Unit Converter
Antibodies to TSH receptor (Anti-TSHR)
(TSH Receptor Antibodies - TRAb / TSI / TBII)
Synonyms
- Anti-TSHR
- TRAb (TSH Receptor Antibodies)
- TSI (Thyroid-Stimulating Immunoglobulin)
- TBII (TSH-Binding Inhibitory Immunoglobulin)
- Thyrotropin receptor autoantibody
- Graves’ antibody
Units of Measurement
- mIU/mL (most common)
- IU/L
(Both units are equivalent numerically.)
Description
Anti-TSHR antibodies target the thyrotropin (TSH) receptor on thyroid follicular cells. These antibodies can stimulate, block, or neutralize the receptor.
Types of TRAb:
- TSI – Thyroid-stimulating immunoglobulins
→ Cause Graves’ disease (hyperthyroidism) - TBII / Blocking antibodies
→ Cause hypothyroidism (rare; autoimmune blocking) - Neutral antibodies
→ No major clinical effect
Anti-TSHR testing is essential for diagnosing:
- Graves’ disease
- Pregnancy-related thyroid disease
- Autoimmune neonatal hyperthyroidism
- Predicting relapse after anti-thyroid drugs
- Differentiating causes of thyrotoxicosis
Physiological Role of the TSH Receptor
The TSH receptor controls:
- Thyroid hormone synthesis
- Iodide uptake
- Thyroid growth (trophic effect)
Anti-TSHR antibodies stimulate or block this pathway, causing hyperthyroidism or hypothyroidism.
Clinical Significance
1. Elevated Anti-TSHR (TRAb / TSI)
Seen in:
A) Graves’ Disease (Most common)
- TRAb positive in >95% of cases
- Essential in ambiguous cases:
- Pregnancy
- Subclinical hyperthyroidism
- Nodular goiter with thyrotoxicosis
- Postpartum period
- Pregnancy
B) Neonatal Thyrotoxicosis
Maternal TSI crosses placenta → fetal hyperthyroidism.
C) Hashimoto Thyroiditis (rare subset)
Blocking antibodies may be present in:
- Atrophic thyroiditis
- Hypothyroid phase of Hashimoto disease
D) Post-Radioiodine or Anti-thyroid Drug Monitoring
TRAb helps:
- Predict relapse
- Assess remission probability
2. Negative Anti-TSHR
Usually seen in:
- Toxic nodular goiter
- Thyroiditis (subacute, silent)
- Drug-induced thyrotoxicosis
- Pregnancy-related hyperthyroidism (gestational thyrotoxicosis)
Negative TRAb helps differentiate non-autoimmune thyrotoxicosis.
Reference Intervals
(Tietz 8E + ATA 2016 + Mayo + ARUP)
TSH Receptor Antibody (TRAb / TBII):
- Normal: < 1.75 IU/L (assay dependent)
- Borderline: 1.75–2.0 IU/L
- Positive: > 2.0 IU/L
TSI (Stimulating Antibodies):
- Negative: < 1.3 TSI index
- Positive: ≥ 1.3–1.8 (method-specific cutoff)
Pregnancy Monitoring
- TRAb > 3× upper limit → significant fetal risk
- Monitor in 2nd and 3rd trimester
Diagnostic Uses
1. Diagnosis of Graves’ Disease
Most accurate test when:
- TSH suppressed
- Free T4/T3 elevated
- Ultrasound or uptake unavailable
- Pregnancy (cannot use radioiodine uptake)
- Pediatrics
2. Predicting Graves’ Disease Relapse
- High TRAb → high relapse risk
- Low/negative TRAb after therapy → remission likely
3. Pregnancy & Neonatal Monitoring
Maternal TRAb can cause:
- Fetal tachycardia
- Fetal goiter
- Neonatal hyperthyroidism
Monitoring recommended in:
- Previous Graves disease
- History of RAI or surgery
- High TRAb levels
4. Distinguishing Thyrotoxicosis Types
| Condition | Anti-TSHR |
| Graves disease | Positive |
| Thyroiditis | Negative |
| Toxic nodules | Negative |
| Gestational thyrotoxicosis | Negative |
| Hashimoto (rare) | Occasionally positive (blocking) |
Analytical Notes
- Measured via automated chemiluminescent immunoassays.
- Different assays measure stimulating antibodies (TSI) vs binding antibodies (TBII).
- Biotin ingestion (>5 mg/day) may interfere - stop 48 hours prior.
- Autoimmune diseases may mildly elevate TRAb.
Clinical Pearls
- TRAb is more sensitive for Graves disease than ultrasound or clinical signs.
- Anti-TSHR positivity predicts orbitopathy risk in Graves patients.
- TSI is better for fetal risk prediction during pregnancy.
- TRAb does not track severity of hyperthyroidism directly.
- In postpartum thyroiditis: Anti-TPO positive, TRAb negative.
Interesting Fact
Anti-TSHR antibodies were first discovered in the 1950s as the “long-acting thyroid stimulator (LATS),” which led to the recognition of autoimmune mechanisms behind Graves disease.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Thyroid Autoimmunity.
- American Thyroid Association (ATA) 2016 Guidelines.
- ESAP Endocrine Society - TRAb Interpretation Guide.
- Mayo Clinic Laboratories - TSH Receptor Antibodies.
- ARUP Consult - Autoimmune Hyperthyroidism Diagnostic Algorithm.
- IFCC Immunoassay Standardization.
- MedlinePlus / NIH - TRAb Overview.