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      Long-term cardiovascular and cerebrovascular morbidity in Israeli thyroid cancer survivors

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          Abstract

          Objective

          Thyroid cancer (TC) survivors may be at risk of subsequent cardiovascular and cerebrovascular (CaV&CeV) morbidity. The 2009 American Thyroid Association (ATA) guidelines recommended less aggressive treatment for low-risk TC patients. The aim of this study was to assess the atherosclerotic CaV&CeV outcome of Israeli TC survivors compared to individuals with no thyroid disease, and the atherosclerotic CaV&CeV outcome before (2000–2008) and after (2009–2011) implementation of the 2009 ATA guidelines.

          Methods

          All members of the largest Israeli healthcare organization who were diagnosed with TC from 1/2000 to 12/2014 (study group) and age- and sex-matched members with no thyroid disease (controls) were included. Adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards models.

          Results

          The mean follow-up was 7.6 ± 4.2 and 7.8 ± 4.1 years for the study ( n = 5,677, 79% women) and control ( n = 23,962) groups, respectively. The former had an increased risk of new atherosclerotic CaV&CeV events (adjusted HR 1.26, 95% CI 1.15–1.39). The 5-year incidence of CaV&CeV was lower (adjusted HR 0.49, 95% CI 0.38–0.62) from 2009 to 2011 compared to 2000 to 2008, but remained higher in the study group than in the control group (adjusted HR 1.5, 95% CI 1.14–1.69).

          Conclusions

          This large Israeli population-based cohort study showed greater atherosclerotic CaV&CeV morbidity in TC survivors compared to individuals with no thyroid diseases. There was a trend toward a decreased 5-year incidence of atherosclerotic CaV&CeV events among TC survivors following the implementation of the 2009 ATA guidelines, but it remained higher compared to the general population.

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          Most cited references30

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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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            Population-based study evaluating and predicting the probability of death resulting from thyroid cancer and other causes among patients with thyroid cancer.

            The purpose of this study was to evaluate the probability of death for patients with thyroid cancer and construct a comprehensive nomogram based on a competing risks model to predict cumulative incidence of death resulting from thyroid cancer, other cancers, and non-cancer-related causes. Patients diagnosed with thyroid cancer between 1988 and 2003 were selected for the study from the Surveillance, Epidemiology, and End Results program. We estimated probabilities of death resulting from thyroid cancer, other cancers, and noncancer causes and analyzed associations of patient and tumor characteristics with probability of death. A nomogram for predicting probability of death was built using a proportional subdistribution hazard competing risks model. The entire cohort comprised 29,225 patients with malignant thyroid cancer. Median duration of follow-up until censoring or death was 85 months (range, 0 to 239 months). Five-year probabilities of death resulting from thyroid cancer, other cancer, and noncancer causes were 1.9%, 0.8%, and 1.7%, respectively. Increasing age and tumor size, male sex, poorly differentiated carcinoma, lymph node involvement, and regional and metastatic disease were associated with increased cumulative incidence of death resulting from thyroid cancer. A nomogram based on a competing risks model was developed for predicting the probability of death for patients with thyroid cancer. Performance of the model was excellent. This nomogram may be useful for patients and clinicians when predictions are needed.
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              Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study.

              Thyroid dysfunction has been associated with both increased all-cause and cardiovascular mortality, but limited data are available on mild thyroid dysfunction and cause-specific mortality. The objective of the study was to examine the risk of all-cause mortality, major adverse cardiovascular events (MACEs), and cause-specific events in subjects with overt and subclinical thyroid dysfunction. This was a retrospective cohort study. Participants in the study were subjects who underwent thyroid blood tests, without prior thyroid disease, consulting their general practitioner in 2000-2009 in Copenhagen, Denmark. All-cause mortality, MACEs, and cause-specific events identified in nationwide registries were measured. A total of 47 327 (8.4%) deaths occurred among 563 700 included subjects [mean age 48.6 (SD ± 18.2) y; 39% males]. All-cause mortality was increased in overt and subclinical hyperthyroidism [age adjusted incidence rates of 16 and 15 per 1000 person-years, respectively; incidence rate ratios (IRRs) 1.25 [95% confidence interval (CI) 1.15-1.36] and 1.23 (95% CI 1.16-1.30)] compared with euthyroid (incidence rate of 12 per 1000 person-years). Risk of MACEs was elevated in overt and subclinical hyperthyroidism [IRRs 1.16 (95% CI 1.05-1.27) and 1.09 (95% CI 1.02-1.16)] driven by heart failure [IRRs 1.14 (95% CI 0.99-1.32) and 1.20 (95% CI 1.10-1.31)]. A reduction of all-cause mortality was observed in subclinical hypothyroidism with TSH of 5-10 mIU/L [IRR 0.92 (95% CI 0.86-0.98)]. Heart failure is the leading cause of an increased cardiovascular mortality in both overt and subclinical hyperthyroidism. Subclinical hypothyroidism with TSH 5-10 mIU/L might be associated with a lower risk of all-cause mortality.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                April 2019
                13 March 2019
                : 8
                : 4
                : 398-406
                Affiliations
                [1 ]Institute of Endocrinology , Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
                [2 ]Sackler Faculty of Medicine , Tel Aviv University, Tel Aviv, Israel
                [3 ]School of Public Health , Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
                [4 ]Community Division , Clalit Health Services, Tel Aviv, Israel
                [5 ]The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes , National Center for Childhood Diabetes, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel
                [6 ]Department of Cardiology , Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
                [7 ]National Cancer Registry , Israel Center for Disease Control, Ministry of Health, Israel, Ramat Gan, Israel
                Author notes
                Correspondence should be addressed to E Izkhakov: elenaiz@ 123456tlvmc.gov.il

                *(E Izkhakov and J Meyerovitch contributed equally to this work)

                Article
                EC-19-0038
                10.1530/EC-19-0038
                6454303
                30865929
                fdc1c384-2321-42d9-a76f-b76763e4d953
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 26 February 2019
                : 13 March 2019
                Categories
                Research

                thyroid carcinoma,cardiovascular morbidity,cerebrovascular morbidity,hyperlipidemia,hypertension

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