Clinical studies have suggested that excess dietary iodine promotes autoimmune thyroiditis; however, the lack of a suitable animal model has hampered investigation of the phenomenon. In this study, different amounts of potassium iodide were added to the diets of chicken strains known to be genetically susceptible to autoimmune thyroiditis. Administration of iodine during the first 10 weeks of life increased the incidence of the disease, as determined by histology and the measurement of autoantibodies to triiodothyronine, thyroxine, and thyroglobulin. Further support for the relation between iodine and autoimmune thyroiditis was provided by an experiment in which iodine-deficient regimens decreased the incidence of thyroid autoantibodies in a highly susceptible strain. These results suggest that excessive consumption of iodine in the United States may be responsible for the increased incidence of autoimmune thyroiditis.

Induction of Autoimmune Thyroiditis in Chickens by Dietary Iodine

The current iodine status and the impact of silent iodine prophylaxis on the prevalence of autoimmune thyroiditis among schoolchildren in a formerly iodine-deficient community in northwestern Greece, were investigated. The findings were compared to those obtained from a similar survey conducted 7 years previously in the same area. A total of 302 schoolchildren (12-18 years of age) from a mountainous area of northwestern Greece were examined for the presence of goiter, and blood and urine samples were collected for assessment of thyroid function, antithyroid antibodies and urinary iodine excretion. In those children (n = 42) with palpable goiter or positive antibodies and/or a thyrotropin (TSH) level greater than 5 mU/L, thyroid ultrasonography was performed to estimate thyroid gland size and morphology. Median urinary iodine concentration in the children was 20.21 microg/dL, indicating sufficient iodine intake. Thyroid function was normal in all but 7 children, who had subclinical hypothyroidism (2.5%). Antithyroid antibodies (antithyroid peroxidase [TPO] and/or antithyroglobulin [Tg]) were positive in 32 children, including those with subclinical hypothyroidism (10.6%). Twenty-nine of these children (9.6%) also had the characteristic echo pattern of thyroiditis on ultrasound and were diagnosed to have autoimmune thyroiditis. In comparison to data from our previous survey 7 years ago, there has been a threefold increase in the prevalence of autoimmune thyroiditis among schoolchildren. In conclusion, silent iodine prophylaxis has resulted in the elimination of iodine deficiency in Greece, and this has been accompanied by an increase in the prevalence of autoimmune thyroiditis.

High prevalence of autoimmune thyroiditis in schoolchildren after elimination of iodine deficiency in northwestern Greece.

Objective: With the introduction of iodized salt worldwide, more and more people are exposed to more than adequate iodine intake levels with median urinary iodine excretion (MUI 200–300 mg/l) or excessive iodine intake levels (MUI O300 mg/l). The objective of this study was to explore the associations between more than adequate iodine intake levels and the development of thyroid diseases (e.g. thyroid dysfunction, thyroid autoimmunity, and thyroid structure) in two Chinese populations. Design: A population-based cross-sectional study was conducted in two areas in which people are exposed to different levels of iodine intake (Rongxing, MUI 261 mg/l; Chengshan, MUI 145 mg/l). A total of 3813 individuals were recruited by random sampling. Thyroid hormones, thyroid autoantibodies in serum, and iodine levels in urine were measured. B-mode ultrasonography of the thyroid was also performed for each participant. Results: The prevalence of subclinical hypothyroidism was significantly higher for subjects who live in Rongxing than those who live in Chengshan (5.03 vs 1.99%, P!0.001). The prevalence of positive anti-thyroid peroxidase antibody (TPOAb) and positive anti-thyroglobulin antibody (TgAb) was significantly higher for subjects in Rongxing than those in Chengshan (TPOAb: 10.64 vs 8.4%, PZ0.02; TgAb: 10.27 vs 7.93%, PZ0.01). The increase in thyroid antibodies was most pronounced in the high concentrations of TPOAb (TPOAb: R500 IU/ml) and low concentrations of TgAb (TgAb: 40–99 IU/ml) in Rongxing. Conclusions: More than adequate iodine intake could be a public health concern in terms of thyroid function and thyroid autoimmunity in the Chinese populations.

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More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels.

In the United Kingdom, about half the patients with Graves' disease who are given antithyroid drugs are still in remission one year after treatment is stopped. The most widely held view is that such remission rates are due only to the biochemical effects of the drugs, the disease either spontaneously remitting or abating when the immune system is no longer subject to the stimulatory effects of excessive thyroid hormone. We review here the accumulating evidence against both of these alternatives. In contrast, there is now a large body of work which shows that thyrotrophin receptor antibody levels, central to the aetiology of Graves' hyperthyroidism, fall during antithyroid treatment and that remission may be related to this fall in a fashion which is dependent on the dose and duration of treatment. This immunosuppressive effect is supported by experimental data and on the basis of these results we propose that antithyroid drugs may modify the natural history of Graves' disease and contribute to the remission which occurs in a proportion of treated patients.

Evidence for an effect of antithyroid drugs on the natural history of graves' disease

Objective: Iodine is essential for normal thyroid function and the majority of individuals tolerate a wide range of dietary levels. However, a subset of individuals, on exposure to iodine, develop thyroid dysfunction. In this double-blind trial, we evaluated the efficacy and tolerability of low-dose iodine compared with those of levo-thyroxine (T4) in patients with endemic goitre. Methods: Sixty-two patients were assigned randomly to groups to receive iodine (0.5 mg/day) or T4 (0.125 mg/day) for 6 months. Subsequently, both groups were subject to placebo for another 6 months. Thyroid sonography, determination of thyroid-related hormones and antibodies, and urinary excretion of iodine were carried out at baseline and at 1, 6 and 12 months. Results: At 6 months, markedly increased urinary values of iodine were found in patients receiving iodine (36 mg/24 h at baseline, 415 mg/24 h at 6 months) compared with those receiving T4 (47 mg/ 24 h at baseline, 165 mg/24 h at 6 months; P < 0.0001 compared with iodine group). T4 administration engendered a greater (P < 0.01) decrease in thyroid volume (from 32 ml to 17 ml, P < 0.0001) than did intake of iodine (33 ml to 21 ml, P < 0.005). High microsomal and thyroglobulin autoantibody titres were present in six of 31 patients (19%) receiving iodine, and iodine-induced hypo- and hyperthyroidism developed in four and two of them, respectively. Fine-needle biopsy revealed marked lymphocyte infiltration in all six. After withdrawal of iodine, thyroid dysfunction remitted spontaneously and antibody titres and lymphocyte infiltration decreased markedly. Follow-up of these six patients for an additional 3 years showed normalisation of antibody titres in four of them. Conclusion: Although nearly comparable results were obtained with both treatment regimens regarding thyroid size, partly reversible iodine-induced thyroid dysfunction and autoimmunity were observed among patients with endemic goitre.

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Iodide induces thyroid autoimmunity in patients with endemic goitre: a randomised, double-blind, placebo-controlled trial.

Several studies have suggested that iodide may increase thyroiditis and autoantibody synthesis. We have investigated the effect of iodide in vitro at physiologically relevant concentrations on immunoglobulin synthesis by normal human peripheral blood lymphocytes stimulated with pokeweed mitogen. Both the number of cells which synthesised IgG and the amount of IgG released into the culture supernatant increased significantly after culture in a medium with added iodide compared to a medium with added chloride. No effect of increasing concentrations of the added iodide from 10(-3) mM to 10 mM was observed. These findings suggest that iodides may have a role in enhancing antibody synthesis which may be important when programmes of iodide supplementation are introduced into areas which are deficient.

H. K. Ibbertson

Papers

Iodide enhances IgG synthesis by human peripheral blood lymphocytes in vitro