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      Thyroid function and life expectancy with and without noncommunicable diseases: A population-based study

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          Abstract

          Background

          Variations in thyroid function within reference ranges are associated with increased risk of diseases and death. However, the impact of thyroid function on life expectancy (LE) with and without noncommunicable diseases (NCDs) remains unknown. We therefore aimed to investigate the association of thyroid function with total LE and LE with and without NCD among euthyroid individuals.

          Methods and findings

          The study was embedded in the Rotterdam Study, a prospective population-based study carried out in the Netherlands. In total, 7,644 participants without known thyroid disease and with thyroid-stimulating hormone (TSH) and free thyroxine (FT 4) levels within reference ranges were eligible. NCDs were defined as presence of cardiovascular disease, diabetes mellitus type 2, or cancer. We used the demographic tool of multistate life tables to calculate LE estimates at the age of 50 years, using prevalence, incidence rates, and hazard ratios for three transitions (healthy to NCD, healthy to death, and NCD to death). The total LE and LE with and without NCD among TSH and FT 4 tertiles were calculated separately in men and women. Analyses were adjusted for sociodemographic and cardiovascular risk factors. The mean (standard deviation) age of the participants was 64.5 (9.7) years, and 52.3% were women. Over a median follow-up of 8 years (interquartile range 2.7–9.9 years), 1,396 incident NCD events and 1,422 deaths occurred. Compared with those in the lowest TSH tertile, men and women in the highest TSH tertile were expected to live 1.5 years (95% confidence interval [CI] 0.8–2.3, p < 0.001) and 1.5 years (CI 0.8–2.2, p < 0.001) longer, respectively, of which 1.4 years (CI 0.5–2.3, p = 0.002) and 1.3 years (CI 0.3–2.1, p = 0.004) with NCD. Compared with those in the lowest FT 4 tertile, the difference in LE for men and women in the highest FT 4 tertile was −3.7 years (CI −5.1 to −2.2, p < 0.001) and −3.3 years (CI −4.7 to −1.9, p < 0.001), respectively, of which −1.8 years (CI −3.1 to −0.7, p = 0.003) and −2.0 years (CI −3.4 to −0.7, p = 0.003) without NCD. A limitation of the study is the observational design. Thus, the possibility of residual confounding cannot be entirely ruled out.

          Conclusions

          In this study, we found that people with low–normal thyroid function (i.e., highest tertile of TSH and lowest tertile of FT 4 reference ranges) are expected to live more years with and without NCD than those with high–normal thyroid function (i.e., lowest tertile of TSH and highest tertile of FT 4 reference ranges). These findings provide support for a re-evaluation of the current reference ranges of thyroid function.

          Abstract

          Arjola Bano and colleagues reveal that people with a lower-normal level of thyroid function are more likely to live longer and without NCDs.

          Author summary

          Why was this study done?
          • Thyroid dysfunction is an important public health problem that is associated with an increased risk of noncommunicable diseases (NCDs), such as cardiovascular diseases, diabetes, and cancer. The diagnosis and treatment of thyroid dysfunction is based on thyrotropin and free thyroxine measurements.

          • Accumulating evidence has suggested that the clinical consequences of thyroid dysfunction are extended even within the reference ranges of thyrotropin and free thyroxine levels.

          • However, the impact of thyroid function on life expectancy with and without NCD remains unknown.

          What did the researchers do and find?
          • We performed a large prospective population-based cohort study within the framework of the Rotterdam Study.

          • We investigated the association of thyroid function with life expectancy with and without NCD among euthyroid individuals.

          • We found that individuals with low–normal thyroid function live up to 3.7 years longer overall, of which up to 1.9 years longer with NCD, than individuals with high–normal thyroid function.

          What do these findings mean?
          • Our study provides novel insights about the qualitative and quantitative impact of thyroid function on life expectancy.

          • Our findings provide support for a re-evaluation of the reference ranges of thyroid function in middle-aged and older adults. This can have further implications on the diagnosis and treatment of thyroid disease.

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          Most cited references26

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          Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology.

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            • Article: not found

            The Rotterdam Study: 2018 update on objectives, design and main results

            The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1500 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.
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              Thyroid status, disability and cognitive function, and survival in old age.

              Despite the equivocal outcomes of randomized controlled trials, general clinical opinion favors screening and treatment of elderly individuals with subclinical thyroid disorders. To determine whether subclinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age. A prospective, observational, population-based follow-up study within the Leiden 85-Plus Study of 87% of a 2-year birth cohort (1912-1914) in the municipality of Leiden, the Netherlands. A total of 599 participants were followed up from age 85 years through age 89 years (mean [SD] follow-up, 3.7 [1.4] years). Complete thyroid status at baseline; disability in daily life, depressive symptoms, cognitive function, and mortality from age 85 years through 89 years. Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life, depressive symptoms, and cognitive impairment at baseline or during follow-up. Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status. The hazard ratio (HR) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 (95% confidence interval [CI], 0.63-0.94; P = .009). The HR for mortality per SD increase of 0.21 ng/dL (2.67 pmol/L) of free thyroxine increased 1.16-fold (95% CI, 1.04-1.30; P = .009). In the general population of the oldest old, elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span. However, evidence for not treating elderly individuals can only come from a well-designed, randomized placebo-controlled clinical trial.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                25 October 2019
                October 2019
                : 16
                : 10
                : e1002957
                Affiliations
                [1 ] Department of Internal Medicine and Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, the Netherlands
                [2 ] Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands
                [3 ] Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
                [4 ] Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
                [5 ] Section of Geriatric Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
                Chinese University of Hong Kong, CHINA
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-0956-7145
                http://orcid.org/0000-0003-0372-8585
                Article
                PMEDICINE-D-19-02634
                10.1371/journal.pmed.1002957
                6814213
                31652264
                6d47b443-d90d-42ef-a815-7cd3a9001411
                © 2019 Bano et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 July 2019
                : 2 October 2019
                Page count
                Figures: 1, Tables: 3, Pages: 16
                Funding
                Funded by: Netherlands Organization for Health Research and Development Zon-MWTOP grant
                Award ID: 91212044
                Award Recipient :
                Funded by: Erasmus Medical Center Medical Research Advisory Committee grant
                Award Recipient :
                Funded by: Lecture fees from IBSA and Goodlife Fertility
                Award Recipient :
                Funded by: Netherlands Organization for Scientific Research VENI grant
                Award ID: 91616079
                Award Recipient :
                RPP is supported by the Netherlands Organization for Health Research and Development Zon-MWTOP grant 91212044 and an Erasmus Medical Center Medical Research Advisory Committee grant. RPP has received lecture fees from IBSA and Goodlife Fertility. MK is supported by a Netherlands Organization for Scientific Research VENI grant 91616079. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Endocrine System
                Thyroid
                Medicine and Health Sciences
                Anatomy
                Endocrine System
                Thyroid
                Biology and Life Sciences
                Biochemistry
                Hormones
                Peptide Hormones
                Thyroid-Stimulating Hormone
                Biology and Life Sciences
                Biochemistry
                Hormones
                Thyroid Hormones
                Thyroxine
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Diseases
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Life Expectancy
                Medicine and Health Sciences
                Public and Occupational Health
                Life Expectancy
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Social Sciences
                Sociology
                Education
                Medical Education
                Medicine and Health Sciences
                Medical Humanities
                Medical Education
                Medicine and Health Sciences
                Pulmonology
                Chronic Obstructive Pulmonary Disease
                Custom metadata
                Rotterdam Study data can be made available to interested researchers upon request. Requests can be directed to data manager Frank J.A. van Rooij ( f.vanrooij@ 123456erasmusmc.nl ). We are unable to place data in a public repository due to legal and ethical restraints. Sharing of individual participant data was not included in the informed consent of the study, and there is potential risk of revealing participants’ identities as it is not possible to completely anonymize the data. This is of particular concern given the sensitive personal nature of much of the data collected as part of the Rotterdam Study.

                Medicine
                Medicine

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