A 28-year-old woman presents with weight loss, heat intolerance, tremor, and diffuse goiter with exophthalmos. Her serum contains antibodies that bind the TSH receptor. The mechanism by which these antibodies produce hyperthyroidism is:

• A Complement-mediated lysis of thyroid follicular cells
• B Antibody-dependent cellular cytotoxicity of thyrocytes
• C Blocking of the TSH receptor, preventing pituitary feedback
• D Stimulation of the TSH receptor, mimicking TSH action ✓

Explanation

In Graves disease, autoantibodies against the TSH receptor act as agonists, stimulating adenylate cyclase, increasing cAMP, and driving thyroid hormone synthesis and secretion independent of pituitary control. This is classified as a type II hypersensitivity variant with functional stimulation rather than cell destruction. Blocking antibodies are seen in atrophic hypothyroidism, and anti-TPO antibodies with cytotoxicity characterize Hashimoto thyroiditis, making those distractors mechanistically wrong here.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.