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      Serum concentrations of TNF-α and its soluble receptors in Graves’ disease

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          Abstract

          Graves’ disease (GD), an organ-specific autoimmune disease, is the most common cause of hyperthyroidism. Tumour necrosis factor-alpha (TNF-α) exhibits immunological and metabolic activities involved in the induction and maintenance of immune responses. We attempted to evaluate the relationship between GD and serum TNF-α and its soluble receptors (sTNFRs), soluble TNF receptor 1 and 2 (sTNF-R1 and sTNF-R2). A total of 72 GD patients and 72 matched healthy individuals were recruited for this study. Serum TNF-α and sTNFRs were measured by sandwich ELISA. In our study, no significant difference was observed in TNF-α, but sTNFRs were found to be significantly elevated in GD patients compared to healthy individuals. Serum sTNFR levels were positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and TNF-α was negatively correlated with thyroid-stimulating hormone (TSH) in the GD group. It was also shown that thyrotropin receptor antibody (TRAb) was positively correlated with TNF-α and sTNFRs. Spearman’s correlation analysis showed that only sTNF-R1 was positively correlated with complement C3. Multiple linear regression analysis suggests that serum levels of sTNF-R1 and FT4 may play an important role in the serum level of FT3. According to the median value of FT3 level, GD patients were further divided into a high FT3 group and a low FT3 group. The serum levels of sTNF-R1 in the high FT3 GD group were significantly higher than those in the low FT3 GD group. In conclusion, sTNFRs may play an important role in anti-inflammatory and immune response in GD.

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          Most cited references33

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          2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

          Graves’ disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves’ hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves’ hyperthyroidism are usually medically treated for 12–18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12–18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves’ patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.
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            Tumor necrosis factor: a pleiotropic cytokine and therapeutic target.

            Advances in the molecular biology of human diseases indicate that the most striking manifestations of illness may be caused not by exogenous pathogenic or tumor products, but rather by toxic peptides produced by the host itself. Tumor necrosis factor (TNF), a polypeptide cytokine produced during infection, injury, or invasion, has proved pivotal in triggering the lethal effects of septic shock syndrome, cachexia, and other systemic manifestations of disease. Because removing TNF from the diseased host may prevent development of the illness, this factor has recently been the focus of intensive research. This review discusses the biology of this cytokine, with particular emphasis on its potential therapeutic role in septic shock and cachexia.
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              [Volumetric analysis of thyroid lobes by real-time ultrasound (author's transl)].

              Thyroid volume as measured by real-time ultrasound in cadavers was compared with direct measurements obtained by submersion. Length X width X thickness of the thyroid lobe multiplied by factor pi/6, correspond to a rotation ellipsoid, while the best calculated volume of the lobe is obtained by multiplying with the optimised correction factor f = 0.479. The correctness of this calculation is, by definition, 100%; average error of the method is 16%. The measurements are easy to do and require no additional equipment for planimetry or calculations. Volumetric analysis of the thyroid gland is especially necessary in assessing results of treatment and for measuring dosage in connection with radioiodine therapy.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                July 2020
                02 July 2020
                : 9
                : 7
                : 736-746
                Affiliations
                [1 ]Department of Endocrinology , Nantong City No 1 People’s Hospital and Second Affiliated Hospital of Nantong University, Jiangsu, China
                [2 ]Department of Rheumatology , Nantong City No 1 People’s Hospital and Second Affiliated Hospital of Nantong University, Jiangsu, China
                [3 ]Clinical Medicine Research Center , Nantong City No 1 People’s Hospital and Second Affiliated Hospital of Nantong University, Jiangsu, China
                Author notes
                Correspondence should be addressed to X Wang: wangxueqin108@ 123456163.com
                Article
                EC-20-0162
                10.1530/EC-20-0162
                7424358
                32621585
                b85f4f5f-7319-4d5a-9b65-09aab2ba4892
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 16 May 2020
                : 02 July 2020
                Categories
                Research

                tnf-α,stnf-r1,stnf-r2,graves’ disease,immune
                tnf-α, stnf-r1, stnf-r2, graves’ disease, immune

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