What antibodies are responsible for Grave's disease?

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Graves' Disease Antibodies

The correct answer is B: Anti-TSH antibodies (more precisely, TSH receptor antibodies/TRAb), which are the pathogenic antibodies 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 to produce thyrotoxicosis. 1 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, where it competes with TSH for receptor binding. 1

  • Thyroid-stimulating antibodies (TSAb) act as stimulator antibodies that directly activate the TSH receptor, causing thyroid hormone overproduction. 2, 3

Why Other Antibodies Are Incorrect

  • Anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies are associated with autoimmune thyroid diseases like Hashimoto's thyroiditis and hypothyroidism, NOT the hyperthyroidism characteristic of Graves' disease. 1

  • Anti-TSH releasing antibodies (option A) do not exist as a recognized entity in thyroid autoimmunity. 1

  • Antithyroglobulin and antipyroxidase antibodies (options C and D) may be present in Graves' patients but are not pathogenic for the hyperthyroidism—they indicate general autoimmune thyroid involvement rather than causing the disease. 1

Clinical Diagnostic Utility

  • All 277 untreated Graves' patients in one study had positive TRAb (either TSAb and/or TBII), demonstrating near-universal presence of these antibodies. 3

  • Both TSAb and TBII have high sensitivity (92%) and specificity for diagnosing Graves' disease. 3

  • Serial measurement of these antibodies during therapy reflects clinical course and can predict remission versus persistent hyperthyroidism. 3

Important Caveat

  • Rarely (approximately 7% of cases), patients with active hyperthyroid Graves' disease may not have detectable TSH receptor antibodies initially, possibly due to local antibody production within the thyroid or alternative activation mechanisms. 4

  • Mildly elevated TRAb can occasionally occur in transient thyrotoxicosis without true Graves' disease, requiring cautious interpretation when clinical features are atypical. 5

References

Guideline

Graves' Disease Antibody Diagnosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Graves' disease: Clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy.

Best practice & research. Clinical endocrinology & metabolism, 2020

Research

Hyperthyroid Graves' disease without detectable thyrotropin receptor antibodies.

The Journal of clinical endocrinology and metabolism, 1992

Research

POSITIVE THYROTROPIN RECEPTOR ANTIBODIES IN PATIENTS WITH TRANSIENT THYROTOXICOSIS.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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