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      Subclinical hypothyroidism and the risk of chronic kidney disease in T2D subjects : A case-control and dose-response analysis

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          Abstract

          Evidence indicated a positive association between subclinical hypothyroidism (SCH) and cardiovascular diseases. But the relationship between SCH and chronic kidney diseases (CKD) remains unclear. A case-control study was performed to ascertain this relationship followed by a meta-analysis. In this hospital-based, case-control study, we recruited 3270 type 2 diabetic patients with euthyroidism and 545 type 2 diabetic patients with SCH. All English studies were searched upon the relationship between SCH and CKD up to October 2016. Meta-analysis was performed using STATA 13.0 software. Our case-control study indicated an association between SCH and CKD in patients with type 2 diabetes [OR (95% CI): 1.22 (1.09–1.36)]. Five observational studies reporting risk of CKD in SCH individuals were enrolled. A significant relationship between SCH and CKD was shown [pooled OR 1.80, (95% CI) 1.38–2.35]. Among normal TSH range, individuals with TSH ≥3.0 μIU/ml had a significantly higher rate of CKD (Fisher exact test, P = 0.027). Dose-response linear increase of CKD events was explored [pooled OR 1.09 (95% CI): 1.03–1.16 per1 mIU/L increase of TSH]. The present evidence suggests that SCH is probably a significant risk factor of CKD in T2D. Linear trend is shown between TSH elevation and CKD in T2D. This relationship between serum TSH and renal impairment in type 2 diabetic patients needs further studies to investigate.

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          The clinical significance of subclinical thyroid dysfunction.

          Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's age.
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            Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999.

            Knowledge of the excess risk posed by specific cardiovascular syndromes could help in the development of strategies to reduce premature mortality among patients with chronic kidney disease (CKD). The rates of atherosclerotic vascular disease, congestive heart failure, renal replacement therapy, and death were compared in a 5% sample of the United States Medicare population in 1998 and 1999 (n = 1,091,201). Patients were divided into the following groups: 1, no diabetes, no CKD (79.7%); 2, diabetes, no CKD (16.5%); 3, CKD, no diabetes (2.2%); and 4, both CKD and diabetes (1.6%). During the 2 yr of follow-up, the rates (per 100 patient-years) in the four groups were as follows: atherosclerotic vascular disease, 14.1, 25.3, 35.7, and 49.1; congestive heart failure, 8.6, 18.5, 30.7, and 52.3; renal replacement therapy, 0.04, 0.2, 1.6, and 3.4; and death, 5.5, 8.1, 17.7, and 19.9, respectively (P < 0.0001). With use of Cox regression, the corresponding adjusted hazards ratios were as follows: atherosclerotic vascular disease, 1, 1.30, 1.16, and 1.41 (P < 0.0001); congestive heart failure, 1, 1.44, 1.28, and 1.79 (P < 0.0001); renal replacement therapy, 1, 2.52, 23.1, and 38.9 (P < 0.0001); and death, 1, 1.21, 1.38, and 1.56 (P < 0.0001). On a relative basis, patients with CKD were at a much greater risk for the least frequent study outcome, renal replacement therapy. On an absolute basis, however, the high death rates of patients with CKD may reflect accelerated rates of atherosclerotic vascular disease and congestive heart failure.
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              Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts.

              American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                April 2017
                14 April 2017
                : 96
                : 15
                : e6519
                Affiliations
                [a ]Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing
                [b ]Department of General Surgery, Weihaiwei People's Hospital, Weihai
                [c ]Critical Care Medicine, Beijing Jiangong Hospital
                [d ]Beijng Key Laboratory of Diabetes Research and Care, Beijing, China.
                Author notes
                []Correspondence: Jin-Kui Yang, Jian-Bo Zhou, Beijing Tongren Hospital, Capital Medical University, Beijing, China (e-mails: jinkuiyang@ 123456yeah.net , jianbo.zhou@ 123456foxmail.com ).
                Article
                MD-D-16-04185 06519
                10.1097/MD.0000000000006519
                5403080
                28403083
                fa990e75-8185-46fd-ace2-05d931c381dc
                Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0

                History
                : 21 January 2017
                : 23 February 2017
                : 10 March 2017
                Categories
                4300
                Research Article
                Observational Study
                Custom metadata
                TRUE

                chronic kidney disease,dose-response analysis,subclinical hypothyroidism

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