Test ID: TSI
Thyroid-Stimulating Immunoglobulin (TSI), Serum
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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 and/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 anti-thyroid drug treatment
A combination of TSI/8634 Thyroid-Stimulating Immunoglobulin (TSI), Serum and THYRO/81797 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
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Graves Disease
LATS (Long-Acting Thyroid Stimulator)
Long-Acting Thyroid Stimulator (LATS)
Thyroid Receptor Antibody
Thyroid Stimulating Antibody
TSH Receptor Binding Inhibitory Immunoglobulin
TSI (Thyroid-Stimulating Immunoglobulin)
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 0.5 mL
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross OK |
| Lipemia | Mild OK; Gross OK |
| Icterus | Mild OK; Gross OK |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum | Refrigerated (preferred) | 7 days |
| Frozen | 90 days | |
| Ambient | 24 hours |
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 receptor (thyroid-stimulating hormone 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's 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 thyroid-stimulating hormone (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 are aimed 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/81765 Thyroperoxidase (TPO) Antibodies, Serum (most suited for suspected cases of autoimmune hypothyroidism) and THYRO/81797 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 >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 of >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 thyroid-stimulating hormone 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's disease may have an elevated thyroid-stimulating immunoglobulins (TSI) index, which can be >1.8. A TSI index of >1.3 and < or =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 Provides recommendations for further in-depth reading of a clinical nature
1. Morris JC III, Hay ID, Nelson RE, Jiang NS: Clinical utility of thyrotropin-receptor antibody assays: comparison of radio-receptor and bioassay methods. Mayo Clin Proc 1988;63:707-717
2. Volpe R: Rational use of thyroid function tests. Crit Rev Clin Lab Sci 1997;34:405-438
3. Saravanan P, Dayan CM: Thyroid autoantibodies. Endocrinol Metab Clin North Am 2001;30(2):315-335
4. Grebe SKG: Thyroid disease. In The Genetic Basis of Common Diseases. 2nd edition. Edited by RA King, JI Rotter, AG Motulsky. New York, Oxford University Press, 2002, pp 397-430
Method Description Describes how the test is performed and provides a method-specific reference
This bioassay compares the cyclic adenosine monophosphate (cAMP) production of thyroid-stimulating hormone (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 thyroid-stimulating hormone 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 chemiluminesence 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, et al: Comparison of thyrotropin-receptor antibodies measured by four commercially available methods with a bioassay that uses Fisher-rat thyroid cells. Clin Chem 2003;49:1402-1404; Package insert: Thyroid Stimulating Immunoglobulin Assay. Diagnostic Hybrids)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday; 10 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
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 The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
84445
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 8634 | Thyroid-Stimulating Immunoglob, S | 30567-2 |
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