In recent years, the incidence of thyroid disease has been increasing year by year, but the level of diagnosis and treatment of thyroid disease by primary care physicians has not “risen”. Many primary care physicians are not clear about the clinical significance of thyroid autoantibodies and do not pay enough attention to their testing. Many primary care doctors are not clear about the clinical significance of thyroid autoantibodies and do not pay enough attention to their testing. They also do not have a good grasp of indications, which inevitably leads to misdiagnosis, missed diagnosis, improper treatment and wrong prognosis of some thyroid diseases. Li Shijie, Department of Thyroid Surgery, China-Japan Friendship Hospital, Jilin University
1. Topics arising from thyroid test reports
A complete thyroid function test report form usually includes two parts: one is the indicators reflecting the functional status of the thyroid gland (such as T3, thyroid T4, 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 get the antibody to turn negative? What are the clinical options for lowering antibody levels? We will discuss these questions below.
2. Types and significance of autoantibodies to the thyroid gland
Thyroid antibodies are immunoglobulins that are produced by autoimmune disorders against certain components of the thyroid gland. There are two main clinical categories.
(1) Antibodies 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 important for the diagnosis, treatment and prognosis of Graves’ disease (toxic diffuse goiter), and the rate of TRAb positivity in patients with Graves’ disease can be more than 95%, so a positive TRAb can be used as a basis for the diagnosis of Graves’ disease, and is often used to differentiate Graves’ disease from other thyroid diseases. If the TRAb (stimulating antibodies, i.e., TSAb) also turns negative after normalization of thyroid function, the possibility of relapse after stopping medication is low. If the TRAb remains positive after medication, the treatment effect is poor and the possibility of relapse after stopping medication is high. 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, which can pass through the placenta and stimulate the fetal thyroid gland, causing transient hyperthyroidism in the newborn (incidence 1 to 2%).
(3) It helps to diagnose 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 situation can also be diagnosed as Graves’ ophthalmopathy.
(4) TRAb can also be positive in patients with hypothyroidism and autoimmune thyroiditis, and testing TRAb can help diagnose the etiology 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 or absence of blocking antibodies.
(2) Antibodies against the contents of thyroid cells
These include thyroglobulin (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 for thyroid hormone synthesis)” into the bloodstream. TPO-Ab has the same clinical significance as TG-Ab, but TPO-Ab is more sensitive and specific than TGAb, and is the first choice for diagnosing autoimmune thyroid disease. In order to improve the positive detection rate, the clinical practice usually adopts the combination of the two antibodies.
Clinical significance
1) Etiological diagnosis: These antibodies are the main basis for the diagnosis of autoimmune thyroid disease (AITD), with significant elevations (strong positivity) mainly seen 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: TPO-Ab and Tg-Ab turn negative or titer decreases after treatment 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 indicate 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 disorders.
6) evaluation of the risk of inducing thyroid disorders during treatment with drugs acting on the thyroid gland (e.g. lithium salts, amiodarone) or drugs acting on the immune system (e.g. interferon).
(7) Risk assessment of postpartum thyroiditis (during pregnancy or postpartum).
Table Antibody positivity rates for common thyroid disorders
3. Relevant notes
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 even in 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 analyzed and judged comprehensively by combining them with the patient’s medical history, clinical manifestations, thyroid function, ultrasound and cytology.
(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 hyperthyroidism 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 recommended.
(6) Although some studies suggest that the level of TRAb before treatment 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 clinical diagnosis.
Summary
The detection of thyroid autoantibodies is of great clinical value for the diagnosis, differentiation, 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 can be 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.
>>Links to related knowledge
The clinical significance of thyroglobulin (Tg)
Tg is a macromolecular glycoprotein synthesized by thyroid follicular epithelial cells, which is the main component of the glial substance within the thyroid follicle and is the carrier of thyroid hormone synthesis and storage. The synthesized thyroid hormone is stored in the follicular lumen in the form of globulin. Under normal conditions, Tg circulates only in the thyroid lumen and does not leak into the bloodstream. Only when various causes (e.g. inflammation, tumor, physical injury, etc.) lead to damage of the thyroid follicular wall does a large amount of Tg enter the bloodstream.
Thyroglobulin is (Tg) used as a marker for differentiated thyroid cancer (DTC) and is currently used only for observation of the efficacy and monitoring of recurrence of follicular thyroid carcinoma (note: serum Tg levels are decreased in patients with medullary thyroid carcinoma). If blood Tg is elevated after surgery or RAI treatment, it indicates tumor recurrence or metastasis, and if it is decreased to an undetectable level, it indicates a good prognosis. In addition, the detection of Tg should be meaningful only if TGAb is negative, because the presence of TGAb will seriously interfere with the detection results of Tg. Therefore, clinicians should know the situation of TgAb in patients before making accurate judgment.