Severe iodine deficiency during pregnancy has been associated with pregnancy/neonatal loss, and adverse pregnancy outcomes; however, the impact of mild-to-moderate iodine insufficiency, though ...prevalent in pregnancy, is not well-documented. We assessed whether mild iodine deficiency during pregnancy was associated with pregnancy/infant loss, or with other adverse pregnancy outcomes. We used samples and data from the Avon Longitudinal Study of Parents and Children (ALSPAC), from 3140 singleton pregnancies and from a further 42 women with pregnancy/infant loss. The group was classified as mildly-to-moderately iodine deficient with a median urinary iodine concentration of 95.3 µg/L (IQR 57.0-153.0; median urinary iodine-to-creatinine ratio (UI/Creat) 124 µg/g, IQR 82-198). The likelihood of pregnancy/infant loss was not different across four UI/Creat groups (<50, 50-149, 150-250, >250 µg/g). The incidence of pre-eclampsia, non-proteinuric gestational hypertension, gestational diabetes, glycosuria, anaemia, post-partum haemorrhage, preterm delivery, mode of delivery, being small for gestational age, and large for gestational age did not differ significantly among UI/Creat groups, nor were there any significant differences in the median UI/Creat. We conclude that maternal iodine status was not associated with adverse pregnancy outcomes in a mildly-to-moderately iodine-deficient pregnant population. However, in view of the low number of women with pregnancy/infant loss in our study, further research is required.
Summary
Normal physiological changes of pregnancy warrant the need to employ gestation specific reference ranges for the interpretation of thyroid function tests. Thyroid hormones play crucial roles ...in foetal growth and neurodevelopment which are dependent on adequate supply of maternal thyroid hormones from early gestation onwards. The prevention of significant adverse obstetric and neurodevelopmental outcomes from hypothyroidism requires a strategy of empirical levothyroxine dose increases and predictive dose adjustments in pregnancy combined with regular thyroid function testing, starting before pregnancy and until the postpartum period. Subclinical hypothyroidism has been associated with an increased risk of pregnancy loss and neurocognitive deficits in children, especially when diagnosed before or during early pregnancy. Whilst trials of levothyroxine replacement for mild hypothyroidism in pregnancy have not indicated definite evidence of improvements in these outcomes, professional guidelines recommend treatment, especially if evidence of underlying thyroid autoimmunity is present. Studies of isolated hypothyroxinaemia in pregnancy have shown conflicting evidence with regards to adverse obstetric and neurodevelopmental outcomes and no causative relationships have been determined. Treatment of this condition in pregnancy may be considered in those with underlying thyroid autoimmunity. Whilst the evidence for a link between the presence of anti‐TPO antibodies and increased risks of pregnancy loss and infertility is compelling, the results of ongoing randomized trials of levothyroxine in euthyroid women with underlying autoimmunity are currently awaited. Further studies to define the selection of women who require levothyroxine replacement and to determine the benefits of a predictive dose adjustment strategy are required.
Thyroid dysfunction is common in the general population, and mild or subclinical forms can be present in more than 10% of individuals aged >80 years. The diagnosis of abnormal thyroid hormone ...concentrations in people aged >60 years poses a challenge, as the clinical presentation of thyroid dysfunction is usually nonspecific, and ageing is associated with a number of physiological changes that can affect thyroid function test results. Furthermore, the presence of acute or chronic nonthyroidal illnesses and the use of medications that interfere with thyroid function tests are common confounders in the determination of thyroid status in the elderly. Early diagnosis and treatment of overt thyroid dysfunction is crucial in this population in view of the marked effects of abnormal circulating thyroid hormone levels on a number of organ systems, including the heart, the skeleton and the neurological system. The clinical significance of mild thyroid overactivity and underactivity remains uncertain, and the need for treatment of subclinical thyroid dysfunction is much debated. A number of large epidemiological studies have identified associations between mild thyroid dysfunction and short-term as well as long-term adverse outcomes, and a small but increasing number of randomized controlled intervention studies have been reported. Guidelines recommend treatment of thyroid dysfunction on the basis of the degree of abnormal serum TSH concentrations, patient age and associated comorbidities. This Review describes the current evidence on the prevalence, diagnosis, management and long-term consequences of thyroid dysfunction in the elderly.
Results from previous studies show that the cognitive ability of offspring might be irreversibly damaged as a result of their mother's mild iodine deficiency during pregnancy. A reduced intelligence ...quotient (IQ) score has broad economic and societal cost implications because intelligence affects wellbeing, income, and education outcomes. Although pregnancy and lactation lead to increased iodine needs, no UK recommendations for iodine supplementation have been issued to pregnant women. We aimed to investigate the cost-effectiveness of iodine supplementation versus no supplementation for pregnant women in a mildly to moderately iodine-deficient population for which a population-based iodine supplementation programme--for example, universal salt iodisation--did not exist.
We systematically searched MEDLINE, Embase, EconLit, and NHS EED for economic studies that linked IQ and income published in all languages until Aug 21, 2014. We took clinical data relating to iodine deficiency in pregnant women and the effect on IQ in their children aged 8-9 years from primary research. A decision tree was developed to compare the treatment strategies of iodine supplementation in tablet form with no iodine supplementation for pregnant women in the UK. Analyses were done from a health service perspective (analysis 1; taking direct health service costs into account) and societal perspective (analysis 2; taking education costs and the value of an IQ point itself into account), and presented in terms of cost (in sterling, relevant to 2013) per IQ point gained in the offspring. We made data-supported assumptions to complete these analyses, but used a conservative approach that limited the benefits of iodine supplementation and overestimated its potential harms.
Our systematic search identified 1361 published articles, of which eight were assessed to calculate the monetary value of an IQ point. A discounted lifetime value of an additional IQ point based on earnings was estimated to be £3297 (study estimates range from £1319 to £11,967) for the offspring cohort. Iodine supplementation was cost saving from both a health service perspective (saving £199 per pregnant woman sensitivity analysis range -£42 to £229) and societal perspective (saving £4476 per pregnant woman sensitivity analysis range £540 to £4495), with a net gain of 1·22 IQ points in each analysis. Base case results were robust to sensitivity analyses.
Iodine supplementation for pregnant women in the UK is potentially cost saving. This finding also has implications for the 1·88 billion people in the 32 countries with iodine deficiency worldwide. Valuation of IQ points should consider non-earnings benefits--eg, health benefits associated with a higher IQ not germane to earnings.
None.
Radioactive iodine (RAI) therapy is a critical component in the post-surgical management of thyroid cancer patients, as well as being a central therapeutic option in the treatment of hyperthyroidism. ...Previous work suggests that antithyroid drugs hinder the efficacy of RAI therapy in patients. However, the effects of other background medications on RAI treatment efficacy have not been evaluated. Therefore, we performed a systematic review and meta-analysis investigating the potential off-target effects of medication on RAI therapy in patients with thyroid cancer and hyperthyroidism.
Systematic review and meta-analysis according to the 2020 PRISMA guidelines. Databases searched: MEDLINE, EMBASE and Cochrane Library for studies published between 2001 and 2021.
Sixty-nine unique studies were identified. After screening, 17 studies with 3313 participants were included. One study investigated thyroid cancer, with the rest targeted to hyperthyroidism. The majority of studies evaluated the effects of antithyroid drugs; the other drugs studied included lithium, prednisone and glycididazole sodium. Antithyroid drugs were associated with negative impacts on post-RAI outcomes (n = 5 studies, RR = 0.81, p = 0.02). However, meta-analysis found moderate heterogeneity between studies (I2 = 51%, τ2 = 0.0199, p = 0.08). Interestingly, lithium (n = 3 studies), prednisone (n = 1 study) and glycididazole (n = 1 study) appeared to have positive impacts on post-RAI outcomes upon qualitative analysis.
Our systematic review strengthens previous work on antithyroid medication effects on RAI, and highlights that this field remains under researched especially for background medications unrelated to thyroid disease, with very few papers on non-thyroid medications published.
https://www.crd.york.ac.uk/prospero/display_record.php, identifier CRD42021274026.
IntroductionHyperthyroidism is a common condition affecting up to 3% of the UK population. Treatment improves symptoms and reduces the risk of atrial fibrillation and stroke that contribute to ...increased mortality. The most common symptom is weight loss, which is reversed during treatment. However, the weight regain may be excessive, contributing to increased risk of obesity. Current treatment options include antithyroid drugs, radioiodine and thyroidectomy. Whether there are differences in either weight change or the long-term cardiometabolic risk between the three treatments is unclear.Methods and analysisThe study will establish the natural history of weight change in hyperthyroidism, investigate the risk of obesity and risks of cardiometabolic conditions and death relative to the treatment. The data on patients diagnosed with hyperthyroidism between 1 January 1996 and 31 December 2015 will come from Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office of National Statistics Death Registry. The weight changes will be modelled using a flexible joint modelling, accounting for mortality. Obesity prevalence in the general population will be sourced from Health Survey for England and compared with the post-treatment prevalence of obesity in patients with hyperthyroidism. The incidence and time-to-event of major adverse cardiovascular events, other cardiometabolic outcomes and mortality will be compared between the treatments using the inverse propensity weighting model. Incidence rate ratios of outcomes will be modelled with Poisson regression. Time to event will be analysed using Cox proportional hazards model. A competing risks approach will be adopted to estimate comparative incidences to allow for the impact of mortality.Ethics and disseminationThe study will bring new knowledge on the risk of developing obesity, cardiometabolic morbidity and mortality following treatment for hyperthyroidism to inform clinical practice and public health policies. The results will be disseminated via open-access peer-reviewed publications and directly to the patients and public groups (Independent Scientific Advisory Committee protocol approval #20_000185).
Glucocorticoids (GCs) are frequently used to treat glomerular diseases but are associated with multiple adverse effects including hypothalamic-pituitary-adrenal axis inhibition that can lead to ...adrenal insufficiency (AI) on withdrawal. There is no agreed GC tapering strategy to minimise this risk.
This is a single centre retrospective study, between 2013 to 2016, of patients with glomerular disease on GC therapy for more than 3 months screened for GC induced AI with short synacthen stimulation tests (SSTs) done prior to complete GC withdrawal. We investigated the prevalence of AI, predictors, choice of screening tool and recovery.
Biochemical evidence of GC induced AI was found in 57 (46.3%) patients. Total duration of GC did not differ between those with and without AI (p = 0.711). Patients with GC induced AI had a significantly lower pre-synacthen baseline cortisol as compared to patients without AI. A cut off pre-synacthen baseline cortisol of ≥223.5 nmol/l had a specificity of 100% for identifying individuals without biochemical AI. Patients with GC induced AI took a mean of 8.7 ± 4.6 months (mean ± SD) to recover. Patients with persistent AI had a significantly lower index post-synacthen cortisol measurement.
We demonstrate that biochemically proven GC induced AI is common in patients with glomerular diseases, is not predicted by daily dose or duration and takes a considerable time to recover. The study supports the use of morning basal cortisol testing as an appropriate means to avoid the need for SSTs in all patients and should be performed in all patients prior to consideration of GC withdrawal after 3 months duration.
Summary
Objective
In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH).
Context
Thyroid dyshormonogenesis comprises 10–15% of all cases of congenital ...hypothyroidism (CH), which is the most common neonatal endocrine disorder, and might result from disruptions at any stage of thyroid hormone biosynthesis. Currently seven genes (NIS, TPO, PDS, TG, IYD, DUOX2 and DUOXA2) have been implicated in the aetiology of the disease.
Design
As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi‐case families.
Patients
One hundred and four patients with congenital TDH all coming from consanguineous and/or multi‐case families.
Measurements
Initially, we performed potential linkage analysis of cases to all seven causative‐TDH loci as well as direct sequencing of the TPO gene in cases we could not exclude linkage to this locus. In addition, in silico analyses of novel missense mutations were carried out.
Results
TPO had the highest potential for linkage and we identified 21 TPO mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct TPO mutations detected in this study were novel (A5T, Y55X, E596X, D633N).
Conclusions
This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases.
PDF
