Inge Bülow Pedersen

Context: To prevent goiter and nodular hyperthyroidism, iodine fortification (IF) of salt was introduced in Denmark in 1998. We prospectively registered all new cases of overt hyperthyroidism in two areas of Denmark before and for the first 6 yr after iodine fortification. Methods: We used a computer-based register of all new cases of hyperthyroidism in two population subcohorts with moderate iodine deficiency (Aalborg, n = 310,124) and mild iodine deficiency (Copenhagen, n = 225,707), respectively. Data were obtained 1) before IF (1997–1998); 2) during voluntary IF (1999–2000); 3) during the early (2001–2002) period of mandatory IF; and 4) during the late (2003–2004) period with mandatory IF. Results: The overall incidence rate of hyperthyroidism increased [baseline, 102.8/100,000/year; voluntary IF, 122.8; early mandatory IF, 140.7; late mandatory IF, 138.7 (P for trend P < 0.001) and in all age groups: 0–19, 20–39, 40–59, and 60+ yr (P for trend P < 0.001; age 40–59, 29%, P < 0.01; age 60+ yr, 13%, P = not significant. Conclusion: Even a cautious iodization of salt results in an increase in the incidence rate of hyperthyroidism. Contrary to current concepts, many of the new cases were observed in young subjects, and are presumably of autoimmune origin. Furthermore, monitoring is expected to show a decrease in the number of elderly subjects suffering from nodular hyperthyroidism.

Background: Thyroid autoimmunity is more common in females than in males. One possible explanation for this female preponderance may be the effect of oestrogens on the immune system. It has also been suggested that foetal microchimerism involving transfer of foetal cells into maternal tissue during pregnancy may play an important role. Objective: We investigated the association between the presence of circulating thyroid autoantibodies and previous pregnancy, parity and the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) in a population cohort. Methods: We examined 3712 women randomly selected from the general population. Serum was analysed for thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) using assays based on an RIA technique (DYNO test). Data were analysed in logistic regression models to adjust for possible confounders. Women previously treated for thyroid disease or with pregnancy within 1 year prior to the study were excluded from the analyses. Results: In both univariate and multivariate models and whether the presence of TPO-Ab and Tg-Ab was investigated alone or in combination, findings were negative with respect to an association between circulating thyroid antibodies and previous pregnancy, number of pregnancies, parity and previous abortion. There was no association between thyroid autoantibodies and use of OCs. Women aged 60–65 years receiving HRT now or previously had a lower prevalence of Tg-Ab (univariate, P = 0.01; multivariate, P = 0.02). No such association was observed between HRT and TPO-Ab. Conclusion: In this population study there was no association between previous pregnancy, parity and thyroid antibodies, which argues against the role of microchimerism as a trigger of thyroid autoimmunity. Exogenous oestrogens may reduce aspects of autoimmunity.

Summary: Objective  Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism.Design  A population study including 4649 randomly selected subjects.Measurements  Blood tests were used to analyse for thyroid peroxidase autoantibodies (TPO‐Ab), thyroglobulin autoantibodies (Tg‐Ab), TSH, fT3 and fT4.Results  Thyroid volume was categorized as small (< 6·6 ml) in 4·7%, normal (6·6–14·9 ml) in 60·4% and large (> 14·9 ml) in 34·9% of participants. Thyroid nodules were found in 29·7%. Serum TSH was low (< 0·4 mIU/l) in 4·7%, normal (0·4–3·6) in 91·0% and high (> 3·6) in 4·3%. The prevalence rate of subclinical goitrous Hashimoto's disease was 0·62% and of subclinical autoimmune atrophic thyroiditis 0·24%. There was a strong association between large volume and autoantibodies, but only in subjects with elevated TSH (P < 0·001). An association between thyroid nodules and TPO‐Ab in univariate analyses (P < 0·001) was due to confounding by sex and age (multivariate model, P = 0·23).Conclusion  We identified a subgroup of the population with subclinical goitrous Hashimoto's disease and a smaller subgroup with subclinical autoimmune atrophic thyroiditis. This relationship between small and large thyroid volume in subclinical disease is opposite to that in overt disease, which may suggest that the period between development of a small volume with circulating autoantibodies and overt hypothyroidism is relatively short.

Summary: background and aims Autoimmune thyroiditis is one of the most common autoimmune disorders. Autoantibodies against the thyroid gland, with thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (Tg‐Ab) as the most common autoantibodies, can often be demonstrated in serum in population surveys. In the present study we evaluated if TPO‐Ab and Tg‐Ab tend to develop in parallel or whether one or the other may be more prevalent in subsets of the population.methods In a cross‐sectional comparative study, performed in two areas of Denmark with mild and moderate iodine deficiency, 4649 randomly selected subjects in age groups between 18 and 65 years were examined. Blood tests were analysed for TPO‐Ab and Tg‐Ab using assays based on the radioimmunoassay (RIA) technique. The participants answered questionnaires, were clinically examined and had urine samples collected.results The overall prevalence rate of thyroid autoantibodies (TPO‐Ab and/or Tg‐Ab) was 18·8%. The prevalence rates of TPO‐Ab and Tg‐Ab were similar (13·1 vs. 13·0%). Both antibodies were more frequent in females than in males, and in females the prevalence rates increased with age. In the age group 60–65 years thyroid antibodies were more frequently measured in sera from moderate than from mild iodine‐deficient area (P = 0·02), whereas no differences were seen in younger subjects. In 38·8% of participants with thyroid autoantibodies in serum, both antibodies were present. In sera with both TPO‐Ab and Tg‐Ab present the concentrations of the antibodies were generally higher than in sera with only one type of antibody present.conclusion The prevalence rates of TPO‐Ab and Tg‐Ab were similar in this large population survey. The results suggest that TPO‐Ab and Tg‐Ab predominantly develop due to a general alteration in the immune system, whereas specific antigenic mechanisms are probably of less importance. However, further studies are needed to clarify the mechanisms involved in the development of thyroid autoantibodies.

OBJECTIVES Graves' disease is characterized by stimulating autoantibodies to the TSH‐receptor (TRAb). The aim of this study was to compare the performance of a new TRAb assay based on competitive binding to recombinant human TSH‐receptors (H‐TRAb) with an assay employing purified porcine TSH‐receptors (P‐TRAb). Furthermore, to evaluate the applicability of the H‐TRAb assay to discriminate between patients with hyperthyroidism due to Graves' disease (GD) and multinodular toxic goitre (MNTG).DESIGN AND MEASUREMENTS H‐TRAb and P‐TRAb were measured in patients with newly diagnosed hyperthyroidism due to GD (n = 106) and MNTG (n = 94). For comparison, TRAb was measured in patients with primary autoimmune hypothyroidism, euthyroid subjects with an enlarged thyroid gland by ultrasound, and healthy controls (n = 100 for each group). Patients were consecutively included from a population survey.RESULTS If the cut‐off values recommended by the manufacturer for TSH‐receptor antibody positivity were used for evaluation, the sensitivity of the H‐TRAb assay vs. the P‐TRAb assay in diagnosing GD was: 95·3/67·9% (P < 0·001). Specificity was (H/P‐TRAb): 99/99%. The sensitivity of P‐TRAb was increased if the upper 97·5% limit of measurements in controls was used as cut‐off (H‐TRAb vs. P‐TRAb: 95·3/80·2%, P < 0·001). Specificity (H/P‐TRAb): 98/98%. The difference between assay performance may partly be due to a better technical performance of the H‐TRAb assay with more reliable results in the low range of measurements. However, even in GD patients with clearly measurable TRAb, 25% had a P‐TRAb < 50% of the value expected from the H‐TRAb measurement. This suggests that a subgroup of patients produce TRAb with a higher affinity for the human than the porcine TSH receptor. A relatively high proportion of patients with MNTG were TRAb positive (H‐TRAb/P‐TRAb: 17/9%). Characteristics of H‐TRAb positive and negative MNTG patients were compared. There was no difference between size of thyroid gland and number of nodules by ultrasonography. H‐TRAb positive patients had significantly higher serum T4 and T3 and a greater number were TPO‐Ab positive.CONCLUSIONS H‐TRAb diagnosed Graves' disease with a high sensitivity and specificity than P‐TRAb. The high occurrence of TRAb in multinodular toxic goitre might in part reflect an overlap between Graves' disease and multinodular toxic goitre in some patients.