In Graves' disease, what is a key mechanism that leads to exophthalmos?

In Graves' disease, a key mechanism that leads to exophthalmos is the activation of the TSH receptor, which results in an increase in glycosaminoglycan (GAG) deposition in the retro-orbital space. This autoimmune hyperthyroid condition is characterized by the production of autoantibodies that stimulate the thyroid-stimulating hormone (TSH) receptor not just in the thyroid gland but also in orbital fibroblasts.

The stimulation of these receptors leads to overproduction of hyaluronic acid and other GAGs, which attract water and cause edema and swelling of the retro-orbital tissues. This accumulation of fluid and tissue expansion ultimately results in the characteristic outward protrusion of the eyes known as exophthalmos.

In summary, while the increased thyroid hormone production does contribute to other symptoms of Graves' disease, it is the specific mechanism of TSH receptor activation and subsequent GAG buildup that directly causes exophthalmos in this condition.