Antibody testing used in the diagnosis of Graves’ disease includes thyroid peroxidase (TPO) antibodies, thyroglobulin receptor antibodies (TRAbs), and thyroglobulin (Tg) antibodies.
Thyroid peroxidase (TPO) is the enzyme in the thyroid that facilitates the incorporation of iodine into thyroid hormones. Antibodies to TPO are present in the majority of individuals with autoimmune thyroid disease e.g., Hashimoto’s thyroiditis and Graves’ disease (Jeena 2013).
Thyroid antibodies are detectable in Graves’ and Hashimoto’s several years prior to clinical diagnosis and early evaluation may help identify those likely to develop disease. A case-control study of 522 female active-duty personnel revealed that TPO antibodies were consistently present throughout the 7-year sample period in the majority of those with Hashimoto’s. In those with Graves’, TPO antibody levels were 31% in the 5-7 years prior to diagnosis and increased to 57% at the time of diagnosis (Hutfless 2011).
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).
Measuring TRAbs can help distinguish Grave’s 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).
Thyroglobulin (Tg) is a protein precursor to thyroid hormones that is stored and metabolized in the thyroid gland. Some Tg can leak into the bloodstream due to inflammation, Hashimoto’s, Graves’, nodular goiter, or cancer, and trigger an immune antibody response. The Tg antibodies can be detected and quantified and should be measured alongside TPO antibodies (Pagana 2021).
Note that higher selenium levels and supplementation where appropriate are associated with lower TPO antibodies in both Graves’ and Hashimoto’s autoimmune thyroiditis, and with reduced symptoms in Graves’ (Rayman 2019).
References
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
Hutfless, Susan et al. “Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease.” The Journal of clinical endocrinology and metabolism vol. 96,9 (2011): E1466-71. doi:10.1210/jc.2011-0228
Jeena, E. Jacob, M. Malathi, and K. Sudeep. "A hospital-based study of anti-TPO titer in patients with thyroid disease." Muller Journal of Medical Sciences and Research 4.2 (2013): 74.
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.
Rayman, Margaret P. “Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease.” The Proceedings of the Nutrition Society vol. 78,1 (2019): 34-44. doi:10.1017/S0029665118001192