The Danish investigation on iodine intake and thyroid disease (DanThyr): history and implications.

Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Social position and functional somatic disorders: The DanFunD study.

BACKGROUND AND AIM: It is generally accepted that functional somatic disorders (FSDs) are a product of biological, psychological, and social factors. Social position might be part of this complex, but the literature on this issue is currently heterogeneous and inconsistent. The aim of the present study was - in a population-based cohort - to test the hypothesis that lower social position would be associated with higher a risk of FSD. METHOD: The association between social position and FSD was examined in a cross-sectional study with various measures of social position (education as measured by vocational training; employment; cohabitation; subjective social status) and delimitations of FSD (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, bodily distress syndrome, and symptom profiles). The associations were analyzed using logistic regressions to calculate odds ratios and 95% confidence intervals. Each social measure was analyzed independently and was adjusted for age and sex. RESULTS: Lower levels of vocational training, being unemployed, and living alone were associated with higher risk of FSD, regardless of the FSD delimitation. There was also a significant negative association between subjective evaluated social status and FSD. The associations remained after multiple adjustments, and seemed to be strongest for the more severe FSD-types. CONCLUSIONS: Lower social position is associated with higher risk of FSD, especially the more severe FSD delimitations, which might constitute an especially vulnerable group. However, the mechanisms behind the relations remain unknown.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis.

BACKGROUND: Previous observational studies have indicated a protective effect of drinking milk on asthma and allergy. In Mendelian Randomization, one or more genetic variants are used as unbiased markers of exposure to examine causal effects. We examined the causal effect of milk intake on hay fever, asthma, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by using the lactase rs4988235 genotype associated with milk intake. METHODS: We performed a Mendelian Randomization study including 363,961 participants from the UK Biobank. RESULTS: Observational analyses showed that self-reported milk-drinkers vs. non-milk drinkers had an increased risk of hay fever: odds ratio (OR) = 1.36 (95% CI 1.32, 1.40, p < 0.001), asthma: OR = 1.33 (95% CI 1.38, 1.29, p < 0.001), yet a higher FEV1: ß = 0.022 (SE = 0.004, p < 0.001) and FVC: ß = 0.026 (SE = 0.005, p < 0.001). In contrast, genetically determined milk-drinking vs. not drinking milk was associated with a lower risk of hay fever: OR = 0.791 (95% CI 0.636, 0.982, p = 0.033), and asthma: OR = 0.587 (95% CI 0.442, 0.779, p = 0.001), and lower FEV1: ß = - 0.154 (standard error, SE = 0.034, p < 0.001) liter, and FVC: ß = - 0.223 (SE = 0.034, p < 0.001) liter in univariable MR analyses. These results were supported by multivariable Mendelian randomization analyses although not statistically significant. CONCLUSIONS: As opposed to observational results, genetic association findings indicate that drinking milk has a protective effect on hay fever and asthma but may also have a negative effect on lung function. The results should be confirmed in other studies before any recommendations can be made.

Reference intervals in Danish children and adolescents for bone turnover markers carboxy-terminal cross-linked telopeptide of type I collagen (ß-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP).

PURPOSE: Bone turnover markers (BTM) are gaining ground in clinical practice but to fully use their potential there is a need for establishing valid reference intervals (RI). Consequently, the purpose of the study was to establish general RI as well as suggested clinical RI for carboxy-terminal cross-linked telopeptide of type I collagen (ß-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP) in children and adolescents. METHOD: BTM were measured on Danish children and adolescents participating in the CHAMPS-study DK. A total of 762 participants were included (8-18 years, 50.4% girls) contributing a total of 1410 study visits. The RI was calculated based on 2-years age spans. Participants with biochemical signs of metabolic bone disease were excluded. RESULTS: The differences in RI between age groups clearly reflect changes in growth with an initial increase in BTM, greatest in boys, and a subsequent decrease most pronounced in girls. ß-CTX and PINP are markers most affected by these changes, compared to OC and bone ALP. The suggested clinical 95% RI included participants with vitamin D insufficiency but no biochemical signs of metabolic bone disease which did not markedly alter the RI. CONCLUSION: RI for ß-CTX, PINP, OC and bone ALP varies with age and sex. ß-CTX and PINP which reflect bone resorption and formation processes are mostly affected by these changes. We suggest a set of clinically applicable 95% RI for the four BTM to heighten the usefulness and generalizability of the RI.

Symptoms and biomarkers associated with undiagnosed celiac seropositivity.

BACKGROUND: Studies have indicated that underdiagnosis and diagnostic delay are common in celiac disease. Therefore, it is important to increase our knowledge of what symptoms and biomarkers could identify undiagnosed cases of celiac disease. METHODS: We screened for celiac disease antibodies in stored blood samples from 16,776 participants in eight population-based studies examined during 1976-2012. Undiagnosed celiac seropositivity was defined as celiac disease antibody positivity (IgG-deamidated gliadin peptide above 10.0 U/mL and/or IgA-tissue transglutaminase (TTG) or IgG-TTG above 7.0 U/mL) without a known diagnosis of celiac disease in the National Patient Register. In all studies general health symptoms were recorded by participant-completed questionnaire, including self-perceived health, tiredness, headache and gastrointestinal symptoms. Furthermore, blood samples were drawn for analyses of biomarkers e.g. hemoglobin, blood glucose, cholesterol, liver parameters and vitamins. The participants with undiagnosed celiac seropositivity were matched by sex, age and study with four controls among the celiac disease antibody negative participants. RESULTS: We excluded, five participants with known celiac disease, resulting in a population of 16,771 participants. In this population 1% (169/16,771) had undiagnosed celiac seropositivity. There were no statistically significant differences in symptoms between cases and controls. Undiagnosed celiac seropositivity was associated with low blood cholesterol (< 5 mmol/L) and low hemoglobin (< 7.3 mmol/L for women and < 8.3 mmol/L for men). CONCLUSION: In this general population study, undiagnosed cases of celiac seropositivity did not have more symptoms than controls, confirming the diagnostic difficulties of celiac disease and the low prognostic value of symptoms for a diagnosis of celiac disease. Furthermore, decreased levels of cholesterol and/or hemoglobin in the blood were associated with undiagnosed celiac seropositivity.

Influence of educational level on test and treatment for incident hypothyroidism.

OBJECTIVE: The incidence of hypothyroidism is not expected to differ by socioeconomic factors. However, the decision to test and initiate treatment may differ. We aimed to examine whether educational level influences the probability of thyroid stimulation hormone (TSH)-measurement and initiation of levothyroxine treatment. DESIGN: Citizens in the greater Copenhagen Area during 2001-2015 were included. Individual-level data on educational level, diagnoses, GP-contact, TSH-measurement and medication were derived from administrative and healthcare registers. The relative risks (RR) between educational levels of annual TSH-measurement and treatment initiation following a TSH-measurement were analysed in Poisson regression models with generalized estimation equations. RESULTS: A TSH-measurement was performed in 19% of 9,390,052 person years. The probability of TSH-measurement was higher with short (RR 1.16 [95% CI 1.15-1.16]) and medium (RR 1.11 [95% CI 1.06-1.12]) compared with long education. Treatment was initiated after 0.8% of 2,049,888 TSH-measurements. For TSH < 5 mIU/L, RR for treatment initiation ranged between 0.47 (95%CI 0.39-0.57) and 0.78 (95%CI 0.67-0.91) for short and medium compared with long education. For TSH 5-10 mIU/L, there was no statistically significant difference. For TSH > 10 mIU/L, RR was 1.07 (95% CI 1.02-1.12) for short and 1.08 (95% CI 1.03-1.13) for medium compared with long education. CONCLUSION: The probability of TSH-measurement was higher with shorter education, and the probability of treatment initiation with TSH > 10 mIU/L was marginally higher with short-medium education compared with long education. However, the probability of treatment initiation with TSH < 5 mIU/L, that is treatment incongruous with guidelines, was substantially higher in persons with long education.

Benefits and Harms of a Prevention Program for Iodine Deficiency Disorders: Predictions of the Decision-Analytic EUthyroid Model.

Background: Iodine deficiency is one of the most prevalent causes of intellectual disability and can lead to impaired thyroid function and other iodine deficiency disorders (IDDs). Despite progress made on eradicating iodine deficiency in the last decades in Europe, IDDs are still prevalent. Currently, evidence-based information on the benefit/harm balance of IDD prevention in Europe is lacking. We developed a decision-analytic model and conducted a public health decision analysis for the long-term net benefit of a mandatory IDD prevention program for the German population with moderate iodine deficiency, as a case example for a European country. Methods: We developed a decision-analytic Markov model simulating the incidence and consequences of IDDs in the absence or presence of a mandatory IDD prevention program (iodine fortification of salt) in an open population with current demographic characteristics in Germany and with moderate ID. We collected data on the prevalence, incidence, mortality, and quality of life from European studies for all health states of the model. Our primary net-benefit outcome was quality-adjusted life years (QALYs) predicted over a period of 120 years. In addition, we calculated incremental life years and disease events over time. We performed a systematic and comprehensive uncertainty assessment using multiple deterministic one-way sensitivity analyses. Results: In the base-case analysis, the IDD prevention program is more beneficial than no prevention, both in terms of QALYs and life years. Health gains predicted for the open cohort over a time horizon of 120 years for the German population (82.2 million inhabitants) were 33 million QALYs and 5 million life years. Nevertheless, prevention is not beneficial for all individuals since it causes additional hyperthyroidism (2.7 million additional cases). Results for QALY gains were stable in sensitivity analyses. Conclusions: IDD prevention via mandatory iodine fortification of salt increases quality-adjusted life expectancy in a European population with moderate ID, and is therefore beneficial on a population level. However, further ethical aspects should be considered before implementing a mandatory IDD prevention program. Costs for IDD prevention and treatment should be determined to evaluate the cost effectiveness of IDD prevention.

The economic impact of prevention, monitoring and treatment strategies for iodine deficiency disorders in Germany.

OBJECTIVE: More than 30% of the German population suffers from mild to moderate iodine deficiency causing goiter and other iodine deficiency disorders (IDDs). The economic burden of iodine deficiency is still unclear. We aimed to assess costs for prevention, monitoring and treatment of IDDs in Germany. DESIGN: We performed a comprehensive cost analysis. METHODS: We assessed direct medical costs and direct non-medical costs for inpatient and outpatient care of IDDs and costs for productivity loss due to the absence of work in 2018. Additionally, we calculated total costs for an IDD prevention program comprising universal salt iodization (USI). We performed threshold analyses projecting how many cases of IDDs or related treatments would need to be avoided for USI to be cost-saving. RESULTS: Annual average costs per case in the year of diagnosis were € 211 for goiter/thyroid nodules; € 308 for hyperthyroidism; and € 274 for hypothyroidism. Average one-time costs for thyroidectomy were € 4184 and € 3118 for radioiodine therapy. Average costs for one case of spontaneous abortion were € 916. Annual costs of intellectual disability were € 14,202. In the German population, total annual costs for USI would amount to 8 million Euro. To be cost-saving, USI would need to prevent, for example, 37,900 cases of goiter/thyroid nodules. CONCLUSION: USI potentially saves costs, if a minimum amount of IDDs per year could be avoided. In order to recommend the implementation of USI, a full health-economic evaluation including a comprehensive benefit-harm assessment is needed.

Long-term Consequences of Undiagnosed Celiac Seropositivity.

INTRODUCTION: Diagnosed celiac disease (CD) is associated with lymphoproliferative malignancy and gastrointestinal cancer, but little is known about the long-term consequences of undiagnosed CD. We aimed to investigate long-term consequences of undiagnosed CD for mortality and incidence of cancer and other chronic diseases. METHODS: We screened biobank serum samples for immunoglobulin (Ig) A and IgG tissue transglutaminase (TTG) and IgG deamidated gliadin peptide in a study of 8 population-based cohort studies comprising 16,776 participants examined during 1976-2012 and followed with >99% complete follow-up in Danish nationwide registries until December 31, 2017, regarding vital status and incidence of diseases. Undiagnosed CD was defined as antibody positivity (IgA-TTG or IgG-TTG ≥ 7 U/mL and/or IgG deamidated gliadin peptide ≥ 10 U/mL) in individuals without a diagnosis of CD recorded in the National Patient Register. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox regression analyses with age as the underlying time scale. RESULTS: The prevalence of undiagnosed CD was 1.0% with no statistically significant increase over time. Undiagnosed CD was associated with increased risk of cancer overall (HR, 1.57; 95% CI, 1.16-2.11), gastrointestinal cancer (HR, 2.33; 95% CI, 1.35-4.04), cancer of the uterus (HR, 3.95; 95% CI, 1.46-10.69), breast cancer (HR, 1.98; 95% CI, 1.02-3.82), head and neck cancer (HR, 3.12; 95% CI, 1.15-8.43), and cardiovascular disease (HR, 1.37; 95% CI, 1.01-1.85). We found no statistically significant association between undiagnosed CD and mortality (HR, 1.19; 95% CI, 0.87-1.61). DISCUSSION: Undiagnosed CD was associated with increased risk of cardiovascular disease and cancer suggesting that untreated CD has serious long-term health consequences not only affecting the gastrointestinal tract (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/AJG/B566).

The association of thyroid stimulation hormone levels with incident ischemic heart disease, incident stroke, and all-cause mortality.

PURPOSE: Thyroid dysfunction may affect the risk of cardiovascular disease and mortality through effects on myocardial and vascular tissue and metabolism. Levels of thyroid stimulating hormone (TSH) indicates thyroid function. We aimed to assess the association between TSH-levels and incident ischemic heart disease (IHD), incident stroke, and all-cause mortality. METHODS: We included 13,865 participants (18-71 years, 51.6% women) from five cohort studies conducted during 1974-2008 were included. TSH was measured at the baseline examination and classified as <0.4; 0.4-2.5 (ref.); 2.5-5.0; 5.0-10, or >10 mU/l. Incident IHD, incident stroke, and all-cause mortality were identified in registries until ultimo 2013. Data were analysed by multivariate Cox regression with age as underlying time axis. Results from the individual cohorts were pooled by random-effects meta-analysis. RESULTS: The crude incidence rate was for IHD 7.8 cases/1000 person years (PY); stroke 5.4 cases/1000 PY; and all-cause mortality 11.3 deaths/1000 PY (mean follow-up: 14 years). Analyses showed no statistically significant associations between TSH-levels and incident IHD or incident stroke in the partly or fully adjusted models. There was a statistically significant association between TSH of 2.5-5 mU/l and all-cause mortality (hazard ratio 1.145 (95% CI 1.004-1.306) compared with TSH of 0.4-2.5 mU/l in the fully adjusted model. CONCLUSION: The results do not provide evidence of a harmful effect of decreased or increased TSH on IHD or stroke in the general population. However, there is some indication of an elevated risk for all-cause mortality with TSH 2.5-5 mU/l compared with 0.4-2.5 mU/l.

Effects of age and sex on osteocalcin and bone-specific alkaline phosphatase-reference intervals and confounders for two bone formation markers.

Bone formation markers bone-specific alkaline phosphatase and osteocalcin are used in many clinical situations. Therefore, we calculated reference intervals for the two markers and investigated how they are influenced by several factors including sex and age. Furthermore, we established clinically relevant reference intervals for the two markers. OBJECTIVE: The bone turnover markers (BTMs), bone-specific alkaline phosphatase (bone ALP), and osteocalcin (OC), are frequently measured formation markers. The purpose of this study was to establish reference intervals (RIs) for the two BTMs in a general adult Danish population. METHODS: Bone ALP and OC were measured on the iSYS (IDS Plc) automatic analyzer in samples from the Danish Health2006 5-year follow-up study on serum from 2308 participants (54% women, age range 24-76). Participants with self-reported diagnosis of osteoporosis or receiving hormonal replacement were excluded from analyses while participants on hormonal contraceptives were included. RESULTS: The geometric mean and 95%RI for bone ALP were 13.9 µg/L (7.6-25.6) for men and 13.8 µg/L (7.0-27.4) for women, while for OC 16.0 µg/L (7.5-34.4) for men and 18.6 µg/L (8.1-42.9) for women. Levels of bone ALP increased with increasing age (ß 1.004, p < 0.001), while female sex had no effect. OC levels decreased with increasing age (ß 0.998, p = 0.009) and increased with female sex (ß 1.104, p < 0.001). Based on our findings, we propose for bone ALP and OC three clinical RIs for men based on age and three clinical RI for women based on age and menopausal status. CONCLUSION: The RI for bone ALP and OC varies with age and sex and the BTMs are influenced differently by the two factors. Consequently, the need for establishing valid RIs is of great importance before the full potential of BTM can be used in clinical practice.

Decision-Analytic Modeling Studies in Prevention and Treatment of Iodine Deficiency and Thyroid Disorders: A Systematic Overview.

Background: Prevention and treatment of iodine deficiency-related diseases remain an important public health challenge. Iodine deficiency can have severe health consequences, such as cretinism, goiter, or other thyroid disorders, and it has economic implications. Our aim was to give an overview of studies applying decision-analytic modeling to evaluate the effectiveness and/or cost-effectiveness of iodine deficiency-related prevention strategies or treatments related to thyroid disorders. Methods: We performed a systematic literature search in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica Database), Tuft's Cost-Effectiveness Analysis Registry, and National Health System Economic Evaluation Database (NHS EED) to identify studies published between 1985 and 2018 comparing different prevention or treatment strategies for iodine deficiency and thyroid disorders by applying a mathematical decision-analytic model. Studies were required to evaluate patient-relevant health outcomes (e.g., remaining life years, quality-adjusted life years [QALYs]). Results: Overall, we found 3950 studies. After removal of duplicates, abstract/title, and full-text screening, 17 studies were included. Eleven studies evaluated screening programs (mainly newborns and pregnant women), five studies focused on treatment approaches (Graves' disease, toxic thyroid adenoma), and one study was about primary prevention (consequences of iodine supplementation on offspring). Most of the studies were conducted within the U.S. health care context (n = 7). Seven studies were based on a Markov state-transition model, nine studies on a decision tree model, and in one study, an initial decision tree and a long-term Markov state-transition model were combined. The analytic time horizon ranged from 1 year to lifetime. QALYs were evaluated as health outcome measure in 15 of the included studies. In all studies, a cost-effectiveness analysis was performed. None of the models reported a formal model validation. In most cases, the authors of the modeling studies concluded that screening is potentially cost-effective or even cost-saving. The recommendations for treatment approaches were rather heterogeneous and depending on the specific research question, population, and setting. Conclusions: Overall, we predominantly identified decision-analytic modeling studies evaluating specific screening programs or treatment approaches; however, there was no model evaluating primary prevention programs on a population basis. Conclusions deriving from these studies, for example, that prevention is cost-saving, need to be carefully interpreted as they rely on many assumptions.

The unifying diagnostic construct of bodily distress syndrome (BDS) was confirmed in the general population.

OBJECTIVES: Bodily distress syndrome (BDS) has been shown to encompass a range of functional somatic syndromes (FSS) such as irritable bowel syndrome (IBS), fibromyalgia (FM), and chronic fatigue syndrome (CFS) in clinical samples. This study aimed to explore symptom clusters and test classification of individuals with illness similar to the BDS criteria in a general population sample. METHODS: A stratified subsample of 1590 individuals from the DanFunD part two cohort was included. Symptoms were assessed with the Research Interview for Functional somatic Disorders, performed by trained physicians. In 44 symptoms pooled from criteria of IBS, FM, CFS, and BDS, symptom clusters were explored with explorative factor analysis. Confirmation of symptom clusters of BDS in the previously described 25- and 30-item BDS checklists was performed with confirmatory factor analysis. Classification of individuals into illness groups was investigated with latent class analysis. RESULTS: Four symptom clusters (cardiopulmonary, gastrointestinal, musculoskeletal, general symptoms/fatigue) corresponding to the BDS subtypes and their corresponding FSS were identified and confirmed. A three-class model including 25 BDS items had the best fit for dividing participants into classes of illness: One class with low probability, one class with medium probability, and one class with high probability of having ≥4 symptoms in all symptom clusters. CONCLUSION: The BDS concept was confirmed in the general population and constitutes a promising approach for improved FSS classification. It is highly clinical relevant being the only diagnostic construct defining the complex multi-organ type.

Changes in subtypes of overt thyrotoxicosis and hypothyroidism following iodine fortification.

OBJECTIVE: To investigate the impact of mandatory iodine fortification (IF) on the incidence of nosological subtypes of overt thyrotoxicosis and hypothyroidism. DESIGN: We identified and scrutinized all possible new cases of overt thyrotoxicosis and hypothyroidism in an open cohort in Northern Jutland (n = 309 434; 1 January 1997) during the years 2014-2016. Individual medical history was evaluated to verify and detail the incidence of overt thyroid dysfunction and for classification into nosological subtypes. A number of cases were excluded during final verification due to spontaneous normalization of thyroid function, as they had no medical history suggesting a known condition, which could transiently affect thyroid function (subacute/silent thyroiditis, PPTD and iatrogenic thyroid dysfunction). An identical survey was conducted in 1997-2000 prior to mandatory IF of salt (13 µg/g) that was in effect from year 2001. RESULTS: The standardized incidence rate (SIR) of verified overt thyrotoxicosis decreased markedly from 97.5/100 000/year in 1997-2000 to 48.8 in 2014-2016 (SIRR: 0.50 [95% CI: 0.45-0.56]). This was due to a distinct decrease in the SIR of multinodular toxic goitre (SIRR: 0.18 [0.15-0.23]), solitary toxic adenoma (SIRR: 0.26 [0.16-0.43]) and to a lesser degree Graves' disease (SIRR: 0.67 [0.56-0.79]). SIR for overt hypothyroidism was unaltered by 2014-2016 (SIRR: 1.03 [0.87-1.22]). However, age distribution shifted with more young and fewer elderly cases of verified overt hypothyroidism. CONCLUSION: Mandatory IF caused a substantial reduction in SIR of verified overt thyrotoxicosis (especially of nodular origin) while avoiding an increase in SIR of verified overt hypothyroidism.

Predictors of accelerated FEV1 decline in adults with airflow limitation-Findings from the Health2006 cohort.

To investigate predictors of accelerated decline in forced expiratory volume in 1 s (FEV1) in individuals with preexisting airflow limitation (AL). Participants in the Health2006 baseline study aged ≥ 35 with FEV1/ forced vital capacity (FVC) < lower limit of normal (LLN) were invited for a 10-year follow-up. At both examinations, data were obtained on demographics, spirometry, fitness level, allergy, and exhaled nitric oxide. We used multiple regression modeling to predict the annual decline in FEV1, reported as regression coefficients ( R) and 95% confidence intervals (CIs). A total of 123 (43% of those invited) participated in the follow-up examination, where more had exercise-induced dyspnea but fewer had asthma symptoms. Being female ( R = -29.8 ml, CI: -39.7 to -19.8), diagnosed with asthma ( R = -13.7, CI: -20.4 to -7.0) or atopic dermatitis ( R = -29.0, CI: -39.7 to -18.4), and having current asthma symptoms or nightly respiratory symptoms ( R = -22.1, CI: -31.9 to -12.4 and R = -14.3, CI: -19.9 to -8.7, respectively) were significantly associated with a steeper decline in FEV1. Although to a smaller extent, a steeper decline was also predicted by age, baseline FEV1, waist/hip-ratio, and number of pack-years smoked. In individuals with preexisting AL, being female and having ever or current respiratory symptoms were associated with an accelerated annual decline in FEV1.

Determinants of airflow limitation in Danish adults - findings from the Health2006 cohort.

Background and aim: Airflow limitation may be found in patients with both asthma and COPD and is often associated with more symptoms and poorer outcome. We aimed to identify factors associated with airflow limitation in a well-characterized, population-based sample of adults. Methods: From the Health2006 cohort, we selected participants aged ≥35 years at enrolment (n=2,959). Airflow limitation was defined as FEV1/FVC < lower limit of normal. Participants with (cases) and without (controls) airflow limitation were compared with regard to self-reported symptoms, medical history, atopy, lung function and exhaled nitric oxide. Between-group differences were analyzed using Chi-square and Mann-Whitney U tests, and effect size was estimated by logistic regression (reported as OR and 95% CI). Results: We identified 313 cases, majority of which were female, reported poor overall health, physically inactivity and experienced respiratory symptoms within the previous year. The presence of airflow limitation was associated with BMI (OR 3.1 for overweight, P<0.001, CI 1.97-4.78), age (OR 2.3, P<0.001 for age 55+, CI 1.7-3.2), tobacco exposure (OR 1.6, P=0.01, CI 1.1-2.32, and OR 1.76, P=0.019, CI 1.2-2.3 for former and current smokers, respectively), sex (OR 1.6 for being female, P=0.002, CI 1.2-2.2), presence of specific IgE to common aeroallergen(s) (OR 1.4, P=0.041, CI 1.2-2.0), and ever being diagnosed with asthma (OR 1.6, P=0.003, CI 1.3-2.0). Conclusion: Apart from tobacco exposure and age, the presence of airflow limitation was associated with being overweight, female, sensitized to common aeroallergens or ever having a diagnosis of asthma.

The association of celiac disease and allergic disease in a general adult population.

Background: The relationship between allergy and celiac disease (CD) is not clear. Objective: The objective of this article is to investigate the association of CD and CD antibody positivity with hay fever, asthma and immunoglobulin (Ig)E sensitization in a general adult population. Methods: A total of 2297 individuals were screened for CD antibodies and underwent allergy testing. CD antibody-positive participants were invited to undergo clinical evaluation including biopsies. Additionally, biobank blood samples from four population-based studies (6423, 973, 1718 and 1101 participants) with data on IgE sensitization to inhalant allergens were screened for CD antibodies. CD antibody-positive participants were screened for serum IgE against food allergens in three biobank studies. CD-antibody positivity was defined as IgA or IgG tissue transglutaminase ≥7 U/ml and/or IgG deamidated gliadin peptide ≥10 U/ml. Results: The nine participants (0.4%) diagnosed with CD had significantly higher prevalence of IgE sensitization to wheat and dust mites. The prevalence of CD antibody positivity was 0.8% (18/2297), and these participants had a significantly higher prevalence of IgE sensitization to food allergens (Fx5), egg, dust mites and mugwort. In the biobank studies, the prevalence of CD antibody positivity was 0.8% to 1.2%. One study showed a positive association between CD antibody positivity and IgE sensitization for dog, horse and food allergens. Conclusion: We found a possible association of CD and IgE sensitization to some food and inhalant allergens in the Health2006 study. In further studies, however, we could not consistently replicate these associations.

Association of alcohol consumption with allergic disease and asthma: a multi-centre Mendelian randomization analysis.

AIMS: To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E. DESIGN: Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions. SETTING: Europe. PARTICIPANTS: We included a total of 466 434 people aged 15-82 years from 17 population-based studies conducted from 1997 to 2015. MEASUREMENTS: The rs1229984 (ADH1B) was genotyped; alcohol consumption, hay fever and asthma were self-reported. Specific and total IgE were measured from serum samples. FINDINGS: Observational analyses showed that ever-drinking versus non-drinking, but not amount of alcohol intake, was positively associated with hay fever and inversely associated with asthma but not with allergic sensitization or serum total immunoglobulin (Ig)E. However, Mendelian randomization analyses did not suggest that the observational associations are causal. The causal odds ratio (OR) per genetically assessed unit of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019; P = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019; P = 0.095) for asthma, an OR = 0.971 (95% CI =  0.804, 1.174; P = 0.763) for allergic sensitization and a 4.7% change (95% CI = -5.5%, 14.9%; P = 0.366) for total IgE. CONCLUSIONS: In observational analyses, ever-drinking versus not drinking was positively associated with hay fever and negatively associated with asthma. However, the Mendelian randomization results were not consistent with these associations being causal.