Chemokines in hyperthyroidism.
Ontology highlight
ABSTRACT:
SUBMITTER: Ferrari SM
PROVIDER: S-EPMC6536457 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Chemokines in hyperthyroidism.
Ferrari Silvia Martina SM Ruffilli Ilaria I Elia Giusy G Ragusa Francesca F Paparo Sabrina Rosaria SR Patrizio Armando A Mazzi Valeria V Antonelli Alessandro A Fallahi Poupak P
Journal of clinical & translational endocrinology 20190517
The term "hyperthyroidism" indicates a condition due to an exaggerate production of thyroid hormone; the most frequent cause is Graves' disease (GD). We review cytokines and chemokines in hyperthyroidism, with a special focus in GD. In GD, recruited Th1 lymphocytes are responsible for enhanced IFN-γ and TNF-α production, which in turn stimulates Th1 chemokines release from thyrocytes, initiating and perpetuating the autoimmune process. Circulating levels of these chemokines are associated with t ...[more]
Similar Datasets
Project description:Congenital hypothyroidism is a condition in which the thyroid gland does not produce enough thyroid hormones. It occurs in 1:2000-4000 newborns. Common clinical features include decreased activity and increased sleep, feeding difficulty, constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, distended abdomen with umbilical hernia, and hypotonia. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Without treatment, congenital hypothyroidism leads to severe intellectual deficit and short stature. Congenital hyperthyroidism occurs when the thyroid gland produces too much of the hormone thyroxine, which can accelerate body metabolism, causing unintentional weight loss and a rapid or irregular heartbeat. Hyperthyroidism is very rare and its prevalence is unknown. Common clinical features include unintentional weight loss, tachycardia, arrhythmia, palpitations, anxiety, tremor and sweating. Here we summarize the genes involved in congenital hypo- and hyperthyroidism and the tests we use for genetic analysis.
| S-EPMC7233645 | biostudies-literature
Project description:Tremelimumab and ipilimumab are monoclonal antibodies directed against the extracellular domain of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and have been used as immunotherapies against immune checkpoints that suppress T-cell activation. Anti-CTLA-4 antibody-based therapies have been shown to be effective in treating various cancers including metastatic melanoma. However, a few immune-related adverse events including hypophysitis and thyroid disorder have been reported, mostly developed within the first year of receiving treatment. We report a case of tremelimumab-induced Graves hyperthyroidism in a 55-year-old man who was diagnosed with metastatic melanoma after 8 years of tremelimumab therapy. He had no personal or family history of thyroid or autoimmune diseases. His biochemical profile was in keeping with Graves disease, with raised serum free thyroid hormones, suppressed thyroid-stimulating hormone concentration, and raised thyrotropin receptor antibody level. He was treated with carbimazole as part of the block and replace therapy, without complications. Tremelimumab therapy was temporarily discontinued and recommenced when he was rendered biochemically euthyroid. There has been no further relapse of Graves hyperthyroidism since the discontinuation of block and replace therapy. The mechanistic profile of anti-CTLA-4-induced thyroid dysfunction and the long-term endocrine safety of this therapeutic approach remain unclear. It is important to monitor thyroid functions in patients receiving anti-CTLA-4 therapies, as their effects on endocrine systems could be more latent or prolonged than the data from current clinical trials suggest. Antithyroid drug therapy was safe and effective alongside anti-CTLA-4 therapy without compromising antitumour treatment efficacy.
| S-EPMC5527187 | biostudies-literature
Project description:IntroductionHyperthyroid patients who are unresponsive to medical treatment remain a challenging clinical problem.ObjectiveThe goal of our study was to evaluate the use of therapeutic plasma exchange (TPE) in hyperthyroid patients and their outcome after TPE.MethodWe retrospectively reviewed 22 patients who underwent TPE for refractory thyrotoxicosis in our institution: 13 with Graves' disease, 7 with amiodarone-induced thyrotoxicosis (AIT), 1 with toxic goiter, and 1 pregnant patient with familial nonautoimmune thyrotoxicosis.ResultsBefore TPE, all patients had severe hyperthyroidism, and antithyroid drugs were either contraindicated or not sufficiently effective to restore euthyroidism promptly. After all the TPEs, free T4 (fT4) decreased significantly by 48% (p = 0.001) and fT3 by 52% (p = 0.0001). The median number of TPE sessions per patient was 4 (range: 1-10). There were no complications during the 91 TPE sessions. Total thyroidectomy with no severe side effects was performed on 16/22 patients and 1 other patient was treated with radioactive iodine. One patient died from severe thyrotoxicosis during medical care. The remaining 4 patients were followed up without any radical treatment. For all 7 patients with AIT, iterative TPE led to a significant clinical improvement, and amiodarone was continued for 1 patient. Available treatments were continued between TPE sessions (cholestyramine for 13 patients [60%] and glucocorticoids for 16 patients [73%]).ConclusionTPE allowed a safe decrease of 50% in thyroid hormone levels, and it should be considered for refractory hyperthyroid patients when medical treatments are contraindicated or have failed to restore euthyroidism, irrespective of the etiology of the thyrotoxicosis.
| S-EPMC7983568 | biostudies-literature
Project description:ObjectiveThe commonly held association of hyperthyroidism with sinus tachycardia and widened pulse pressure (PP) has not been reassessed in decades despite patients with hyperthyroidism in current practice not always present with these signs. The study objective was to assess prevalence and variability of sinus tachycardia and widened PP in present day among individuals with different degrees of hyperthyroidism.MethodsData was collected retrospectively from 248 adult patients in an outpatient setting with biochemical evidence of hyperthyroidism, recorded heart rate (HR) and blood pressure (BP) who were not treated with medications that can influence these parameters.ResultsMean age was 42.0 ± 14.2 years with 66.9% being female. Median free thyroxine (fT4) level was 3.49 (IQR 2.42-4.58) ng/dL and thyroid stimulating hormone (TSH) 0.02 (IQR 0.01-0.03) mIU/L. Tachycardia, defined as HR >100 bpm, was present in 28.2%. In the lowest and highest fT4 quartiles, tachycardia was present in 16.4% and 38.7% respectively. Using logistic regression, tachycardia was associated with higher fT4 and diastolic BP. More lenient outcome of tachycardia with HR >90 bpm was seen in 47.2%. Widened PP, defined as >50 mmHg, was observed in 64.1% of patients and correlated with higher fT4 and BP.ConclusionsTachycardia is not a common feature of hyperthyroidism today. The relatively infrequent finding of tachycardia in this study compared to older studies may reflect differences in the way medicine is practiced today. The increased ordering of thyroid function tests most likely unmasked cases of mild or asymptomatic thyrotoxicosis. A widened PP was a more prevalent clinical finding in this study.
| S-EPMC9439220 | biostudies-literature
Project description: Not available
| S-EPMC3153549 | biostudies-literature
Project description:Graves' hyperthyroidism is characterized by the presence of autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), resulting in uncontrolled secretion of excessive thyroid hormone. Conventional treatments, including antithyroid medication, radioiodine, or surgery have remained largely unchanged for the past 70 years and either lack efficacy for many patients, or result in lifelong thyroid hormone replacement therapy, in the case of the latter 2 options. The demand for new therapeutic options, combined with greater insight into basic immunobiology, has led to the emergence of novel approaches to treat Graves' hyperthyroidism. The current therapies under investigation include biologics, small molecules, and peptide immunomodulation. There is a growing focus on TSHR-specific treatment modalities, which carry the advantage of eliciting a specific, targeted approach, with the aim of avoiding disruption of the functioning immune system. These therapies present a new opportunity to supersede the inadequate treatments currently available for some Graves' patients, offering hope of successful restoration of euthyroidism without the need for ongoing therapy. Several of these therapeutic options have the potential to translate into clinical practice in the near future. This review provides a comprehensive summary of the recent advances and various stages of development of the novel therapeutic approaches to treat Graves' hyperthyroidism.
| S-EPMC7567404 | biostudies-literature
Project description:Cysteine cathepsins are primarily lysosomal proteases involved in general protein turnover, but they also have specific proteolytic functions in antigen presentation and bone remodeling. Cathepsins are most stable at acidic pH, although growing evidence indicates that they have physiologically relevant activity also at neutral pH. Post-translational proteolytic processing of mature chemokines is a key, yet underappreciated, level of chemokine regulation. Although the role of selected serine proteases and matrix metalloproteases in chemokine processing has long been known, little has been reported about the role of cysteine cathepsins. Here we evaluated cleavage of CXC ELR (CXCL1, -2, -3, -5, and -8) and non-ELR (CXCL9-12) chemokines by cysteine cathepsins B, K, L, and S at neutral pH by high resolution Tris-Tricine SDS-PAGE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Whereas cathepsin B cleaved chemokines especially in the C-terminal region, cathepsins K, L, and S cleaved chemokines at the N terminus with glycosaminoglycans modulating cathepsin processing of chemokines. The functional consequences of the cleavages were determined by Ca(2+) mobilization and chemotaxis assays. We show that cysteine cathepsins inactivate and in some cases degrade non-ELR CXC chemokines CXCL9-12. In contrast, cathepsins specifically process ELR CXC chemokines CXCL1, -2, -3, -5, and -8 N-terminally to the ELR motif, thereby generating agonist forms. This study suggests that cysteine cathepsins regulate chemokine activity and thereby leukocyte recruitment during protective or pathological inflammation.
| S-EPMC4447957 | biostudies-literature
Project description:Neonatal immune hyperthyroidism is a rare but potentially fatal condition. It occurs in 1-5% of infants born to women with Graves' disease (GD). In most of the cases it is due to maternal antibodies transferred from the mother into the fetal compartment, stimulating the fetal thyroid by binding thyrotropin (thyroid-stimulating hormone, TSH) receptor. We present a case of neonatal thyrotoxicosis due to maternal GD detected at 25 days of age and discuss the potential pitfalls in the diagnosis.
| S-EPMC4368938 | biostudies-literature
Project description:Chemoattractant cytokines or chemokines constitute a family of structurally related proteins found in vertebrates, bacteria, or viruses. So far, 48 chemokine genes have been identified in humans, which bind to around 20 chemokine receptors. These receptors belong to the seven transmembrane G-protein-coupled receptor family. Chemokines and their receptors were originally studied for their role in cellular trafficking of leukocytes during inflammation and immune surveillance. It is now known that they exert different functions under physiological conditions such as homeostasis, development, tissue repair, and angiogenesis but also under pathological disorders including tumorigenesis, cancer metastasis, inflammatory, and autoimmune diseases. Physicochemical properties of chemokines and chemokine receptors confer the ability to homo- and hetero-oligomerize. Many efforts are currently performed in establishing new therapeutically compounds able to target the chemokine/chemokine receptor system. In this review, we are interested in the role of chemokines in inflammatory disease and leukocyte trafficking with a focus on vascular inflammatory diseases, the operating synergism, and the emerging therapeutic approaches of chemokines.
| S-EPMC3394994 | biostudies-literature
Project description:Twenty five hyperthyroid patients and 25 healthy volunteers were evaluated for carbohydrate metabolic disturbance with an oral glucose tolerance test and glycosylated haemoglobin percentage. Insulin secretory response was studied in 17 hyperthyroids and 10 controls. A varying degree of abnormality was noted in hyperthyroids. Forty per cent patients had a significantly higher glycosylated haemoglobin and 3 (12%) patients had impaired glucose tolerance and 1 (4%) patient had frank diabetes mellitus. Significant hyperinsulinism was seen in the hyperthyroid group. Our data suggests that carbohydrate metabolic aberration exists in hyperthyroids and may reflect insulin resistance.
| S-EPMC5530406 | biostudies-other