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23190 Thyrotropin Receptor Antibody (THYRO)

Thyrotropin Receptor Antibody (THYRO)
Test Code: THRECSO
Synonyms/Keywords
​Antibodies to TSH receptor, Inhibitory Immunoglobulin, Long-Acting Thyroid Stimulator (LATS), TBII (TSH-Binding Inhibiting Immunoglobulin), Thyroid-Stimulating Hormone Receptor (TSH Receptor) Antibody, TRAb (Thyrotropin Receptor Antibody), TSH (Thyroid-Stimulating Hormone) Receptor Binding, TSH Binding Inhibition Index, TSH Receptor (Thyroid-Stimulating Hormone Receptor) Antibody, TSH-Binding Inhibiting Immunoglobulin (TBII), Graves Disease
Test Components

​​

Useful For
​Recommended first-line test for detection of thyrotropin receptor (TSHR) antibodies, and used in the following situations:
-Differential diagnosis of etiology of thyrotoxicosis in patients with ambiguous clinical findings and/or contraindicated (eg, pregnant or breast-feeding) or nondiagnostic thyroid radioisotope scans
-Diagnosis of clinically suspected Graves disease (eg, extrathyroidal manifestation of Graves disease include endocrine exophthalmos, pretibial myxedema, thyroid acropachy) in patients with normal thyroid function tests
-Determining the risk of neonatal thyrotoxicosis in a fetus of a pregnant female with active or past active Graves disease
-Differential diagnosis of gestational thyrotoxicosis versus first trimester manifestation or recurrence of Graves disease
-Assessing the risk of Graves disease relapse after antithyroid drug treatment
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​Serum Serum Separator Tube (SST)​ Red Top Tube (RTT)
1 mL​ 0.75 mL​ ​​
Collection Processing Instructions

​For 12 hours before specimen collection do NOT take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.

Patient should not be receiving heparin treatment.

Specimen Stability Information
Specimen Type Temperature Time
Serum​ ​​
Refrigerated (preferred)​ 7 days​
Frozen ​ 90 days​
Rejection Criteria
Gross hemolysis
Interference

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. The presence of antibodies to streptavidin or ruthenium can also rarely occur and may also interfere in this assay. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.

Performing Laboratory Information
Performing Location Day(s) Test Performed Report Available
Methodology/Instrumentation
Mayo Clinic Laboratories
Monday through Saturday ​
1-3 day​s
Electrochemiluminescence Immunoassay​
Reference Lab
Test Information

​​Autoimmune thyroid disease is characterized by the presence of autoantibodies against various thyroid components, namely the thyrotropin receptor, thyroid peroxidase, and thyroglobulin, as well as by an inflammatory cellular infiltrate of variable severity within the gland.

Among the autoantibodies found in autoimmune thyroid disease, thyrotropin receptor autoantibodies (TRAb) are most closely associated with disease pathogenesis. All forms of autoimmune thyrotoxicosis (Graves disease; GD, Hashitoxicosis, neonatal thyrotoxicosis) are caused by the production of stimulating TRAb-. These autoantibodies, also known as long-acting-thyroid-stimulator (LATS) or thyroid-stimulating immunoglobulins (TSI), bind to the receptor and transactivate it, leading to stimulation of the thyroid gland independent of the normal feedback-regulated thyrotropin (TSH) stimulation.

Some patients with GD also have TRAb, which do not transactivate the thyrotropin receptor. The balance between stimulating and blocking antibodies, as well as their individual titers, is felt to be a determinant of GD severity. Some patients with autoimmune hypothyroidism also have evidence of either blocking TRAb or, rarely, TSI.

TRAb may be detected before autoimmune thyrotoxicosis becomes biochemically or clinically manifest. Since none of the treatments for GD are aimed at the underlying disease process, but rather ablate thyroid tissue or block thyroid hormone synthesis, TSI may persist after apparent clinical cure. This is of particular relevance for pregnant women with a history of GD that was treated with thyroid-ablative therapy. Some of these women may continue to produce TSI. Since TSI are IgG antibodies, they can cross the placental barrier causing neonatal thyrotoxicosis.

While the gold standard for thyroid-stimulating immunoglobulins is the bioassay (see TSI / Thyroid-Stimulating Immunoglobulin [TSI], Serum), the TRAb test  has a shorter turnaround time, less analytical variability, and is less expensive.

Reference Range Information
<= 1.75 IU/L
Interpretation
​The sensitivity and specificity of an elevated thyrotropin receptor antibody (TRAb) test for Graves disease diagnosis depends on whether patients have disease treated with antithyroid drugs or clinically active, untreated disease. Based on a study that included specimens from 436 apparently healthy individuals, 210 patients with thyroid diseases without diagnosis of Graves disease, and 102 patients with untreated Graves disease, a decision limit of 1.75 IU/L showed a sensitivity of 97% and a specificity of 99% for detection of Graves disease. In healthy individuals and in patients with thyroid disease without diagnosis of Graves disease, the upper limit of antithyrotropin receptor (anti-TSHR) values are 1.22 IU/L and 1.58 IU/L, respectively (97.5th percentiles). A Mayo study of 115 patients, including 42 patients with Graves disease, showed a sensitivity of 95% and a specificity of 97% for detection of Graves disease at a decision limit of 1.75 IU/L.
 
Assessment of TRAb status is particularly relevant in women who have undergone thyroid ablative therapy or are on active antithyroid treatment and, therefore, no longer display biochemical or clinical evidence of thyrotoxicosis. Significant neonatal thyrotoxicosis is likely if a pregnant woman with a history of Graves disease has TRAb concentrations of >3.25 IU/L during the last trimester, regardless of her clinical remission status. Lesser elevations are only occasionally associated with neonatal thyrotoxicosis. Gestational thyrotoxicosis, which is believed to be due to a combination of human chorionic gonadotropin cross-reactivity on the TSHR and transient changes in thyroid hormone protein binding, is only very rarely associated with an elevated TRAb test. Finding an elevated TRAb test in this setting suggests usually underlying Graves disease.
 
An elevated TRAb test at the conclusion of a course of antithyroid drug treatment is highly predictive of relapse of Graves disease. However, the converse, a normal TRAb test, is not predictive of prolonged remission.
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​83520
Synonyms/Keywords
​Antibodies to TSH receptor, Inhibitory Immunoglobulin, Long-Acting Thyroid Stimulator (LATS), TBII (TSH-Binding Inhibiting Immunoglobulin), Thyroid-Stimulating Hormone Receptor (TSH Receptor) Antibody, TRAb (Thyrotropin Receptor Antibody), TSH (Thyroid-Stimulating Hormone) Receptor Binding, TSH Binding Inhibition Index, TSH Receptor (Thyroid-Stimulating Hormone Receptor) Antibody, TSH-Binding Inhibiting Immunoglobulin (TBII), Graves Disease
Test Components

​​

Ordering Applications
Ordering Application Description
​Cerner ​Thyrotropin Receptor Antibody (THYRO)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​Serum Serum Separator Tube (SST)​ Red Top Tube (RTT)
1 mL​ 0.75 mL​ ​​
Collection Processing

​For 12 hours before specimen collection do NOT take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.

Patient should not be receiving heparin treatment.

Specimen Stability Information
Specimen Type Temperature Time
Serum​ ​​
Refrigerated (preferred)​ 7 days​
Frozen ​ 90 days​
Rejection Criteria
Gross hemolysis
Interference

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. The presence of antibodies to streptavidin or ruthenium can also rarely occur and may also interfere in this assay. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.

Useful For
​Recommended first-line test for detection of thyrotropin receptor (TSHR) antibodies, and used in the following situations:
-Differential diagnosis of etiology of thyrotoxicosis in patients with ambiguous clinical findings and/or contraindicated (eg, pregnant or breast-feeding) or nondiagnostic thyroid radioisotope scans
-Diagnosis of clinically suspected Graves disease (eg, extrathyroidal manifestation of Graves disease include endocrine exophthalmos, pretibial myxedema, thyroid acropachy) in patients with normal thyroid function tests
-Determining the risk of neonatal thyrotoxicosis in a fetus of a pregnant female with active or past active Graves disease
-Differential diagnosis of gestational thyrotoxicosis versus first trimester manifestation or recurrence of Graves disease
-Assessing the risk of Graves disease relapse after antithyroid drug treatment
Test Components

​​

Reference Range Information
<= 1.75 IU/L
Interpretation
​The sensitivity and specificity of an elevated thyrotropin receptor antibody (TRAb) test for Graves disease diagnosis depends on whether patients have disease treated with antithyroid drugs or clinically active, untreated disease. Based on a study that included specimens from 436 apparently healthy individuals, 210 patients with thyroid diseases without diagnosis of Graves disease, and 102 patients with untreated Graves disease, a decision limit of 1.75 IU/L showed a sensitivity of 97% and a specificity of 99% for detection of Graves disease. In healthy individuals and in patients with thyroid disease without diagnosis of Graves disease, the upper limit of antithyrotropin receptor (anti-TSHR) values are 1.22 IU/L and 1.58 IU/L, respectively (97.5th percentiles). A Mayo study of 115 patients, including 42 patients with Graves disease, showed a sensitivity of 95% and a specificity of 97% for detection of Graves disease at a decision limit of 1.75 IU/L.
 
Assessment of TRAb status is particularly relevant in women who have undergone thyroid ablative therapy or are on active antithyroid treatment and, therefore, no longer display biochemical or clinical evidence of thyrotoxicosis. Significant neonatal thyrotoxicosis is likely if a pregnant woman with a history of Graves disease has TRAb concentrations of >3.25 IU/L during the last trimester, regardless of her clinical remission status. Lesser elevations are only occasionally associated with neonatal thyrotoxicosis. Gestational thyrotoxicosis, which is believed to be due to a combination of human chorionic gonadotropin cross-reactivity on the TSHR and transient changes in thyroid hormone protein binding, is only very rarely associated with an elevated TRAb test. Finding an elevated TRAb test in this setting suggests usually underlying Graves disease.
 
An elevated TRAb test at the conclusion of a course of antithyroid drug treatment is highly predictive of relapse of Graves disease. However, the converse, a normal TRAb test, is not predictive of prolonged remission.
For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Report Available
Methodology/Instrumentation
Mayo Clinic Laboratories
Monday through Saturday ​
1-3 day​s
Electrochemiluminescence Immunoassay​
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​83520
For most current information refer to the Marshfield Laboratory online reference manual.