Understanding the test results: What does a positive thyroid autoantibody test mean?

Thyroid globulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb) and thyroid stimulating hormone receptor antibodies (TRAb) are three indicators that are frequently checked by endocrinology departments and are often viewed together. The three indicators are easy to confuse in their indication of autoimmune thyroid diseases. This article will help you clarify them.

Essential basic knowledge

1. Thyroglobulin (Tg) is a soluble iodinated glycoprotein synthesized and secreted by thyroid epithelial cells. It is mainly stored in the thyroid follicle cavity in the form of colloids. Under pathological conditions, it is secreted or leaked into the blood to induce the production of TgAb. After TgAb binds to thyroglobulin, it activates NK cells to attack target cells and catalyzes the hydrolysis of Tg, leading to the destruction of thyroid cells.

2. Thyroid peroxidase (TPO) is a membrane-bound glycoprotein containing a heme cofactor, located at the brush edge of the apical cell membrane of the thyroid follicular epithelium. TPO is directly involved in the oxidation of iodine, the iodination of tyrosine, and the coupling of iodinated tyrosine in thyroid cells, and is a key enzyme in the synthesis of thyroid hormone. TPO is the main antigen component of thyroid microsomes (TM), and the so-called thyroid microsomal antigen (TMAg) in the past is actually TPO.

Under normal circumstances, TPO does not overflow from the thyroid gland into the blood. However, when the thyroid gland becomes diseased and the filtration cell structure is damaged, it overflows into the peripheral blood and acts as an autoimmune antigen to stimulate the body to produce TPOAb. TPOAb can damage the thyroid follicles through ADCC and sensitized T cell killing, thereby inhibiting the synthesis of thyroid hormones and leading to hypothyroidism.

3. TRAb is a type of polyclonal antibody, a heterogeneous specific immunoglobulin (IgG), produced by thyroid B lymphocytes. TRAb includes thyroid stimulating antibodies and thyroid stimulation blocking antibodies. In clinical practice, TRAbs detected in the serum of Graves' disease (GD) patients are all regarded as thyroid stimulating antibodies. TRAb acts on TSH receptors, mimicking the effects of TSH, and increases the synthesis and release of T3 and T4 through the mediation of cAMP.

Clinical application

1. TPOAb and TgAb are the gold standard for diagnosing Hashimoto's thyroiditis.

High titer of TPOAb is a risk factor for hypothyroidism. The higher the TPOAb concentration, the more severe the lymphocyte infiltration and the more severe the thyroid follicle damage. In the diagnosis and prognosis of autoimmune thyroid disease, the sensitivity and specificity of TgAb are not as good as TPOAb, but TgAb is a powerful supplement to TPOAb. The simultaneous appearance of both indicates the severity of thyroid function damage.

2. TRAb level is an important marker for the diagnosis of GD and can distinguish it from hyperthyroidism caused by other causes.

TRAb is one of the factors causing hyperthyroidism in Hashimoto's thyroiditis, but it is not the main cause of Hashimoto's thyroiditis. Detection of TRAb is helpful in evaluating the treatment effect of GD. It is necessary to continue treatment with small doses of antithyroid drugs until TRAb turns negative, which can reduce the recurrence rate of GD.

3. In patients with thyroid nodules, serum TPOAb and TgAb levels are positively correlated with the risk of thyroid cancer and are independent risk factors.

4. During the treatment of patients with Hashimoto's thyroiditis and hyperthyroidism, TgAb and TPOAb remain high for a long time or do not decrease. Patients are prone to hypothyroidism or relapse of hyperthyroidism, and hypothyroidism is mainly clinical.

5. TPOAb positivity is an auxiliary indicator for diagnosing Graves' disease, especially for patients with negative TRAb. TPOAb and TgAb levels are positively correlated with the incidence of hypothyroidism after 131I treatment of hyperthyroidism. Therefore, it is recommended to test antibody indicators, especially TPOAb, before isotope treatment. For hyperthyroid patients with high TPOAb and TgAb positive titers, the 131I dosage should be reduced as appropriate.