Graves' Ophthalmopathy

Abstract

Graves’ ophthalmopathy, also called Graves’ orbitopathy, is a potentially sight-threatening ocular disease that has puzzled physicians and scientists for nearly two centuries.1–3 Generally occurring in patients with hyperthyroidism or a history of hyperthyroidism due to Graves’ disease, Graves’ ophthalmopathy is also known as thyroid-associated ophthalmopathy or thyroid eye disease, because it sometimes occurs in patients with euthyroid or hypothyroid chronic autoimmune thyroiditis. The condition has an annual adjusted incidence rate of 16 women and 3 men per 100,000 population.4 This review explores the perplexing relationship between Graves’ ophthalmopathy, hyperthyroidism, and thyroid dermopathy, the associated skin condition. I examine clinical features, histologic findings, and laboratory studies, with an emphasis on mechanisms that could be targeted in the development of new treatments for this debilitating disease.

Gene expression of estrogen receptor-alpha in orbital fibroblasts in Graves’ ophthalmopathy

“…The orbital fibroblasts represent the target of the autoimmune process (2), through the expression of TSHR, which is recognized by TRAb (13). Some distinct orbital fibroblasts subtypes, when activated by TRAb, differentiate into adipocytes, while others, which express thymocyte antigen-1, are stimulated by cytokines to produce hyaluronan (13).…”

“…The orbital fibroblasts represent the target of the autoimmune process (2), through the expression of TSHR, which is recognized by TRAb (13). Some distinct orbital fibroblasts subtypes, when activated by TRAb, differentiate into adipocytes, while others, which express thymocyte antigen-1, are stimulated by cytokines to produce hyaluronan (13). The stimulus of the insulin growth factor (IGF) receptor present in such cells results in secretion of cytokines that increase the recruitment of activated T cells and other mononuclear immune cells into the orbit (13).…”

“…Some distinct orbital fibroblasts subtypes, when activated by TRAb, differentiate into adipocytes, while others, which express thymocyte antigen-1, are stimulated by cytokines to produce hyaluronan (13). The stimulus of the insulin growth factor (IGF) receptor present in such cells results in secretion of cytokines that increase the recruitment of activated T cells and other mononuclear immune cells into the orbit (13). The interaction of these cells with orbital fibroblasts results in synthesis of prostaglandins and hydrophilic hyaluronan that accumulates in the orbital tissue, expanding its volume (13).…”

“…The stimulus of the insulin growth factor (IGF) receptor present in such cells results in secretion of cytokines that increase the recruitment of activated T cells and other mononuclear immune cells into the orbit (13). The interaction of these cells with orbital fibroblasts results in synthesis of prostaglandins and hydrophilic hyaluronan that accumulates in the orbital tissue, expanding its volume (13). Moreover, prostaglandins bind to the nuclear receptor PPARG present in preadipocytes, thus stimulating its differentiation into mature adipocytes, further increasing orbital volume (13).…”

Radiotherapy for Graves’ disease. The possible role of low-dose radiotherapy

“…GO is an invalidating and disfiguring disease affecting appearance and functioning of the eyes as well as impairing the quality of life of patients. [9][10][11] The symptoms of GO result from the inflammatory and fibrotic reactions in the retroorbital space. Exophthalmos, impaired muscle involvement, diplopia, blurred vision, periorbital oedema, chemosis, lid retraction and compressive optic neuropathy may be present.…”