A 35-year-old woman presents with palpitations, heat intolerance, weight loss of 6 kg over 3 months, and a diffuse goiter. TSH is < 0.01 mIU/L, free T4 is 3.8 ng/dL (elevated). Thyroid-stimulating immunoglobulin (TSI) is markedly positive. She has proptosis bilaterally. Which of the following best describes the pathophysiology of her thyroid disease?
- A Cytotoxic T-cells destroy thyroid follicles releasing stored hormone
- B Ectopic thyroid tissue autonomously secretes thyroid hormone
- C Excess TSH secretion from a pituitary adenoma drives thyroid hyperplasia
- D IgG antibodies activate TSH receptor, mimicking TSH stimulation ✓
Explanation
Graves' disease is an autoimmune hyperthyroidism caused by IgG autoantibodies (thyroid-stimulating immunoglobulins, TSI) directed against the TSH receptor, which bind and constitutively activate the receptor, mimicking TSH and stimulating continuous thyroid hormone synthesis and gland growth. This explains the suppressed TSH (negative feedback from elevated T4/T3), elevated free T4, diffuse goiter, and hyperthyroid symptoms. Cytotoxic T-cell destruction describes Hashimoto's thyroiditis (hypothyroidism). Ectopic thyroid tissue is seen in struma ovarii. TSH-secreting pituitary adenoma (thyrotropinoma) causes secondary hyperthyroidism with elevated TSH, which is the opposite of what is found here.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.