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Concept: Graves' disease

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The endocrine system and particular endocrine organs, including the thyroid, undergo important functional changes during aging. The prevalence of thyroid disorders increases with age and numerous morphological and physiological changes of the thyroid gland during the process of aging are well-known. It is to be stressed that the clinical course of thyroid diseases in the elderly differs essentially from that observed in younger individuals, because symptoms are more subtle and are often attributed to normal aging. Subclinical hypo- and hyperthyroidism, as well as thyroid neoplasms, require special attention in elderly subjects. Intriguingly, decreased thyroid function, as well as thyrotropin (TSH) levels – progressively shifting to higher values with age – may contribute to the increased lifespan.This short review focuses on recent findings concerning the alterations in thyroid function during aging, including these which may potentially lead to extended longevity, both in humans and animals.

Concepts: Thyroid disease, Hypothyroidism, Hashimoto's thyroiditis, Hyperthyroidism, Thyroid, Graves' disease, Endocrine system, Triiodothyronine

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In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the ‘cytokine milieu’ that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders.

Concepts: Pharmacology, Medicine, Bioinformatics, Interleukin 1, Interleukin, Autoimmune disease, Graves' disease, Taoism

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Cowden syndrome (CS) is dominantly inherited and predisposes patients to tumors in multiple organs. We characterized CS-associated malignant and benign thyroid disease.

Concepts: Cancer, Medical terms, Benign tumor, Thyroid disease, Thyroid, Graves' disease, Thyroidectomy, Cowden syndrome

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CD40-CD40 ligand (CD40L) interactions appear to play pathogenic roles in autoimmune disease. Here we quantify CD40 expression on fibrocytes, circulating, and bone marrow-derived progenitor cells. The functional consequences of CD40 ligation are determined since these may promote tissue remodeling linked with thyroid-associated ophthalmopathy (TAO).

Concepts: Bacteria, Progenitor cell, Autoimmune disease, Graves' disease, Autoimmune diseases, Clusters of differentiation

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Context: Graves' disease (GD) and Hashimoto´s thyroiditis (HT) are the most common autoimmune thyroid diseases (AITD). The exact etiology of the immune response to the thyroid is still unknown. MicroRNAs (miRNAs) critically control gene-expression. It has become evident that some miRNAs play an important role in regulating the immune response, as well as immune cell development. However, data on the role of miRNAs in autoimmune thyroid diseases are lacking. Objective: The aim of this study was to determine levels of key immunoregulatory miRNAs in thyroid glands of AITD patients and healthy controls Design: Several miRNAs were amplified by a semiquantitative TaqMan PCR from fine needle aspiration biopsies of thyroid tissue of 28 patients with GD, HT, and healthy controls. Results: miRNA 146a1 is significantly decreased in the thyroid tissue of GD (mean relative expression 5,17 in GD group vs. 8,37 in controls, p = 0.019) whereas miRNA 200a1 is significantly decreased (mean 8,30 in HT group vs. 11,20 in controls, p = 0.001) and miRNA 155 2 is significantly increased (mean 12,02 in HT group vs. 8,01 in controls, p = 0.016) in the thyroid tissue of HT compared to controls. Conclusion: Although limited by small sample size and some other limitations (e.g. missing matching for age and medication), our preliminary data open up a new field of research concerning miRNAs in thyroid diseases. Further studies in this interesting field are clearly warranted.

Concepts: Immune system, Medicine, Immunology, Thyroid disease, Hyperthyroidism, Thyroid, Graves' disease, Needle aspiration biopsy

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Graves' disease (GD), including Graves' ophthalmopathy or orbitopathy (GO), is an autoimmune disease with an environmental and genetic component to its etiology. The genetic contribution to the GO clinical phenotype remains unclear. Previous data from our laboratory and others have suggested that GO has no specific genetic component distinct from GD itself, while other reports have occasionally appeared suggesting that polymorphisms in genes such as CTLA4 and IL23R specifically increase the risk for GO. One of the criticisms of all these reports has been the clinical definition of the GO phenotype as distinct from hyperthyroid GD devoid of clinically significant eye involvement. The objective of this study was to take advantage of a phenotypically pure group of GD patients with GO and examine a series of genes associated with GD to determine if any were more definitively associated with GO rather than Graves' thyroid disease itself.

Concepts: Gene, Thyroid disease, Hyperthyroidism, Thyroid, Autoimmune disease, Graves' disease, Thyroidectomy, Graves' ophthalmopathy

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BACKGROUND: Transdermal methimazole is an acceptable alternative to oral treatment for hyperthyroid cats. There are, however, no studies evaluating the duration of T4 suppression after transdermal methimazole application. Such information would be valuable for therapeutic monitoring. OBJECTIVE: To assess variation in serum T4 concentration in hyperthyroid cats after once- and twice-daily transdermal methimazole administration. ANIMALS: Twenty client-owned cats with newly diagnosed hyperthyroidism. METHODS: Methimazole was formulated in a pluronic lecithin organogel-based vehicle and applied to the pinna of the inner ear at a starting dose of 2.5 mg/cat q12h (BID group, 10 cats) and 5 mg/cat q24h (SID group, 10 cats). One and 3 weeks after starting treatment, T4 concentrations were measured immediately before and every 2 hours after gel application over a period of up to 10 hours. RESULTS: Significantly decreased T4 concentrations were observed in week 1 and 3 compared with pretreatment concentrations in both groups. All cats showed sustained suppression of T4 concentration during the 10-hour period, and T4 concentrations immediately before the next methimazole treatment were not significantly different compared with any time point after application, either in the BID or SID groups. CONCLUSIONS: Because transdermal methimazole application led to prolonged T4 suppression in both the BID and SID groups, timing of blood sampling does not seem to be critical when assessing treatment response.

Concepts: Evaluation, Concentration, Hyperthyroidism, Graves' disease, Ear, Inner ear, Methimazole, Propylthiouracil

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Thyrotoxicosis is mainly caused by autonomous adenomas of the thyroid gland and by Graves' disease. A less frequent cause for thyrotoxicosis is Hashimoto’s thyroiditis. Thyrotoxicosis in autonomous adenomas and Graves' disease is caused by an increased thyroid hormone production whereas hyperthyroidism in Hashimoto’s thyroiditis results from destruction of the thyroid gland. Drug therapy depends on the cause of the disease. Autonomous adenomas and Graves' disease are treated with methimazole and potentially with β-blockers. Regarding thyroid ablative therapy, radioiodine is mostly preferred compared to thyroidectomy. Drug therapy of Hashimoto’s thyroiditis is purely symptomatic using β-blockers and rarely corticosteroids. Hyperthyroidism in pregnancy is a major issue and pregnant women in the first trimester are treated with propylthiouracil (PTU) whereas women in the second and third trimesters are treated with methimazole. The aim is to maintain the serum fT4 levels within the upper normal range.

Concepts: Pregnancy, Thyroid disease, Hypothyroidism, Hashimoto's thyroiditis, Hyperthyroidism, Thyroid, Graves' disease, Methimazole

27

Not much has been reported aboutthe effects of hyperthyroidismand its correction on resistance vessels, and just two inconsistent studies have investigatedthe impacts of restored euthyroidism on vascular reactivity.In this regard, we designed the current study toevaluatethe vascular reactivity of mesenteric arteries of hyperthyroid and restored euthyroid rats.Hyperthyroidism was induced by administration of triiodothyronine(T(3); 300µg/kg, i.p, for 12 weeks in T(3) group).Euthyroidismwas restored by administration of T(3) for 8 weeks and then T(3)+Methimazole (0.003% in drinking water)for 4 weeks (T(3)+MMI group). According to the McGregor Method, vascular relaxation and contractility response was measured in response to acetylcholine or phenylephrine respectively.We found that maximal contractility response (E(max)) to phenylephrine in T(3) groupwas significantly decreased (P<0.001), and E(max) to acetylcholine was significantly increasedcompared with salinegroup (P<0.05). When N(G)-nitro-L-arginine methyl ester (L-NAME, 3×10(-4)M) was used,E(max)to acetylcholine inT(3) group was still higher than saline group(P<0.05). However, decrease in maximal response of T3 groupwas significantly greater than saline group(P<0.01). We also showed that when euthyroidism is restored by methimazole therapy, enhanced acetylcholine -induced vasorelaxation and impaired contractility response to phenylephrinewere normalized, as there were no significant difference in E(max) of T3+MMI group versus salinegroup(P>0.05).In conclusion, synthesis of both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)in mesenteric arteries significantly increased as a consequence of hyperthyroidism and this abnormal vascular reactivity is corrected by methimazole therapy.

Concepts: Blood vessel, Statistical significance, Hyperthyroidism, Nitric oxide, Graves' disease, Triiodothyronine, Methimazole, Methyl acetate

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Control of thyroid function in hyperthyroid women during pregnancy is based on antithyroid drugs (ATD) [propylthiouracil (PTU) and methimazole (MMI)]. While a teratogenic effect has been suggested for MMI and, more recently, for PTU, a clear demonstration is still lacking. Aim of this study was to assess the safety of ATD during pregnancy.

Concepts: Hyperthyroidism, Thyroid, Graves' disease, Triiodothyronine, Methimazole, Propylthiouracil, Antithyroid drugs