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Reference Intervals for Serum Thyroid-Stimulating Hormone Based on a Recent Nationwide Cross-Sectional Study and Meta-Analysis.
Wang, X, Li, Y, Zhai, X, Wang, H, Zhang, F, Gao, X, Liu, S, Teng, W, Shan, Z
Frontiers in endocrinology. 2021;:660277
Abstract
OBJECTIVE The aim of our study was to compare the reference intervals (RIs) [median (2.5th-97.5th percentiles)] for thyroid-stimulating hormone (TSH) between subgroups stratified by ethnicity and iodine status in a global context. DESIGN AND METHODS Primary data were derived from a recently published cross-sectional study in mainland China. Secondary data were obtained from online databases. The RIs for TSH were calculated in the reference population according to the National Academy of Clinical Biochemistry (NACB) standard and in the disease-free population. A meta-analysis of ethnicity- and iodine status-specific TSH RIs was performed. RESULTS The primary data showed that the TSH RI (mU/L) in the disease-free population was 2.33 (0.67, 7.87), which is wider than the published RI [2.28 (0.74, 7.04)] in the reference population. The meta-analysis showed that whether in the reference or disease-free population, the RIs in Yellows were much higher than those in Caucasians. In the reference population, the median and 2.5th percentile in the iodine-sufficient subgroup were both lower than the iodine-deficient or more-than-adequate subgroup, while the 97.5th percentile showed a positive trend with increasing sufficiency of iodine. However, in the disease-free population, the iodine-sufficient subgroup had a lower median and 97.5th percentile but higher 2.5th percentile than the iodine-deficient subgroup. CONCLUSION Yellows have a higher TSH RI than Caucasians. In the reference population, both the median and 2.5th percentile TSH in the iodine-sufficient population were the lowest among the different iodine status subgroups, while the 97.5th percentile of TSH showed an upward trend with increasing iodine sufficiency.
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The Relationship between High Iodine Consumption and Levels of Autoimmune Thyroiditis-Related Biomarkers in a Chinese Population: a Meta-Analysis.
Wan, S, Jin, B, Ren, B, Qu, M, Wu, H, Liu, L, Boah, M, Shen, H
Biological trace element research. 2020;(2):410-418
Abstract
To comprehensively evaluate the relationship between high iodine concentration and biomarker abnormalities related to autoimmune thyroiditis in a Chinese population. Medline, PubMed, and Embase electronic databases were searched for articles published domestically and internationally on the relationship between high iodine concentrations and thyroid hormone antibodies and thyroid-stimulating hormone in China before March 2019. Articles published in Chinese were searched in the China Biology Medicine (CBM) disc, Wanfang Database, and China National Knowledge Infrastructure (CNKI). A total of 16 cross-sectional articles were included in this study, including 9061 participants. A meta-analysis was conducted in Stata 14.0. The binary categorical and continuous variables used odds ratios (ORs) and standardized mean differences (SMDs) with the corresponding 95% confidence intervals (CIs) as the effect statistics, respectively. The results showed that high iodine concentrations had a minimal association with the abnormal rates of thyroid peroxidase antibody (TPOAb) (OR = 1.274, 95% CI (0.957, 1.695), P > 0.05) and thyroglobulin antibody (TGAb) (OR = 1.217, 95% CI (0.911, 1.626), P > 0.05) in the entire population. The thyroid-stimulating hormone (TSH) level in the high iodine group was greater than that in the adaptive iodine group (SMD = 0.202, 95% CI (0.096, 0.309), P < 0.05). The results of the subgroup analysis showed that the abnormal TPOAb rate in pregnant women (OR = 1.519, 95% CI (1.007, 2.291), P < 0.05) and children (OR = 3.365, 95% CI (1.966, 5.672), P < 0.05) in the high iodine group was greater than that in the adaptive iodine group, and the abnormal TGAb rate of children in the high iodine group was greater than that in the adaptive iodine group. The TSH levels of lactating women (SMD = 0.24, 95% CI (0.053, 0.427), P < 0.05), pregnant women (SMD = 0.301, 95% CI (0.176, 0.426), P < 0.05), and children (SMD = 0.25, 95% CI(0.096, 0.309), P < 0.05) in the high iodine group were higher than those in the adaptive iodine group. Egger's and Begg's tests showed no significant (P > 0.1) publication bias. High iodine can increase the risk of abnormal levels of TPOAb, TGAb, and TSH related to autoimmune thyroiditis in pregnant women, lactating women, and children in China.
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The Two Faces of Janus: Why Thyrotropin as a Cardiovascular Risk Factor May Be an Ambiguous Target.
Dietrich, JW, Hoermann, R, Midgley, JEM, Bergen, F, Müller, P
Frontiers in endocrinology. 2020;:542710
Abstract
Elevated concentrations of free thyroid hormones are established cardiovascular risk factors, but the association of thyrotropin (TSH) levels to hard endpoints is less clear. This may, at least in part, ensue from the fact that TSH secretion depends not only on the supply with thyroid hormones but on multiple confounders including genetic traits, medication and allostatic load. Especially psychosocial stress is a still underappreciated factor that is able to adjust the set point of thyroid function. In order to improve our understanding of thyroid allostasis, we undertook a systematic meta-analysis of published studies on thyroid function in post-traumatic stress disorder (PTSD). Studies were identified via MEDLINE/PubMed search and available references, and eligible were reports that included TSH or free thyroid hormone measurements in subjects with and without PTSD. Additionally, we re-analyzed data from the NHANES 2007/2008 cohort for a potential correlation of allostatic load and thyroid homeostasis. The available evidence from 13 included studies and 3386 euthyroid subjects supports a strong association of both PTSD and allostatic load to markers of thyroid function. Therefore, psychosocial stress may contribute to cardiovascular risk via an increased set point of thyroid homeostasis, so that TSH concentrations may be increased for reasons other than subclinical hypothyroidism. This provides a strong perspective for a previously understudied psychoendocrine axis, and future studies should address this connection by incorporating indices of allostatic load, peripheral thyroid hormones and calculated parameters of thyroid homeostasis.
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Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials.
Xu, C, Wang, P, Miao, H, Xie, T, Zhou, X, Zhang, Q, Jiang, S, Zhang, R, Liao, L, Dong, J
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2020;(12):841-849
Abstract
A potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.
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Association of Thyroid Function Genetic Predictors With Atrial Fibrillation: A Phenome-Wide Association Study and Inverse-Variance Weighted Average Meta-analysis.
Salem, JE, Shoemaker, MB, Bastarache, L, Shaffer, CM, Glazer, AM, Kroncke, B, Wells, QS, Shi, M, Straub, P, Jarvik, GP, et al
JAMA cardiology. 2019;(2):136-143
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Abstract
IMPORTANCE Thyroid hormone levels are tightly regulated through feedback inhibition by thyrotropin, produced by the pituitary gland. Hyperthyroidism is overwhelmingly due to thyroid disorders and is well recognized to contribute to a wide spectrum of cardiovascular morbidity, particularly the increasingly common arrhythmia atrial fibrillation (AF). OBJECTIVE To determine the association between genetically determined thyrotropin levels and AF. DESIGN, SETTING, AND PARTICIPANTS This phenome-wide association study scanned 1318 phenotypes associated with a polygenic predictor of thyrotropin levels identified by a previously published genome-wide association study that included participants of European ancestry. North American individuals of European ancestry with longitudinal electronic health records were analyzed from May 2008 to November 2016. Analysis began March 2018. MAIN OUTCOMES AND MEASURES Clinical diagnoses associated with a polygenic predictor of thyrotropin levels. EXPOSURES Genetically determined thyrotropin levels. RESULTS Of 37 154 individuals, 19 330 (52%) were men. The thyrotropin polygenic predictor was positively associated with hypothyroidism (odds ratio [OR], 1.10; 95% CI, 1.07-1.14; P = 5 × 10-11) and inversely associated with diagnoses related to hyperthyroidism (OR, 0.64; 95% CI, 0.54-0.74; P = 2 × 10-8 for toxic multinodular goiter). Among nonthyroid associations, the top association was AF/flutter (OR, 0.93; 95% CI, 0.9-0.95; P = 9 × 10-7). When the analyses were repeated excluding 9801 individuals with any diagnoses of a thyroid-related disease, the AF association persisted (OR, 0.91; 95% CI, 0.88-0.95; P = 2.9 × 10-6). To replicate this association, we conducted an inverse-variance weighted average meta-analysis using AF single-nucleotide variant weights from a genome-wide association study of 17 931 AF cases and 115 142 controls. As in the discovery analyses, each SD increase in predicted thyrotropin was associated with a decreased risk of AF (OR, 0.86; 95% CI, 0.79-0.93; P = 4.7 × 10-4). In a set of AF cases (n = 745) and controls (n = 1680) older than 55 years, directly measured thyrotropin levels that fell within the normal range were inversely associated with AF risk (OR, 0.91; 95% CI, 0.83-0.99; P = .04). CONCLUSIONS AND RELEVANCE This study suggests a role for genetically determined variation in thyroid function within a physiologically accepted normal range as a risk factor for AF. The clinical decision to treat subclinical thyroid disease should incorporate the risk for AF as antithyroid medications to treat hyperthyroidism may reduce AF risk and thyroid hormone replacement for hypothyroidism may increase AF risk.
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Thyroid-stimulating hormone levels in the normal range and incident type 2 diabetes mellitus.
de Vries, TI, Kappelle, LJ, van der Graaf, Y, de Valk, HW, de Borst, GJ, Nathoe, HM, Visseren, FLJ, Westerink, J, ,
Acta diabetologica. 2019;(4):431-440
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Abstract
AIM: To evaluate the relationship between thyroid-stimulating hormone (TSH) levels within the normal range and the risk of type 2 diabetes mellitus (T2DM) in a cohort of patients at high cardiovascular risk, and to perform a systematic review and meta-analysis of previous studies. METHODS We included 5542 patients without T2DM from the prospective Secondary Manifestations of ARTerial disease study with TSH levels between 0.35 and 5.0 mIU/L without anti-thyroid medication or thyroid-hormone replacement therapy. Cox regression was used to investigate the relationship between baseline plasma TSH levels and incident T2DM. MEDLINE, EMBASE, and Cochrane were searched for prospective cohorts assessing TSH and incident T2DM. Hazard ratios (HR) from included prospective cohort studies were pooled using a random-effects model. RESULTS In patients at high cardiovascular risk, higher plasma TSH levels in the normal range were not associated [HR 1.07 per mIU/L increase in TSH (95% confidence interval (95% CI) 0.95-1.22)] with an increased risk of T2DM, adjusted for age, sex, smoking, total and HDL cholesterol, and triglycerides. In the meta-analysis involving three prospective cohort studies, including the present study, including 29,791 participants with 1930 incident events, there was no relation between plasma TSH levels in the normal range and incident T2DM [pooled HR 1.06 (95% CI 0.99-1.14)]. CONCLUSION There is no apparent relation between plasma TSH levels in the normal range and incident T2DM in patients at high cardiovascular risk.