Thyroid hypofunction in Down's syndrome: is it related to oxidative stress?
Oxidative stress affecting the thyroxin biosynthesis might explain the proneness of patients with Down's syndrome (DS) (trisomia 21) to develop hypothyroidism. Thyroideal cells are exposed to endogenous H2O2 that acts as a cofactor for the iodination of thyroxin precursors. The gland has high levels of selenium-containing proteins, including peroxide-detoxicating enzyme proteins. The object of the present study was to explore the hypothesis of a role of an imbalance between toxic oxygen production and protective metalloenzymes during the development of thyroid hypofunction in DS patients. We analyzed serum levels of thyroid hormones and trace metals in 38 institutionalized adults with DS, using mentally retarded subjects matched for age, sex, and behavioral function as controls. The DS patients had significantly lower mean values of free thyroxin (fT4) and increased TSH (thyroid stimulating hormone), as compared to the controls. They had lower serum selenium than the controls. A positive correlation was observed between serum concentrations of fT4 and selenium in the DS patients (r = 0.393, p < 0.05). No significant differences were found between the fT4 or the TSH concentrations in the patients with and without circulating antithyroid autoantibodies. Our results support the suggestion that thyroid hypofunction in patients with Down's syndrome in some way is linked to the low serum levels of selenium found in these patients. It is suggested that selenium-containing proteins are involved in thyroid hormonal synthesis, by protecting biosynthetic processes against the toxicity of free oxygen radicals.
Kanavin
O J
OJ
Department of Pediatry, Buskerud Central Hospital, Drammen, Norway.
Aaseth
J
J
Birketvedt
G S
GS
D000328:Adult; D016022:Case-Control Studies; D004314:Down Syndrome / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000378:metabolism*; D008607:Intellectual Disability / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D012643:Selenium / Q000097:blood*; D013961:Thyroid Gland / Q000502:physiology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D013975:Thyroxine-Binding Proteins / Q000378:metabolism; D015032:Zinc / Q000097:blood
D013975:Thyroxine-Binding Proteins; D013972:Thyrotropin; D012643:Selenium; D015032:Zinc; D013974:Thyroxine