Lone Banke Rasmussen

Iodine intake as a determinant of thyroid disorders in populations

UNLABELLED 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 (Hashimotos 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.

Dietary iodine intake and urinary iodine excretion in a Danish population: effect of geography, supplements and food choice

I deficiency diseases remain a health problem even in some developed countries. Therefore, measurement of I intake and knowledge about food choice related to I intake is important. We examined I intake in 4649 randomly selected participants from two cities in Denmark (Copenhagen and Aalborg) with an expected difference in I intake. I intake was assessed both by a food frequency questionnaire and by measuring I in casual urine samples. I excretion was expressed as a concentration and as estimated 24-h l excretion. Further, subgroups with low I intake were recognized. I intake was lower in Aalborg than in Copenhagen for all expressions, and lower than recommended in both cities if I intake from supplements was not included. Milk was the most important I source, accounting for about 44% of the I intake, and milk (P<0.001) and fish (P=0.009) intake was related to I excretion in a multiple linear regression model. Thus, risk groups for low I intake were individuals with a low milk intake, those with a low intake of fish and milk, those not taking I supplements and those living in Aalborg where the I content in drinking water is lower. Even individuals who followed the advice regarding intake of 200-300 g fish/week and 0.5 litres milk/d had an intake below the recommended level if living in Aalborg.

Iodine intake before and after mandatory iodization in Denmark: results from the Danish Investigation of Iodine Intake and Thyroid Diseases (DanThyr) study

Iodine deficiency is still common in some European countries. In Denmark an iodine fortification programme was introduced in 1998 and a monitoring programme was established prior to iodization. This study reports the change in urinary iodine excretion caused by fortification and investigates determinants of iodine intake after fortification. Iodine excretion in casual urine samples was assessed in 4649 subjects in 1997-8 and in 3570 comparable subjects in 2004-5 in women 18-22, 25-30, 40-45 and 60-65 years of age and in men 60-65 years of age living in Aalborg (western part of Denmark) or Copenhagen (eastern part of Denmark). These areas had moderate and mild iodine deficiency, respectively, before iodine fortification. All subjects filled in a FFQ and a questionnaire regarding lifestyle factors. Iodine excretion, expressed as the estimated 24 h urinary iodine excretion and as urinary iodine concentration, increased significantly in all age and sex groups. However, the iodine intake was still below the recommended in the youngest age groups in both cities and in women 40-45 years of age living in Aalborg. Intake of milk and salt had strong significant direct associations with iodine excretion (P < 0.001). It is concluded that although the median iodine intake in the whole study population is at the recommended level, some groups still have an intake below the recommended. It is important to have a moderate milk intake to obtain a sufficient iodine intake in Denmark.

A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population

Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (Tg‐Ab) as the most common can often be demonstrated in serum. The effect of public iodization programmes on antibody prevalence is uncertain.

Thyroglobulin as a marker of iodine nutrition status in the general population

OBJECTIVE The iodine status of a population is traditionally evaluated by either urinary iodine (UI) excretion or by some measure of thyroid volume and the prevalence of goitre. In this prospective study of a mandatory iodization programme, we aimed to evaluate serum thyroglobulin (Tg) as a marker of iodine status in the population. METHODS Two identical cross-sectional studies were performed before (1997-1998, n=4649) and after (2004-2005, n=3570) the initiation of the Danish iodization programme in two areas with mild and moderate iodine deficiency. Serum Tg was measured from blood samples. Thyroid volume was measured by ultrasonography. RESULTS Before iodization, the median serum Tg was considerably higher in moderate than in mild iodine deficiency. Iodization led to a lower serum Tg in all examined age groups. The marked pre-iodization difference in Tg level between the regions was eliminated. The prevalence of Tg above the suggested reference limit (40 microg/l) decreased from 11.3 to 3.7% (P<0.0001). Using bootstrapping, we demonstrated a higher efficacy of Tg than of thyroid volume to show a difference between pre- and post-iodization values. CONCLUSION We found serum Tg to be a suitable marker of iodine nutrition status in the population. The results may suggest that the Danish iodization programme has led to a sufficient iodine intake, even if the median UI excretion is still marginally low according to WHO criteria.

Low compliance with recommendations on folic acid use in relation to pregnancy: is there a need for fortification?

OBJECTIVE As a means to prevent neural tube defects (NTDs), women planning pregnancy in Denmark are recommended to take a dietary supplement of 400 microg folic acid daily during the periconceptional period. We examined compliance with this recommendation in a national survey. DESIGN Cohort study on pregnant women in Denmark. SETTING The Danish National Birth Cohort (DNBC). SUBJECTS From November 2000 to February 2002, 22,000 pregnant women were recruited for DNBC. Use of dietary supplements was recorded at enrollment. Compliance with the recommendation was related to an information campaign that took place during the second half of 2001, and to lifestyle factors provided in a telephone interview by the end of the first trimester of pregnancy. RESULTS An increase was seen in the proportion of women complying with the recommendation in the study period and this coincided with the information campaign events. However, even at the end of the period, only 22.3% of the women who had planned their pregnancy fully complied with the recommendation. No increase at all was seen in periconceptional folic acid use among women with unplanned pregnancies. Young age, low education and smoking were identified as factors that determined non-compliance. CONCLUSIONS Alternative and more effective strategies are needed if the Danish population is to benefit fully from the knowledge that folic acid prevents NTDs. Future strategies should not only target vulnerable groups, such as the less educated and the young, but also women who get pregnant without planning this. The only possible way to reach the last group may be through fortification of foods with folic acid.

Smoking is negatively associated with the presence of thyroglobulin autoantibody and to a lesser degree with thyroid peroxidase autoantibody in serum : a population study

BACKGROUND Autoimmune thyroid diseases are common and the prevalence of circulating thyroid antibodies (thyroid peroxidase antibody, TPO-Ab and thyroglobulin antibody, Tg-Ab) is high in the population. The knowledge of a possible association between lifestyle factors and circulating thyroid antibodies is limited. AIM To evaluate the correlation between smoking habits and the presence of circulating TPO-Ab and Tg-Ab. MATERIAL AND METHODS In a cross-sectional comparative population study performed in two areas of Denmark with moderate and mild iodine deficiency, 4649 randomly selected subjects from the population in some predefined age groups between 18 and 65 years were examined. Blood tests were analysed for TPO-Ab and Tg-Ab using assays based on the RIA technique. The participants answered questionnaires, were clinically examined and blood and urine samples collected. RESULTS Data were analysed in multivariate logistic regression models. There was a negative association between smoking and the presence of thyroid autoantibodies in serum. This association was observed for the presence of TPO-Ab and/or Tg-Ab, TPO-Ab (without respect to Tg-Ab status), Tg-Ab (without respect to TPO-Ab status) and both antibodies together. The association between smoking and thyroid autoantibodies was stronger for Tg-Ab than for TPO-Ab. There was no association between smoking and TPO-Ab measured alone or between smoking and TPO-Ab when Tg-Ab was included in the model as an explanatory variable. CONCLUSION Smoking was negatively associated with the presence of thyroid autoantibodies with the strongest association between smoking and Tg-Ab. The study design precludes any conclusions as to the cause of the negative association between smoking thyroid autoantibodies.

Selenium status, thyroid volume and multiple nodule formation in an area with mild iodine deficiency

OBJECTIVE The objective was to study the associations between serum selenium concentration and thyroid volume, as well as the association between serum selenium concentration and risk for an enlarged thyroid gland in an area with mild iodine deficiency before and after iodine fortification was introduced. Another objective was to examine the association between serum selenium concentration and prevalence of thyroid nodules. DESIGN Cross-sectional study. METHODS We studied participants of two similar cross-sectional studies carried out before (1997-1998, n=405) and after (2004-2005, n=400) introduction of iodine fortification. Serum selenium concentration and urinary iodine were measured, and the thyroid gland was examined by ultrasonography in the same subjects. Associations between serum selenium concentration and thyroid parameters were examined in multiple linear regression models or logistic regression models. RESULTS Serum selenium concentration was found to be significantly, negatively associated with thyroid volume (P=0.006), and a low selenium status significantly increased the risk for thyroid enlargement (P=0.007). Furthermore, low serum selenium status had a tendency to increase the risk for development of multiple nodules (P=0.087). CONCLUSIONS Low serum selenium concentration was associated with a larger thyroid volume and a higher prevalence of thyroid enlargement.

Validation of the Danish 7-day pre-coded food diary among adults: energy intake v. energy expenditure and recording length.

Under-reporting of energy intake (EI) is a well-known problem when measuring dietary intake in free-living populations. The present study aimed at quantifying misreporting by comparing EI estimated from the Danish pre-coded food diary against energy expenditure (EE) measured with a validated position-and-motion instrument (ActiReg). Further, the influence of recording length on EI:BMR, percentage consumers, the number of meal occasions and recorded food items per meal was examined. A total of 138 Danish volunteers aged 20-59 years wore the ActiReg and recorded their food intake for 7 consecutive days. Data for 2504 participants from the National Dietary Survey 2000-2 were used for comparison of characteristics and recording length. The results showed that EI was underestimated by 12 % on average compared with EE measured by ActiReg (PreMed AS, Oslo, Norway). The 95 % limits of agreement for EI and EE were - 6.29 and 3.09 MJ/d. Of the participants, 73 % were classified as acceptable reporters, 26 % as under-reporters and 1 % as over-reporters. EI:BMR was significantly lower on 1-3 consecutive recording days compared with 4-7 recording days (P < 0.03). Percentage consumers of selected food items increased with number of recording days. When recording length was 7 d, the number of reported food items per meal differed between acceptable reporters and under-reporters. EI:BMR was the same on 4 and 7 consecutive recording days. This was, however, a result of under-reporting in the beginning and the end of the 7 d reporting. Together, the results indicate that EI was underestimated at group level and that a 7 d recording is preferable to a 4 d recording period.

Evaluation of a semi-quantitative food frequency questionnaire to estimate iodine intake

Objective: To evaluate a food frequency questionnaire (FFQ) used to assess the dietary intake of iodine.Design: The iodine intake determined by the FFQ was compared with 4-day dietary records and with iodine excretion in 24 h urine samples in a subgroup of participants in a cross-sectional study of iodine intake and thyroid diseases in Denmark. Furthermore, the intake of fish determined from the FFQ was compared with the intake of fish from a simple record kept for 3 months.Subjects: Women aged 25–30 y and 60–65 y.Results: Median iodine intake was similar when determined from the FFQ and from dietary records and the correlation between these measures was 0.52 (P<0.001). Iodine intake was higher than iodine excretion (P<0.001). The cross-check questions in the FFQ (for example the question ‘How often did you get any kind of fish?’) underestimated the intake. In contrast, the intake of a specific fish tended to be overestimated by the FFQ when compared with the 3 month record of fish intake.Conclusion: The FFQ can be used to classify subjects into low and high iodine intake groups, but the level of iodine tends to be overestimated.Sponsorship: The Danish Medical Foundation and the 1991 Pharmacy Foundation.European Journal of Clinical Nutrition (2001) 55, 287–292