The Effects Of Chronic Iodine Excess On Thyroid Function And Structure In Autoimmune-prone NOD.H-2～(h4) Mice

ObjectiveAutoimmune thyroid diseases (AITD) are a group of autoimmune diseases which are organ - specific autoimmune diseases. It has been reported that the prevalence of silent autoimmune thyroiditis in autopsy was more than 25%. The positive rate of thyroid autoantibodies in females was 8 - 26% , and 3 - 6% in males. So there were a large number of people with recessive autoimmune thyroiditis.The 5 - year prospective, epidemiological study by our group found that iodine excess not only increased the incidence of autoimmune thyroiditis and hypo-thyroidism but also drive thyroid normal function with positive autoantibodies to hypothyroidism, indicating that iodine excess may initiate and promote the development of autoimmune thyroiditis. So the great harm resulted from iodine excess is just on these vulnerable people.To explain the phenomenon occurred in people, we made the animal models of iodine excess which imitated normal and vulnerable people respectively to further explore the mechanism of iodine - induced hypothyroidism and iodine - induced thyroiditis.The research results by Man Na, Chen Wei, and Tong Yajie of our group showed that 3 - fold iodine excess may injure the morphological structure and deiodinase activity in Wistar rat (an animal model of normal people), but have no effect on autoimmune thyroiditis and hypothyroidism.In the present study, we aim to explore the mechanism of iodine - induced thyroid injure and iodine - induced thyroiditis by virtue of NOD. H - 2^h4 mice,an animal model of vulnerable people of autoimmune thyroid diseases.MethodsNOD. H -2Mmice were purchased from Jackson Company and bred in our animal facility under specific pathogen free conditions. 274 mice with 5 - week old were randomly divided into 5 groups;normal iodine, 5 -fold, 10 fold, 100 fold, 1000 fold iodine excess. Mice from each group were anesthetized by dieth-yl ether and bleed from eye socket vein, then their thyroids were collected. Iodine concentration was determined in thyroid tissue homogenate by arsenic cerium catalytic spectrophotometry method (WS/T107 -1999). Radioimmunoassay was used to determine TSH, lT4and TT3 in mice serum. 15|xCi of Na1 I was injected ip 2 hours before sacrifice, thyroid homogenates were counted to calculate in vivo 125I uptake. After fixed with paraformaldehyde and embedded in paraffin thyroid sections were stained with HE and used for morphometrical analysis. Ul-trathin sections were cut and examined with electron microscope. All data managements were completed in SPSS 11.5 software.ResultsWith the increase of iodine concentration, the weight of thyroid increased too, and showed a positive correlation with iodine dose (r=0.56 -0.88, P < 0.05). A time and dose dependent increase in positive rate of serum TgAb and titers of serum TgAb was found, and there was a positive correlation between iodine levels and titers of serum TgAb. The incidence of autoimmune thyroiditis, as well as infiltration degree of lymph cells increased with iodine dose increased. In the control group, tissue iodine and tissue thyroid hormone concentrations were stable in each point, but lower than that in the other groups, and a positive correlation between iodine concentration and thyroid iodine or tissue thyroid hormones were found. In the control, before the time point of 8 weeks after iodiza-tion, the iodine uptake rate varied little, but decreased at the point of 24 weeks. There was a negative relationship between iodine dose and iodine uptake rate (r= -0.71 ⁰. 81, P <0.001). Compared with the control group, the uptake rate decreased by 3, 6, 40, and 200 times in each iodine group respectively. With the iodine dose increased, the areas of follicle cavities increased, the number of follicle cells, as well as capillaries decreased, and the destruction of follicle structure was severe. ITie ultramicrostructure study showed iodine excess might also result in RER dilatation, mitochondrial abnormalities, secondary ly-sosomes increasing, nuclear degeneration, destruction of cell membrane, and infiltration of lymph cells. Although no difference was found in serum TT4 between control and other iodine groups, serum TT4increased with length of time in 5 - fold iodine excess group, and showed an inverse V shape in 10 -1000 fold groups.Conclusions1. Iodine excess may result in iodine - induced goiter in NOD. H - 2 mice.2. Iodine excess may initiate and accelerate the development of autoimmune thyroiditis.3. Iodine excess may promote the development of serum TgAb in a dose and time dependent way, and titers of serum TgAb correlated positively with infiltration degree of lymph cells.4. Iodine excess may decrease the number of follicle epidermal cells and capillaries, as well as destroy the follicle structure.5. Iodine excess may injure ultramicrostructure of follicle epidermal cells in a dose and time dependent way.