative within 1 to 4 years.
Indications
1) Elevated TSH of unknown etiology;
2) Goiter of unknown etiology;
3) Differential diagnosis of hyperthyroidism of unknown etiology;
4) suspected polyglandular autoimmune disease;
5) Familial evaluation of autoimmune thyroid disease;
6) evaluation of the risk of thyroid disorders during treatment with thyroid drugs (e.g., lithium, amiodarone) or drugs that act on the immune system (e.g., interferon);
7) Risk assessment for postpartum thyroiditis (during pregnancy or postpartum);
Precautions
1) Thyroid antibodies are not very specific and low to moderate levels of TPO-Ab and/or Tg-Ab can be detected in the sera of not only patients with autoimmune thyroid disease (AITD) but also some healthy individuals (26% in adult females and 9% in males), therefore, caution should be exercised when evaluating their significance.
2) Antibody levels often overlap between patients and healthy individuals and between different diseases (e.g., between Graves’ disease and Hashimoto’s thyroiditis). Clinical diagnosis should not rely exclusively on antibody levels, but should be integrated with patient history, clinical manifestations, thyroid function, ultrasound and cytology for comprehensive analysis and judgment.
3) There is no direct relationship between the level of thyroid antibodies (Tg-Ab, TPO-Ab, etc.) and the severity of thyroid function abnormalities. For example, in the late stage of Hashimoto’s disease, when the thyroid follicles are extensively atrophied and degenerated, the antibody level may not even be high.
4) A positive TRAb supports the diagnosis of Graves’ disease, but a negative TRAb does not exclude Graves’ disease. For hyperthyroid patients with negative TRAb, if the TPOAb is significantly elevated by the test, Graves’ disease can also be diagnosed.
5) The main goal of treatment for thyroid disease is to correct the thyroid function abnormalities, not to get the antibodies to turn negative. Because of the side effects of immunosuppressive therapy, the long-term use of large amounts of glucocorticoids and immunosuppressive drugs to make antibodies negative is generally not advocated.
6) Although some studies suggest that the level of TRAb before treatment in Graves’ disease is positively correlated with the course of treatment, if the clinical and laboratory tests of hyperthyroidism have been normalized after treatment and the course of treatment has reached the requirements, the course of treatment should not be extended indefinitely because the TRAb has not turned negative.
7) The greatest significance of antibody testing is to assist in clinical diagnosis.
The detection of thyroid autoantibodies is of great clinical value for the diagnosis, identification, treatment guidance and prognosis of autoimmune thyroid diseases.
TRAb is mainly used for the diagnosis of Graves’ disease and risk assessment of recurrence; TPOAb is used for the diagnosis of Hashimoto’s thyroiditis, and TgAb is used as a monitoring indicator for thyroid cancer.
Testing of thyroid function and autoantibodies in pregnant women can help improve maternal and infant health. It should also be noted that: thyroid autoantibodies also have limitations in terms of specificity, sensitivity and standardization, and their clinical role must be evaluated scientifically and objectively.