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Test ID: THYRO Thyrotropin Receptor Antibody, Serum

Reporting Name

Thyrotropin Receptor Ab, S

Useful For

Recommended first-line test for detection of /thyrotropin receptor antibodies

 

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 (GD) (eg, extrathyroidal manifestation of GD 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 GD

-Differential diagnosis of gestational thyrotoxicosis versus first trimester manifestation or recurrence of Graves’ disease

-Assessing the risk of GD relapse after antithyroid drug treatment

Clinical 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.

Interpretation

The sensitivity and specificity of an elevated thyrotropin receptor antibody (TRAb) test for Graves disease (GD) 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 GD, and 102 patients with untreated GD, a decision limit of 1.75 IU/L showed a sensitivity of 97% and a specificity of 99% for detection of GD.(1) In healthy individuals and in patients with thyroid disease without diagnosis of GD, the upper limit of antithyrotropin receptor 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 GD, showed a sensitivity of 95% and a specificity of 97% for detection of GD 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 GD has TRAb concentrations of more than 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 thyrotropin receptor and transient changes in thyroid hormone protein binding, is only very rarely associated with an elevated TRAb test. Finding an elevated test result in this setting usually suggests underlying GD.

 

An elevated TRAb test at the conclusion of a course of antithyroid drug treatment is highly predictive of relapse of GD. However, the converse, a normal TRAb test, is not predictive of prolonged remission.

Analytic Time

Same day/1 day

Day(s) and Time(s) Performed

Monday through Friday; 5 a.m.-12 a.m.

Saturday; 6 a.m.-6 p.m.

Clinical Reference

1. Schott M, Hermsen D, Broecker-Preuss M, et al: Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves disease: an international multicentre trial. Clin Endocrinol (Oxf). 2009 Oct;71(4):566-573

2. Hermsen D, Broecker-Preuss M, Casati M, et al: Technical evaluation of the first fully automated assay for the detection of TSH receptor autoantibodies. Clin Chim Acta. 2009 Mar;401(1-2):84-89

3. Diana T, Olivo PD, Kahaly GJ: Thyrotropin receptor blocking antibodies. Horm Metab Res. 2018 Dec;50(12):853-862

4. Kotwal A, Stan M: Thyrotropin receptor antibodies-an overview. Ophthalmic Plast Reconstr Surg. 2018 Jul/Aug; 34(4S Supple 1) S20-S27

Method Name

Electrochemiluminescence Immunoassay

Specimen Type

Serum


Specimen Required


Patient Preparation:

1. 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.

2. Patient should not be receiving heparin treatment.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 1 mL


Specimen Minimum Volume

0.75 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 7 days
  Frozen  30 days

Reference Values

≤1.75 IU/L

Test Classification

This test has been cleared, approved or is exempt by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information

83520

LOINC Code Information

Test ID Test Order Name Order LOINC Value
THYRO Thyrotropin Receptor Ab, S 5385-0

 

Result ID Test Result Name Result LOINC Value
THYRO Thyrotropin Receptor Ab, S 5385-0

Forms

If not ordering electronically, complete, print, and send a General Request (T239) with the specimen.

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Neuroimmunology, mml-Pediatric