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Test ID: TSI Thyroid-Stimulating Immunoglobulin, Serum

Reporting Name

Thyroid-Stimulating Immunoglob, S

Useful For

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

Autoimmune thyroid disease is characterized by the presence of autoantibodies against various thyroid components, namely the thyrotropin (formerly 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 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 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.


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.

Report Available

2 to 6 days

Day(s) Performed

Monday through Friday

Clinical Reference

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 Oct;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 Aug;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 Jun 1;23(11):2028-2043

5. De Leo S, Pearce EN: Autoimmune thyroid disease during pregnancy. Lancet Diabetes Endocrinol. 2018 Jul;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 Feb;32(2):170-176. doi: 10.1089/thy.2021.0299

Method Name

Recombinant Bioassay

Specimen Type


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

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.

Specimen Minimum Volume

0.1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Frozen (preferred) 60 days
  Refrigerated  7 days
  Ambient  24 hours

Reference Values

≤1.3 TSI index

Reference values apply to all ages.

Test Classification

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


LOINC Code Information

Test ID Test Order Name Order LOINC Value
TSI Thyroid-Stimulating Immunoglob, S 30567-2


Result ID Test Result Name Result LOINC Value
8634 Thyroid-Stimulating Immunoglob, S 30567-2


If not ordering electronically, complete, print, and send a General Request (T239) with the specimen.

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