Search Results

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.

Objective

Iodization of salt was introduced in Denmark in 1998 because of mild-to-moderate iodine deficiency (ID). The aim of this study was to analyze the utilization rate of surgery and radioiodine therapy for benign thyroid disorders before and after the introduction of iodization, and to study a possible association between the changes and the raised iodine intake.

Design

A nationwide register study.

Methods

Information on operations and radioiodine treatments for benign thyroid disorders was extracted from nationwide registers in the years 1990 to 2007. Treatment rates are presented for surgery and for radioiodine separately, and as a combined rate, both nationwide and split by the regions of prior mild and moderate ID.

Results

A total of 65 605 treatments were identified: 26 456 operations and 39 149 radioiodine treatments. In the first years of iodization (1998–2000; rate ratio 2000/1997), the combined treatment rate increased with 2.5% (95% confidence interval (CI): −1.8–7.1). Split by prior ID level, the increase was seen in the region of moderate ID, but a decrease was seen in the region of mild ID. After 2000, the combined rate decreased, and ended up being 11.1% (95% CI: 7.1–15.0) lower in 2007 than before iodization (rate ratio 2007/1997). The changes were primarily due to changes in the use of radioiodine therapy as the surgery rates remained almost constant.

Conclusions

Iodization seemed to be associated with a temporary increase in the utilization rate of surgery and radioiodine therapy in the region of prior moderate ID, probably as a result of treatment of iodine-induced hyperthyroidism, but the rates ended up being lower than before iodization.

Objective

Few population-based studies have described the epidemiology of subtypes of hyperthyroidism.

Design

A prospective population-based study, monitoring two well-defined Danish cohorts in Aalborg with moderate iodine deficiency (n=311 102) and Copenhagen with only mild iodine deficiency (n=227 632).

Methods

A laboratory monitoring system identified subjects with thyroid function tests suggesting overt hyperthyroidism (low s-TSH combined with high s-thyroxine or s-triiodothyronine). For all subjects, we collected information on medical history, thyroid scintigraphy and thyroid hormone receptor antibody (TRAb) measurement. Information was used to disprove or verify primary overt hyperthyroidism and to subclassify hyperthyroidism into nosological disorders.

Results

From 1997 to 2000 (2 027 208 person-years of observation), we verified 1682 new cases of overt hyperthyroidism. The overall standardized incidence rate (SIR) per 100 000 person-years was 81.6, and was higher in Aalborg compared with Copenhagen (96.7 vs 60.0, P<0.001), giving an SIR ratio (SIRR (95% confidence interval (CI))) between moderate versus mild iodine-deficient areas of 1.6 (1.4–1.8). Nosological types of hyperthyroidism (percentage/SIRR (95% CI)): multinodular toxic goitre (MNTG) 44.1%/1.9 (1.6–2.2), Graves' disease (GD) 37.6%/1.2 (0.99–1.4), solitary toxic adenoma (STA) 5.7%/2.4 (1.3–3.5), ‘mixed type’ hyperthyroidism (TRAb-positive, scintigraphicly multinodular) 5.4%/6.0 (3.0–12), subacute thyroiditis 2.3%/0.9 (0.4–1.4), postpartum thyroid dysfunction 2.2%/1.6 (0.8–3.0), amiodarone-associated hyperthyroidism 0.8%/7.1 (1.1–65), hyperthyroidism after thyroid radiation 0.7%/12.3 (0.8–50), lithium-associated hyperthyroidism 0.7%/0.97 (0.4–4.8) and hyperthyroidism caused by various other factors 0.7%. Lifetime risk for overt hyperthyroidism was 10.5%/6.5%/2.4% (females/all/males).

Conclusion

Hyperthyroidism was common in Denmark with MNTG and GD as dominating entities. The higher incidence of hyperthyroidism in the most iodine-deficient region was caused by higher frequency of MNTG, ‘mixed-type’, STA and amiodarone-associated hyperthyroidism.

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.

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 μg/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.

Objective

Alcohol consumption is an important protective risk factor for many autoimmune diseases. We wished to study the association between alcohol consumption and autoimmune hypothyroidism.

Design

Population-based, case–control study, 1997–2001, Denmark.

Methods

Patients with newly diagnosed autoimmune overt hypothyroidism (n=140) were prospectively identified in a population (2 027 208 person-years of observation), and their matched controls with normal thyroid function (n=560) were recruited simultaneously from the same population. Participants gave information on alcohol intake, smoking, previous diseases, education, and family history of hypothyroidism. The association between alcohol intake and development of hypothyroidism was analyzed in conditional regression models.

Results

Hypothyroid cases had reported a lower alcohol consumption than controls (median units of alcohol (12 g) per week: 3 vs 5, P=0.002). In a multivariate regression model, alcohol consumption was associated with a reduction in risk for development of overt autoimmune hypothyroidism. Odds ratios (95% confidence interval) compared with the reference group with a recent (last year) consumption of 1–10 units of alcohol per week were as follows: 0 units/week, 1.98 (1.21–3.33); 11–20 units/week, 0.41 (0.20–0.83); and ≥21 units/week, 0.90 (0.41–2.00). Similar results were found for maximum previous alcohol consumption during a calendar year. No interaction was found with type of alcohol consumed (wine vs beer), sex, or region of inhabitancy.

Conclusions

Alcohol consumption seems to confer considerable protection against development of overt autoimmune hypothyroidism irrespective of sex and type of alcohol consumed.

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 (P<0.05) for thyroid volume decrease >20% during the follow-up period (women aged 40–45 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.

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.

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.