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S. Chang, C. J. Hwang, K. K. L. Chong, R. S. Douglas, J. Said, R. A. Goldberg; Orbital and Brow Fat Histology in Thyroid-Associated Orbitopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3929.
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In addition to the classic orbital changes seen clinically in patients with thyroid-associated orbitopathy (TAO), we observed enlargement in the brow fat compartments of these patients. We previously showed that orbital fat specimens from patients with TAO exhibit increased fibrosis and expression of certain immune markers, specifically insulin-like growth factor (IGFR) and thyroid stimulating hormone receptor (TSHR). In addition, orbital fibroblasts in culture produce hyaluronic acid, a mucopolysaccharide. We propose that brow fat enlargement occurs secondary to the same autoimmune process affecting orbital fibroblasts in patients with TAO, and that the histological changes occurring in brow fat are identical to those seen in orbital fat.
Brow and orbital fat were obtained from patients undergoing orbital decompression and/or blepharoplasty with brow fat removal. Orbital fat was obtained from 24 patients, 14 with TAO and 10 control patients with no significant past medical history. Brow fat was obtained from 10 patients, 5 with TAO and 5 controls. Histological stains were performed on the specimens, using hematoxylin and eosin, Masson trichrome, and alcian blue. Qualitative assessment of hyaluronic acid production and extent of fibrosis was graded on a 0-4 scale. Immunohistochemical stains for IGFR and TSHR were also performed, and levels of expression were graded quantitatively by manual cell counting assisted by Image J software.
Specimens from patients with TAO showed increased fibrosis, fibrous septae formation, and hyaluronic acid production. TSHR and IGFR expression are markedly increased in both orbital and brow fat specimens harvested from patients with TAO, especially in the fibrotic areas, and minimally present in the control specimens. Orbital and brow fat from control patients were histologically unremarkable and did not stain for TSHR and IGFR.
Histological changes previously described in orbital fibroblasts from TAO patients are identical to those found in clinically abnormal brow fat harvested from TAO patients. In addition, increased TSHR and IGFR expression in both brow and orbital fat in TAO patients support the role of TSHR and IGFR as potential putative serologic markers of ophthalmic involvement in patients with Graves’ disease.
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