Why does increased TSH receptor endocytosis occur during prolonged exposure to high levels of thyroid-stimulating immunoglobulins (TSI) in Graves' disease, ultimately reducing thyroid hormone synthesis?

💡 Explanation

Increased TSH receptor endocytosis results from prolonged TSI stimulation, leading to internalization and degradation of TSH receptors. Because the thyroid follicular cells reduce the number of TSH receptors on their surface, their sensitivity to TSH decreases, which lowers T3 and T4 synthesis; therefore, this effect is driven by receptor internalization rather than direct transcriptional downregulation or iodine uptake deficiencies.

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