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      Subclinical and overt hypothyroidism is associated with reduced glomerular filtration rate and proteinuria: a large cross-sectional population study

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          Abstract

          Subclinical hypothyroidism has been associated with dyslipidemia, hypertension, and increased risk of coronary artery disease. However, limited is known for its effect on renal function. Here we aimed to investigate whether subclinical hypothyroidism is associated with reduced estimated glomerular filtration rate (eGFR) and proteinuria in the general population. A cross-sectional cohort of 74,356 adults aged ≥20 year participating in voluntary health examinations without previous thyroid diseases were recruited in Taiwan. The mean eGFR of persons with euthyroidism, subclinical, and overt hypothyroidism are 87.99, 83.46, and 72.22 mL/min/1.73 m2, respectively (P-for- trend < 0.001). The proportion of proteinuria in persons with euthyroidism, subclinical and overt hypothyroidism is 1.29%, 2.2%, and 2.97%, respectively (P-for-trend: 0.001). The odds ratio of CKD for subclinical, clinical, and all hypothyroidism is 2.04 (95% confidence interval (CI): 1.67-2.50) and 7.61 (95% CI: 4.92-11.77), and 2.41 (95% CI: 2.01–2.89), respectively as compared to euthyroidism. These odd ratios remained significant after further adjustments. The odds ratios for proteinuria is 2.04 (95% CI: 1.67–2.50), 7.61 (95% CI: 4.92–11.77), and 2.41 (95% CI: 2.01–2.89) for subclinical, clinical, and total hypothyroidism, respectively, although the odds ratios were attenuated after further adjustment. Our results suggest subclinical hypothyroidism is a novel risk factor of reduced renal function but not proteinuria.

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          Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease.

          Previous studies have suggested a higher prevalence of thyroid abnormalities in persons with end-stage renal disease. However, little is known regarding the epidemiology of thyroid disorders in persons with less severe kidney dysfunction. We used data from the Third National Health and Nutrition Examination Survey to examine the prevalence of hypothyroidism (clinical and subclinical) at different levels of estimated glomerular filtration rate (GFR). We used multivariable logistic regression to evaluate the association between GFR and prevalent hypothyroidism. Among 14,623 adult participants with serum creatinine and thyroid function test results, the mean age was 48.7 years, and 52.6% were women. The prevalence of hypothyroidism increased with lower levels of GFR (in units of mL/min/1.73 m(2)), occurring in 5.4% of subjects with GFR >/=90, 10.9% with GFR 60-89, 20.4% with GFR 45-59, 23.0% with GFR 30-44, and 23.1% with GFR /=90 mL/min/1.73 m(2), reduced GFR was associated with an increased risk of hypothyroidism, after adjusting for age, gender, and race/ethnicity: adjusted odds ratio 1.07 (95% confidence interval: 0.86-1.32) for GFR 60-89, 1.57 (1.11-2.22) for GFR 45-59, 1.81 (1.04-3.16) for GFR 30-44, and 1.97 (0.69-5.61) for GFR <30 mL/min/1.73 m(2) (P= 0.008 for trend). Among a nationally representative sample of adults, reduced glomerular filtration rate was associated with a higher prevalence of hypothyroidism, with many subclinical cases. Future studies are needed to determine the potential adverse effects of subclinical and clinical hypothyroidism in persons with chronic kidney disease.
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            Prevalence of subclinical hypothyroidism in patients with chronic kidney disease.

            Subclinical primary hypothyroidism is highly prevalent in the general population, especially in the elderly. However, the prevalence of subclinical primary hypothyroidism in persons with chronic kidney disease (CKD) not requiring chronic dialysis is not well defined. Cross-sectional data from 3089 adult outpatients, who were consecutively referred by general practitioners for routine blood testing over the last two years, were analyzed. Glomerular filtration rate (GFR) was estimated by the abbreviated Modification of Diet in Renal Disease equation. Multivariable logistic regression was used to evaluate the independent association between prevalent subclinical primary hypothyroidism and estimated GFR. Among 3089 adult participants, 293 (9.5%) had subclinical primary hypothyroidism and 277 (9%) had an estimated GFR or=90 ml/min per 1.73 m(2) to 17.9% at an estimated GFR or=60 ml/min per 1.73 m(2), those with estimated GFR <60 ml/min per 1.73 m(2) had an increased odds of subclinical primary hypothyroidism after adjusting for age, gender, fasting plasma glucose, total cholesterol, and triglyceride concentrations. These findings suggest that subclinical primary hypothyroidism is a relatively common condition ( approximately 18%) among persons with CKD not requiring chronic dialysis, and it is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults.
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              Subclinical hypothyroidism is associated with increased risk for all-cause and cardiovascular mortality in adults.

              This study sought to evaluate the relationship between subclinical hypothyroidism (SCH) and all-cause and cardiovascular disease (CVD) mortality. SCH may increase the risks of hypercholesterolemia and atherosclerosis. The associations between SCH and all-cause or CVD mortality are uncertain, on the basis of the results of previous studies. A baseline cohort of 115,746 participants without a history of thyroid disease, ≥20 years of age, was recruited in Taiwan. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.0 to 19.96 mIU/l with normal total thyroxine concentrations. Euthyroidism was defined as a serum TSH level of 0.47 to 4.9 mIU/l. Cox proportional hazards regression analysis was used to estimate the relative risks (RRs) of death from all-cause and CVD for adults with SCH during a 10-year follow-up period. There were 3,669 deaths during the follow-up period; 680 deaths were due to CVD. Compared with subjects with euthyroidism, after adjustment for age, sex, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol consumption, betel nut chewing, physical activity, income, and education level, the RRs (95% confidence interval) of deaths from all-cause and CVD among subjects with SCH were 1.30 (1.02 to 1.66), and 1.68 (1.02 to 2.76), respectively. Adult Taiwanese with SCH had an increased risk for all-cause mortality and CVD death. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                yukangtu@ntu.edu.tw
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                1 February 2018
                1 February 2018
                2018
                : 8
                : 2031
                Affiliations
                [1 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Graduate Institute of Medical Genomics and Proteomics, , National Taiwan University, ; Taipei, Taiwan
                [2 ]ISNI 0000 0004 0572 7815, GRID grid.412094.a, Department of Internal Medicine, , National Taiwan University Hospital, ; Taipei, Taiwan
                [3 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Department of Medicine, College of Medicine, , National Taiwan University, ; Taipei, Taiwan
                [4 ]ISNI 0000 0001 2287 1366, GRID grid.28665.3f, Institue of Biomedical Science, , Academia Sinica, ; Taipei, Taiwan
                [5 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Institute of Epidemiology and Preventive Medicine, College of Public Health, , National Taiwan University, ; Taipei, Taiwan
                Article
                19693
                10.1038/s41598-018-19693-4
                5795015
                29391480
                476d8156-1503-4e45-a637-d3ebca037c51
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                : 19 July 2017
                : 2 January 2018
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