Test Id : TSI
Thyroid-Stimulating Immunoglobulin, Serum
Useful For
Suggests clinical disorders or settings where the test may be helpful
Second-order testing for autoimmune thyroid disease, including:
-Differential diagnosis of etiology of thyrotoxicosis in patients with ambiguous clinical signs or contraindicated (eg, pregnant or breast-feeding) or indeterminate thyroid radioisotope scans
-Diagnosis of clinically suspected Graves disease (eg, extrathyroidal manifestations of Graves disease: endocrine exophthalmos, pretibial myxedema, thyroid acropachy) but normal thyroid function tests
-Determining the risk of neonatal thyrotoxicosis in a fetus of a pregnant female with active or past Graves disease
-Differential diagnosis of gestational thyrotoxicosis versus first-trimester manifestation or recurrence of Graves disease
-Assessing the risk of Graves disease relapse after antithyroid drug treatment
A combination of TSI / Thyroid-Stimulating Immunoglobulin, Serum and THYRO / Thyrotropin Receptor Antibody, Serum is useful as an adjunct in the diagnosis of unusual cases of hypothyroidism (eg, Hashitoxicosis).
Method Name
A short description of the method used to perform the test
Recombinant Bioassay
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Autoimmune Thyroid Stimulator
LATS (Long-Acting Thyroid Stimulator)
Long-Acting Thyroid Stimulator (LATS)
TSH Receptor Binding Inhibitory Immunoglobulin
TSI (Thyroid-Stimulating Immunoglobulin)
Thyretain
Thyrotropin receptor auto-antibody
Thyroid Stimulating auto-antibody
Graves' Disease
Specimen Type
Describes the specimen type validated for testing
Serum
Ordering Guidance
This test is used for second-order testing for autoimmune thyroid disease.
For suspected cases of autoimmune hypothyroidism, the first-order testing is TPO / Thyroperoxidase Antibodies, Serum.
For suspected cases of autoimmune thyroid disease, first-order testing includes TPO and THYRO / Thyrotropin Receptor Antibody, Serum.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 0.5 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Forms
If not ordering electronically, complete, print, and send a General Request (T239) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
0.3 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Gross lipemia | OK |
| Gross icterus | OK |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Frozen (preferred) | 60 days | |
| Ambient | 24 hours | ||
| Refrigerated | 7 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Second-order testing for autoimmune thyroid disease, including:
-Differential diagnosis of etiology of thyrotoxicosis in patients with ambiguous clinical signs or contraindicated (eg, pregnant or breast-feeding) or indeterminate thyroid radioisotope scans
-Diagnosis of clinically suspected Graves disease (eg, extrathyroidal manifestations of Graves disease: endocrine exophthalmos, pretibial myxedema, thyroid acropachy) but normal thyroid function tests
-Determining the risk of neonatal thyrotoxicosis in a fetus of a pregnant female with active or past Graves disease
-Differential diagnosis of gestational thyrotoxicosis versus first-trimester manifestation or recurrence of Graves disease
-Assessing the risk of Graves disease relapse after antithyroid drug treatment
A combination of TSI / Thyroid-Stimulating Immunoglobulin, Serum and THYRO / Thyrotropin Receptor Antibody, Serum is useful as an adjunct in the diagnosis of unusual cases of hypothyroidism (eg, Hashitoxicosis).
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Autoimmune thyroid disease is characterized by the presence of autoantibodies against various thyroid components, namely the thyrotropin (formerly thyroid-stimulating hormone: TSH) receptor (TSHR), thyroid-peroxidase (TPO), and thyroglobulin (Tg), as well as an inflammatory cellular infiltrate of variable severity within the gland. Among the autoantibodies found in autoimmune thyroid disease, TSHR autoantibodies are most closely associated with disease pathogenesis. All forms of autoimmune thyrotoxicosis (Graves disease, hashitoxicosis, neonatal thyrotoxicosis) are caused by the production of TSHR-stimulating autoantibodies. The role of the TPO and Tg autoantibodies in either autoimmune thyrotoxicosis or autoimmune hypothyroidism is less well established; they may merely represent epiphenomena. Detectable concentrations of anti-TPO antibodies are observed in most patients with autoimmune thyroid disease (eg, Hashimoto thyroiditis, idiopathic myxedema, and Graves disease).
Autoantibodies that bind and transactivate the TSHR lead to stimulation of the thyroid gland independent of the normal feedback-regulated TSH stimulation. These TSHR autoantibodies also are known as long-acting thyroid-stimulator or thyroid-stimulating immunoglobulins (TSI). Some patients with Graves disease also have TSHR-blocking antibodies, which do not transactivate the TSHR. The balance between TSI and TSHR-blocking antibodies, as well as their individual titers, are felt to be determinants of Graves disease severity. At least 20% of patients with autoimmune hypothyroidism also have evidence either of TSHR-blocking antibodies or, less commonly, TSI.
TSHR autoantibodies may be found before autoimmune thyrotoxicosis becomes biochemically or clinically manifest. Since none of the treatments for Graves disease aim at the underlying disease process, but rather ablate thyroid tissue or block thyroid hormone synthesis, TSI may persist after apparent cure.
TSI are IgG antibodies and can, therefore, cross the placental barrier causing neonatal thyrotoxicosis.
First-order tests for autoimmune thyroid disease include TPO / Thyroperoxidase Antibodies, Serum (most suited for suspected cases of autoimmune hypothyroidism) and THYRO / Thyrotropin Receptor Antibody, Serum. Thyrotropin receptor antibody (TSHR-antibody) is a binding assay that detects both TSI and TSHR-blocking autoantibodies; it can be used instead of this TSI assay for most applications, as long as the results are interpreted in the clinical context. The TSHR-antibody test has a shorter turnaround time than the TSI assay, is less expensive, and if interpreted within the clinical context, has excellent correlation with the TSI assay. Specific detection of TSI is accomplished by this second-order bioassay.
Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =1.3 TSI index
Reference values apply to all ages.
Interpretation
Provides information to assist in interpretation of the test results
The sensitivity and specificity of an elevated thyroid-stimulating immunoglobulins (TSI) index for Graves disease diagnosis depends on whether patients have clinically active, untreated disease or disease treated with antithyroid drugs. Using a TSI index of 1.3 as the cutoff level in newly diagnosed, untreated patients, the sensitivity and specificity are higher than 90%. For a higher cutoff of 1.8, specificity approaches 100%, but sensitivity decreases somewhat. In patients with inactive or treated Graves disease the specificity is similar, while sensitivity is lower, ranging from 50% to 80%.
Significant neonatal thyrotoxicosis is likely if a pregnant woman with a history of Graves disease has a TSI index above 3.9 during the last trimester, regardless of her remission status. Lesser elevations are only occasionally associated with neonatal thyrotoxicosis. This is particularly relevant for women who have previously undergone thyroid-ablative therapy or are on active antithyroid drug treatment and therefore, no longer display biochemical or clinical evidence of thyrotoxicosis.
Gestational thyrotoxicosis, which is believed to be due to a combination of human chorionic gonadotropin cross-reactivity on the thyrotropin receptor (TSHR) and transient changes in thyroid hormone protein binding, is not associated with an elevated TSI index. Finding an elevated TSI index in this setting suggests underlying Graves disease.
An elevated TSI index at the conclusion of a course of anti-thyroid drug treatment is highly predictive of relapse of Graves disease. However, the converse, a normal TSI index, is not predictive of prolonged remission.
In patients with thyroid function tests that fluctuate between hypo- and hyperthyroidism or vice versa, a clearly elevated TSHR-antibody level (>25%) and a simultaneous TSI index that is normal or only minimally elevated (1.3-1.8) suggest a diagnosis of possible Hashitoxicosis.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Positive results are strongly indicative of Graves disease but do not always correlate with the presence and severity of hyperthyroidism.
Patients with Hashimoto disease may have an elevated thyroid-stimulating immunoglobulins (TSI) index, which can be above 1.8. A TSI index of above 1.3 and less than or equal to 1.8 also is occasionally observed in various other thyroid disorders, including nodular goiter, and subacute thyroiditis.
Supportive Data
Pediatric data is based on a Mayo study of 50 male and 50 female children between the ages of 10 days and 18 years.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Grebe SKG. Thyroid disease. In: King RA, Rotter JI, Motulsky AG, eds. The Genetic Basis of Common Diseases. 2nd ed. Oxford University Press; 2002:397-430
2. 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;26(10):1343-1421. doi:10.1089/thy.2016.0229
3. Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism. Eur Thyroid J. 2018;7(4):167-186
4. Lytton SD, Schluter A, Banga PJ. Functional diagnostics for thyrotropin hormone receptor autoantibodies: bioassays prevail over binding assays. Front Biosci (Landmark Ed). 2018;23(11):2028-2043
5. De Leo S, Pearce EN. Autoimmune thyroid disease during pregnancy. Lancet Diabetes Endocrinol. 2018;6(7):575-586
6. Stan MN, Algeciras-Schimnich A, Murthy V, Thapa P, Araki N. Diagnostic utility of a new assay for thyroid stimulating immunoglobulins in Graves' disease and thyroid eye disease. Thyroid. 2022;32(2):170-176. doi:10.1089/thy.2021.0299
Method Description
Describes how the test is performed and provides a method-specific reference
This bioassay compares the cyclic adenosine monophosphate (cAMP) production of thyrotropin (TSH)-responsive cells upon exposure to patient serum with that obtained in the same cells after exposure to normal control serum.
The assay uses Chinese hamster ovary cells that have been permanently transfected with the human TSH receptor (TSHR) and a luciferase expression construct under the control of a cAMP responsive promoter. Luciferase transcription in these cells is proportional to the concentration of intracellular cAMP.
The cells are grown to near confluence. An aliquot of cells is then incubated with each diluted patient serum. Cells are lysed at the end of incubation, luciferase substrate is added, and chemiluminescence is measured in a luminometer. The ratio of the light-units produced in the cell-lysate exposed to patient serum divided by a control cell-lysate light-signal is the TSI index.(Preissner CM, Wolhuter PJ, Sistrunk JW, Homburger HA, Morris JC III. Comparison of thyrotropin-receptor antibodies measured by four commercially available methods with a bioassay that uses Fisher-rat thyroid cells. Clin Chem. 2003;49(8):1402-1404; package insert: Thyroid Stimulating Immunoglobulin Assay. Diagnostic Hybrids; PI4035011EN00, 10/2020)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Monday through Friday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.
CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
84445
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| TSI | Thyroid-Stimulating Immunoglob, S | 30567-2 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 8634 | Thyroid-Stimulating Immunoglob, S | 30567-2 |