Antithyroid Antibody

Antithyroid antibody studies are used to evaluate for autoimmune thyroid problems.

The reference ranges for antithyroid antibodies are as follows:

• Thyroid peroxidase antibody (TPOAb): Titer less than 9 IU/mLco ^[1]

• Thyroglobulin antibody (TgAb): Less than 116 IU/mL ^[1]

• Thyroid-stimulating immunoglobulin antibody (TSI): Less than 130% of basal activity ^[1]

• Thyroid-stimulating hormone (TSH) receptor binding inhibitor immunoglobulin (TBII)/TRAb: 1.75 IU/L or less ^[2]

Antibodies directed against 3 major thyroid antigens are as follows:

• Thyroglobulin: Antithyroglobulin antibody (TgAb)

• Thyroid peroxidase (microsomal antigen): Antithyroid peroxidase antibody (TPOAb)

• TSH receptor: Anti-TSH receptor antibody (TRAb)

The presence of serum thyroid antibodies usually indicates an autoimmune thyroid disorder, but elevated levels may also be detected in other conditions.

Conditions associated with elevated serum TPOAb levels include the following:

• Hashimoto disease (90%-100%) ^{[3, 4]}

• Graves disease (50%-80%) ^[5]

• Other autoimmune diseases (eg, type 1 diabetes mellitus) (40%)

• Pregnancy (14%)

• Sporadic multinodular goiter, isolated thyroid nodule, and thyroid cancer

Relatives of patients with an autoimmune thyroid disorder (40%-50%) may have elevated serum TPOAb levels.

Conditions associated with elevated serum TgAb levels include the following:

• Hashimoto disease (80%-90%)

• Graves disease (50%-70%) ^[5]

• Other autoimmune diseases (eg, type 1 diabetes mellitus) (40%)

• Pregnancy (14%)

• Sporadic multinodular goiter, isolated thyroid nodule, and thyroid cancer

Relatives of patients with an autoimmune thyroid disorder (40%-50%) may have elevated serum TgAb levels.

Assays for TgAb and TPOAb are highly sensitive but less specific; therefore, the absolute concentration is very important in the interpretation of the test. Monitoring antibody titers is important to evaluate the disease progression/regression over time, as well as among different patients, but the same assay should be used for this purpose.

TRAb are classified as stimulating, blocking, and neutral antibodies in relation to thyroid function and can be measured with 2 techniques. The TSI bioassay is used to measure the net stimulatory activity of all TRAb, and the TBII assay is used to measure all 3 types of TRAb. In some laboratories, TRAb refers exclusively to the TBII assay.

Conditions associated with elevated serum TSI levels include the following:

• Graves disease (80%-90% of untreated patients)

• Toxic multinodular goiter (15%)

• Conditions associated with elevated serum TBII levels include the following:

• Graves disease (>90% of untreated patients)

• Hashimoto disease (15%)

Antithyroid peroxidase antibody

Specimen type: Blood serum; hemolyzed specimen not acceptable

Collection tube: Red-top tube or gel-barrier tube

Specimen preparation: Separate serum from cells and transfer to transport tube

Storage/transport temperature: Refrigerated

Stability: 7 days refrigerated, 1 month frozen

Patient instruction: No need for fasting

Thyroglobulin antibody

Specimen type: Blood serum; hemolyzed specimen not acceptable

Collection tube: Red-top tube or gel-barrier tube

Specimen preparation: Separate serum from cells and transfer to transport tube

Storage/transport temperature: Refrigerated

Stability: 7 days refrigerated, 1 month frozen

Patient instruction: No need for fasting

Thyroid-stimulating immunoglobulin antibody

Specimen type: Blood serum

Collection tube: Red-top tube or gel-barrier tube

Specimen preparation: Separate serum from cells and transfer to transport tube

Storage/transport temperature: Refrigerated or frozen

Stability: 7 days refrigerated, 3 months frozen

Patient instruction: No need for fasting

Thyroid-stimulating hormone receptor antibodies/thyroid-stimulating hormone receptor binding inhibitor immunoglobulin

Specimen type: Blood serum; hemolyzed specimen not acceptable

Collection tube: Red-top tube or gel-barrier tube

Specimen preparation: Separate serum from cells and transfer to transport tube

Storage/transport temperature: Frozen

Stability: 3 days refrigerated, 1 month frozen:

Patient instruction: No need for fasting

Description

Autoimmune thyroid disease, including Hashimoto disease and Graves disease, is characterized by lymphocytic infiltration. Animal studies have shown that B lymphocytes in the thyroid gland are the major source of antithyroid antibodies. As described above, 3 major thyroid antibodies exist: TPOAb, TgAb, and TRAb.

TPOAb and TgAb are polyclonal antibodies of the immunoglobulin G (IgG) class. They have a complement fixing and cytotoxic capacity, but their role in Hashimoto disease still is not clear and seems to be a response to thyroid injury.

TRAb are divided into 3 types: stimulating, blocking, and neutral antibody in relation to the thyroid function. The stimulating TRAb are oligoclonal antibodies of the immunoglobulin G1 (IgG1) subclass. TRAb bind to TSH receptors and activate the signaling pathway. They can induce thyroid growth, as well as thyroid hormone production and secretion; this finding suggests that TRAb are the primary cause of Graves disease.

It is now believed that Graves disease and Hashimoto disease are closely related. In Graves disease, the goiter can result from TSH receptor stimulation, whereas, in Hashimoto disease, it results from lymphocytic infiltration, causing follicular cell destruction.

Indications/Applications

Indications for TSI and TRAb/TBII measurements include the following:

• For diagnostic purposes in euthyroid patients with exophthalmos or other extrathyroidal manifestation or when thyroid uptake and scan is contraindicated or nondiagnostic

• In pregnant women with Graves disease to determine the likelihood of neonatal thyrotoxicosis (risk increases with antibody concentration)

• To assess the degree of disease activity

• To assess the risk of Graves disease relapse after treatment with antithyroid agents (risk increases with antibody concentration)

• To differentiate between gestational thyrotoxicosis and Graves disease in the first trimester of pregnancy

TSI and TRAb/TBII measurements are not routinely indicated for the diagnosis of Graves disease.

Indications for TPOAb measurement include the following:

• To help confirm the diagnosis of Hashimoto disease (in some cases)

• To help with the treatment decision in the patient with subclinical hypothyroidism (in some cases)

Indications for TgAb measurement include the following:

• In conjunction with other thyroid antibody tests for diagnosis of autoimmune thyroid disease

• To monitor the disease status of thyroid canceraftertreatment

Considerations

Persistence of TgAb in patients with thyroid cancer for more than 1 year after therapy indicates the presence of residual thyroid tissue and perhaps an increased risk of recurrence.

High TPOAb levels in pregnant euthyroid women increases the risk of spontaneous miscarriage and preterm birth. Treatment with levothyroxine in these women seems to decrease the miscarriage rate, but it is not yet recommended to treat pregnant euthyroid women with positive antibody test results. ^{[6, 7]}

An elevated serum level of TPOAb and/or TgAb is essential for the diagnosis of the controversial disorder of Hashimoto encephalopathy.

A retrospective study by Muir et al indicated that in patients who have been newly diagnosed with Graves disease, those who are positive for TPOAbs have a reduced relapse risk subsequent to antithyroid drug treatment. The odds ratio for relapse in study patients who were not TPOAb-positive was 2.21. ^[8]

TBII assays are less expensive and more precise in detecting TRAb than the TSI bioassay.