Autoimmunity
	Strieder et al., Amsterdam, The Netherlands, evaluated the relative contribution of genetic and environmental factors on the development of autoimmune thyroid disease in females. They recruited 803 healthy female relatives of patients with autoimmune thyroid disease who were followed for 5 years. Hypothyroidism was detected in 3.6 and hyperthyroidism in 1.9% of relatives (including both overt and subclinical forms). Relative to euthyroid participants, hypothyroid subjects were older and hyperthyroid subjects had a lower frequency of estrogen use (p=0.002) and a higher frequency of being ever pregnant (p=0.006). The authors conclude that prevalence of undetected autoimmune disease of the thyroid is high in female relatives of patients known with this condition. In addition estrogens seems to modulate the risk of developing autoimmunity of the thyroid. Smoking and a history of excessive iodine intake were similar in relatives and controls. Comment: Apparently estrogen use and pregnancy have opposing effects on the risk of developing hyperthyroidism. Bülow Pedersen et al., Aalborg, Glostrup, and Copenhagen, Denmark, evaluated serum TPO-Ab and Tg-Ab prevalences in a cross-sectional study in Denmark. By random selection 4,659 subjects (age 18 to 65 years) were included. The overall prevalence of TPO-Ab and/or Tg-Ab was 18.8 %, whereas that of TPO-Ab and Tg-Ab was virtually the same (13.1 vs. 13.0 %). Both antibodies were more prevalent in females and prevalences in both genders increased with age. In areas with moderate iodine deficiency in the age group 60 to 65 years, thyroid antibodies were more frequently present than in the same age group in mild iodine deficiency (22.1 vs. 17.3% respectively, p=0.02). No differences however were seen in younger subjects from both areas. Duntas et al., Athens, Greece, assessed the effects of selenium (Se) in the form of selenomethionine (SeMe) as a single or adjunctive treatment with L-T4 in patients with autoimmune thyroiditis (AIT). Three groups of patients were studied. Gr I (n = 31) treated with SeMe 200 µg/day plus L-T4 to normalize TSH between 0.3 and 2.0 µU/ml, Gr II (n = 17) SeMe plus placebo and Gr III (n = 29) L-T4 plus placebo. The study period was 6 months and the patients were assessed at baseline and after 3 and 6 months of treatment. In Gr I 16/31 patients showed a decrease of anti-TPO by 37 % at 3 months and 86 % at 6 months. In 11/31 the decrease was only 28 % and 4/31 did not show any decrease of TPO. In Gr II in 13/17 patients TPO decrease was 77 and 81 % respectively, while in 4/17 no change was observed. In Gr III 23/29 showed a decrease of 28 % and 44 % respectively, and in 6/29 these values were 13 and 22 % respectively. It was additionally shown that SeMe is slowly and effectively absorbed. The authors conclude that selenium may be effective as a sole treatment of autoimmune thyroid disease. Comment: Selenium became of interest in thyroidology in the last decade for several reasons. First it was shown that it is a necessary element in the function of thyroid hormone deiodinases that play an essential role in thyroid hormone metabolism and production of the metabolic active iodothyronine T3 from the prohormone T4. Furthermore, it has been shown that addition of selenium to children living in areas of severe iodine deficiency may prevent permanent damage to the thyroid. This report is interesting in that selenium may also have a role in suppression of thyroid autoimmunity. Further studies are necessary to confirm these findings and to elucidate the mechanism of immune suppression. One possibility could be that administration of selenium activates enzymes, such as glutathion peroxidase and thioredoxin reductase, that have anti-oxidant activity by inactivating free radicals. Free radicals have been implicated in stimulation of autoimmunity. Emral et al., Ankara, Turkey, measured thyroid volume, autoimmunity and function in 939 adolescents living in an iodine sufficient area (mean urinary iodine excretion 139 µg/L, Gr I) and compared results in 725 adolescents from an iodine deficient area (mean urinary iodine excretion 61 µg/L, Gr II). Mean thyroid volumes (ml) were Gr I vs. Gr II 13 ± 5 vs. 17 ± 5, respectively, p<0.01, goiter prevalence: 28.2% vs. 61.9 %, p<0.01, prevalence of hyperthyroidism 3.6% vs. 0.7 %, p<0.001 and of hypothyroidism 1.8% vs. 1.4% (NS). Thyroid volume of hyperthyroid subjects (19 ± 7 ml) was significantly higher than in hypothyroid subjects, and euthyroid subjects (both 13 ± 4 ml, p<0.001). Urinary iodine excretions were significantly higher both in hyper- and hypothyroid subjects as compared to euthyroid subjects. Anti-Tg was present in 36.1% of hyperthyroid subjects being significantly different from 17 % in euthyroid and 5.6% in hypothyroid patients (p<0.001 and p<0.001 respectively). The here reported studies were done after iodinization of the two areas apparently with different results in that Gr II subjects were still moderately iodine deficient. The authors conclude that successful iodine supplementation in iodine deficiency triggers thyroid autoimmunity leading to abnormal thyroid function in some patients. Comment: The phenomenon of induction of thyroid autoimmunity after iodine suppletion has been described earlier. Bourdoux et al., Brussels, Belgium, and Goma, Congo, also found evidence for induction of thyroid autoimmunity by iodine administration in a study in 119 unselected subjects from an area where by iodine supplementation urinary iodine excretion increased from 1.7 µg/dl to 37 µg/dl. Of these subjects 75 were euthyroid, 40 were hyperthyroid, and 4 hypothyroid. The frequency in these groups of TPO-Ab was 2/75, 10/40, and 0/4. Tg-Ab were found in only 4% of samples. As TPO-Ab were not present in the sera of the inhabitants of this area before iodine supplementation the authors conclude, despite the fact that this is not an epidemiological study, that this high frequency of thyroid autoimmunity is caused by iodine supplementation. In contrast to these two reports, Zimmermann et al., Zürich, Switzerland, could not find any induction or aggravation of thyroid autoimmunity one year after introduction of iodized salt in goitrous children in an area of severe iodine deficiency. Thus, they did a prospective longitudinal trial in 319 children, 6 to 15 years of age. Urinary iodine excretion at baseline was 17 µg/L, 71% of children were goitrous, 17 % were hypothyroid. After iodized salt supplementation urinary iodine excretion was constant between 150 and 200 µg/L over the course of the study. The goiter rate (ultrasound) decreased to 38 % after one year and prevalence of hypothyroidism decreased substantially (p<0.001). No significant increases in the prevalence of TPO-Ab or Tg-Ab were noted. The overall prevalence of TPO-Ab was 1% and 0% of Tg-Ab. Comment: These findings contrast sharply with not only the previous two reports but also other reports from the literature. Maybe the explanation of this discrepancy is that the follow-up of this group was very short and that induction of thyroid autoimmunity after iodine supplementation in iodine deficiency takes a longer time. I hope that the authors do continue to follow these subjects for more years. Poppe et al., Brussels, Belgium, prospectively evaluated the impact of thyroid autoimmunity on the outcome of in vitro fertilization (IVF). Two hundred and three women were followed for one year after a first IVF procedure. They were subdivided in group 1 (TPO positive) and group 2 (TPO negative). Group 1 consisted of 15% of the cohort. Results; group 1 vs. group 2: no significant differences between age and serum TSH. Pregnancy rate: 55 % vs. 41 %, (ns), miscarriage rate 53 % vs. 26 % (p=0.035), and life birth 47 % vs. 74 % (p=0.035). The authors suggest screening of candidates for IVF on thyroid autoimmunity. Comment: Autoimmunity in general has been described as a risk factor for successful IVF. However, of interest is a study by Müller et al., Vertil.Steril.1999;70:30, who showed that in a study in 489 women in an IVF program, no association was found between the presence of TPO-Ab before pregnancy and miscarriage. In other words this latter study is at variance with the present report regarding the risk for miscarriage.) Kuchinskaya et al., Minsk, Belarus, measured Tg-Ab and TPO-Ab levels in 157 children and adolescents with autoimmune thyroiditis (AT) and 126 patients with diabetes mellitus type 1 (DM1). They found a significantly higher (p<0.05) levels of Tg-Ab and TPO-Ab in AT patients living in the Gomel region that received a high dose of radioactivity after the Chernobyl fallout as compared to AT patients in Minsk that served as a control in a non-irradiated area. Similarly, TPO-Ab were higher in DM1 patients from Gomel as compared to Minsk (40% vs. 27 %, p<0.05). The authors also found in increased frequency of antibodies against glutamic acid decarboxylase and protein tyrosine phosphatase in DM1 patients in the irradiated area as compared to the control area. They suggest that the radiation incurred by the Chernobyl accident may induce autoimmune reactions.