In recent years, the incidence of thyroid diseases has been increasing year by year.Among them, the prevalence of Autoimmune Thyroid Diseases (AITD) in the general population is approximately 10%.Some retrospective studies even suggest that AITD may be associated with the development of thyroid cancer.Therefore, an increasing number of medical professionals have begun to focus on the diagnosis and treatment of these conditions.
Changes in thyroid hormone levels in the blood indicate alterations in thyroid function.Consequently, convenient thyroid function testing has become the preferred choice for most endocrinologists.A complete thyroid function report now includes not only thyroid hormone parametersbut also various humoral immune markers such as TRAb, TgAb, and TPOAb.
Hormones like T3, T4, and TSH are relatively easy to interpret and manage clinically.But what do these antibodies mean?What do they represent?And is it necessary to keep them within the normal range?
TRAb – TSH Receptor Antibody
TRAb is a member of the G‑protein‑coupled receptor superfamily,with its antigen being the TSH receptor on thyroid cells.
Broadly, it can be divided into three subtypes:
TSAb (Thyroid-Stimulating Antibody)
TSBAb (TSH-Stimulating Blocking Antibody)
TBII (TSH-Binding Inhibitory Immunoglobulin)In the context of hyperthyroidism, TRAb is often defined as TBII.
By binding to the TSH receptor on thyroid cells,these antibodies cause thyroid hyperplasia and excessive or insufficient secretion of thyroid hormones.They are recognized as one of the key factors leading to autoimmune thyroid diseases.
TgAb – Thyroglobulin Antibody
TgAb was the first thyroid autoantibody discovered.Its main antigen is thyroglobulin in the colloid of thyroid follicles.
It exerts cytotoxic effects,which can lead to excessive destruction of thyroid epithelial cells and result in hypothyroidism.However, the titer of TgAb shows no significant correlation with the severity of thyroid diseaseand may merely be a secondary result of the autoimmune response.
TPOAb – Thyroid Peroxidase Antibody
Previously known as thyroid microsomal antibody (AMA),TPOAb is induced by microsomal antigens from the cytoplasm of thyroid epithelial cells.
It exerts antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC),which sustain and worsen thyroid injury,but it does not initiate thyroid immune damage.
Why Do These Antibody Levels Keep Fluctuating?
Before clarifying the meaning of antibody results,one critical point must be emphasized:test results from different hospitals or laboratories are not directly comparable!
Despite advances in testing technology that have greatly improved the sensitivity and accuracy of antibody assays,and despite the adoption of unified international reference standards,differences in testing methods and reagents across laboratories still lead to substantial variability.
Therefore, each laboratory must establish its own unique normal reference range.If the brand or model of reagents is changed,the reference values must be adjusted accordingly.
As a result, if thyroid antibody tests are performed at different hospitals,the comparability of results is limited.We can only judge whether the values are within the normal range,not whether the condition has improved or worsened by simply comparing numerical values.
What Diseases Do Abnormal Antibody Levels Indicate?
TRAb
TRAb, especially TSAb, is mainly used for the diagnosis, differential diagnosis, and prognostic evaluation of Graves’ disease.
Since some patients with Graves’ disease may be TRAb-negative,TRAb cannot be used as the sole diagnostic criterion.In general, a negative TRAb helps distinguish Graves’ disease from other thyrotoxicosessuch as subacute thyroiditis, painless thyroiditis, postpartum thyroiditis, and toxic nodular goiter.
TRAb also serves as a predictor of Graves’ disease recurrence after treatment,with specificity and sensitivity above 50%.However, current results reflect the percentage of TSH receptor activation or inhibitionand are affected by the ratio of TSAb to TSBAb,so interpretation requires caution.
In Graves’ ophthalmopathy,TRAb helps differentiate unilateral exophthalmos and euthyroid exophthalmosand predicts the risk of developing Graves’ ophthalmopathy after radioactive iodine therapy.
Because TRAb can cross the placenta,TSAb and TSBAb may enter the fetus and cause neonatal hyperthyroidism or hypothyroidism,impairing neurological development.Women should be tested for TRAb before pregnancy;if positive, treatment should be given to normalize levels before conception.
TgAb
TgAb is a hallmark antibody of autoimmune thyroid diseases,often appearing together with TPOAb.Its positivity rate is higher in women and increases with age.
In regions with endemic goiter,TgAb should be monitored during iodine supplementation,as iodine can increase the immunogenicity of thyroglobulin,especially in a pre-injured thyroid,potentially progressing simple goiter to AITD.
TgAb also plays an important role as an adjunctive marker for monitoring thyroid cancer:
Serum thyroglobulin (Tg) is key for prognosis and surveillance in well-differentiated thyroid cancer,
but its measurement is easily affected by TgAb.
Therefore, TgAb should be measured before Tg.
In differentiated thyroid cancer patients,
serial monitoring of TgAb can replace Tg as an independent tumor marker.
Normally, TgAb levels gradually decline after radical surgery and become negative within 1–4 years.
A re‑rise in TgAb is an early indicator of tumor recurrence.TPOAb
TPOAb is another hallmark antibody of autoimmune thyroid diseases.Its level reflects the degree of lymphocyte infiltration.It is highly positive in Hashimoto’s thyroiditis, Graves’ disease, and postpartum thyroiditis,with some positivity in the general population.
Studies show significantly elevated TPOAb positivity in patients with other autoimmune diseases(e.g., type 1 diabetes, pernicious anemia)and in first‑degree relatives of AITD patients,indicating potential risk of thyroid dysfunction.
TPOAb is the gold standard for diagnosing Hashimoto’s thyroiditis,even more sensitive and accurate than fine‑needle aspiration.A positive TPOAb is sufficient to confirm autoimmune thyroid disease.
It also assists in diagnosing Graves’ disease,especially in TRAb-negative cases.Very high TPOAb titers in Graves’ disease suggest coexisting Hashimoto’s thyroiditis,with increased risk of spontaneous hypothyroidism during treatment.
In early pregnancy,maternal TPOAb positivity predicts a higher risk of postpartum thyroiditis.Studies also show that TPOAb positivity in early pregnancy,especially combined with subclinical hypothyroidism or low thyroid hormone levels,may damage early fetal neurological development and reduce intellectual outcomes.
Summary
Testing for thyroid autoantibodies is crucial for diagnosing and differentiating autoimmune thyroid diseases,but each laboratory must establish its own normal reference range.
TRAb: Mainly for the diagnosis of Graves’ disease.
TPOAb: Mainly for the diagnosis of Hashimoto’s thyroiditis.
TgAb: Serves as an adjunctive marker for thyroid cancer surveillance.All pregnant women should undergo thyroid function and autoantibody testingto reduce neurological damage to the fetus and ensure healthy childbearing.