Graves' Disease Antibodies
The correct answer is B: Anti-TSH antibodies (more precisely, TSH receptor antibodies/TRAb), which are responsible for Graves' disease.
Primary Pathogenic Antibodies
TSH receptor antibodies (TRAb) are the causative antibodies in Graves' disease, binding to and stimulating the TSH receptor on thyroid cells, leading to unregulated thyroid hormone production and hyperthyroidism 1, 2. These antibodies can be measured through several assays:
TSH receptor antibody (TRAb) or thyroid-stimulating immunoglobulin (TSI) testing is recommended by the Endocrine Society to confirm Graves' disease and distinguish it from other causes of thyrotoxicosis 1.
TSH-binding inhibitor immunoglobulin (TBII) can be measured by competitive receptor assay, competing with TSH for receptor binding, as suggested by the American College of Endocrinology 1.
Thyroid-stimulating antibodies (TSAb) act as stimulatory antibodies in the pathogenesis, with circulating TSAb being determinant in both thyrotoxicosis and extrathyroidal manifestations like Graves' ophthalmopathy 2.
Diagnostic Sensitivity
All 277 untreated Graves' disease patients in one large study had positive TRAb (either TSAb and/or TBII), demonstrating the high diagnostic utility of these antibodies 3.
Both TSAb and TBII showed high sensitivity (92% had both positive) and specificity for diagnosing Graves' disease 3.
Why Other Antibodies Are Incorrect
Anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies (options C and D) are associated with Hashimoto's thyroiditis and hypothyroidism, not the hyperthyroidism characteristic of Graves' disease 1.
Anti-TSH releasing antibodies (option A) are not the pathogenic mechanism in Graves' disease.
Important Clinical Caveat
A small proportion of patients (approximately 7% in one study) with active hyperthyroid Graves' disease may not have detectable TSH receptor antibodies initially, though antibodies typically appear after radioiodine therapy 4.
Mildly elevated TRAb can rarely occur in transient thyrotoxicosis without true Graves' disease, requiring cautious interpretation in clinically stable patients without pathognomonic features 5.