Thyroid orbitopathy

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BACKGROUND: Rapamycin (alternatively known as sirolimus) is a macrolide immunosuppressant commonly used for organ transplantation. It acts both on lymphocytes through the mechanistic target of rapamycin (mTOR) pathway to reduce their sensitivity to interleukin-2 (IL-2) and, importantly, also has anti-fibrotic properties by acting on myofibroblasts. The latter have been implicated in the pathogenesis of thyroid eye disease (TED). AIM: To describe successful treatment and reversal of extraocular muscle fibrosis in TED with sirolimus...

Context: Serum thyrotropin receptor autoantibody (TSH-R-Ab) is a biomarker of Graves' disease. Studies have shown that the levels of this TSH-R-Ab have clinical significance. Objective: To differentiate between Graves' thyroidal disease only (GD) and Graves' thyroidal and orbital disease (GD+GO). Design: Controlled, follow-up study. Setting: Academic tertiary referral center for GD+GO. Subjects: Sixty patients with GD, GD+GO and controls...

Periorbital adipose tissue expansion is a key pathological change in thyroid-associated orbitopathy (TAO). Bone morphogenic protein 4 (BMP4) is instrumental in adipogenesis. We compared site-specific BMP4 expression and its effect on adipogenesis using donor-matched adipose tissue-derived stromal cells (ADSC) from TAO patients. In this study, ADSC were generated from periorbital (eyelid, orbital) and subcutaneous (abdominal) adipose tissue. BMP4 expression was characterized by RT-PCR and immunofluorescent staining and compared among ADSC from the three anatomic depots...

3-Hydroxy-3-methyl-gutaryl coenzyme A (HMG-CoA) reductase inhibitors or 'statins' are a class of lipid lowering drugs with anti-inflammatory, immunomodulatory, and vascular effects. Statins are increasingly being used in the treatment of a variety of medical conditions. We examine the actions of statins on the eye and its associated ophthalmic disorders. Statins can be synthetic or non-synthetic, and their differentiating derivations may contribute to their varying cholesterol-lowering and pleiotropic effects...

Background Thyroid Eye Disease (TED) develops in around 25% of those with Graves' Disease (GD). Patients with TED may present late to ophthalmologists, when debilitating orbital inflammatory changes have already occurred. The reasons for this are multifactorial, but poor knowledge of TED in GD patients may be contributory. We aimed to assess the knowledge of TED in those with established TED, GD without orbitopathy and control subjects. Methods A validated, anonymised questionnaire, with 20 knowledge-based questions, was prospectively completed by 100 GD patients, 100 TED patients and 100 age- and sex-matched controls (with no history of thyroid disease or TED) in two tertiary referral Thyroid and Orbital Diseases clinic...

Graves' orbitopathy is a debilitating disorder which occurs in patients with autoimmune thyroid disease, mainly Graves' disease, and adds layers of complexity to management of both conditions. We conducted a comprehensive review of literature for publications relating to established and new management options for Graves' orbitopathy and have summarized key articles in this review. Initial evaluation of patients with Graves' disease should also include clinical evaluation for orbitopathy. If eye disease is present, patients are best managed by a multi-specialty team including an endocrinologist and ophthalmologist...

BACKGROUND: Ophthalmopathy is a rare extra-thyroid manifestation of Graves' disease, in paediatrics. Intravenous corticosteroids are the main treatment of moderate-to-severe Graves' orbitopathy. In this paper, we describe a moderate-to-severe active Graves' ophthalmopathy in a child and the response to oral therapy with prednisone. CASE PRESENTATION: A nine-year-old male child suffering for a few months, from palpitations, tremors, and paresthesia was hospitalized in our Pediatric Clinic...

BACKGROUND: Thyroid-associated orbitopathy (TAO) constitutes an immune-mediated inflammation of the orbital tissues of unclear etiopathogenesis. TAO is most prevalent in hyperthyroid patients with Graves' disease (GD); however, severe cases of orbitopathy associated with Hashimoto's thyroiditis (HT) have rarely been described. CASE PRESENTATION: Herewith we report an unusual case of a middle-aged clinically and biochemically euthyroid woman with a stable HT, who developed a severe unilateral left-sided TAO...

Cyclic peptides derived from some cylindrical loops of the leucin-rich repeat domain (LRD) of the thyroid-stimulating hormone receptor (TSHR) have been shown to treat disease manifestations in a mouse model of Graves´ disease during a long-term protocol of 4-weekly immunisations with adenovirus coding for the TSHR A subunit (Ad-TSHR289). In a follow-up study, we tested two additional cyclic peptides which were shortened in order to obtain additional information on the minimally involved epitopes, and to enable easier production conditions...

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), along with its receptor fibroblast growth factor-inducible (Fn)14, is associated with various biological activities including inflammation. However, its role in the pathogenesis of Graves' orbitopathy (GO) is unknown. In this study, we investigated the mechanism by which TWEAK regulates inflammatory signaling in orbital fibroblasts from GO patients. We found that TWEAK and tumor necrosis factor-α (TNFA) mRNA levels were upregulated in GO as compared to non-GO tissue samples...

Purpose: We characterize the effect of bimatoprost on orbital adipose tissue in thyroid-associated orbitopathy (TAO) with clinicopathologic correlation. Methods: Orbital adipose-derived stem cells (OASCs) from types 1 and 2 TAO and control patients with and without exposure to 1 μm bimatoprost were examined via immunohistochemistry, RT-PCR, and Western blot for cell viability, migration capacity, lipid content, adipocyte morphology, mitochondrial content, and levels of adipogenic markers...

Thyroid stimulating hormone and insulin-like growth factor 1 receptors (TSHRs and IGF1Rs, respectively) interact leading to additive or synergistic stimulation of cellular responses. Recent findings provide evidence that the interaction between TSHRs and IGF1Rs is similar to that described for other G protein-coupled receptors and receptor tyrosine kinases. These types of interactions occur at or proximal to the receptors and are designated "receptor cross-talk." Herein, we describe our studies in human thyrocytes, human retro-orbital fibroblasts from Graves' orbitopathy patients and a model cell line that support the concept of TSHR/IGF1R cross-talk...

No abstract text is available yet for this article.

Paraneoplastic syndrome is a rare but reversible cause of non-thyroid-related extraocular muscle enlargement. We present a 71-year-old lady with diplopia, restricted eye movements, suppressed thyroid-stimulating hormone and enlargement of all extraocular muscles while on thyroxine replacement for hypothyroidism. She had distant history of metastatic breast cancer treated with chemotherapy, surgical resection and tamoxifen. She had negative anti-thyroid autoantibodies and thyroid ultrasound was not consistent with autoimmune thyroid disease...

Alemtuzumab-a monoclonal antibody targeting the CD52 glycoprotein expressed by most mature leucocytes-effectively decreases relapse rate and disability progression in early, relapsing-remitting multiple sclerosis (MS). However, secondary autoimmune disorders complicate therapy in nearly 50% of treated patients, with Graves' disease being the most common. Rarely, thyroid eye disease (TED) ensues; only seven such cases have been reported. Our aim was to analyse the largest series of MS patients developing thyroid eye disease after alemtuzumab treatment...

BACKGROUND: Previous techniques resulted with low rates of successful fusion after the surgeries and high necessity of additional surgeries in the treatment of thyroid orbitopathy related strabismus. In this study, reviewing the results of our patients who had surgical correction with relaxed muscle positioning technique due to thyroid orbitopathy related strabismus to evaluate the effectiveness of the surgery was aimed. METHODS: The medical records of 8 patients who had surgical correction with intraoperative relaxed muscle positioning (IRMP) technique were studied retrospectively...

PURPOSE: Early detection and control of inflammation are important to manage Graves' orbitopathy (GO). We investigated the effects of calprotectin (S100A8/A9) on orbital fibroblast inflammation and GO pathogenesis. METHODS: We measured serum calprotectin, S100A8 and S100A9 mRNA expression in orbital fat/connective tissue from GO patients and healthy controls, and proinflammatory cytokines in primary cultured orbital fibroblasts. RESULTS: The serum levels of S100A8/A9 and the expression of S100A8/A9 mRNA in orbital tissue were higher in the GO patients than in the healthy controls...

Thyroid-associated orbitopathy (TAO) is a common manifestation of Graves' disease. The aim of the study was to assess the six percent of patients with TAO that develop dysthyroid optic neuropathy (DON), which is the most serious complication of TAO. As DON can cause perma-nent damage, it is essential to detect DON early when visual loss is still reversible. Color Doppler ultrasound is a noninvasive diagnostic method, which may be useful in early detection of DON. Thirty-six patients with confirmed Graves' disease and active TAO were included, 21 (58%) of them with early DON (eDON) and 15 (42%) free from any signs of eDON...

The Thyrotropin receptor antibody (TRAb) is the main driver of Graves' disease (GD) and its most common extra-thyroidal manifestation: thyroid eye disease (TED). Though key to diagnosis, it has not been used routinely as a marker of disease activity or to guide treatment. Here we demonstrate, through a retrospective review of 105 patients with TED, that serial TRAb levels vary with time, correlate with disease activity and are affected by smoking and endocrine control. Such serial measurements can guide the modern management of thyroid eye disease, helping to prevent the more serious manifestations...