Histopathology of Brow Fat in Thyroid-Associated Orbitopathy

Purpose: We propose that brow enlargement seen in patients with thyroid-associated orbitopathy (TAO) occurs secondary to the autoimmune process in Graves disease and that the changes in brow fat are histologically identical to those seen in orbital fat. Methods: With informed consent, brow and orbital fat was obtained from patients with TAO and from patients with no significant past medical history undergoing orbital decompression, blepharoplasty, and/or brow fat removal. Histologic examination was performed on the orbital and brow fat. Results: Fat histologies obtained from patients with TAO and those without known systemic disease were compared. Specimens from patients with TAO showed an increase of fibrosis and fibrous septae. Furthermore, certain biologic markers, including insulin-like growth factor 1 receptor &bgr; (IGF-1R&bgr;) and thyroid-stimulating hormone receptor (TSHR), were increased in the fat obtained from patients with TAO. This was identical in both the brow and the orbital fat. Fat from patients with no significant past medical history showed normal fat histology, absence of fibrous septae, and decreased marker expression. Conclusion: Graves disease is a systemic autoimmune disease that affects patients in a variety of ways. In addition to the orbital changes seen in these patients, we have observed an increase in the brow fat compartment. We are intrigued to find that the histologic changes are identical in both the orbital and the brow fat of patients with TAO. The increased IGF-1R&bgr; and TSHR expression in both the brow and the orbital fat further support their role as putative markers in patients with Graves disease.

[1]  L. Chuang,et al.  Lysosome-related genes are regulated in the orbital fat of patients with graves' ophthalmopathy. , 2008, Investigative ophthalmology & visual science.

[2]  Terry J. Smith,et al.  Evidence for an Association between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors: A Tale of Two Antigens Implicated in Graves’ Disease1 , 2008, The Journal of Immunology.

[3]  M. Kazim,et al.  Prominent Premalar and Cheek Swelling: A Sign of Thyroid-associated Orbitopathy , 2006, Ophthalmic plastic and reconstructive surgery.

[4]  Terry J. Smith,et al.  Immunoglobulin G from patients with Graves' disease induces interleukin-16 and RANTES expression in cultured human thyrocytes: a putative mechanism for T-cell infiltration of the thyroid in autoimmune disease. , 2006, Endocrinology.

[5]  Terry J. Smith,et al.  Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor I Receptor Pathway1 , 2003, The Journal of Immunology.

[6]  C. Marcocci,et al.  Real-time PCR provides evidence for thyrotropin receptor mRNA expression in orbital as well as in extraorbital tissues. , 2002, European journal of endocrinology.

[7]  Terry J. Smith,et al.  Igs from Patients with Graves’ Disease Induce the Expression of T Cell Chemoattractants in Their Fibroblasts1 , 2002, The Journal of Immunology.

[8]  D. Sarraf,et al.  Involvement of the Eyebrow Fat Pad in Graves' Orbitopathy , 1994, Ophthalmic plastic and reconstructive surgery.