What is TRAb (Thyroid Receptor Antibodies)?
TRAb (Thyroid Receptor Antibodies), also called TSH receptor antibodies, are autoantibodies that bind to the TSH receptor on thyroid cells and are the primary cause of Graves' disease hyperthyroidism. 1, 2
Clinical Significance in Newborns of Mothers with Graves' Disease
In newborns born to mothers with Graves' disease, TRAb measurement is essential because these antibodies cross the placenta and can cause fetal and neonatal thyrotoxicosis. 1, 2
Why TRAb Matters in This Context
- Maternal TRAb crosses the placenta during pregnancy and can stimulate the fetal thyroid gland, causing fetal hyperthyroidism, goiter, and potential complications 2
- High maternal TRAb titers during pregnancy require careful fetal monitoring to detect thyrotoxicosis, as elevated antibody levels significantly increase risk 1
- Pregnancies in women with Graves' disease who have negative TRAb are highly unlikely to result in fetal hyperthyroidism, making this test crucial for risk stratification 1
Mechanism of Action
- TRAb acts as TSH agonists (stimulating antibodies) in nearly all patients with Graves' disease, mimicking TSH action and causing unregulated thyroid hormone production 3
- The antibodies bind to the TSH receptor on thyroid follicular cells, triggering continuous thyroid stimulation independent of normal TSH regulation 4, 3
- In the fetus and newborn, this results in hyperthyroidism that persists until maternal antibodies are cleared from the infant's circulation, typically over several weeks to months 2
Clinical Testing and Interpretation
- Third-generation TRAb assays have excellent diagnostic performance with sensitivity and specificity in the upper 90% range for Graves' disease 1
- TRAb should be measured in all pregnant women with current or past Graves' disease to assess fetal risk, ideally during the first trimester and again in the third trimester 1, 2
- Elevated maternal TRAb levels (particularly >3-5 times upper limit of normal) warrant intensive fetal surveillance including ultrasound monitoring for goiter, growth restriction, and signs of thyrotoxicosis 2
Management Implications for the Newborn
- The newborn's physician must be aware that the mother has Graves' disease because of the associated risk of neonatal thyroid dysfunction 5
- Fetal goiter may be associated with elevated maternal TRAb during pregnancy, and overtreatment of the mother with antithyroid drugs can paradoxically lead to fetal hypothyroidism 2
- Although suppression of fetal and neonatal thyroid function can occur with thioamide therapy for maternal Graves' disease, it is usually transient and treatment is rarely required 5
Important Caveats
- Not all TRAb are stimulating antibodies—approximately 20% of patients with autoimmune hypothyroidism have blocking TRAb (TSH antagonists) that can cause neonatal hypothyroidism rather than hyperthyroidism 3
- TRAb levels can remain elevated even after the mother achieves remission from Graves' disease, so testing is necessary even in women with treated or resolved hyperthyroidism 1, 6
- Regular TRAb monitoring during pregnancy guides antithyroid medication dosing to prevent both fetal thyrotoxicosis and fetal hypothyroidism from overtreatment 2