A survey of current practices by the British Oculoplastic Surgery Society (BOPSS) and recommendations for delivering a sustainable multidisciplinary approach to thyroid eye disease in the United Kingdom

The Royal College of Physicians (RCP) and Thyroid Eye Disease Amsterdam Declaration Implementation Group (TEAMeD-5) have the common goal of improving access to high quality care for thyroid eye disease (TED). The TEAMeD-5 programme recommends all patients with moderate-to-severe TED should have access to multidisciplinary clinics (MDT) with combined Ophthalmology and Endocrinology expertise

Fetal Microchimeric Cells in Blood of Women with an Autoimmune Thyroid Disease

CONTEXT: Hashimoto's thyroiditis (HT) and Graves' disease (GD), two autoimmune thyroid diseases (AITD), occur more frequently in women than in men and show an increased incidence in the years following parturition. Persisting fetal cells could play a role in the development of these diseases. OBJECTIVE: Aim of this study was to detect and characterize fetal cells in blood of postpartum women with and without an AITD. PARTICIPANTS: Eleven patients with an AITD and ten healthy volunteers, all given birth to a son maximum 5 years before analysis, and three women who never had been pregnant, were included. None of them had any other disease of the thyroid which could interfere with the results obtained. METHODS: Fluorescence in situ hybridization (FISH) and repeated FISH were used to count the number of male fetal cells. Furthermore, the fetal cells were further characterized. RESULTS: In patients with HT, 7 to 11 fetal cells per 1.000.000 maternal cells were detected, compared to 14 to 29 fetal cells in patients with GD (p=0.0061). In patients with HT, mainly fetal CD8(+) T cells were found, while in patients with GD, fetal B and CD4(+) T cells were detected. In healthy volunteers with son, 0 to 5 fetal cells were observed, which was significantly less than the number observed in patients (p<0,05). In women who never had been pregnant, no male cells were detected. CONCLUSION: This study shows a clear association between fetal microchimeric cells and autoimmune thyroid diseases

A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments

<p>Abstract</p> <p>Background</p> <p>Anti-thyroid antibodies (ATA), even if not associated with thyroid dysfunction, are suspected to cause poorer outcome of in vitro fertilization (IVF).</p> <p>Methods</p> <p>We retrospectively analyzed: (a) the prevalence of ATA in euthyroid infertile women, (b) IVF outcome in euthyroid, ATA+ patients, and (c) the effect of adjuvant treatments (levothyroxine alone or associated with acetylsalicylic acid and prednisolone) on IVF results in ATA+ patients. One hundred twenty-nine euthyroid, ATA+ women undergoing IVF were compared with 200 matched, ATA-controls. During IVF cycle, 38 ATA+ patients did not take any adjuvant treatment, 55 received levothyroxin (LT), and 38 received LT +acetylsalicylic acid (ASA)+prednisolone (P).</p> <p>Results</p> <p>The prevalence of ATA among euthyroid, infertile patients was 10.5%, similar to the one reported in euthyroid women between 18 and 45 years. ATA+ patients who did not receive any adjuvant treatment showed significantly poorer ovarian responsiveness to stimulation and IVF results than controls. ATA+ patients receiving LT responded better to ovarian stimulation, but had IVF results as poor as untreated ATA+ women. Patients receiving LT+ASA+P had significantly higher pregnancy and implantation rates than untreated ATA+ patients (PR/ET 25.6% and IR 17.7% vs. PR/ET 7.5% and IR 4.7%, respectively), and overall IVF results comparable to patients without ATA (PR/ET 32.8% and IR 19%).</p> <p>Conclusion</p> <p>These observations suggest that euthyroid ATA+ patients undergoing IVF could have better outcome if given LT+ASA+P as adjuvant treatment. This hypothesis must be verified in further randomized, prospective studies.</p

Reverse Effect of Mammalian Hypocalcemic Cortisol in Fish: Cortisol Stimulates Ca2+ Uptake via Glucocorticoid Receptor-Mediated Vitamin D3 Metabolism

Cortisol was reported to downregulate body-fluid Ca2+ levels in mammals but was proposed to show hypercalcemic effects in teleostean fish. Fish, unlike terrestrial vertebrates, obtain Ca2+ from the environment mainly via the gills and skin rather than by dietary means, and have to regulate the Ca2+ uptake functions to cope with fluctuating Ca2+ levels in aquatic environments. Cortisol was previously found to regulate Ca2+ uptake in fish; however, the molecular mechanism behind this is largely unclear. Zebrafish were used as a model to explore this issue. Acclimation to low-Ca2+ fresh water stimulated Ca2+ influx and expression of epithelial calcium channel (ecac), 11β-hydroxylase and the glucocorticoid receptor (gr). Exogenous cortisol increased Ca2+ influx and the expressions of ecac and hydroxysteroid 11-beta dehydrogenase 2 (hsd11b2), but downregulated 11β-hydroxylase and the gr with no effects on other Ca2+ transporters or the mineralocorticoid receptor (mr). Morpholino knockdown of the GR, but not the MR, was found to impair zebrafish Ca2+ uptake function by inhibiting the ecac expression. To further explore the regulatory mechanism of cortisol in Ca2+ uptake, the involvement of vitamin D3 was analyzed. Cortisol stimulated expressions of vitamin D-25hydroxylase (cyp27a1), cyp27a1 like (cyp27a1l), 1α-OHase (cyp27b1) at 3 dpf through GR, the first time to demonstrate the relationship between cortisol and vitamin D3 in fish. In conclusion, cortisol stimulates ecac expression to enhance Ca2+ uptake functions, and this control pathway is suggested to be mediated by the GR. Lastly, cortisol also could mediate vitamin D3 signaling to stimulate Ca2+ uptake in zebrafish

Sterol Intermediates of Cholesterol Biosynthesis Inhibit Hair Growth and Trigger an Innate Immune Response in Cicatricial Alopecia

Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders

Radiotherapy in the treatment of Graves ophthalmopathy—to do it or not?

To the objective of this study is to evaluate the role and toxicity of radiotherapy in the treatment of Graves ophthalmopathy. In the years 2000–2003, 121 patients with malignant exophthalmos were treated with radiotherapy of the retrobulbar area to the total dose of 20 Gy in ten fractions with a 6 MeV photon beam. The treatment was performed by the team of the Clinic of Oncology of the Jagiellonian University Medical College in Cracow. The radiotherapy was preceded by intravenous steroid therapy: methylprednisolone acetate administered at the dose of 2 g/week for four consecutive weeks. The highest efficacy, expressed as improvement of all ocular symptoms, was observed for the combined treatment. Female and non-diabetic patients responded positively to the combined treatment. Radiotherapy combined with steroid therapy in the treatment of Graves ophthalmopathy seems to be an effective treatment for strictly defined indications. In the treatment of Graves–Basedow disease, radiotherapy is a well-tolerated treatment modality. Diabetes is a factor that worsens prognosis in Graves ophthalmopathy and female sex is a favourable factor for this condition

Do serum biomarkers really measure breast cancer?

Background Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. Methods This study used a set of 98 serum proteins and chose diagnostically relevant subsets via various feature-selection techniques. Because of significant noise in the data set, we applied iterated Bayesian model averaging to account for model selection uncertainty and to improve generalization performance. We assessed generalization performance using leave-one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) curve analysis. Results The classifiers were able to distinguish normal tissue from breast cancer with a classification performance of AUC = 0.82 ± 0.04 with the proteins MIF, MMP-9, and MPO. The classifiers distinguished normal tissue from benign lesions similarly at AUC = 0.80 ± 0.05. However, the serum proteins of benign and malignant lesions were indistinguishable (AUC = 0.55 ± 0.06). The classification tasks of normal vs. cancer and normal vs. benign selected the same top feature: MIF, which suggests that the biomarkers indicated inflammatory response rather than cancer. Conclusion Overall, the selected serum proteins showed moderate ability for detecting lesions. However, they are probably more indicative of secondary effects such as inflammation rather than specific for malignancy.United States. Dept. of Defense. Breast Cancer Research Program (Grant No. W81XWH-05-1-0292)National Institutes of Health (U.S.) (R01 CA-112437-01)National Institutes of Health (U.S.) (NIH CA 84955