Search

Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are known to influence serum vitamin D concentrations. Genetic epidemiology of vitamin D is in its infancy and a better understanding on how genetic variation influences vitamin D concentration is needed. We aimed to analyse previously reported vitamin D-related polymorphisms in relation to serum 25(OH)D concentrations in 201 healthy Danish families with dependent children in late summer in Denmark. Serum 25(OH)D concentrations and a total of 25 SNPs in GC, VDR, CYP2R1, CYP24A1, CYP27B1, C10or88 and DHCR7/NADSYN1 genes were analysed in 758 participants. Genotype distributions were in Hardy–Weinberg equilibrium for the adult population for all the studied polymorphisms. Four SNPs in CYP2R1 (rs1562902, rs7116978, rs10741657 and rs10766197) and six SNPs in GC (rs4588, rs842999, rs2282679, rs12512631, rs16846876 and rs17467825) were statistically significantly associated with serum 25(OH)D concentrations in children, adults and all combined. Several of the SNPs were in strong linkage disequilibrium, and the associations were driven by CYP2R1-rs10741657 and rs10766197, and by GC-rs4588 and rs842999. Genetic risk score analysis showed that carriers with no risk alleles of CYP2R1-rs10741657 and rs10766197, and/or GC rs4588 and rs842999 had significantly higher serum 25(OH)D concentrations compared to carriers of all risk alleles. To conclude, our results provide supporting evidence that common polymorphisms in GC and CYP2R1 are associated with serum 25(OH)D concentrations in the Caucasian population and that certain haplotypes may predispose to lower 25(OH)D concentrations in late summer in Denmark. [ABSTRACT FROM AUTHOR]

Objective: To characterize thyroid hormone levels at the time of diagnosis in the nosological types of thyrotoxicosis diagnosed in the population and to analyze determinants for serum thyroxine (T4) and tri-iodothyronine (T3). Design: Population-based study of thyrotoxicosis at disease onset. Methods: In the period 1997-2000, we prospectively identified all patients diagnosed with incident primary overt thyrotoxicosis in a Danish population cohort and classified patients into ten well-defined nosological types of disease (n=1082). Untreated levels of serum T3, T4, and T3:T4 ratio were compared and related to sex, age, level of iodine deficiency, smoking status, alcohol intake, iodine supplement use, co-morbidity, and TSH receptor antibodies (TRAbs) in multivariate models. Results: Graves' disease (GD) patients had much higher levels of T3 and higher T3:T4 ratio at diagnosis compared with other thyrotoxic patients, but with a profound negative association between hormone levels and age. In GD, patients diagnosed in the area with more severe iodine deficiency had lower levels of T3 and T4. TRAb-negative GD patients had biochemically mild thyrotoxicosis. Higher age was also associated with lower degree of biochemical thyrotoxicosis in nodular toxic goiter. We found no association between serum T3 and T4 and sex, smoking habits, iodine supplements, alcohol intake, or co-morbidity in any type of thyrotoxicosis. Conclusions: The study gives new insight into the hormonal presentation of thyrotoxicosis and showed that young age, positive TRAb levels, but also residency in the area with higher iodine intake was positively associated with biochemical disruption in GD. [ABSTRACT FROM AUTHOR]

Background We recently demonstrated that moderate alcohol consumption is associated with a considerable reduction in the risk of autoimmune hypothyroidism, similar to findings in other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. We aimed to study a possible association between alcohol intake and autoimmune Graves′ hyperthyroidism. Design This is a population-based, case-control study. Methods In a well-defined Danish population (2 027 208 person-years of observation), we prospectively identified patients with new overt thyroid dysfunction and studied 272 patients with Graves′ hyperthyroidism. For each patient, we recruited four age-gender-region-matched controls with normal thyroid function ( n = 1088). Measurements Participants gave detailed information on current and previous alcohol intake as well as other factors to be used for analyses. The association between alcohol intake and development of hyperthyroidism was analysed in conditional multivariate Cox regression models. Results Graves′ patients had a lower reported alcohol consumption than controls (median units of alcohol (12 g) per week: 2 vs 4, P < 0·001). In a multivariate regression model, alcohol consumption was associated with a dose-dependent reduction in risk for development of overt Graves′ hyperthyroidism. Odds ratios (95% confidence interval) compared with the reference group with a recent (last year) consumption of 1-2 units of alcohol per week were as follows: 0 units/week 1·73 (1·17-2·56), 3-10 units/week 0·56 (0·39-0·79), 11-20 units/week 0·37 (0·21-0·65), ≥21 units/week 0·22 (0·08-0·60). Similar results were found for maximum previous alcohol consumption during a calendar year. No interaction was found with the type of alcohol consumed (wine vs beer), smoking habit, age, gender or region of inhabitancy. Conclusions Moderate alcohol consumption is associated with a considerable reduction in the risk of Graves′ disease with hyperthyroidism - irrespective of age and gender. Autoimmune thyroid disease seems to be much more dependent on environmental factors than hitherto anticipated. [ABSTRACT FROM AUTHOR]

Depending on the availability of iodine, the thyroid gland is able to enhance or limit the use of iodine for thyroid hormone production. When compensation fails, as in severely iodine-deficient populations, hypothyroidism and developmental brain damage will be the dominating disorders. This is, out of all comparison, the most serious association between disease and the level of iodine intake in a population. In less severe iodine deficiency, the normal thyroid gland is able to adapt and keep thyroid hormone production within the normal range. However, the prolonged thyroid hyperactivity associated with such adaptation leads to thyroid growth, and during follicular cell proliferation there is a tendency to mutations leading to multifocal autonomous growth and function. In populations with mild and moderate iodine deficiency, such multifocal autonomous thyroid function is a common cause of hyperthyroidism in elderly people, and the prevalence of thyroid enlargement and nodularity is high. The average serum TSH tends to decrease with age in such populations caused by the high frequency of autonomous thyroid hormone production. On the other hand, epidemiological studies have shown that hypothyroidism is more prevalent in populations with a high iodine intake. Probably, this is also a complication to thyroid adaptation to iodine intake. Many thyroid processes are inhibited when iodine intake becomes high, and the frequency of apoptosis of follicular cells becomes higher. Abnormal inhibition of thyroid function by high levels of iodine is especially common in people affected by thyroid autoimmunity (Hashimoto''s thyroiditis). In populations with high iodine intake, the average serum thyroid-stimulating hormone (TSH) tends to increase with age. This phenomenon is especially pronounced in Caucasian populations with a genetically determined high tendency to thyroid autoimmunity. A small tendency to higher serum TSH may be observed already when iodine intake is brought from mildly deficient to adequate, but there is at present no evidence that slightly elevated serum TSH in elderly people leads to an increase in morbidity and mortality. Conclusion: Even minor differences in iodine intake between populations are associated with differences in the occurrence of thyroid disorders. Both iodine intake levels below and above the recommended interval are associated with an increase in the risk of disease in the population. Optimally, iodine intake of a population should be kept within a relatively narrow interval where iodine deficiency disorders are prevented, but not higher. Monitoring and adjusting of iodine intake in a population is an important part of preventive medicine. [Copyright &y& Elsevier]

Abstract: Selenium is an essential micronutrient important to human health. The main objective of this study is to describe serum selenium and selenoprotein P status in two samples of the Danish population. In addition, the influence of various factors potentially associated with selenium status was investigated. Blood samples from a total of 817 randomly selected subjects from two cities in Denmark were analyzed. Half of the samples were collected in 1997–1998 and the other half in 2004–2005. Samples from women aged 18–22, 40–45 and 60–65 years, and men aged 60–65 years were selected for this study. All subjects had filled in a food frequency questionnaire (FFQ) and a questionnaire with information about smoking habits, alcohol consumption and exercise habits. Mean serum selenium level was 98.7±19.8μg/L and median selenoprotein P level was 2.72 (2.18–3.49)mg/L. Serum selenium and selenoprotein P increased with age, and selenoprotein P was higher in men than in women. Serum selenium levels decreased by 5% on average from 1997–98 to 2004–05 (P<0.001), whereas selenoprotein P level increased (P<0.001). The intake of fish correlated weakly with serum selenium level (r=0.14, P<0.001) but not with selenoprotein P level. Smoking status, alcohol intake, exercise habits, BMI and medicine use did not influence selenium status. It is concluded that selenium status in this Danish population is at an acceptable level. No major groups with regard to age, sex or lifestyle factors could be identified as being in risk for selenium deficiency. [Copyright &y& Elsevier]

Objective: To characterise misreporters of energy intake (EI) and energy expenditure (EE).Design: Cross-sectional study, using a validated position and motion instrument, ActiReg, as the reference method to study misreporters of EI and of EE. EI was measured using a dietary record and EE using a physical activity questionnaire (PAQ). Misreporters were defined as subjects outside the 95% confidence limits of agreement between EI or EE reported/EE measured.Setting: Free-living Danish volunteers.Subjects: One hundred and thirty-eight volunteers aged between 20 and 59 years.Results: Body mass index, smoking, 'try to eat healthily' and worries about weight were related to degree of under-reported EI. The percentage energy from added sugar was lowest (P < 0.001) and the percentage energy from protein (P < 0.001) highest in under-reporters compared with acceptable reporters. Subjects who reported being very physically active at work or in leisure time reported a higher EE than measured EE compared with less physically active subjects (P < 0.05). Likewise, subjects who regard themselves as fit or very fit reported a higher EE than subjects who regard themselves as moderately fit (P < 0.05). Possible over-reporters reported less time as very light activity (P = 0.007), more time as moderate activity (P = 0.01) and more time as vigorous activity (P = 0.02) than acceptable reporters.Conclusions: Under-reporting of EI should always be taken into consideration; however, only a few characteristics of under-reporters are consistent among studies. Misreporting of EI was more prevalent than misreporting of EE. The level of physical activity more than the time spent involved in various activities was misreported. [ABSTRACT FROM AUTHOR]

Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism.A population study including 4649 randomly selected subjects.Blood tests were used to analyse for thyroid peroxidase autoantibodies (TPO-Ab), thyroglobulin autoantibodies (Tg-Ab), TSH, fT3 and fT4.Thyroid volume was categorized as small (< 6·6 ml) in 4·7%, normal (6·6–14·9 ml) in 60·4% and large (> 14·9 ml) in 34·9% of participants. Thyroid nodules were found in 29·7%. Serum TSH was low (< 0·4 mIU/l) in 4·7%, normal (0·4–3·6) in 91·0% and high (> 3·6) in 4·3%. The prevalence rate of subclinical goitrous Hashimoto's disease was 0·62% and of subclinical autoimmune atrophic thyroiditis 0·24%. There was a strong association between large volume and autoantibodies, but only in subjects with elevated TSH (P < 0·001). An association between thyroid nodules and TPO-Ab in univariate analyses (P < 0·001) was due to confounding by sex and age (multivariate model,P = 0·23).We identified a subgroup of the population with subclinical goitrous Hashimoto's disease and a smaller subgroup with subclinical autoimmune atrophic thyroiditis. This relationship between small and large thyroid volume in subclinical disease is opposite to that in overt disease, which may suggest that the period between development of a small volume with circulating autoantibodies and overt hypothyroidism is relatively short. [ABSTRACT FROM AUTHOR]

To examine the impact of a co-created culturally sensitive diabetes self-management education and support (DSMES) intervention on the physical and mental health of immigrants with type 2 diabetes (T2D). Pre- and post-test among people with T2D whose primary language was Urdu, Arabic or Turkish (n = 97). Participants were offered a six-week intervention based on a person-centred approach using research-based dialogue tools to facilitate learning and reflection, which was developed in co-creation with immigrants and healthcare professionals. Data were collected at baseline, post-intervention and after 6 months and analysed using paired t-tests, Wilcoxon signed-rank tests, chi-square tests and regression models when appropriate. Several clinical outcomes were improved post-intervention, including HbA1c (P < 0.001), body fat percentage (P = 0.002), self-rated general health (P = 0.05), well-being (P = 0.004) and several self-management behaviours, e.g., physical activity (P < 0.001). Most outcomes remained improved after 6 months, but the effect on HbA1c was no longer statistically significant. Some outcomes were improved only at 6 months, including waist circumference (P < 0.001) and diabetes-related emotional distress (P < 0.001). Fatigue did not change. Attendance at more programme sessions was associated with better outcomes. The DSMES intervention developed in a co-creation process was highly effective in improving the health of immigrants with T2D. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Studies of hypothyroidism are often based on patients referred to hospital. It is unknown, to what extent such studies are referral biased. Thus, the aim of the present study was to evaluate the magnitude of selection bias in a study of patients newly diagnosed with hypothyroidism. Study Design and Setting: A computer-based system linked to laboratory databases identified patients with incident overt hypothyroidism (n =346) from 1997 to 2000 in Aalborg, Denmark. An electronic patient administrative system identified patients referred to Department of Endocrinology, Aalborg Hospital. Among patient characteristics recorded at the time of diagnosis—age, gender, nosological subgroup of hypothyroidism, thyroid stimulating hormone (TSH), total thyroxine (T4), total triiodothyronine (T3), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and calendar year—we searched for predictors of referral state. Results: Of all hypothyroid patients, 86 (25%) were referred to our endocrine unit. The referred patients were younger (50.4 vs. 66.0 years, P <0.001), had higher serum TSH (53.6 vs. 32.6 mU/L, P =0.002) and lower serum total T4 (37.0 vs. 44.0nmol/L, P =0.03) compared with nonreferred patients. In a multivariate model, only less age (P <0.001) and serum total T4 (P =0.03) were statistically associated with referral state. Conclusion: Hypothyroid patients referred to a specialized hospital unit were younger and marginally more hypothyroid than nonreferred patients. Thus, referral bias should always be considered in hospital-based studies of hypothyroid patients. [Copyright &y& Elsevier]

Background: Few studies have scrutinized the spectrum of symptoms in subclinical hypothyroidism.Methods: From 3 Danish Investigation on Iodine Intake and Thyroid Diseases (DanThyr) cross-sectional surveys performed in the period 1997 to 2005, a total of 8903 subjects participated in a comprehensive investigation including blood samples and questionnaires on previous diseases, smoking habits, alcohol intake, and education. From the 3 surveys we included patients with subclinical hypothyroidism (n = 376) and euthyroid controls (n = 7619). We explored to what extent patients with subclinical hypothyroidism reported 13 previously identified hypothyroidism-associated symptoms (tiredness, dry skin, mood lability, constipation, palpitations, restlessness, shortness of breath, wheezing, globus sensation, difficulty swallowing, hair loss, dizziness/vertigo, and anterior neck pain). In various uni- and multivariate regression models we searched for circumstances predicting why some patients have more complaints than others.Results: Subclinically hypothyroid patients did not report higher hypothyroidism score [(median, interquartile range), 2 (0-4) vs 2 (0-4), P = .25] compared with euthyroid controls. Within the group of subclinical hypothyroid patients, comorbidity had the highest impact on symptoms (tiredness, shortness of breath, wheezing; all P < .001); TSH level had no impact on symptom score; and younger age was accompanied by higher mental burden (tiredness, P < .001; mood lability, P < .001; restlessness, P = .012), whereas shortness of breath was associated with high body mass index (P < .001) and smoking (P = .007).Conclusion: Patients with a thyroid function test suggesting subclinical hypothyroidism do not experience thyroid disease-related symptoms more often than euthyroid subjects. In subclinical hypothyroidism, clinicians should focus on concomitant diseases rather than expecting symptomatic relief following levothyroxine substitution. [ABSTRACT FROM AUTHOR]

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.

Objective: To test whether an intervention consisting of four patient-centered consultations improves glycemic control and self-management skills in patients with poorly regulated type 2 diabetes (T2DM), compared to a control group receiving usual care., Methods: Unblinded parallel randomized controlled trial including 97 adults diagnosed with T2DM ≥ 1 year and hemoglobin A1c (HbA1c) levels ≥ 8.0% (64 mmol/mol). Consultations incorporated tools supporting self-reflection, learning processes, and goal setting. Primary outcome was HbA1c. Secondary outcomes were autonomy support, motivation, self-management skills, and well-being., Results: Average HbA1c decreased slightly in both groups. Autonomy support and frequency of healthy eating were significantly higher in the intervention group. Most participants in the intervention group chose to set goals related to diet and physical exercise. Implementation of the intervention was inconsistent., Conclusion: Despite increased autonomy support and individual goal-setting, the intervention was not superior to usual care in terms of glycemic control. More research is needed on how individual preferences and goals can be supported in practice to achieve sustainable behavior changes., Practice Implications: The intervention promoted participant engagement and supported exploration of participants' challenges and preferences. Further exploration of more flexible use of tools adapted to individual contexts is recommended., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Iodine is essential for the production of thyroid hormones. In pregnancy, physiological changes occur that can lead to iodine deficiency and impairment of fetal neurological development. We aimed to assess the iodine intake in pregnant women in Eastern Denmark, compare iodine levels in Eastern and Western Denmark and to identify potentially vulnerable groups., Methods: This was a cross-sectional cohort study of pregnant Danish women (n = 240). Questionnaires and urine samples were collected at the Ultrasound Clinic, Hvidovre Hospital, Denmark, and urinary iodine concentrations (UIC) (µg/l) were measured. Predictors of iodine supplement use were examined by multivariate logistic regression models., Results: The pregnant women from Eastern Denmark had a median age of 30 years and the median gestational week at which they were included in the study was week 19. The majority took iodine-containing supplements (86%). The median UIC was 118 (interquartile range (IQR): 79-196) µg/l in iodine supplement users and 82 (IQR: 41-122) µg/l in non-users (p < 0.001). Predictors of not using iodine supplement in Eastern and Western Denmark were short maternal education, non-Danish origin and pre-pregnancy obesity., Conclusions: The iodine status in Danish pregnant women was below WHO recommendations. Iodine supplement non-users are at a particular risk of iodine deficiency. Low maternal education, non-Danish origin and pre-pregnancy obesity are predictors of non-iodine supplement use. An increase in iodine fortification may be recommended to improve the iodine status in pregnant Danish women., Funding: none., Trial Registration: not relevant.

Context: Limited longitudinal data are available on changes in the thyroid gland structure in a population and how this is influenced by iodine fortification (IF)., Objective: Our objective was to clarify how IF influenced thyroid gland structure in 2 regions with different iodine intake at baseline (Copenhagen, mild iodine deficiency [ID]; Aalborg, moderate ID)., Design and Setting: We conducted a longitudinal population-based study (DanThyr) where participants were examined before (1997) and after (2008) the Danish mandatory IF of salt (2000)., Participants: We examined 2465 adults, and ultrasonography was performed by the same sonographers using the same equipment, after controlling performances., Main Outcome Measure: Change in thyroid gland structure was evaluated., Results: The follow-up period saw an increased prevalence of multinodularity (9.8%-13.8 %, P < .001), especially in the previously moderate ID region of Aalborg (9.1%-15.4%, P < .001), whereas no change in prevalence was seen for solitary nodules (5.6%-5.1%, P = .34). In individual participants, changes in thyroid structure and disappearance of thyroid nodules during the 11 years was common with an overall normalization rate of 21.2 (95% confidence interval [CI] = 17.9-24.9) per 1000 person-years. Solitary nodules had a significantly higher normalization rate than multiple nodules (normalization rate ratio 0.47 [95% CI = 0.32-0.67]). A regional difference (Aalborg vs Copenhagen) was seen between normalization rates of multiple nodules (normalization rate ratio 0.29 [95% CI = 0.12-0.64]), but not for solitary nodules (normalization rate ratio 0.81 [95% CI = 0.53-1.21])., Conclusions: Changes in the thyroid gland structure with both appearance and disappearance of thyroid nodules are common after an iodization program.

Context: The 1-year postpartum period is often accompanied by increased risk for thyroid disease., Objective: The objective of the study was to investigate the role of reproductive risk factors in the development of autoimmune overt hypothyroidism in the years after the 1-year postpartum period., Design, Setting, and Subjects: In a population study, we included Danish women with new autoimmune overt hypothyroidism not diagnosed within the first year after a pregnancy (n = 117; median age 53.0 y) and age- and region-matched euthyroid controls from the same population (n = 468)., Main Outcome Measures: In conditional multivariate logistic regression models, we analyzed the associations between the development of autoimmune hypothyroidism and age at menarche/menopause, years of menstruations, pregnancies, spontaneous and induced abortions, live births, and years on oral contraceptives and postmenopausal hormone replacement therapy, also taking various possible confounders into account., Results: In multivariate regression models with no event as reference, the odds ratios (ORs) for hypothyroidism [95% confidence interval (CI)] after one/two/three or more live births were 1.72 (0.56-5.32)/3.12 (1.14-8.48)/4.51 (1.65-12.3) and 1.02 (0.57-1.81)/2.70 (1.27-5.75) after one/two or more induced abortions. Findings were valid only for women having hypothyroidism diagnosed before the age of 55 years. We found no association between disease development and other reproductive risk factors investigated., Conclusions: Previous live births and induced abortions were major risk factors for the development of autoimmune overt hypothyroidism in women aged up to 55 years. The increased risk for hypothyroidism after giving birth extends longer than just to the 1-year postpartum period, and numbers of previous pregnancies should be taken into account when evaluating the risk of hypothyroidism in a young women.

Until 2000 Denmark was iodine deficient with moderate deficiency in the western part and mild deficiency in the eastern part. The occurrence of goitre and autonomous hyperthyroidism was high, and pregnancy was associated with a reduction in thyroid function. After cautious mandatory iodization of household salt and salt used for bread production, the iodine intake in Denmark is now low normal. The DanThyr monitoring has shown a transient increase in hyperthyroidism followed by a decrease, and goitre is becoming less common. Hypothyroidism has become more common, and this has to be followed.

Introduction: We analyzed the trend in body mass index (BMI) as well as in the prevalence of overweight and obesity among Danish adults, mainly women, from 1997/1998 to 2004/2005 and evaluated any regional differences., Material and Methods: Data were drawn from two cross-sectional population-based studies conducted in parallel in Aalborg and Copenhagen from 1997/1998 and 2004/2005. Height and weight were measured in a total of 7,487 participants in the two cohorts., Results: In the total cohort, we found no significant difference in BMI from 1997/1998 to 2004/2005 (p = 0.828). There was an increase in BMI in Aalborg of 0.32 (p = 0.030), while in Copenhagen we observed a statistically significant decrease in BMI of 0.30 (p = 0.017). The difference in change over time in BMI between the two regions was significant (p = 0.002). Also the difference in the trend in prevalence of overweight and obesity was statistically significant between the two cities (p = 0.010)., Conclusion: Our results indicate that the obesity epidemic is leveling off - at least among women - and that it may even be receding in Copenhagen. Nevertheless, the absolute average BMI values and the prevalence of overweight and obesity in both cities are high which underlines the need for further initiatives to prevent obesity-related health risks in the future., Funding: The DanThyr studies were supported by funding from the Tømmerhandler Vilhelm Bang Foundation, the Copenhagen Corporation Research Foundation, the 1991 Pharmacy Foundation, the Danish Medical Foundation, the Health Insurance Foundation, the Agnes and Knut Mørk Foundation, the Wedel Wedelsborg Foundation, the Ortho-Clinical Foundation and BRAHMS Diagnostica., Trial Registration: not relevant.

Iodization of salt is an effective strategy to prevent iodine deficiency disorders. Recent studies, however, indicate that increasing the iodine intake in a population may give rise to an increased incidence of hypothyroidism, but the association has not been fully clarified. In Denmark, iodization of salt was initiated in 1998 because of mild-to-moderate iodine deficiency. The aim of this study was to evaluate the effect of the raised iodine intake on the nationwide incident use of thyroid hormone replacement therapy (levothyroxine) to treat hypothyroidism. Data on all use of levothyroxine was extracted from the Register of Medicinal Product Statistics during the period 1995-2009 and linked to other nationwide registers by use of the Danish identification number. Persons with previous thyroid surgery were excluded. In the studied period 71,565 incident users were identified. The incidence rate increased 75% in the moderately iodine deficient region (72.2 incident users/100,000 person-years in 1997 to 126.6 in 2008) and 87% in the mildly deficient region (86.9-162.9). When stratified by sex and age-group (00-39, 40-64, 65+) the largest relative increase was seen among women in the youngest age-group, where more than a doubling was seen. The mechanisms behind the increase may be a result of iodine-induced hypothyroidism, although a higher diagnostic activity with regard to thyroid dysfunction and intensified treatment of subclinical hypothyroidism may also play a role. Our findings stress the need for caution when initiating iodine fortification programs to keep the intake within the optimal range, and the need for continuous monitoring.

Context: Iodine fortification (IF) of salt was introduced in Denmark in 1998. Little is known about the effect of a minor increase in iodine intake on the incidence of hypothyroidism. We prospectively identified all new cases of overt hypothyroidism in two areas of Denmark before and for the first 7 yr after IF had been introduced., Methods: A computer-based register was used to identify continuously all new cases of overt hypothyroidism in two subcohorts with previous moderate and mild iodine deficiency (ID), respectively (Aalborg, n = 310,124, urinary iodine = 45 microg/liter; and Copenhagen, n = 225,707, urinary iodine = 61 microg/liter). Data were obtained 1) before IF (1997-1998), 2) during voluntary IF (1999-2000), 3) during early (2001-2002) and 4) during late (2003-2005) period with mandatory IF., Results: The overall incidence rate of hypothyroidism increased during the study period: baseline, 38.3/100,000.yr; voluntary IF, 43.7 (not significant vs. baseline); early mandatory IF, 48.7 [vs. baseline, rate ratio (RR) = 1.27; 95% confidence interval (CI) = 1.10-1.47]; and late mandatory IF, 47.2 (vs. baseline, RR = 1.23; 95% CI = 1.07-1.42). There was a geographic difference because hypothyroidism increased only in the area with previous moderate ID: Aalborg, late mandatory IF vs. baseline, 40.3/29.7 (RR = 1.11; 95% CI = 1.11-1.66); Copenhagen, 56.7/51.6 (RR = 1.10; 95% CI = 0.90-1.34). The increase occurred in young and middle-aged adults., Conclusion: Even a cautious iodization of salt was accompanied by a moderate increase in the incidence rate of overt hypothyroidism. This occurred primarily in young and middle-aged subjects with previous moderate ID.

Selenium is an essential micronutrient. The average selenium intake in Danish adults is close to the recommended level of 40-50 mg/day. There is no scientific documentation showing that an increased selenium intake will result in disease prevention. However, a preventive effect on some cancers and hearth disease cannot be ruled out. Fortification of foods via increased selenium content in fertilizers is a possible way of increasing selenium intake. The tolerable upper intake level of 60 mg/day in children 1-3 years old must not be exceeded, which makes fortification difficult.

Background: Thyroid autoimmunity is more common in females than in males. One possible explanation for this female preponderance may be the effect of oestrogens on the immune system. It has also been suggested that foetal microchimerism involving transfer of foetal cells into maternal tissue during pregnancy may play an important role., Objective: We investigated the association between the presence of circulating thyroid autoantibodies and previous pregnancy, parity and the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) in a population cohort., Methods: We examined 3712 women randomly selected from the general population. Serum was analysed for thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) using assays based on an RIA technique (DYNO test). Data were analysed in logistic regression models to adjust for possible confounders. Women previously treated for thyroid disease or with pregnancy within 1 year prior to the study were excluded from the analyses., Results: In both univariate and multivariate models and whether the presence of TPO-Ab and Tg-Ab was investigated alone or in combination, findings were negative with respect to an association between circulating thyroid antibodies and previous pregnancy, number of pregnancies, parity and previous abortion. There was no association between thyroid autoantibodies and use of OCs. Women aged 60-65 years receiving HRT now or previously had a lower prevalence of Tg-Ab (univariate, P = 0.01; multivariate, P = 0.02). No such association was observed between HRT and TPO-Ab., Conclusion: In this population study there was no association between previous pregnancy, parity and thyroid antibodies, which argues against the role of microchimerism as a trigger of thyroid autoimmunity. Exogenous oestrogens may reduce aspects of autoimmunity.