Article type
Year
Abstract
Objective: To estimate mortality from all causes in patients with subclinical hyper- or hypothyroidism compared with euthyroid control individuals.
Methods: Data Sources: We searched for English and non-English articles using MEDLINE (Ovid and PubMed) and EMBASE.com, with the last computerized search undertaken in April 2007. The search terms included 'subclinical hyperthyroidism', 'subclinical hypothyroidism', 'mortality', and 'survival'. The computerized search was supplemented by a manual search of the bibliographies of all retrieved articles. Study Selection: We included longitudinal (cohort) studies published in full that reported data on mortality from all causes in patients with subclinical hyper- and/or hypothyroidism vs. euthyroid controls. Studies were required to define thyroid status unequivocally as a subclinical hyper- or hypothyroidism, and to report (or provide information allowing to compute) a hazard ratio for death from all causes with a 95% confidence interval. If a particular patient population was reported in more than 1 publication, we selected the article that provided the most complete data set. Reviews, case-control studies, uncontrolled studies, studies in which mortality from all causes was not reported as a separate outcome, and studies in which patients had any ongoing thyroid illness other than subclinical hyper- or hypothyroidism were excluded. Data Extraction: Independent extraction by 3 authors using predefined data fields, including potential sources of heterogeneity.
Data Synthesis: From the eligible studies, the (log) hazard ratio (HR) and its standard error were retrieved as reported in each study, or they were calculated from the original data. The log hazard ratio and its standard error were calculated directly if the observed and the expected number of events were available for the group with thyroid dysfunction and the control group; indirectly, if the p-value for the logrank, Mantel-Haenszel, or chi-squared test were reported; or graphically, based on the published survival curves, if insufficient information was available for direct or indirect estimation. All pooled analyses were based on random effects models. Two meta-analyses were conducted: one compared subclinical hyperthyroid patients vs. euthyroid controls, the other compared subclinical hypothyroid patients vs. euthyroid controls. Based on 5 cohorts involving 185 patients with subclinical hyperthyroidism the pooled hazard ratio (HR) for all-cause mortality was 1.83 (95% confidence interval [CI], 1.39-2.41; P<.0001). No significant heterogeneity was demonstrated between these 5 cohort studies (Q test P=0.35; I²=10%). For the 7 cohorts involving 1317 patients with subclinical hypothyroidism, the pooled HR for all-cause mortality was 1.07 (95% CI, 0.82-1.39; P=.63). Significant heterogeneity among cohorts was observed (Q test P=.01; I²=64%), which disappeared after pooling cohorts in subgroups according to geographic region, separately. In doing so, the pooled HR for all cause mortality was 0.84 in Europe (95% CI, 0.68-1.03; P=.09), 1.14 in the Americas (95% CI, 0.89-1.45; P=.29), and 1.64 (95% CI, 2.20-1.39; P=.001) in the Western Pacific region.
Conclusions: Patients with subclinical hyperthyroidism demonstrate a significant 83% increase in mortality from all causes vs. euthyroid control individuals. For patients with subclinical hypothyroidism, on the other hand, the relative risk of mortality from all causes is increased in the Western Pacific region only.
Methods: Data Sources: We searched for English and non-English articles using MEDLINE (Ovid and PubMed) and EMBASE.com, with the last computerized search undertaken in April 2007. The search terms included 'subclinical hyperthyroidism', 'subclinical hypothyroidism', 'mortality', and 'survival'. The computerized search was supplemented by a manual search of the bibliographies of all retrieved articles. Study Selection: We included longitudinal (cohort) studies published in full that reported data on mortality from all causes in patients with subclinical hyper- and/or hypothyroidism vs. euthyroid controls. Studies were required to define thyroid status unequivocally as a subclinical hyper- or hypothyroidism, and to report (or provide information allowing to compute) a hazard ratio for death from all causes with a 95% confidence interval. If a particular patient population was reported in more than 1 publication, we selected the article that provided the most complete data set. Reviews, case-control studies, uncontrolled studies, studies in which mortality from all causes was not reported as a separate outcome, and studies in which patients had any ongoing thyroid illness other than subclinical hyper- or hypothyroidism were excluded. Data Extraction: Independent extraction by 3 authors using predefined data fields, including potential sources of heterogeneity.
Data Synthesis: From the eligible studies, the (log) hazard ratio (HR) and its standard error were retrieved as reported in each study, or they were calculated from the original data. The log hazard ratio and its standard error were calculated directly if the observed and the expected number of events were available for the group with thyroid dysfunction and the control group; indirectly, if the p-value for the logrank, Mantel-Haenszel, or chi-squared test were reported; or graphically, based on the published survival curves, if insufficient information was available for direct or indirect estimation. All pooled analyses were based on random effects models. Two meta-analyses were conducted: one compared subclinical hyperthyroid patients vs. euthyroid controls, the other compared subclinical hypothyroid patients vs. euthyroid controls. Based on 5 cohorts involving 185 patients with subclinical hyperthyroidism the pooled hazard ratio (HR) for all-cause mortality was 1.83 (95% confidence interval [CI], 1.39-2.41; P<.0001). No significant heterogeneity was demonstrated between these 5 cohort studies (Q test P=0.35; I²=10%). For the 7 cohorts involving 1317 patients with subclinical hypothyroidism, the pooled HR for all-cause mortality was 1.07 (95% CI, 0.82-1.39; P=.63). Significant heterogeneity among cohorts was observed (Q test P=.01; I²=64%), which disappeared after pooling cohorts in subgroups according to geographic region, separately. In doing so, the pooled HR for all cause mortality was 0.84 in Europe (95% CI, 0.68-1.03; P=.09), 1.14 in the Americas (95% CI, 0.89-1.45; P=.29), and 1.64 (95% CI, 2.20-1.39; P=.001) in the Western Pacific region.
Conclusions: Patients with subclinical hyperthyroidism demonstrate a significant 83% increase in mortality from all causes vs. euthyroid control individuals. For patients with subclinical hypothyroidism, on the other hand, the relative risk of mortality from all causes is increased in the Western Pacific region only.