In areas with severe selenium deficiency there is a higher incidence of 
thyroiditis due to a decreased activity of selenium-dependent glutathione 
peroxidase activity within thyroid cells. Selenium-dependent enzymes also have 
several modifying effects on the immune system. Therefore, even mild selenium 
deficiency may contribute to the development and maintenance of autoimmune 
thyroid diseases. We performed a blinded, placebo-controlled, prospective study 
in female patients (n = 70; mean age, 47.5 +/- 0.7 yr) with autoimmune 
thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies 
(TgAb) above 350 IU/ml. The primary end point of the study was the change in 
TPOAb concentrations. Secondary end points were changes in TgAb, TSH, and free 
thyroid hormone levels as well as ultrasound pattern of the thyroid and quality 
of life estimation. Patients were randomized into 2 age- and antibody 
(TPOAb)-matched groups; 36 patients received 200 microg (2.53 micromol) sodium 
selenite/d, orally, for 3 months, and 34 patients received placebo. All patients 
were substituted with L-T(4) to maintain TSH within the normal range. TPOAb, 
TgAb, TSH, and free thyroid hormones were determined by commercial assays. The 
echogenicity of the thyroid was monitored with high resolution ultrasound. The 
mean TPOAb concentration decreased significantly to 63.6% (P = 0.013) in the 
selenium group vs. 88% (P = 0.95) in the placebo group. A subgroup analysis of 
those patients with TPOAb greater than 1200 IU/ml revealed a mean 40% reduction 
in the selenium-treated patients compared with a 10% increase in TPOAb in the 
placebo group. TgAb concentrations were lower in the placebo group at the 
beginning of the study and significantly further decreased (P = 0.018), but were 
unchanged in the selenium group. Nine patients in the selenium-treated group had 
completely normalized antibody concentrations, in contrast to two patients in 
the placebo group (by chi(2) test, P = 0.01). Ultrasound of the thyroid showed 
normalized echogenicity in these patients. The mean TSH, free T(4), and free 
T(3) levels were unchanged in both groups. We conclude that selenium 
substitution may improve the inflammatory activity in patients with autoimmune 
thyroiditis, especially in those with high activity. Whether this effect is 
specific for autoimmune thyroiditis or may also be effective in other endocrine 
autoimmune diseases has yet to be investigated.