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.

Does Subclinical Hypothyroidism Add Any Symptoms? Evidence from a Danish Population-Based Study.

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.

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.

Increased Incidence Rate of Hypothyroidism After Iodine Fortification in Denmark: A 20-Year Prospective Population-Based Study.

OBJECTIVE: To monitor the impact of a cautious iodine fortification (IF) on the incidence of overt hypothyroidism in two subpopulations with different levels of preexisting iodine deficiency (ID). DESIGN: A 20-year (1997 to 2016) prospective population-based study identified all new cases of diagnosed overt biochemical hypothyroidism in two open cohorts: a western cohort with moderate ID (n = 309,434; 1 January 1997) and an eastern cohort with mild ID (n = 224,535; 1 January 1997). A diagnostic algorithm was applied to all thyroid function tests performed within the study areas, and possible new cases were verified individually. Mandatory IF of salt was initiated in mid-2000 (13 ppm). The current study is a part of the DanThyr study. RESULTS: At baseline, standardized incidence rates (SIRs) of hypothyroidism were 32.9 and 47.3/100.000/y in the cohorts with moderate and mild ID, respectively. The SIR of hypothyroidism increased significantly in both cohorts after implementing mandatory IF, with peak values of 150% in 2014 to 2016 for the moderate ID cohort and 130% in 2004 to 2005 for the mild ID cohort. Significant increases in SIR were seen among the young and middle-aged participants of both cohorts, whereas no changes were seen among the elderly participants (≥60 years). The follow-up period for the mildly iodine-deficient cohort was restricted up to and including 2008. CONCLUSION: The cautious initiation of the IF program in Denmark caused a sustained increase in hypothyroidism incidence among subjects residing in areas of moderate and mild ID but only among the young and middle-aged participants.

Thyrotoxicosis after iodine fortification. A 21-year Danish population-based study.

OBJECTIVE: Monitoring the influence of cautious iodine fortification (IF) on the incidence rate of overt thyrotoxicosis in Denmark with formerly frequent multinodular toxic goitre. DESIGN: A 21-year (1997-2017) prospective population-based study identified all new cases of overt biochemical thyrotoxicosis in two open cohorts: a Western cohort with moderate iodine deficiency (ID) and an Eastern cohort with mild ID (total n = 533 969 by 1 January 1997). A diagnostic algorithm was applied to all thyroid function tests performed within the study areas. Mandatory IF of salt was initiated in mid-2000 (13 ppm). This study is a part of DanThyr. RESULTS: The standardized incidence rate (SIR) of thyrotoxicosis at baseline (1997-1998) was 128.5/100.000/year in the cohort with moderate ID and 80.1 in the cohort with mild ID. SIR increased markedly in both cohorts during the initial years of IF (moderate/mild ID: +39/+52% in 2000-2001/2004-2005) and subsequently decreased to baseline level (mild ID) or below (moderate ID) by 2008. The decline was due to a marked decrease in the incidence rate among elderly subjects and a moderate decrease among the middle aged. The follow-up period for the mildly iodine deficient cohort was restricted to 2008. A continuous decline in SIR was observed for the remainder of the study period in the area with moderate ID (33% below baseline in 2016-2017). CONCLUSION: The rise in thyrotoxicosis incidence with cautious mandatory IF returned to baseline level after 7-8 years and levelled out at 33% below baseline in the population with previously moderate ID after 16-17 years.

Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population-Based Case-Control Study.

BACKGROUND: Clinic-based studies have indicated that older hypothyroid patients may present only few symptoms. METHODS: In this population-based study of hypothyroidism, we investigated how the power of symptom presence predicts overt hypothyroidism in both young and older subjects. We identified patients newly diagnosed with overt autoimmune hypothyroidism in a population (n = 140, median thyroid-stimulating hormone, 54.5; 95% confidence interval [CI], 28.3-94.8; median total T4, 37; 95% CI, 18-52) and individually matched each patient with 4 controls free of thyroid disease (n = 560). Participants filled out questionnaires concerning the presence and duration of symptoms. We compared the usefulness of hypothyroidism-associated symptoms in predicting overt hypothyroidism in different age groups (young: <50 years, middle age: 50-59 years, old: ≥60 years) also taking various confounders into account. RESULTS: In young hypothyroid patients, all 13 hypothyroidism-associated symptoms studied were more prevalent than in their matched controls, whereas only 3 of those (tiredness, shortness of breath, and wheezing) were more prevalent in old patients. The mean numbers of symptoms presented at disease onset were 6.2, 5.0, and 3.6 at the ages of 0 to 49 years, 50 to 59 years, and 60+ years, respectively. In young versus old people with 0 to 1 symptoms, the odds ratio for being hypothyroid was 0.04 (95% CI, 0.007-0.18) versus 0.34 (95% CI, 0.15-0.78) (reference all other groups). In young versus old subjects reporting ≥4 symptoms, the odds ratio for being hypothyroid was 16.4 (95% CI, 6.96-40.0) versus 2.22 (95% CI, 1.001-4.90). Receiver operating characteristic analyses revealed that the symptom score was an excellent tool for predicting hypothyroidism in young men (area under the receiver operating characteristic curve, 0.91; 95% CI, 0.82-0.998), whereas it was poor in evaluating older women (area under the receiver operating characteristic curve, 0.64; 95% CI, 0.54-0.75). CONCLUSION: Hypothyroid symptom score is a good discriminating tool to identify hypothyroidism in young patients but fails to identify hypothyroidism in the elderly. Thus, thyroid function should be tested on wide indications in old age.

Iodine excretion in school children in Copenhagen.

INTRODUCTION: Studies of dietary habits show a high iodine intake in children in Denmark. Iodine excretion in children has not previously been assessed. Iodine excretion in adults is below the recommended threshold, and it is therefore being discussed to increase the fortification level. The main objective of this study was to assess iodine excretion in children living in Copenhagen to establish whether a moderate increase in iodine fortification would lead to excess iodine intake in this group. METHODS: Children in first and fifth grade were recruited through schools in Copenhagen. In total, 244 children de-ivered a urine sample. Urine samples were analysed for iodine and creatinine, and the results were expressed as urinary iodine concentration (UIC) and as estimated 24-h iodine excretion. Iodine excretion in children was also compared with that of adults living in the same area, investigated in a prior study. RESULTS: The median UIC was within the recommended level; 145 (range: 116-201) µg/l for boys and 128 (range: 87-184) µg/l for girls, and was lower in fifth grade students than in first grade students. Estimated 24-h iodine excretion was higher in boys than in girls, but did not differ according to grade. The UIC was higher in children than in adults from the same area. CONCLUSIONS: The iodine excretion among schoolchildren in Copenhagen, an area with a relatively high iodine content in tap water, was within the recommended range as assessed by the UIC. An increased iodine fortification will not have negative consequences for this group. FUNDING: The Ministry of Food, Agriculture and Fisheries. TRIAL REGISTRATION: not relevant.

Serum thyroglobulin as a biomarker of iodine deficiency in adult populations.

OBJECTIVE: To clarify which factors may influence the serum Tg level in an adult population and how this may affect Tg as a biomarker of iodine deficiency (ID). DESIGN AND METHODS: Two identical cross-sectional studies were performed before (C1a: 1997-98, n = 4649) and after (C2: 2004-05, n = 3570) the Danish mandatory iodine fortification (IF) of salt (2000). Additionally, a follow-up study of C1a was performed after IF (C1b: 2008-10, n = 2465). The studies took place in two regions with mild (Copenhagen) and moderate (Aalborg) ID before IF. Serum Tg was measured by immunoradiometric method and investigated as outcome variable in multivariate models. RESULTS: Multiple factors were associated with serum Tg. Some were directly related to iodine intake (cohort, urinary iodine concentration (UIC) level and region), and some were likely mediators of iodine intake effects on Tg (thyroid nodularity, thyroid size and autonomy with low TSH). Others were caused by Tg assay interference (Tg-Ab positivity), aggravation of ID (childbirths and smoking) or TSH stimulation of the thyroid. Estimated 24-h urinary iodine excretion was a more sensitive predictor of Tg than UIC. Iodine supplement users had low median Tg values compared with nonusers both before and after IF. CONCLUSIONS: Multiple factors should be taken into consideration when evaluating Tg as a marker of ID in adult populations, and the Tg results may depend on the assay used. Still, Tg is a sensitive marker of ID. We suggest including a reference population with known sufficient iodine intake when Tg is used to evaluate ID.

Parity and 11-Year Serum Thyrotropin and Thyroid Autoantibody Change: A Longitudinal Population-Based Study.

BACKGROUND: A role for female reproductive factors in the pathogenesis of thyroid autoimmunity has been suggested. This study investigated the prospective association between parity, abortion, use of oral contraceptive pill (OCP), and use of hormone replacement therapy (HRT), and 11-year change in serum thyrotropin (TSH), as well as change in thyroid peroxidase autoantibody (TPOAb) status. METHODS: A random sample of 4649 people aged 18-65 years participated in a population-based study in the period 1997-1998. In the study presented here, 1749 non-pregnant women with no history of thyroid disease were included who participated in the 11-year follow-up examination in the period 2008-2010. Gynecological exposures were reported in a self-administered questionnaire at baseline and follow-up. TSH and TPOAb were measured at baseline and follow-up. Increased TPOAb status during follow-up was defined as a TPOAb below the assay cutoff (<30 kIU/L) at baseline and a TPOAb ≥30 kIU/L at follow-up. Multiple linear regression models were used, adjusted for age, smoking status, and urinary iodine excretion. RESULTS: An inverse association was found between the number of years on HRT and the risk (odds ratio) of increased TPOAb status during follow-up (0.735 [confidence interval 0.558-0.968], p = 0.03). However, this association was not statistically significant when applying the Bonferroni adjusted significance level. The remaining reproductive factors showed no statistically significant association with risk of increased TPOAb during follow-up. Furthermore, parity, abortions, use of OCP, HRT use, age at menarche, and being pre- or postmenopausal were not significantly associated with 11-year TSH change. CONCLUSIONS: No statistically significant association was found between the studied female reproductive measures and 11-year risk of TSH or TPO change. A possible protective role for HRT in the etiology of thyroid autoimmunity, however, deserves further research.

Serum thyroglobulin before and after iodization of salt: an 11-year DanThyr follow-up study.

OBJECTIVE: Our objective was to investigate individual serum thyroglobulin (Tg) changes in relation to iodine fortification (IF) and to clarify possible predictors of these changes. DESIGN: We performed a longitudinal population-based study (DanThyr) in two regions with different iodine intake at baseline: Aalborg (moderate iodine deficiency (ID)) and Copenhagen (mild ID). Participants were examined at baseline (1997) before the mandatory IF of salt (2000) and again at follow-up (2008) after IF. METHODS: We examined 2465 adults and a total of 1417 participants with no previous thyroid disease and without Tg-autoantibodies were included in the analyses. Serum Tg was measured by immunoradiometric method. We registered participants with a daily intake of iodine from supplements in addition to IF. RESULTS: Overall, the follow-up period saw no change in median Tg in Copenhagen (9.1/9.1 µg/l, P=0.67) while Tg decreased significantly in Aalborg (11.4/9.0 µg/l, P<0.001). Regional differences were evident before IF (Copenhagen/Aalborg, 9.1/11.4 µg/l, P<0.001), whereas no differences existed after IF (9.1/9.0 µg/l, P=1.00). Living in Aalborg (P<0.001) and not using iodine supplements at baseline (P=0.001) predicted a decrease in Tg whereas baseline thyroid enlargement (P=0.02) and multinodularity (P=0.01) were associated with an individual increase in Tg during follow-up. CONCLUSIONS: After IF we observed a decrease in median Tg in Aalborg and the previously observed regional differences between Aalborg and Copenhagen had levelled out. Likewise, living in Aalborg was a strong predictor of an individual decrease in serum Tg. Thus, even small differences in iodine intake at baseline were very important for the individual response to IF.

Gender differences in symptoms of hypothyroidism: a population-based DanThyr study.

OBJECTIVES: We examined the gender-specific symptom prevalences in hypothyroidism and in healthy controls and explored the extent to which symptoms indicative of thyroid status may be different in women and men. DESIGN AND METHODS: Patients newly diagnosed with overt autoimmune hypothyroidism (n = 140) and controls free of thyroid disease (n = 560) recruited from the same population participated in a population-based study of The Danish Investigation of Iodine Intake and Thyroid Diseases (DanThyr). Participants underwent a comprehensive programme including blood tests and completion of questionnaires. The gender-specific distribution of 13 hypothyroidism-associated symptoms and a simple combined score (0-13) was explored in conditional uni- and multivariate models taking into account a broad spectrum of possible confounders. Diagnostic odds ratios (DORs) were calculated as measures for the association between participant status (case vs control) and presence of symptoms (yes vs no). RESULTS: In overt autoimmune hypothyroidism, 94·9% of women and 91·3% of men (P = 0·62) reported at least one of the hypothyroidism-associated symptoms, with tiredness as the most common symptom followed by dry skin and shortness of breath. In contrast, women free of thyroid disease self-reported at least one hypothyroidism-associated symptom considerably more often than men (73·7% vs 51·1%, P < 0·001). DORs (±SEM) for 0-1/2-3/4-13 symptoms were 0·07 (0·04-0·10)/2·15 (1·57-2·94)/7·99 (6·15-10·4) in men and 0·21 (0·16-0·28)/0·62 (0·58-0·66)/1·99 (1·90-2·09) in women. CONCLUSION: The presence of symptoms is more indicative for overt autoimmune hypothyroidism in men than in women, and presumably persistent symptoms after therapy of hypothyroidism will be more common in women.

Iodine excretion has decreased in Denmark between 2004 and 2010--the importance of iodine content in milk.

Fortification with the essential trace element iodine is widespread worldwide. In the present study, results on iodine excretion and intake of iodine-rich foods from a cross-sectional study carried out in 2004-5, 4 to 5 years after the implementation of mandatory iodine fortification, were compared with data in a study carried out in 2008-10. The 2008-10 study was a follow-up of a cross-sectional study carried out before iodine fortification was implemented. Participants in the cross-sectional studies were randomly selected. Both studies were carried out in the cities of Aalborg and Copenhagen in Denmark. The median urinary iodine concentration decreased in women from 97 µg/l (n 2862) to 78 µg/l (n 2041) (P< 0.001). The decrease persisted after adjustment for age, city and education, and if expressed as estimated 24 h iodine excretion. The prevalence of users of iodine containing dietary supplements increased from 29.4 to 37.3 % (P< 0.001). The total fluid intake increased in women (P< 0.001), but the intake of other iodine-rich foods did not change. The median urinary iodine concentration did not change in men (114 µg/l (n 708) and 107 µg/l (n 424), respectively), while the total fluid intake decreased (P= 0.001). Iodine content was measured in milk sampled in 2000-1 and in 2013. The iodine content was lower in 2013 (12 (sd 3) µg/100 g) compared with that in 2000-1 (16 (sd 6) µg/100 g) (P< 0.001). In conclusion, iodine excretion in women has decreased below the recommended level. The reason might probably, at least partly, be a decreased content of iodine in milk.

Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study.

BACKGROUND: It is generally accepted that patients suffering from hypothyroidism may express few symptoms, but this has not been studied in a population-based study design. OBJECTIVES: To study the array of symptoms as they are reported in newly diagnosed overt autoimmune hypothyroidism using a population-based case-control design. METHODS: Patients with new overt autoimmune hypothyroidism (n=140) and their individually matched thyroid disease-free controls (n=560) recruited from the same population underwent a comprehensive program and self-reported a number of symptoms. We identified the symptoms associated with overt hypothyroidism and calculated positive (LR+) and negative (LR-) likelihood ratios as well as diagnostic odds ratios (DORs) as measures for the association between disease state and symptoms. RESULTS: Among 34 symptoms investigated, 13 symptoms were statistically overrepresented in hypothyroidism. Hypothyroid patients suffered mostly from tiredness (81%), dry skin (63%), and shortness of breath (51%). Highest DORs (95% CI) were reported for tiredness (5.94 (3.70-9.60)), hair loss (4.58 (2.80-7.51)), and dry skin (4.09 (2.73-6.16)). A hypothyroidism-component-score was defined as the number of hypothyroidism-associated symptoms (range: 0-13). LR+ for participants with a hypothyroidism-component-score of 0 was 0.21 (0.09-0.39), meaning that the post-test probability was lowered to 21% of what it was before asking for symptoms. LR+ for scores of 1-2/3/4-6/7-9/10-13 were: 0.47 (0.30-0.72)/1.16 (0.70-1.87)/1.90 (1.29-2.45)/3.52 (2.30-5.36)/6.29 (2.30-17.7). CONCLUSIONS: None of the individual symptoms of hypothyroidism had high LRs or DORs. Thus, neither the presence nor absence of any individual hypothyroidism symptom was reliable in the decision making of who should have their thyroid function tested. Therefore, even minor suspicion should lead to a blood test.

Thyroid nodules in an 11-year DanThyr follow-up study.

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.

Thyroid function and body weight: a community-based longitudinal study.

OBJECTIVE: Body weight and overt thyroid dysfunction are associated. Cross-sectional population-based studies have repeatedly found that thyroid hormone levels, even within the normal reference range, might be associated with body weight. However, for longitudinal data, the association is less clear. Thus, we tested the association between serum thyrotropin (TSH) and body weight in a community-based sample of adult persons followed for 11 years. METHODS: A random sample of 4,649 persons aged 18-65 years from a general population participated in the DanThyr study in 1997-8. We included 2,102 individuals who participated at 11-year follow-up, without current or former treatment for thyroid disease and with measurements of TSH and weight at both examinations. Multiple linear regression models were used, stratified by sex and adjusted for age, smoking status, and leisure time physical activity. RESULTS: Baseline TSH concentration was not associated with change in weight (women, P = 0.17; men, P = 0.72), and baseline body mass index (BMI) was not associated with change in TSH (women, P = 0.21; men, P = 0.85). Change in serum TSH and change in weight were significantly associated in both sexes. Weight increased by 0.3 kg (95% confidence interval [CI] 0.1, 0.4, P = 0.005) in women and 0.8 kg (95% CI 0.1, 1.4, P = 0.02) in men for every one unit TSH (mU/L) increase. CONCLUSIONS: TSH levels were not a determinant of future weight changes, and BMI was not a determinant for TSH changes, but an association between weight change and TSH change was present.

Development of autoimmune overt hypothyroidism is highly associated with live births and induced abortions but only in premenopausal women.

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.

Iodine fortification may influence the age-related change in thyroid volume: a longitudinal population-based study (DanThyr).

OBJECTIVE: To assess the individuals' thyroid volume changes after the mandatory nationwide iodine fortification (IF) program in two Danish areas with different iodine intake at baseline (Copenhagen, mild iodine deficiency (ID) and Aalborg, moderate ID). DESIGN: A longitudinal population-based study (DanThyr). METHODS: We examined 2465 adults before (1997) and after (2008) the Danish IF of salt (2000). Ultrasonography was carried out by the same sonographers using the same equipment, after controlling performances. Participants treated for thyroid disease were excluded from analyses. RESULTS: Overall, median thyroid volume had increased in Copenhagen (11.8-12.2 ml, P=0.001) and decreased in Aalborg, although not significantly (13.3-13.1 ml, P=0.07) during the 11 years of follow-up. In both regions, there was an age-related trend in individual changes in thyroid volume from baseline to follow-up; thyroid volume increased in women <40 years of age and decreased in women >40 years of age. IN A MULTIVARIATE REGRESSION MODEL, HIGHER AGE AT ENTRY WAS A PREDICTOR (P0.05) FOR THYROID VOLUME DECREASE 20% DURING THE FOLLOW-UP PERIOD (WOMEN AGED 4045 YEARS: odds ratio (OR) 4.3 (95% CI, 2.2-8.2); women aged 60-65 years: 5.8 (2.9-11.6)) and individuals of higher age were also less likely to have an increase in thyroid volume (women aged 40-45 years: OR 0.2 (0.1-0.3); women aged 60-65: OR 0.3 (0.2-0.4)). CONCLUSIONS: Age-dependent differences in thyroid volume and enlargement had leveled out after the Danish iodization program. Thus, the previously observed increase in thyroid volume with age may have been caused by ID.

Estimating salt intake in a Caucasian population: can spot urine substitute 24-hour urine samples?

BACKGROUND: A simple and valid alternative for 24-hour urine collection to estimate populational 24-hour urinary sodium excretion would be desirable for monitoring sodium intake in populations. AIM: To assess the validity of the predicted 24-hour urinary sodium excretion using spot urine and two different prediction methods in a Danish population. METHODS: Overall, 473 Danish individuals provided a para-aminobenzoic acid-validated complete 24-hour urine collection and a spot urine sample. Data were collected in the DanThyr study (248 women aged 25-30 years and 60-65 years) and the Inter99 study (102 men and 113 women aged 30-60 years), respectively. The measured 24-hour urine sodium excretion was compared with the predicted 24-hour sodium excretion from a causal urine specimen, using both the Tanaka prediction method and a prediction model developed in a Danish population. RESULTS: The measured 24-hour sodium excretion (median, 5th to 95th percentile) was men 195 (110 to 360) and women 139 (61 to 258), whereas the predicted 24-hour sodium excretion for the Tanaka model was men 171 (117 to 222) and women 153 (92 to 228) and for the Danish model was men 207 (146 to 258); women 134 (103 to 163). The Spearman correlation between predicted and measured 24-hour sodium excretion was 0.39 and 0.49 for the Tanaka and the Danish model, respectively. For both prediction models, the proportion of individuals classified in the same or adjacent quintile was 74% for men and 64% for women. CONCLUSIONS: Both prediction models gave a reasonable classification of individuals according to their sodium excretion. However, the median daily sodium intake was estimated more precisely by the Danish model, especially among men.

Mandatory iodine fortification of bread and salt increases iodine excretion in adults in Denmark - a 11-year follow-up study.

BACKGROUND & AIMS: Iodine fortification is widespread. Systematic monitoring of iodine fortification programs should be carried out to secure an optimal fortification level. Our aim was to investigate the effectiveness of the Danish iodine fortification program by comparing iodine excretion at baseline and at 11-year follow-up, and to study determinants for any change in iodine intake including dietary habits, education, life style factors and health parameters. METHODS: A follow-up study based on the Danish DanThyr cohort examined in 1997-1998 just before iodine fortification was introduced, and reexamined in 2008-2010. In total, 2465 (59.1%) adult participants were reexamined. RESULTS: Median (IQR) iodine concentration in urine had increased by 19 (-25-68) µg/L to 83 (47-133) µg/L. Estimated 24-h iodine excretion had increased by 36 (-21-95) µg/24-h to 134 (93-206), and calculated total iodine intake (diet plus supplements) had increased by 16 (-18-48) µg/day. Iodine excretion had increased significantly in all age and gender groups, but was still below the recommended amount at follow-up. The increase in iodine excretion was positively associated with changes in milk intake, with changes in the use of iodine supplements, and with bread intake at follow-up. Salt intake, education, self-rated health, smoking, alcohol intake and physical activity were not associated with the increase in iodine excretion. CONCLUSIONS: The strategy to combat iodine deficiency in Denmark seems to be working because the fortification led to increased urinary iodine excretion in (almost) all participants. However, the level of iodine fortification of salt is too low.

Determinants of serum T4 and T3 at the time of diagnosis in nosological types of thyrotoxicosis: a population-based study.

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.