Thyroid-stimulating Immunoglobulin (TSI)

CPT: 84445
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Test Details

Synonyms

  • Human Thyroid Stimulator (HTS)
  • Long-acting Thyroid Stimulator (LATS)

Use

The measurement of thyroid stimulating autoantibodies, in conjunction with other clinical and laboratory findings, is used as an aid in the diagnosis of patients suspected of having Graves' disease.1

Limitations

Heterophilic antibodies in human serum can react with the immunoglobulins included in the assay components causing interference with in vitro immunoassays. For diagnostic purposes, the results obtained from this assay should be used in combination with the clinical examination, patient medical history, and other findings.

Methodology

The IMMULITE 2000 TSI assay designed for the specific Semi- Quantitative detection of stimulating autoantibodies using a bridging format and human TSH receptor fragment chimeric recombinant proteins. The capture and detection proteins are designed to be specific for antibodies that stimulate the native receptor. This method provides a determination of thyroid stimulating autoantibodies that are specific to TSH receptors in human serum or plasma. The assay is traceable to WHO NIBSC 08/204.1

Reference Interval

0.00-0.55 IU/L

Additional Information

Graves' disease (GD) is an autoimmune disorder and the most common cause of hyperthyroidism.2-7 In GD, thyroid stimulating immunoglobulins (TSI) bind to the TSH receptor (TSHR) and mimic TSH stimulation of the thyroid gland. Because TSI induced thyroid hormone secretion is not controlled by negative feedback, such stimulation causes uncontrolled hyperthyroidism.8 Extrathyroidal manifestations of GD include endocrine exophthalmos, pretibial myxedema. GD is characterized thyroid acropachy, i.e., the soft-tissue swelling of the hands and clubbing of the fingers. Radiographic imaging of affected extremities typically demonstrates periostitis, most commonly the metacarpal bones. TSI are IgG antibodies that can cross the placental barrier and cause neonatal thyrotoxicosis in newborns delivered by mothers with GD.9,10

The TSH receptor contains a large extracellular domain that presents epitopes for a variety of autoantibodies, including TSI and Thyroid Blocking Immunoglobulins TBI.11-13 In contrast to TSI, TBI bind to the TSH receptor and inhibit TSH stimulation of thyroid cells, leading to hypothyroidism. Commonly used Thyrotropin Receptor Autoantibody (TRAb) assays do not distinguish between TSI and TBI. The IMMULITE 2000 TSI assay utilizes recombinant human TSH receptors (hTSHR) for the specific detection of thyroid stimulating autoantibodies.1

The clinical utility of TSI measurement includes a determination of the autoimmune etiology of thyrotoxicosis,2-7 monitoring GD patient therapy,14 prediction of remission or relapse,15 confirmation of Graves' ophthalmopathy,16 and prediction of hyperthyroidism in neonates.9,17,18 TheTSI test is used for the differential, diagnosis of etiology of thyrotoxicosis in patients with ambiguous clinical signs or indeterminate thyroid radioisotope scans.3 TSI can also be of value in determining the risk of neonatal thyrotoxicosis in a fetus of a pregnant female with active or past GD and the differential diagnosis of gestational thyrotoxicosis versus first-trimester manifestation or recurrence of GD.9,10 TSI can also be ordered to assess the risk of GD relapse after antithyroid drug treatment.

Several published studies have evaluated the sensitivity and specificity of the Siemens TSI assay for diagnosing GD patients and discriminating them from patients with other thyroid diseases.19-22 Kembel and coworkers23 evaluated three commercially available anti-TSHR autoantibody measurement methods and found equivalent performance in patients with untreated GD. However, discordant results were observed when testing specimens collected from patients undergoing treatment for GD. In these patients, the Siemen TSI assay more frequently generated results consistent with clinical history, results of other laboratory tests, and imaging studies than the TSI bioassay and Roche TRAb assay. In the validation for FDA submission,11 serum samples from 361 treated and untreated hyperthyroid Graves' disease patients, and 404 individuals with other thyroid or autoimmune diseases were evaluated. The TSI values for patients without GD with other thyroid or autoimmune diseases had an upper limit of 0.39 IU/L. At the 0.55 IU/L cut-off, the clinical sensitivity and specificity for GD were 98.6% and 98.5%, respectively.

Specimen Requirements

Specimen

Serum (preferred) or plasma (EDTA or heparin)

Volume

3 mL

Minimum Volume

0.3 mL (Note: This volume does not allow for repeat testing.)

Container

Red-top tube, gel-barrier tube, lavender-top (EDTA) tube or green-top (heparin) tube

Patient Preparation

Prepare sterile venipuncture site.

Collection

Serum or plasma must be separated from blood cells by centrifugation, ideally within 2 hours of collection. If red-top tube or plasma, transfer separated serum or plasma to a plastic transport tube.

Storage Instructions

Refrigerate.

Room temperature: 3 days; Refrigerated: 3 days; Frozen: 14 days; Freeze/thaw cycles: Stable x2

Causes for Rejection

Sample submitted other than serum, EDTA or heparin plasma

Clinical Information

Footnotes

1. Thyroid Stimulating Immunoglobulin (TSI) on Siemens Immulite 2000; PIL2KTSID-8, 2016-03-09.
2. De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016;388(10047):906-918.27038492
3. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26(10):1343-1421.27521067
4. Smith TJ, Hegeds L. Graves' Disease. N Engl J Med. 2016 Oct 20;375(16):1552-1565.27797318
5. Burch HB, Cooper DS. Management of Graves Disease: A Review. JAMA. 2015 Dec 15;314(23):2544-2554.26670972
6. Menconi F, Marcocci C, Marin M. Diagnosis and classification of Graves' disease. Autoimmun Rev. 2014 Apr-May;13(4-5):398-402.24424182
7. Bartalena L, Tanda ML. Clinical practice. Graves' ophthalmopathy. N Engl J Med. 2009 Mar 5;360(10):994-1001.19264688
8. Rapoport B, Chazenbalk GD, Jaume JC, McLachlan SM. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr Rev. 1998 Dec;19(6):673-716.9861544
9. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017 Mar;27(3):315-389.28056690
10. Bucci I, Giuliani C, Napolitano G. Thyroid-stimulating hormone receptor antibodies in pregnancy: Clinical Relevance. Front Endocrinol (Lausanne). 2017 Jun 30;8:137.28713331
11. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: Potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid. 2013 Jan;23(1):14-24.23025526
12. Evans M, Sanders J, Tagami T, et al. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample. Clin Endocrin (Oxf). 2010 Sep;73(3):404-12.20550534
13. Morgenthaler NG, Ho SC, Minich WB. Stimulating and blocking thyroid-stimulating hormone (TSH) receptor autoantibodies from patients with Graves' disease and autoimmune hypothyroidism have very similar concentration, TSH receptor affinity, and binding sites. J Clin Endocrinol Metab. 2007 Mar;92(3):1058-1065.17179194
14. Laurberg P, Wallin G, Tallstedt L, Abraham-Nordling M, Lundell G, Torring O. TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol. 2008 Jan;158(1):69-75.18166819
15. Giuliani C, Cerrone D, Harii N, et al. A TSHR-LH/CGR chimera that measures functional thyroid-stimulating autoantibodies (TSAb) can predict remission or recurrence in Graves' patients undergoing antithyroid drug (ATD) treatment. J Clin Endocrinol Metab. 2012 Jul;97(7):E1080-1087.22492869
16. Eckstein AK, Plicht M, Lax H, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves' ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006 Sep;91(9):3464-3470.16835285
17. Bjrgaas MR, Farstad H, Christiansen SC, Blaas HG. Impact of thyrotropin receptor antibody levels on fetal development in two successive pregnancies in a woman with Graves' disease. Horm Res Paediatr. 2013;79(1):39-43.23154300
18. American College of Obstetricians and Gynecologists. Practice Bulletin No. 148: Thyroid disease in pregnancy. Obstet Gynecol. 2015 Apr;125(4):996-1005.25798985
19. Allelein S, Ehlers M, Goretzki S, et al. Clinical Evaluation of the First Automated Assay for the Detection of Stimulating TSH Receptor Autoantibodies. Horm Metab Res. 2016 Dec;48(12):795-801.27923250
20. Autilio C, Morelli R, Locantore P, Pontecorvi A, Zuppi C, Carrozza C. Stimulating TSH receptor autoantibodies immunoassay: analytical evaluation and clinical performance in Graves' Disease. Ann Clin Biochem. 2018 Jan;(55)1:172-177.28388869
21. Frank CU, Braeth S, Dietrich JW, Wanjura D, Loos U. Bridge Technology with TSH Receptor Chimera for Sensitive Direct Detection of TSH Receptor Antibodies Causing Graves' Disease: Analytical and Clinical Evaluation. Horm Metab Res. 2015 Nov;47(12):880-888.26079838
22. Tozzoli R, D'Aurizio F, Villalta D, Giovanella L. Evaluation of the first fully automated immunoassay method for the measurement of stimulating TSH receptor autoantibodies in Graves' disease. Clin Chem Lab Med. 2017 Jan 1;55(1):58-64.27331310
23. Kemble DJ, Jackson T, Morrison M, Cervinski M, Narenz R. Analytical and Clinical Validation of Two Commercially Available Immunoassays Used in the Detection of TSHR Antibodies. J Applied LabMed. Sep 2017.10.1373/jalm.2017.024067

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
140749 Thyroid Stim Immunoglobulin 30166-3 140754 Thyroid Stim Immunoglobulin IU/L 30166-3

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