Thyroid Biomarkers: Thyrotropin Receptor Antibodies

Optimal Takeaways

Antibodies to the thyrotropin (TSH) receptor (TRAbs) may stimulate the receptor and cause increased production of thyroid hormone as in Graves’ disease or may block the receptor and decrease hormone production as in Hashimoto’s thyroiditis. TRAbs may be neutral as well. Elevated TRAbs are associated with hyperthyroidism, hypothyroidism, myxedema, and exophthalmos. Levels may be falsely elevated in individuals taking high dose biotin.

Standard Range: 00.0 – 2.00 IU/L

The ODX Range: 0.00 – 0.55 IU/L

Low TRAbs suggest the absence of Graves’ disease and autoimmune thyroid disease in general.

High TRAbs are associated with hyperthyroidism, Graves’ disease, malignant exophthalmos, Hashimoto’s thyroiditis (Pagana 2021), Graves’ ophthalmopathy, pretibial myxedema, and false elevation due to high biotin levels (Kotwal 2018)

Overview

Thyrotropin receptor antibodies (TRAbs) interact with the TSH (thyrotropin) receptor and may stimulate or block the receptor depending on the type of TRAb. Graves’ disease, an autoimmune thyroid disorder, is characterized by unregulated stimulation of the TSH receptor whereas Hashimoto’s autoimmune thyroiditis is characterized by antagonization or blocking of the TSH receptor. Evaluation of TRAbs is particularly useful in the diagnosis and monitoring of Graves’ disease as the stimulating TRAbs are responsible for many of the extrathyroidal clinical manifestations of the disease (Kahaly 2017). However, individuals with Graves’ disease can also have blocking TRAbs and it is the balance between stimulating and blocking TRAbs that may determine severity of the disease (Pagana 2021).

The systemic effects of Graves’ can involve the eyes, skin, bones, heart, liver, and other organs. Measuring TRAbs can help distinguish Gravess from subacute painless thyroiditis (SPT) in which the thyroid toxicosis resolves fairly quickly. Both conditions can have positive TPO antibodies but TRAbs are primarily associated with Graves’ disease (Barbesino 2013). Elevated TRAbs are observed in at least 99% of Graves’ cases. Clinical trials suggest a cut-off of 1.75 IU/L for the diagnosis of Graves’ and a cut-off of 1.58 IU/L for non-Graves’ thyroid disease, while the upper limit for healthy individuals should not exceed 1.22 IU/L. Evaluation of TRAb is considered a diagnostic tool for hyperthyroidism and is recommended by the American Thyroid Association (Kotwal 2018).

A cut-off of above 1.0 IU/L for TRAbs was used to diagnose Graves’ in a retrospective cohort study of 146 subjects. Researchers noted that elevations in GGT, ALT, AST, and alkaline phosphatase were common in diagnosed patients and reflected severity of thyrotoxicosis better than the degree of TRAbs elevation did (Hsieh 2019).

References

Baral, Suman et al. “Serum Free T3 to Free T4 Ratio as a Useful Indicator for Differentiating Destruction Induced Thyrotoxicosis from Graves' Disease.” Journal of clinical and diagnostic research : JCDR vol. 11,7 (2017): OC12-OC14. doi:10.7860/JCDR/2017/28293.10180

Barbesino, Giuseppe, and Yaron Tomer. “Clinical review: Clinical utility of TSH receptor antibodies.” The Journal of clinical endocrinology and metabolism vol. 98,6 (2013): 2247-55. doi:10.1210/jc.2012-4309

Hsieh, Albert et al. “Liver enzyme profile and progression in association with thyroid autoimmunity in Graves' disease.” Endocrinology, diabetes & metabolism vol. 2,4 e00086. 15 Jul. 2019, doi:10.1002/edm2.86

Kahaly, George J, and Tanja Diana. “TSH Receptor Antibody Functionality and Nomenclature.” Frontiers in endocrinology vol. 8 28. 15 Feb. 2017, doi:10.3389/fendo.2017.00028

Kotwal, Anupam, and Marius Stan. “Thyrotropin Receptor Antibodies-An Overview.” Ophthalmic plastic and reconstructive surgery vol. 34,4S Suppl 1 (2018): S20-S27. doi:10.1097/IOP.0000000000001052

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.