Measuring TSH receptor antibody to influence treatment choices in Graves’ disease

TSH receptor antibody (TRAb) plays a key role in the pathogenesis of Graves’ disease (GD), and its levels correlate with the clinical course. The second‐ and third‐generation TRAb assays have >95% sensitivity and specificity for the diagnosis of GD and have improved the utility of TRAb to predict relapse. TRAb levels decline with antithyroid drug (ATD) therapy and after thyroidectomy. Its level increases for a year following radioactive iodine (RAI) therapy, with a gradual fall thereafter. TRAb level >12 IU/l at diagnosis of GD is associated with 60% risk of relapse at 2 years and 84% at 4 years. The prediction of risk of relapse improves further to >90% with TRAb >7·5 IU/l at 12 months or >3·85 IU/l at cessation of ATD therapy. TRAb tests are not expensive, and hence, TRAb measurements at presentation, after 12 months and/or 18 months (at cessation) of ATD therapy, could potentially guide treatment choices in GD. Elevated TRAb favours definitive treatment in the form of RAI or thyroidectomy, depending on the presence or absence of moderate‐to‐severe Graves’ ophthalmopathy (GO) and the ability to comply with radiation protection requirements. Use of ATDs in early pregnancy is associated with increased risk of congenital anomalies; early ablative treatment (RAI/surgery) should be considered in women of childbearing age at higher risk of relapse of GD. TRAb ≥5 IU/l in pregnant women with current or previously treated GD is associated with increased risk of foetal and neonatal thyrotoxicosis, and hence needs close monitoring. TRAb levels parallel the course of GO, and elevated TRAb is an indication for steroid prophylaxis to prevent progression of GO with RAI therapy.

[1]  S. Mandel,et al.  2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. , 2011, Thyroid : official journal of the American Thyroid Association.

[2]  L. Gordon,et al.  Cost-utility analysis comparing radioactive iodine, anti-thyroid drugs and total thyroidectomy for primary treatment of Graves' disease. , 2016, European journal of endocrinology.

[3]  S. Rivkees,et al.  2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. , 2016, Thyroid : official journal of the American Thyroid Association.

[4]  J. Seckl,et al.  Thyrotropin Receptor Antibody Levels at Diagnosis and After Thionamide Course Predict Graves' Disease Relapse. , 2016, Thyroid : official journal of the American Thyroid Association.

[5]  W. Wiersinga,et al.  The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy , 2016, European Thyroid Journal.

[6]  A. Zwinderman,et al.  Predicting the Risk of Recurrence Before the Start of Antithyroid Drug Therapy in Patients With Graves' Hyperthyroidism. , 2016, The Journal of clinical endocrinology and metabolism.

[7]  P. Laurberg,et al.  Antithyroid Drug Side Effects in the Population and in Pregnancy. , 2016, The Journal of clinical endocrinology and metabolism.

[8]  I. Shimon,et al.  Glucocorticoid regimens for prevention of Graves' ophthalmopathy progression following radioiodine treatment: systematic review and meta-analysis. , 2014, Thyroid : official journal of the American Thyroid Association.

[9]  F. Borson‐Chazot,et al.  Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism. , 2014, European journal of endocrinology.

[10]  Sy Jang,et al.  Relevance of TSH-receptor antibody levels in predicting disease course in Graves’ orbitopathy: comparison of the third-generation TBII assay and Mc4-TSI bioassay , 2013, Eye.

[11]  Zhen Wang,et al.  Comparative effectiveness of therapies for Graves' hyperthyroidism: a systematic review and network meta-analysis. , 2013, The Journal of clinical endocrinology and metabolism.

[12]  G. Barbesino,et al.  Clinical Utility of TSH Receptor Antibodies , 2013 .

[13]  S. Y. Lee,et al.  Relevance of TSH-receptor antibody levels in predicting disease course in Graves’ orbitopathy: comparison of the third-generation TBII assay and Mc4-TSI bioassay , 2013, Eye.

[14]  D. Giavarina,et al.  TSH receptor autoantibody immunoassay in patients with Graves' disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis. , 2012, Autoimmunity reviews.

[15]  R. Bahn,et al.  Immunopathogenesis of Graves' ophthalmopathy: the role of the TSH receptor. , 2012, Best practice & research. Clinical endocrinology & metabolism.

[16]  S. Mandel,et al.  Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. , 2007, The Journal of clinical endocrinology and metabolism.

[17]  Ernest Frimpong Asamoah,et al.  Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I : practice recommendations of the American Thyroid Association. , 2011, Thyroid : official journal of the American Thyroid Association.

[18]  Seema Kumar,et al.  A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves' ophthalmopathy , 2011, Journal of molecular endocrinology.

[19]  R. Negro,et al.  2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. , 2011, Thyroid : official journal of the American Thyroid Association.

[20]  K. Zöphel,et al.  Clinical review about TRAb assay's history. , 2010, Autoimmunity reviews.

[21]  W. Scherbaum,et al.  Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves’ disease (GD): an international multicentre trial , 2009, Clinical endocrinology.

[22]  C. Massart,et al.  Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow-up of antithyroid drug treated Graves' disease: comparison with the second generation human TRAb assay. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[23]  P. Glendenning Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. , 2008, Clinical biochemist reviews.

[24]  O. Tørring,et al.  TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. , 2008, European journal of endocrinology.

[25]  L. Mansi,et al.  Radioiodine in the management of benign thyroid disease: clinical guidelines. Report of a Working Party, 2007. Royal College of Physicians (RCP) , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[26]  N. Morgenthaler,et al.  Patients with severe Graves’ ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission , 2007, Clinical endocrinology.

[27]  N. Morgenthaler,et al.  Thyrotropin receptor autoantibodies are independent risk factors for Graves' ophthalmopathy and help to predict severity and outcome of the disease. , 2006, The Journal of clinical endocrinology and metabolism.

[28]  M. Vanderpump,et al.  The cost effectiveness of treatment modalities for thyrotoxicosis in a U.K. center. , 2006, Thyroid : official journal of the American Thyroid Association.

[29]  Y. Okamoto,et al.  TSH receptor antibody measurements and prediction of remission in Graves' disease patients treated with minimum maintenance doses of antithyroid drugs. , 2006, Endocrine journal.

[30]  C. Carella,et al.  Serum thyrotropin receptor antibodies concentrations in patients with Graves' disease before, at the end of methimazole treatment, and after drug withdrawal: evidence that the activity of thyrotropin receptor antibody and/or thyroid response modify during the observation period. , 2006, Thyroid : official journal of the American Thyroid Association.

[31]  U. Roggenbuck,et al.  Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease. , 2005, Thyroid : official journal of the American Thyroid Association.

[32]  A. Avenell,et al.  Antithyroid drug regimen for treating Graves' hyperthyroidism. , 2005, The Cochrane database of systematic reviews.

[33]  Terry J. Smith,et al.  Current perspective on the pathogenesis of Graves' disease and ophthalmopathy. , 2003, Endocrine reviews.

[34]  J. Sanders,et al.  Thyroid-stimulating monoclonal antibodies. , 2002, Thyroid : official journal of the American Thyroid Association.

[35]  P. Carayon,et al.  Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long term remission after medical therapy of Graves' disease. , 1994, The Journal of clinical endocrinology and metabolism.

[36]  D. Kritchevsky,et al.  Lignin and bile acid binding. , 1981, Lancet.

[37]  B. Smith,et al.  THYROID-STIMULATING IMMUNOGLOBULINS IN GRAVES' DISEASE , 1974 .