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      Thyroid and Cardiovascular DiseaseResearch Agenda for Enhancing Knowledge, Prevention, and Treatment

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          Abstract

          Thyroid hormones have long been known to have a range of effects on the cardiovascular system. However, significant knowledge gaps exist regarding the precise molecular and biochemical mechanisms governing these effects and the optimal strategies for management of abnormalities in thyroid function in patients with and without pre-existing cardiovascular disease. In September 2017, The National Heart, Lung, and Blood Institute convened a working group with the goal of developing priorities for future scientific research relating thyroid dysfunction to the progression of cardiovascular disease. The working group reviewed and discussed the roles of normal thyroid physiology, the consequences of thyroid dysfunction, and the effects of therapy in three cardiovascular areas: cardiac electrophysiology and arrhythmias, the vasculature and atherosclerosis, and the myocardium and heart failure. This report describes the current state of the field, outlines barriers and challenges to progress, and proposes research opportunities to advance the field, including strategies for leveraging novel approaches using omics and big data. The working group recommended research in three broad areas: 1) investigation into the fundamental biology relating thyroid dysfunction to the development of cardiovascular disease and into the identification of novel biomarkers of thyroid hormone action in cardiovascular tissues; 2) studies that define subgroups of patients with thyroid dysfunction amenable to specific preventive strategies and interventional therapies related to cardiovascular disease; and 3) clinical trials focused on improvement in cardiovascular performance and cardiovascular outcomes through treatment with thyroid hormone or thyromimetic drugs.

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          Most cited references87

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          Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association.

          Hypothyroidism has multiple etiologies and manifestations. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions. This paper describes evidence-based clinical guidelines for the clinical management of hypothyroidism in ambulatory patients. The development of these guidelines was commissioned by the American Association of Clinical Endocrinologists (AACE) in association with American Thyroid Association (ATA). AACE and the ATA assembled a task force of expert clinicians who authored this article. The authors examined relevant literature and took an evidence-based medicine approach that incorporated their knowledge and experience to develop a series of specific recommendations and the rationale for these recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach outlined in the American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Guidelines-2010 update. Topics addressed include the etiology, epidemiology, clinical and laboratory evaluation, management, and consequences of hypothyroidism. Screening, treatment of subclinical hypothyroidism, pregnancy, and areas for future research are also covered. Fifty-two evidence-based recommendations and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medical practice for the diagnosis and care of hypothyroidism. A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations. The standard treatment is replacement with L-thyroxine. The decision to treat subclinical hypothyroidism when the serum thyrotropin is less than 10 mIU/L should be tailored to the individual patient.
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            Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists.

            Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition. The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis. One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.
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              Direct effects of thyroid hormones on hepatic lipid metabolism

              It has been known for a long time that thyroid hormones have prominent effects on hepatic fatty acid and cholesterol synthesis and metabolism. Indeed, hypothyroidism has been associated with increased serum levels of triglycerides and cholesterol as well as non-alcoholic fatty liver disease (NAFLD). Advances in areas such as cell imaging, autophagy and metabolomics have generated a more detailed and comprehensive picture of thyroid-hormone-mediated regulation of hepatic lipid metabolism at the molecular level. In this Review, we describe and summarize the key features of direct thyroid hormone regulation of lipogenesis, fatty acid β-oxidation, cholesterol synthesis and the reverse cholesterol transport pathway in normal and altered thyroid hormone states. Thyroid hormone mediates these effects at the transcriptional and post-translational levels and via autophagy. Given these potentially beneficial effects on lipid metabolism, it is possible that thyroid hormone analogues and/or mimetics might be useful for the treatment of metabolic diseases involving the liver, such as hypercholesterolaemia and NAFLD.
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                Author and article information

                Journal
                Circulation
                Circulation
                Ovid Technologies (Wolters Kluwer Health)
                0009-7322
                1524-4539
                May 13 2019
                May 13 2019
                Affiliations
                [1 ]Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
                [2 ]Cardiovascular Division, Brigham and Women's Hospital, Boston, MA
                [3 ]Department of Internal Medicine and Erasmus MC Academic Center for Thyroid Diseases, Erasmus MC, Rotterdam, The Netherlands
                [4 ]DDivision of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD
                [5 ]Office of Clinical and Regulatory Affairs, National Center for Complementary and Integrative Health, Bethesda, MD
                [6 ]Division of Cardiology, NYU School of Medicine, New York, NY
                [7 ]Sarver Heart Center, University of Arizona, Tucson, AZ
                [8 ]Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD
                [9 ]Divisions of Preventive and Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA
                [10 ]Division of Cardiology, Arrhythmia Services, the University of Washington, Seattle, WA
                [11 ]Department of Medicine, Weill Cornell Medicine, New York, NY
                Article
                10.1161/CIRCULATIONAHA.118.036859
                6851449
                31081673
                325e651a-c9bf-4834-a28f-c1e38ae74806
                © 2019
                History

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