Anne Krejbjerg

Predictors of Change in Serum TSH after Iodine Fortification: An 11-Year Follow-Up to the DanThyr Study

CONTEXT Few data are available on the effect of iodine fortification on thyroid function development in a population. OBJECTIVE Our objective was to evaluate changes in thyroid function after iodine fortification in a population and to identify predictors for changes in serum TSH. DESIGN AND SETTING A longitudinal population-based study of the DanThyr C1 cohort examined at baseline (1997-1998) and reexamined 11 yr later (2008-2010). The mandatory program for iodization of salt was initiated in 2000. PARTICIPANTS A total of 2203 individuals, with no previous thyroid disease, living in two areas with different levels of iodine intake, with measurement of TSH and participation in follow-up examination were included in the analysis. MAIN OUTCOME MEASURE Change in serum TSH was evaluated. RESULTS During the 11-yr follow-up, mean TSH increased significantly from 1.27 mU/liter [95% confidence interval (CI) = 1.23-1.30] to 1.38 mU/liter (CI = 1.34-1.43) (P < 0.001). The most pronounced increase was observed in the area with the highest iodine intake [1.30 mU/liter (CI = 1.25-1.35) to 1.49 mU/liter (CI = 1.43-1.55), P < 0.001], whereas the increase was not significant in the low-iodine-intake area [1.24 (CI = 1.19-1.29) to 1.28 (CI = 1.23-1.34), P = 0.06)]. Change in TSH was positively associated with the presence of thyroid peroxidase antibody at baseline (P < 0.001) and negatively associated with baseline thyroid enlargement (P < 0.001) and multiple nodules (P < 0.001). CONCLUSIONS Even small differences in the level of iodine intake between otherwise comparable populations are associated with considerable differences in TSH change at the 11-yr follow-up. Multinodular goiter predicted a less pronounced TSH increase during follow-up, which may be explained by iodine-dependent activity of autonomous nodules.

Epidemiology of nodular goitre. Influence of iodine intake

More than one tenth of the world population is to some degree affected by goitre and most of these harbour nodules. The large differences in thyroid disease prevalence between populations may be caused by genetic and environmental factors. Among the latter, iodine deficiency seems by far to be the most important risk factor. Thus, nodular goitre is a condition predominantly seen in iodine deficient areas of the world. In the present review, we evaluated in detail autopsy and ultrasound studies of the thyroid gland. In autopsy studies, large thyroid volumes and high frequencies of goitres have been reported in countries affected by iodine deficiency. Many cross-sectional studies using thyroid ultrasound investigations have been performed world-wide and reported high thyroid volumes and goitre prevalences, and to some extent also high prevalences of thyroid nodules in iodine-deficient countries. Most of these goitres were classified as nodular goitres. On the other hand, few studies have shown that abundant iodine intake may lead to development of diffuse goitres, but world-wide this has been a minor problem compared with development of nodular goitres. In the past century we have observed a trend towards smaller thyroid glands, and hopefully less than 10% of the world population will experience goitre within a few decades.

Relapse following antithyroid drug therapy for Graves' hyperthyroidism

Purpose of reviewIn most patients with hyperthyroidism caused by Graves’ disease, antithyroid drug (ATD) therapy is followed by a gradual amelioration of the autoimmune abnormality, but about half of the patients will experience relapse of hyperthyroidism when the ATDs are withdrawn after a standard 1 to 2 years of therapy. This is a major drawback of ATD therapy, and a major concern to patients. We review current knowledge on how to predict and possibly reduce the risk of such relapse. Recent findingsSeveral patient and disease characteristics, as well as environmental factors and duration of ATD therapy, may influence the risk of relapse after ATD withdrawal. Depending on the presence of such factors, the risk of relapse after ATD withdrawal may vary from around 10 to 90%. Risk factors for relapse should be taken into account when choosing between therapeutic modalities in a patient with newly diagnosed disease, and also when discussing duration of ATD therapy. SummaryProlonged low-dose ATD therapy may be feasible in patients with high risk of relapse, such as children and patients with active Graves’ orbitopathy, and in patients with previous relapse who prefer such therapy rather than surgery or radioiodine.

Challenges in the Evaluation of Urinary Iodine Status in Pregnancy: The Importance of Iodine Supplement Intake and Time of Sampling

Objectives: Median urinary iodine concentration (UIC) is the recommended method to evaluate iodine status in pregnancy, but several factors may challenge the interpretation of the results. We evaluated UIC in pregnant women according to (1) sampling in the hospital versus at home, (2) time of the most recent iodine supplement intake prior to sampling, and (3) members of their household. Study Design: Danish cross-sectional study in the year 2012. Pregnant women (n = 158), their male partners (n = 157) and children (n = 51) provided a questionnaire with detailed information on iodine supplement intake and a spot urine sample obtained in the hospital and/or at home for measurement of UIC and urinary creatinine concentration. Results: In the pregnant women providing a urine sample both in the hospital and at home (n = 66), individual UIC (p = 0.002) and urinary creatinine concentration (p = 0.042), but not estimated 24-hour urinary iodine excretion (p = 0.79), were higher when sampling was at home. Median UIC was dependent on the time of the most recent iodine supplement intake prior to sampling [same day (n = 79): 150 µg/l (95% CI 131-181 µg/l), the day before (n = 51): 105 µg/l (78-131 µg/l), several days ago/non-user (n = 28): 70 µg/l (56-94 µg/l), p < 0.001]. The pattern was similar in the male partners. Apart from a more frequent iodine supplement intake in pregnancy (87.3% vs. partners 15.9%), no systematic differences were observed in urinary measurements between the pregnant women and their partners. Conclusions: Time of spot urine sampling and time span from iodine supplement intake to spot urine sampling should be considered when evaluating urinary iodine status in pregnancy.

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.

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.

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

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).

Iodine status in Danish pregnant and breastfeeding women including studies of some challenges in urinary iodine status evaluation

Denmark was previously iodine deficient with regional differences. Moderate iodine deficiency appeared in West Denmark and mild iodine deficiency in East Denmark and also Danish pregnant and breastfeeding women suffered from iodine deficiency. The Danish mandatory iodine fortification of salt was introduced in the year 2000 and has increased iodine intake in the Danish population. However, median urinary iodine concentration in the general population and in pregnant and breastfeeding women is still below the level recommended, corresponding to mild iodine deficiency. Certain characteristics may challenge the evaluation of urinary iodine status in pregnancy and during breastfeeding. This review also addresses methodological challenges related to spot urine sampling conditions and the use of iodine supplement and discusses the use of non-pregnant population groups as a proxy for iodine intake in pregnant women.

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.

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.