Search Results (10)

Graves’ ophthalmopathy is the most common extrathyroidal manifestation of Graves–Basedow disease. Radiotherapy is effective especially when used in synergy with the administration of glucocorticoids. The aim of our study was to analyze the effectiveness and safety of radiotherapy, using different protocols, to improve ocular symptoms and quality of life. Methods: We retrospectively analyzed the clinical data of two-hundred and three patients treated with retrobulbar radiotherapy between January 2002 and June 2023. Ninety-nine patients were treated with a schedule of 10 Gy in 10 fractions and one-hundred and four were treated with 10 Gy in 5 fractions. Radiotherapy (RT) was administrated during the 12 weeks of pulse steroid therapy. Patients were evaluated with a clinical exam, orbital CT, thyroid assessment, and Clinical Activity Score (CAS). Results: The median follow-up was 28.6 months (range 12–240). Complete response was found in ninety-four pts (46.31%), partial response or stabilization in one hundred pts (49.26%), and progression in nine pts (4.43%). In most subjects, an improvement in visual acuity and a reduction in CAS of at least 2 points and proptosis by more than 3 mm were observed. Three patients needed decompressive surgery after treatment. Only G1 and G2 acute eye disorders and no cases of xerophthalmia or cataract were assessed. Conclusions: RT is an effective and well-tolerated treatment in this setting, especially when associated with the administration of glucocorticoids. Although the most used fractionation schedule in the literature is 20 Gy in 10 fractions, in our clinical practice, we have achieved comparable results with 10 Gy in 5 or 10 fractions with a lower incidence of toxicity. Full article

Thyroid eye disease (TED) is a common extrathyroidal manifestation of hyperthyroidism, typically associated with Graves’ disease (GD). This condition can cause severe functional limitations as well as significant aesthetic concerns. Treatment for TED patients aims to restore functionality and address aesthetic concerns. Surgical TED treatment is usually performed by orbital wall resection, which effectively decompresses intraorbital tissues and corrects the orbital/ocular disorders. Several different scenarios of surgical TED treatment including one-, two-, and three-wall resections are known. More recently, a new minimally invasive technique, the so-called lateral valgization (LAVA) of the orbital wall, was reported to show promising results comparable to conventional wall resection techniques. Due to the relatively limited data on TED treatment, only a few quantitative investigations of alternative TED surgery scenarios exist. In this feasibility study, we estimate the soft tissue outcome of LAVA treatment using computational simulation. Our experimental results show that the amount of intraorbital tissue released into the extraorbital space by LAVA treatment is comparable with the outcome of two-wall resection. Our computational simulation confirms previously reported isolated clinical findings suggesting that the minimally invasive LAVA approach represents an attractive alternative to conventional wall resection approaches for surgical TED treatment. Full article

Graves’ ophthalmopathy (GO), or thyroid eye disease (TED), is the most frequent extrathyroidal manifestation of Graves’ disease (GD). Inflammation and subsequent aberrant tissue remodeling with fibrosis are important pathogenesis. There are many proposed mechanisms and molecular pathways contributing to tissue remodeling and fibrosis in GO, including adipogenesis, fibroblast proliferation and myofibroblasts differentiation, oxidative stress, endoplasmic reticulum (ER) stress, hyaluronan (HA) and glycosaminoglycans (GAGs) accumulation in the extracellular matrix (ECM) and new concepts of epigenetics modification, such as histone modification, DNA methylation, non-coding RNAs, and gut microbiome. This review summarizes the current understanding of ECM proteins and associated tissue remodeling in the pathogenesis and potential mediators for the treatment of GO. Full article

Thyroid eye disease (TED) is an extrathyroidal manifestation of Graves’ disease (GD). Similar to GD, TED is caused by an autoimmune response. TED is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, swelling, redness, conjunctivitis, and bulging eyes. The pathophysiology of TED is complex, with the infiltration of activated T lymphocytes and activation of orbital fibroblasts (OFs) and autoantibodies against the common autoantigen of thyroid and orbital tissues. Better understanding of the multifactorial pathogenesis of TED contributes to the development of more effective therapies. In this review, we present current and potential drug targets. The ideal treatment should slow progression of the disease with as little interference with patient immunity as possible. In the future, TED treatment will target the immune mechanism involved in the disease and will be based on a strategy of restoring tolerance to autoantigens. Full article

COVID-19, a contagious disease caused by the novel coronavirus SARS-CoV-2, emerged in 2019 and quickly became a pandemic, infecting more than 700 million people worldwide. The disease incidence, morbidity and mortality rates have started to decline since the development of effective vaccines against the virus and the widespread immunization of the population. SARS-CoV-2 vaccines are associated with minor local or systemic adverse reactions, while serious adverse effects are rare. Thyroid-related disorders have been reported after vaccination for COVID-19, and Graves’ disease (GD) is the second most common amongst them. Thyroid eye disease (TED), an extrathyroidal manifestation of GD, is rarely observed post-COVID-19 vaccination. All TED cases followed mRNA-based vaccinations, but two new onset mild TED cases post-viral vector vaccine (ChAdox1nCoV-19) have also been reported. We report the case of a 63-year-old woman who presented with new onset hyperthyroidism and moderate-to-severe and active TED 10 days after she received the first dose of a viral vector vaccine against SARS-CoV-2. This is the first case of moderate-to-severe TED after such a vaccine. Our patient was initially treated with intravenous glucocorticoids, and subsequently with intravenous rituximab, due to no response. The disease was rendered inactive after rituximab, but constant diplopia persisted, and the patient was referred for rehabilitative surgery. Full article

Graves’ orbitopathy (GO) is an extrathyroidal manifestation of Graves’ disease (GD), which can be associated with corneal ulcerations or optic neuropathy in severe forms. Transnasal endoscopic orbital decompression (TEOD) is a surgical procedure performed in order to decrease the intraorbital pressure by removing part of its bony borders in cases with excessive mass in orbit. The aim of this study was to present the results and evaluate the efficacy of TEOD for GO. The retrospective study included 28 orbits (16 patients) who underwent TEOD from 2017 to 2020. Outcome was evaluated based on visual acuity improvement, clinical activity score (CAS) decrease, proptosis, and intraocular pressure (IOP) reduction. A preoperative best-corrected visual acuity (BCVA) increased from 0.69 ± 0.385 (mean ± standard deviation) to 0.74 ± 0.332 (p = 0.17) postoperatively. CAS decreased in 15 orbits postoperatively. Proptosis decreased from 22.89 ± 1.873 mm to 21.25 ± 2.053 mm (p < 0.05). IOP decreased from a preoperative 16.11 ± 3.93 mmHg to 14.40 ± 3.27 mmHg (p < 0.05) postoperatively. In addition, postoperative relief of exposure keratitis was observed. The analysis of development of iatrogenic diplopia revealed increasing in degree of diplopia. TEOD shows rare complications, but significant improvements in BCVA, CAS, proptosis, and IOP. Full article

Graves’ ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease. It is characterized initially by an inflammatory process, followed by tissue remodeling and fibrosis, leading to proptosis, exposure keratopathy, ocular motility limitation, and compressive optic neuropathy. The pathogenic mechanism is complex and multifactorial. Accumulating evidence suggests the involvement of oxidative stress in the pathogenesis of GO. Cigarette smoking, a major risk factor for GO, has been shown to induce reactive oxygen species (ROS) generation and oxidative damage in GO orbital fibroblasts. In addition, an elevation in ROS and antioxidant enzymes is observed in tears, blood, and urine, as well as orbital fibroadipose tissues and fibroblasts from GO patients. In vitro and in vivo studies have examined the efficacy of various antioxidant supplements for GO. These findings suggest a therapeutic role of antioxidants in GO patients. This review summarizes the current understanding of oxidative stress in the pathogenesis and potential antioxidants for the treatment of GO. Full article

Thyroid-stimulating hormone receptor (TSHR) belongs in a subfamily of the G protein-coupled receptors. Thyroid-stimulating hormone receptor gene (TSHR), a gene encoding TSHR, is a major controller of thyroid cell metabolism, and its gain of function mutation leads to non-autoimmune hyperthyroidism (NAH), a condition of a prolonged state of hyperthyroidism. Diverse human diseases, and genetic, constitutional, or environmental factors contribute to the phenotypic variations of TSHR mutations; however, the underlying mechanisms leading to various extrathyroidal manifestations across ages are poorly understood. In 2018, the first Korean case of persistent sporadic NAH due to missense mutation of TSHR was reported, and this report highlights the extrathyroidal manifestations of NAH. Further investigation is warranted to clarify the roles of functional mutations of TSHR by investigating the correlation between G protein-dependent signaling properties and clinical phenotypes associated with persistent hyperthyroidism in order to develop novel therapies that could be provided for numerous conditions caused by NAH. Full article

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age ± standard deviation 51 ± 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 ± 0.25 vs. 0.9 ± 0.16; p = 0.0001), CAS (4.64 ± 1.5 vs. 1.05 ± 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 ± 4.1 vs. 16.73 ± 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 ± 2.1 months, low disease activity (CAS ≤ 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or inefficacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment. Full article

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. At admission, the thyroid function laboratory tests showed hyperthyroidism with elevated free thyroxine (FT4) and free triiodothyronine (FT3) levels and suppressed thyroid-stimulating hormone (TSH) levels. These findings, combined with the clinical conditions—an ophthalmologic evaluation (that showed the presence of exophthalmos without lagophthalmos and visual acuity deficiency), thyroid ultrasound, and TSH receptor antibody positivity—led to a diagnosis of Graves’ disease. Therefore, methimazole was administered at a dose of 0.4 mg/kg/day. After 4 months, thyroid function was clearly improved, with normal FT3 and FT4 values and increasing TSH values, without adverse effects. Nevertheless, an eye examination showed ophthalmopathy with signs of activity, an increase in the exophthalmos of the right eye with palpebral retraction, soft tissue involvement (succulent and oedematous eyelids, caruncle and conjunctival hyperaemia and oedema) and keratopathy, resulting from exposure. We began steroid therapy with oral administration of prednisone (1 mg/kg/day) for four weeks, followed by gradual tapering. After one week of therapy with prednisone, an eye assessment showed reduced retraction of the upper eyelid of the right eye, improvement of right eye exophthalmometry and reduction of conjunctival hyperaemia. After four weeks of therapy with prednisone, an eye assessment showed reduction of the right palpebral retraction without conjunctival hyperaemia and no other signs of inflammation of the anterior segment; after twelve weeks, an eye assessment showed a notable decrease in the right palpebral retraction and the absence of keratitis, despite persisting moderate conjunctival hyperaemia. No adverse event associated with steroid use was observed during the treatment period and no problem in compliance was reported. Conclusion: Prednisone seems a better choice than intravenous corticosteroids, for treating moderate-to-severe and active Graves’ ophthalmopathy, keeping in mind the importance of quality of life in pediatric patients. Full article