Thyroid-stimulating Immunoglobulin (TSI)

Serum (preferred) or plasma (EDTA or heparin)

3 mL

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

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

Prepare sterile venipuncture site.

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

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.

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

0.00-0.55 IU/L

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.