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Thyroid Function and the Risk of Fibrosis of the Liver, Heart, and Lung in Humans: A Systematic Review and Meta-Analysis.
Bano, A, Chaker, L, Muka, T, Mattace-Raso, FUS, Bally, L, Franco, OH, Peeters, RP, Razvi, S
Thyroid : official journal of the American Thyroid Association. 2020;(6):806-820
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Abstract
Background: Fibrotic diseases have an unclear etiology and poor prognosis. Fluctuations in thyroid function may play a role in the development of fibrosis, but evidence is fragmented and inconclusive. This systematic review and meta-analysis aimed to investigate the association of thyroid function with fibrotic diseases of the liver, heart, and lung in humans. Methods: We searched PubMed, Medline Ovid, Embase Ovid, and Web-of-Science for studies published from inception to 14 June 2019, to identify observational studies that investigated the association of thyroid function with fibrosis of the liver, heart, and lung in humans. Study quality was evaluated by the Newcastle-Ottawa Scale. The Mantel-Haenszel method was used to pool the odds ratios (ORs) of studies investigating the association of hypothyroidism with liver fibrosis. Results: Of the 2196 identified articles, 18 studies were included in the systematic review, of which 11 studies reported on liver fibrosis, 4 on myocardial fibrosis, and 3 on pulmonary fibrosis. The population sample size ranged from 36 to 7259 subjects, with median mean age 51 years (range, 36-69) and median percentage of women 53 (range, 17-100). The risk of bias of studies was low to moderate to high. Higher serum thyrotropin and lower thyroid hormone levels were generally associated with higher likelihood of fibrosis. Compared with euthyroidism, overt and subclinical hypothyroidism was associated with a higher likelihood of fibrosis in the liver (six of seven studies), heart (three of three studies), and lung (three of three studies). Based on the results of the seven studies included in the meta-analysis, overt and subclinical hypothyroidism was associated with an increased risk of liver fibrosis (pooled OR, 2.81; 95% confidence interval [CI], 1.74-4.53; heterogeneity, I2 31.4%; pooled OR, 2.12; CI, 1.45-3.12; heterogeneity, I2 0%; respectively), without evidence of publication bias. Conclusions: This study suggests that low thyroid function is associated with increased likelihood of chronic fibrotic diseases of the liver, heart, and lung. However, the evidence is mainly based on cross-sectional data. Prospective studies and randomized clinical trials are needed to investigate the potential efficacy of thyroid hormone and its analogs on the occurrence and progression of fibrosis.
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Maternal Thyroid Function in Early Pregnancy and Child Attention-Deficit Hyperactivity Disorder: An Individual-Participant Meta-Analysis.
Levie, D, Korevaar, TIM, Mulder, TA, Bath, SC, Dineva, M, Lopez-Espinosa, MJ, Basterrechea, M, Santa-Marina, L, Rebagliato, M, Sunyer, J, et al
Thyroid : official journal of the American Thyroid Association. 2019;(9):1316-1326
Abstract
Background: Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (fT4) concentrations during the first 18 weeks of pregnancy with child attention-deficit hyperactivity disorder (ADHD). Methods: A total of 7669 mother-child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INfancia y Medio Ambiente (INMA; N = 1073, Spain), Generation R (N = 3812, The Netherlands), and Avon Longitudinal Study of Parents and Children (ALSPAC; N = 2784, United Kingdom). Exclusion criteria were multiple pregnancy, fertility treatment, usage of medication affecting the thyroid, and pre-existing thyroid disease. We used logistic regression models to study the association of maternal thyroid function with the primary outcome, ADHD, assessed via the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria by parents and/or teachers at a median child age of 4.5 to 7.6 years, and with the secondary outcome, an ADHD symptom score above the 90th percentile. Effect modification by gestational age and sex was tested with interaction terms and stratified analyses. Results: Overall, 233 (3%) children met the criteria for ADHD. When analyzed continuously, neither fT4 nor TSH was associated with a higher risk of ADHD (odds ratio [OR] 1.1, 95% confidence interval [CI 1.0-1.3], p = 0.060 and OR 0.9 [CI 0.9-1.1], p = 0.385, respectively) or with high symptom scores. When investigating effect modification by gestational age, a higher fT4 was associated with symptoms above the 90th percentile but only in the first trimester (for fT4 per 1 SD: OR 1.2 [CI 1.0-1.4], p = 0.027). However, these differential effects by gestational age were not consistent. No significant effect modification by sex was observed. Conclusions: We found no clear evidence of an association between maternal thyroid function and child ADHD.
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Association Between Diethylhexyl Phthalate Exposure and Thyroid Function: A Meta-Analysis.
Kim, MJ, Moon, S, Oh, BC, Jung, D, Choi, K, Park, YJ
Thyroid : official journal of the American Thyroid Association. 2019;(2):183-192
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BACKGROUND Diethylhexyl phthalate (DEHP) is widely used in industrial products, particularly as plasticizers and softeners. Because it is used extensively, DEHP has been detected in humans worldwide. Although epidemiological studies suggest that DEHP can disrupt the function of the hypothalamic-pituitary-thyroid (HPT) axis, evidence on the association between DEHP exposure and thyroid function remains inconclusive. Therefore, a comprehensive meta-analysis was performed to investigate the association between DEHP exposure and the HPT axis in humans. METHODS A literature search of the MEDLINE, EMBASE, and Web of Science databases was conducted to search for studies in which the correlation coefficient values or regression coefficient values between three major DEHP metabolites (i.e., monoethylhexyl phthalate [MEHP], mono [2-ethyl-5-hydroxyhexyl] phthalate [MEHHP], and mono [2-ethyl-5-oxohexyl] phthalate) and thyrotropin, free thyroxine (T4), or total T4 were determined. The association between DEHPs and thyroid hormone levels were evaluated using Pearson's correlation coefficients. RESULTS Thirteen eligible articles were included. Urinary MEHP and MEHHP concentration was negatively correlated with total T4. Pooled correlation coefficients between MEHP/MEHHP and total T4 were -0.02 [confidence interval (CI) -0.05 to 0.00] and -0.03 [CI -0.05 to -0.01], respectively. Urinary mono (2-ethyl-5-oxohexyl) phthalate concentration was positively correlated with thyrotropin, and the pooled correlation coefficient was 0.02 [CI 0.00-0.04]. CONCLUSIONS The findings of this meta-analysis suggest a significant association between the exposure of DEHP metabolites and the function of the HPT axis.
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Thyroid Function and Dysfunction in Relation to 16 Cardiovascular Diseases.
Larsson, SC, Allara, E, Mason, AM, Michaëlsson, K, Burgess, S
Circulation. Genomic and precision medicine. 2019;(3):e002468
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BACKGROUND Subclinical thyroid dysfunction, defined as thyroid-stimulating hormone levels outside the reference range with normal free thyroxine levels in asymptomatic patients, is associated with alterations in cardiac hemodynamics. We used Mendelian randomization to assess the role of thyroid dysfunction for cardiovascular disease (CVD). METHODS Single-nucleotide polymorphisms associated with thyroid function were identified from a genome-wide association meta-analysis in up to 72 167 individuals. Data for genetic associations with CVD were obtained from meta-analyses of genome-wide association studies of atrial fibrillation (n=537 409 individuals), coronary artery disease (n=184 305 individuals), and ischemic stroke (n=438 847) as well as from the UK Biobank (n=367 703 individuals). RESULTS Genetically predicted thyroid-stimulating hormone levels and hyperthyroidism were statistically significantly associated with atrial fibrillation but no other CVDs at the Bonferroni-corrected level of significance ( P<7.8×10-4). The odds ratios of atrial fibrillation were 1.15 (95% CI, 1.11-1.19; P=2.4×10-14) per genetically predicted 1 SD decrease in thyroid-stimulating hormone levels and 1.05 (95% CI, 1.03-1.08; P=5.4×10-5) for genetic predisposition to hyperthyroidism. Genetically predicted free thyroxin levels were not statistically significantly associated with any CVD. CONCLUSIONS This Mendelian randomization study supports evidence for a causal association of decreased thyroid-stimulating hormone levels in the direction of a mild form of hyperthyroidism with an increased risk of atrial fibrillation but no other CVDs.
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Thyroid Function in Early Pregnancy, Child IQ, and Autistic Traits: A Meta-Analysis of Individual Participant Data.
Levie, D, Korevaar, TIM, Bath, SC, Dalmau-Bueno, A, Murcia, M, Espada, M, Dineva, M, Ibarluzea, JM, Sunyer, J, Tiemeier, H, et al
The Journal of clinical endocrinology and metabolism. 2018;(8):2967-2979
Abstract
CONTEXT Low maternal free T4 (FT4) has been associated with poor child neurodevelopment in some single-center studies. Evidence remains scarce for the potential adverse effects of high FT4 and whether associations differ in countries with different iodine status. OBJECTIVE To assess the association of maternal thyroid function in early pregnancy with child neurodevelopment in countries with a different iodine status. DESIGN, SETTING, AND PARTICIPANTS Meta-analysis of individual participant data from 9036 mother-child pairs from three prospective population-based birth cohorts: INMA [Infancia y Medio Ambiente (Environment and Childhood project) (Spain)], Generation R (Netherlands), and ALSPAC (Avon Longitudinal Study of Parents and Children, United Kingdom). The exclusion criteria were multiple pregnancies, fertility treatments, thyroid-interfering medication usage, and known thyroid disease. MAIN OUTCOMES Child nonverbal IQ at 5 to 8 years of age, verbal IQ at 1.5 to 8 years of age, and autistic traits within the clinical range at 5 to 8 years of age. RESULTS FT4 <2.5th percentile was associated with a 3.9-point (95% CI, -5.7 to -2.2) lower nonverbal IQ and a 2.1-point (95% CI, -4.0 to -0.1) lower verbal IQ. A suggestive association of hypothyroxinemia with a greater risk of autistic traits was observed. FT4 >97.5th percentile was associated with a 1.9-fold (95% CI, 1.0 to 3.4) greater risk of autistic traits. No independent associations were found with TSH. CONCLUSIONS Low maternal FT4 was consistently associated with a lower IQ across the cohorts. Further studies are needed to replicate the findings of autistic traits and investigate the potential modifying role of maternal iodine status. FT4 seems a reliable marker of fetal thyroid state in early pregnancy, regardless of the type of immunoassay.