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.

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.

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.

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.

[Iodine fortification of salt and thyroid disease in Denmark]. / Dansk jodberigelse af salt og forekomst af thyroideasygdom.

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.

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.

Surveyance of disease frequency in a population by linkage to diagnostic laboratory databases. A system for monitoring the incidences of hyper- and hypothyroidism as part of the Danish iodine supplementation program.

UNLABELLED: In Denmark an increase in iodine intake through salt iodization has been introduced in 1998. In parallel a program for surveyance of thyroid diseases in the population was developed as recommended by UNICEF and WHO. OBJECTIVE: To develop and evaluate a computer based system to identify and register new cases of hyper- and hypothyroidism in a well defined cohort, by linkage to diagnostic laboratory databases. DESIGN AND RESULTS: (1) Two sub cohorts for monitoring were defined (n=535,859), and evaluated to minimize loss of new cases. Collaboration was established with laboratories covering thyroid hormone analyses in the cohort; (2) a diagnostic algorithm was defined and evaluated against clinical practice; (3) evaluation of the laboratory methods employed by the four participating laboratories, to ensure they would reach the same diagnosis in a patient; (4) a register database was developed which used data imported from the laboratory databases to automatically identify previously unknown cases of hyper- and hypothyroidism and record diagnostic activity in the area. All parts of the registration were carefully evaluated. CONCLUSION: We describe for the first time a computer based system for prospective measuring the incidence rate of hyper- and hypothyroidism. The system is particularly useful for monitoring of iodine supplementation programmes.