Graves' Disease Antibodies
The antibodies responsible for Graves' disease are anti-TSH receptor antibodies (Answer B), specifically thyroid-stimulating antibodies (TSAb) and TSH-binding inhibitor immunoglobulin (TBII), which stimulate the TSH receptor and cause hyperthyroidism.
Pathophysiology and Antibody Types
Graves' disease is caused by TSH receptor antibodies (TRAb) that bind to and stimulate thyroid-stimulating hormone receptors on thyroid cells, leading to unregulated thyroid hormone production 1. These antibodies are the hallmark of the disease and can be measured in two primary ways:
- Thyroid-stimulating antibodies (TSAb): Measured by stimulator assay, these directly activate the TSH receptor and cause thyroid hormone overproduction 2
- TSH-binding inhibitor immunoglobulin (TBII): Measured by competitive receptor assay, these compete with TSH for receptor binding 3
Both antibody types are clinically valuable for diagnosis, with all 277 untreated Graves' patients in one study having positive TRAb (TSAb and/or TBII), demonstrating near-universal presence 2.
Diagnostic Testing Approach
When evaluating suspected Graves' disease with thyrotoxicosis, the following antibody testing should be performed:
- TSH receptor antibody (TRAb) or thyroid-stimulating immunoglobulin (TSI) testing to confirm Graves' disease and distinguish it from other causes of thyrotoxicosis like thyroiditis 3
- Both TSAb and TBII have high sensitivity (92%) and specificity for diagnosing Graves' disease 2
- Simultaneous measurement of both TSAb and TBII is clinically useful since they reflect different aspects of TRAb activity 2
Important Clinical Caveats
Rare exceptions exist: Approximately 9 out of 130 patients (7%) with active hyperthyroid Graves' disease may not have detectable TSH receptor antibodies initially, though antibodies typically appear after radioiodine therapy 4. This suggests local antibody production within the thyroid or alternative activation mechanisms 4.
False positives can occur: Mildly elevated TRAb (less than twice the upper limit) may occasionally be present in patients with transient thyrotoxicosis rather than true Graves' disease, requiring cautious interpretation and close monitoring 5.
Why Other Answer Choices Are Incorrect
- Anti-thyroglobulin antibodies (Answer C) and anti-thyroid peroxidase antibodies (Answer D) are associated with autoimmune thyroid diseases like Hashimoto's thyroiditis and hypothyroidism, not the hyperthyroidism characteristic of Graves' disease 3
- Anti-TSH releasing antibodies (Answer A) do not exist as a recognized clinical entity
- Anti-TSH antibodies would target TSH itself rather than the TSH receptor, which is not the mechanism in Graves' disease