Trends, determinants, and associations of treated hypothyroidism in the United Kingdom, 2005-2014

Background: Recent reports suggest that prescriptions for thyroid hormones have increased. Recent trends in and determinants of the prevalence of treated hypothyroidism across the United Kingdom were therefore analyzed. Methods: Data covering the whole of the United Kingdom held by the National Health Service and the Office of National Statistics were examined. The main outcome measured was trends in the prevalence of treated hypothyroidism between 2005 and 2014. In addition, linear trend forecasting was performed to estimate projected trends in the prevalence of treated hypothyroidism up to the year 2025. Furthermore, determinants of variation of treated hypothyroidism prevalence across each of the 237 health areas in the United Kingdom in 2014 and its association with other health conditions were explored by multivariate linear regression analyses. Results: The prevalence of treated hypothyroidism increased from 2.3% (1.4 million) to 3.5% (2.2 million) of the total British population between the years 2005 and 2014 and is projected to rise further to 4.2% (2.9 million) by 2025. There was large geographical variation of treated hypothyroidism across the United Kingdom, with London having the lowest (1.4%) and the Western Isles of Scotland having the highest (6.3%) prevalence. This variation was attenuated, but did not completely disappear, after some potential determinants were accounted for. The prevalence of treated hypothyroidism was independently related to health areas, with a higher proportion of individuals who were female, white, and obese, and negatively associated with prevalent cigarette smoking. The prevalence of treated hypothyroidism was significantly associated with the frequency of prevalent atrial fibrillation but not with other major health conditions, including ischemic heart disease and osteoporosis. Conclusions: Between 2005 and 2014, the prevalence of treated hypothyroidism increased across the United Kingdom, has wide geographical variation, and is likely to increase further for the foreseeable future. Clinical effects and cost-effectiveness of the trend in increasing treatment of hypothyroidism remains to be evaluated

Iodine supplementation: compliance and association with adverse obstetric and neonatal outcomes

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/34981750/Objectives: Over 1.9 billion people worldwide are living in areas estimated to be iodine insufficient. Strategies for iodine supplementation include campaigns targeting vulnerable groups, such as women in pre-conception, pregnancy and lactation. Portuguese women of childbearing age and pregnant women were shown to be mildly-to-moderately iodine deficient. As a response, in 2013, the National Health Authority (NHA) issued a recommendation that all women considering pregnancy, pregnant or breastfeeding, take a daily supplement of 150-200 μg iodine. This study explored how the iodine supplementation recommendation has been fulfilled among pregnant and lactating women in Portugal, and whether the reported iodine supplements intake impacted on adverse obstetric and neonatal outcomes. Design and methods: Observational retrospective study on pregnant women who delivered or had a fetal loss in the Braga Hospital and had their pregnancies followed in Family Health Units. Results: The use of iodine supplements increased from 25% before the recommendation to 81% after the recommendation. This was mostly due to an increase in the use of supplements containing iodine only. Iodine supplementation was protective for the number of adverse obstetric outcomes (odds ratio (OR) = 0.791, P = 0.018) and for neonatal morbidities (OR = 0.528, P = 0.024) after controlling for relevant confounding variables. Conclusion: The recommendation seems to have succeeded in implementing iodine supplementation during pregnancy. National prospective studies are now needed to evaluate the impact of iodine supplementation on maternal thyroid homeostasis and offspring psychomotor development and on whether the time of the beginning of iodine supplementation (how early during preconception or pregnancy) is relevant to consider.This work has been funded by National funds, through the Foundation for Science and Technology (FCT) – project UIDB/50026/2020 and UIDP/50026/2020 and by the project NORTE-01-0145-FEDER-000039, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Funding agencies did not participate in any part of the research or in data or manuscript preparationinfo:eu-repo/semantics/publishedVersio

Genetic determinants of thyroid function in children

Objective Genome-wide association studies in adults have identified 42 loci associated with thyroid stimulating hormone (TSH) and 21 loci associated with free thyroxine (FT4) concentrations. While biologically plausible, age-dependent effects have not been assessed. We aimed to study the association of previously identified genetic determinants of TSH and FT4 with TSH and FT4 concentrations in newborns and (pre)school children. Methods We selected participants from three population-based prospective cohorts with data on genetic variants and thyroid function: Generation R (N = 2169 children, mean age 6 years; N = 2388 neonates, the Netherlands), the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3382, age 7.5 years, United Kingdom), and the Brisbane Longitudinal Twin Study (BLTS; N = 1680, age 12.1 years, Australia). The association of single nucleotide polymorphisms (SNPs) with TSH and FT4 concentrations was studied with multivariable linear regression models. Weighted polygenic risk scores (PRSs) were defined to combine SNP effects. Results In childhood, 30/60 SNPs were associated with TSH and 11/31 SNPs with FT4 after multiple testing correction. The effect sizes for AADAT, GLIS3, TM4SF4, and VEGFA were notably larger than in adults. The TSH PRS explained 5.3%-8.4% of the variability in TSH concentrations; the FT4 PRS explained 1.5%-4.2% of the variability in FT4 concentrations. Five TSH SNPs and no FT4 SNPs were associated with thyroid function in neonates. Conclusions The effects of many known thyroid function SNPs are already apparent in childhood and some might be notably larger in children as compared to adults. These findings provide new knowledge about genetic regulation of thyroid function in early life

Association of urinary bisphenols and triclosan with thyroid function during early pregnancy

© 2019 The Authors. Background Bisphenols and triclosan are considered as potential thyroid disruptors. While mild alterations in maternal thyroid function can result in adverse pregnancy and child developmental outcomes, there is still uncertainty whether bisphenols or triclosan can interfere with thyroid function during pregnancy. Objectives We aimed to investigate the association of urinary bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF) and triclosan with early pregnancy thyroid function. Methods This study was embedded in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA), a population-based prospective pregnancy cohort. In total, 1996 participants were included in the current study. Maternal urinary concentrations of three bisphenols and triclosan, collected at median (95% range) 10 (6–14) weeks of pregnancy as well as serum concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were measured. Results Higher BPA levels were associated with lower TT4 concentrations (non-monotonic, P = 0.03), a lower FT4/FT3 ratio (β [SE] -0.02 [0.01], P = 0.03) and a lower TT4/TT3 ratio (β [SE] -0.73 [0.27], P = 0.008). Higher BPF levels were associated with a higher FT3 (β [SE] 0.01 [0.007], P = 0.04). There were no associations between other bisphenols or triclosan and absolute TSH, (F)T4 or (F)T3 concentrations. The association of BPA with thyroid function differed with gestational age. The negative association of BPA with FT4/FT3 and TT4/TT3 ratios was only apparent in early but not late gestation (P for interaction: 0.003, 0.008, respectively). Conclusion These human data during pregnancy substantiate experimental findings suggesting that BPA could potentially affect thyroid function and deiodinase activities in early gestation.European Union of Medical Specialists; European Union's Horizon 2020 Programme for research; echnological development and demonstration; Swedish Research Council; County Council of Värmland, Swede

Risk factors for thyroid dysfunction in pregnancy: an individual participant data meta-analysis

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction

Euthyroid Thyroperoxidase Antibody Positivity during Pregnancy, to Treat or Not to Treat?

Thyroperoxidase antibody (TPOAb) positivity is a well-known risk factor for thyroid dysfunction during pregnancy and is associated with a suboptimal response to thyroidal stimulation by human chorionic gonadotropin. About 75% of TPOAb positive women are euthyroid and there seems to be a higher risk of predominantly miscarriage and preterm birth in this subgroup. Nonetheless, clinical decision making with regards to gestational levothyroxine treatment remains difficult due to a lack of large randomized trials. Future studies assessing dose-dependent associations and additional biomarkers that can distinguish low-risk from high-risk individuals will be key in disentangling the crude clinical data