Selenium and Thyroid Autoantibodies
CHRONIC AUTOIMMUNE thyroiditis with euthyroidism or hypothyroidism is a common disease, affecting more than 10% of females and 2% of males. There are several explanations for the development of this disease. There is a genetic background, as patients with human leukocyte antigens DR3 and DR5 and polymorphism of the cytotoxic T lymphocyte A4 promoter are more susceptible to the development of autoimmune thyroiditis compared with the normal population. There also are environmental factors, such as iodide intake, immunotherapeutic agents, or viral infections, that may initiate the disease (1).
In areas with combined endemic selenium and iodine deficiency, the supplementation of iodide alone leads to myxedematous cretinism (2, 3), which is defined by not only fetal hypothyroidism, but persistent hypothyroidism from early life. The thyroid of these patients is small and firm, suggesting fibrotic degeneration initiated by thyroid cell damage (4). The cause of this cell damage has been further investigated in animal studies. In severe selenium deficiency, the activity of the selenoenzyme glutathione peroxidase (GPx) is decreased, and therefore peroxide cleavage within the thyroid cells is diminished. Severe nutritional selenium deficiency therefore leads to an increased rate of thyroid cell necrosis and invasion of macrophages (5, 6). Whether this also may induce a higher incidence of autoimmune thyroiditis is unknown. It may be assumed, however, that thyroid cell damage may initiate or maintain autoimmune thyroiditis, especially in patients susceptible to the development of autoimmune diseases (7).
Furthermore, selenium has an important impact on immune function (8, 9). Selenium deficiency is accompanied by loss of immune competence. Both cell-mediated immunity and B cell function can be impaired. This might be related to the fact that the selenium-dependent enzymes, GPx and thioredoxin reductase (TxR), have antioxidative effects; they decrease free radical formation and reduce hydrogen peroxide and lipid and phospholipid hydroperoxides (9). In selenium-sufficient environment, the hydroperoxide intermediates of the cyclooxygenase and lipoxygenase pathways are therefore reduced and lead to diminished production of proinflammatory PGs and leukotrienes (10). In addition, both GPx and TxR modulate the respiratory burst and reduce superoxide production (11, 12, 13).
The possible therapeutic effect of selenium has already been shown in a double blind, randomized trial in patients with rheumatoid arthritis, in whom the supplementation of 200 µg selenium for 3 months significantly reduced pain and joint involvement (14). Selenium supplementation of 500-1000 µg has also been shown to improve survival in patients with hemorrhagic pancreatitis (15) and severe sepsis (16), which may be due to the antiinflammatory effect of a higher selenium supply.
The three known deiodinases also are selenium-dependent enzymes (11, 17, 18, 19). Their activity, however, in contrast to GPx activity, is only decreased in extremely severe selenium deficiency. T4 plasma concentrations are then elevated, and selenium supplementation lowers T4 and increases T3 concentrations (20).
In Germany, there is mild iodine deficiency (21) as well as mild selenium deficiency, as in most European countries (22). As selenium deficiency may influence both the immune response as well as peroxidation of thyroid cell components, it seems reasonable to investigate whether a selenium substitution may influence the natural course of chronic autoimmune thyroiditis (23). There is one small pilot study showing a significant decrease in both thyroid peroxidase antibodies (TPOAb) as well as TSH receptor antibody concentrations in patients with lymphocytic autoimmune thyroiditis (24). We therefore conducted a blinded, placebo-controlled study in patients with chronic autoimmune thyroiditis to show whether supplementation with 200 µg (2.53 µmol) sodium selenite has any effect on plasma TPOAb concentrations, free thyroid hormones, and the ultrasound pattern of the affected thyroid in patients with overt autoimmune thyroiditis.
Gärtner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW.
Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.
J Clin Endocrinol Metab.
Department of Endocrinology, Medizinische Klinik Innenstadt, University of Munich, D-80336 Munich, Germany.