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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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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.
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Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis.
Chaker, L, Baumgartner, C, den Elzen, WP, Collet, TH, Ikram, MA, Blum, MR, Dehghan, A, Drechsler, C, Luben, RN, Portegies, ML, et al
The Journal of clinical endocrinology and metabolism. 2016;(11):4270-4282
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CONTEXT The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously. DESIGN AND SETTING We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T4, and stroke outcomes were included, and we collected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L. RESULTS We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age- and sex-adjusted pooled hazard ratio for TSH was 0.78 (95% confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95% CI 0.62-1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95% CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95% CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes. CONCLUSION Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.
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Recombinant human thyrotropin before (131)I therapy in patients with nodular goitre: a meta-analysis of randomized controlled trials.
Lee, YY, Tam, KW, Lin, YM, Leu, WJ, Chang, JC, Hsiao, CL, Hsu, MT, Hsieh, AT
Clinical endocrinology. 2015;(5):702-10
Abstract
BACKGROUND Recombinant human thyrotropin (rhTSH) can be used to enhance radioiodine therapy for shrinking multinodular goitre. The aim of this meta-analysis was to compare the effectiveness of rhTSH pretreatment and radioiodine therapy with that of radioiodine alone for treating benign nodular goitre. METHODS The PubMed, EMBASE, Cochrane Library, Scopus and ClinicalTrials.gov databases were searched to identify studies published before September 2014. A meta-analysis was performed to calculate the pooled effect size using random-effects models. The primary outcome was the reduction in thyroid volume. Secondary outcomes included thyroid function, extent of tracheal compression, radioactive iodine uptake, incidence of hypothyroidism and other complications. RESULTS Nine RCTs including 416 patients were selected. The reductions in thyroid volume were significantly greater in the rhTSH pretreatment groups than those in the radioiodine alone groups at 12 months (weighted mean difference: 14·42%; 95% CI: 4·51-24·34% in high-dose rhTSH vs radioiodine alone; weighted mean difference: 19·66%; 95% CI: 3·67-35·65% in low-dose rhTSH vs radioiodine alone). The incidence of hypothyroidism in the high-dose rhTSH groups was significantly higher than that in the radioiodine alone groups. No significant difference in the incidence of hypothyroidism occurred between the low-dose rhTSH groups and the radioiodine alone groups. CONCLUSIONS The overall results indicated that using rhTSH before radioiodine therapy resulted in a greater thyroid volume reduction than radioiodine therapy alone. An increased incidence of hypothyroidism was observed in patients receiving high-dose rhTSH. Low-dose rhTSH before radioiodine therapy is more efficacious than radioiodine therapy alone for treating nontoxic benign thyroid nodules.
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Recombinant human thyrotropin versus thyroid hormone withdrawal in radioiodine remnant ablation for differentiated thyroid cancer: a meta-analysis.
Fu, H, Ma, C, Tang, L, Wu, F, Liu, B, Wang, H
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... 2015;(1):121-8
Abstract
AIM: We aim to assess the effects of recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal (THW), and rhTSH-aided low doses (1.11 GBq and 1.85 GBq) versus high dose (3.7 GBq) of radioiodine in the residual ablation for differentiated thyroid cancer (DTC). METHODS Studies were obtained from computerized searches of MEDLINE, EMBASE, the Cochrane Library (all until September 2012). Randomized controlled trials were included. RESULTS Altogether 1325 patients with DTC participated in seven trials for residual ablation. Overall, studies had a low risk of bias. We found no statistically significant differences between rhTSH and THW treatment in terms of successful ablation rate (OR 0.87, 95% CI 0.56 to 1.37, P=0.56) but significant benefits in health-related quality of life (mean difference 3.59, 95% CI 2.81 to 4.37, P<0.00001), adverse events during and after ablation (OR 0.57, 95% CI 0.44 to 0.73, P<0.00001), radiation exposure to blood and bone marrow (mean difference -0.01, 95% CI -0.02 to -0.01, P<0.00001). In addition, no significant difference was found in the successful ablation rate between the low dose (1.11 GBq and 1.85 GBq) and high dose (3.7 GBq) of radioiodine aided by rhTSH (OR 0.85, 95% CI 0.49 to 1.47, P=0.56). There were no deaths and no serious adverse effects in DTC patients treated with either rhTSH or THW, maximum follow-up was 12 months. None of the included trials investigated secondary malignancies or economic outcomes. CONCLUSION rhTSH is as effective as THW on radioiodine thyroid remnant ablation with significant benefits on health-related quality of life, adverse effects during and after ablation, decreased whole body radiation exposure. The lower radioiodine doses are as effective as high doses for remnant ablation under rhTSH stimulation.
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Systematic review using meta-analyses to estimate dose-response relationships between iodine intake and biomarkers of iodine status in different population groups.
Ristić-Medić, D, Dullemeijer, C, Tepsić, J, Petrović-Oggiano, G, Popović, T, Arsić, A, Glibetić, M, Souverein, OW, Collings, R, Cavelaars, A, et al
Nutrition reviews. 2014;(3):143-61
Abstract
The objective of this systematic review was to identify studies investigating iodine intake and biomarkers of iodine status, to assess the data of the selected studies, and to estimate dose-response relationships using meta-analysis. All randomized controlled trials, prospective cohort studies, nested case-control studies, and cross-sectional studies that supplied or measured dietary iodine and measured iodine biomarkers were included. The overall pooled regression coefficient (β) and the standard error of β were calculated by random-effects meta-analysis on a double-log scale, using the calculated intake-status regression coefficient (β) for each individual study. The results of pooled randomized controlled trials indicated that the doubling of dietary iodine intake increased urinary iodine concentrations by 14% in children and adolescents, by 57% in adults and the elderly, and by 81% in pregnant women. The dose-response relationship between iodine intake and biomarkers of iodine status indicated a 12% decrease in thyroid-stimulating hormone and a 31% decrease in thyroglobulin in pregnant women. The model of dose-response quantification used to describe the relationship between iodine intake and biomarkers of iodine status may be useful for providing complementary evidence to support recommendations for iodine intake in different population groups.