[Effects of selenium supplementation on antibodies of autoimmune thyroiditis].

OBJECTIVE: To evaluate the effects of selenium (Se) supplementation on concentrations of thyroid peroxidase antibodies (TPOAb) and TPOAb IgG subclasses in autoimmune thyroiditis (AIT) patients with different thyroid functional status. METHODS: A blind and placebo-controlled prospective study was performed for a total of 134 cases with AIT and thyroid peroxidase antibodies above 300 U/ml. Their mean age was 41 years (range: 15-70). All of them were recruited from Department of Endocrinology, First Affiliated Hospital of China Medical University from June 2008 to June 2009 and divided into 2 groups according to thyroid function: euthyroidism or subclinical hypothyroidism (n = 89) and hypothyroidism (n = 45). Then they were randomized into 2 groups: selenium-treated and placebo-treated. And 49 cases in subclinical autoimmune thyroiditis group and 28 cases in hypothyroidism group received 200 µg oral selenium yeast daily for 6 months while others placebo. Serum concentrations of TPOAb, TPOAb IgG subclasses, thyroid-stimulating hormone (TSH), free thyroxine (FT(4)) and Se were measured at baseline and after 3 and 6 months of follow-up. RESULTS: The TPOAb levels showed an overall decrease of 4.3% at 3 months and of 12.6% at 6 months (both P < 0.05) post-supplementation in subclinical autoimmune thyroiditis patients. In overt hypothyroidism patients, the overall decrease of TPOAb concentrations was 21.9% at 3 months and 20.4% at 6 months (both P < 0.05) compared with those at pre-treatment. The predominant TPOAb IgG subclasses in sera from the AIT patients were IgG1, IgG3 and IgG4 and the positive percentages 72%, 41% and 72% respectively. The positive rate and concentrations of IgG3 in the patients with hypothyroidism were significantly higher than those of subclinical autoimmune thyroiditis (P < 0.05). Significant decreases in IgG1 and IgG3 levels were noted in subclinical autoimmune thyroiditis group at 6 months post-supplementation (P < 0.05). IgG1 levels in overt hypothyroidism decreased significantly compared with those at pre-supplementation (P < 0.05). In all patients with supplementation (n = 77), the TPOAb levels decreased in 52 at 6 months while increase or no change occurred in 25. The positive percentage and concentrations of IgG1 in patients whose TPOAb levels decreased at 6 months post-supplementation were markedly higher than those whose TPOAb levels increased (P < 0.05). CONCLUSION: Se is effective in reducing TPOAb concentrations and the predominant decreasing TPOAb IgG subclasses are IgG1 and IgG3. And a high level of IgG1 subclass may explain the difficult decline of TPOAb.

[The changes of thyrotropin level in euthyroid population: a 5-year follow-up study in communities with different iodine intakes].

OBJECTIVE: To determine the factors that influence the development of abnormal thyrotropin (TSH) level in an euthyroid population. METHODS: We conducted a follow-up study in 3 communities with different iodine status. Of the 3403 euthyroid subjects at baseline screened in 1999, 80.1% (n = 2727) was visited and sampled in 2004 for measuring TSH, thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). RESULTS: Iodine status in the 3 communities were stable. Decreased TSH level (< 0.3 mU/L) developed in 2.5% (n = 68) of sampled subjects, while raised TSH level (> 4.8 mU/L) in 2.4% (n = 64). A logistic analysis showed that risk factors for developing decreased TSH level included positive conversion of TPOAb (OR = 5.5), positive TPOAb both in 1999 and in 2004 (OR = 4.0), positive TgAb in 2004 (OR = 3.7) and TSH < 1.0 mU/L in 1999 (OR = 2.6). Risk factors involved in developing raised TSH level included iodine status of Zhangwu community (OR = 4.1), iodine status of Huanghua community (OR = 3.9), positive TgAb in 2004 (OR = 3.7), positive TPOAb both in 1999 and 2004 (OR = 3.6), positive conversion of TPOAb (OR = 2.7) and TSH > 1.9 mU/L in 1999 (OR = 2.6). CONCLUSIONS: Exposure to long-term iodine excess imposes danger of developing hypothyroidism. The risk will be even higher when exposing to iodine adequacy after correction of iodine deficiency. An interval between 1.0 and 1.9 mU/L of TSH level was optimal with the least probability of developing abnormal TSH level.

[A study on the mechanism of iodine-induced thyroid epithelial cell injury in the induction of autoimmune thyroiditis].

OBJECTIVE: To investigate the effect of iodine excess on thyroid follicle epithelial ultrastructure and the relationship between thyroid injury and autoimmune thyroiditis. METHODS: NOD. H-2(h4) mice and Kunming mice were randomly divided into four groups receiving plain water, 5 fold, 10 fold, and 100 fold excessive iodine water. 4, 8 and 24 weeks after receiving iodine water, the mice were killed. After fixation with osmic acid and dual staining with uranyl chloride and citrate lead, thyroid gland ultrastructure was examined with electron microscopy. RESULTS: Iodine treated NOD. H-2(h4) mice exhibited marked accumulation of peroxisome and secondary lysosomes, apoptosis and necrosis of thyroid epithelial cell, damage of thyroid follicles and lymphocytic infiltration. The observed changes induced by iodine were in a dose dependent way. CONCLUSION: The oxidative injury on the thyroid epithelial cells induced by iodine excess might be the prerequisite for the creation of autoimmune thyroiditis.

[A clinical study on gestational transient thyrotoxicosis].

OBJECTIVE: To investigate the prevalence of gestational transient thyrotoxicosis (GTT) and analyze the cause of thyrotoxicosis encountered in this period. METHODS: An epidemiologic survey in ten hospitals in Shenyang was performed and 534 pregnant women during the first trimester of pregnancy filled questionnaire, received physical examination and had serum thyroid-stimulating hormone (TSH), free T(4) (FT(4)), free T(3) (FT(3)), thyroid peroxidase antibody (TPOAb), thyrotrophin receptor antibody (TRAb), and human chorionic gonadotrophin (hCG) tests. RESULTS: (1) The total prevalence of thyrotoxicosis was 9.75% (52/534) in the first trimester and the prevalence of GTT was 7.86%, which accounted for 80.77% of the thyrotoxicosis encountered in this period. A total of 88.89% of the overt GTT showed only elevated FT(3) level. (2) The level of serum hCG increased gradually in the first trimester. The medians of hCG were 25 300, 85 220 and 81 780 IU/L 6, 8 - 10 and 12 weeks after gestation, respectively (P = 0.000). The medians of serum TSH were 1.45, 1.10 and 0.84 mIU/L 6, 8 - 10 and 12 weeks after gestation, respectively (P < 0.01). (3) When serum hCG was more than 50 000 IU/L, the prevalence of GTT increased obviously. When serum hCG was between 80 000 IU/L and 110 000 IU/L, subclinical GTT increased significantly. When serum hCG was more than 110 000 IU/L, overt GTT increased significantly. Correlation analysis showed that serum hCG was related negatively with TSH (r = -0.402, P = 0.000) and positively with FT(3) (r = 0.165, P = 0.000), but not related with FT(4). CONCLUSIONS: The prevalence of GTT is 7.86% in the first trimester and it is the main cause of thyrotoxicosis found in the first trimester, accounting for 80.77% of all the causes. The serological characteristic of overt GTT is mainly the elevation of serum FT(3) level. Serum hCG level is related with the severity of GTT.

[Epidemiological study of the effects of smoking cigarette on thyroid gland].

OBJECTIVE: To investigate the effect of cigarette smoking on thyroid gland volume, thyroid function and thyroid autoantibodies in the areas with different iodine intakes. METHODS: A cross-sectional epidemiological study in Panshan (mild iodine-deficient area), Zhangwu (more than adequate iodine intake area) and Huanghua (iodine-excessive area) was conducted in 3761 subjects in 1999.80.2 % of them were followed up in 2004. Questionnaires, thyroid function, thyroid autoantibodies, urinary iodine concentration,and thyroid B ultrasound were performed. RESULTS: The prevalence of goiter was higher in smokers than in non-smokers (15.1% vs. 11.5%, P< 0.05). The average thyroid volume was higher in smokers with phenomenon more obvious in Panshan and Huanghua areas. Data from logistic analysis showed that smoking cigarette was an independent risk factor of goiter. There was no difference in serum TSH and Tg level between smokers and non-smokers. The positive rate of TPOAb (>100 IU/ml) was higher in smokers than in non-smokers(10.8% vs. 9.0 % , P <0.05) and was especially obvious in Huanghua area. Smoking was a independent risk factor of increasing positive rate of TPOAb. During the prospective observation,it was found that the incidence of positive TPOAb(>,100 IU/ml) was 7.4% in the subjects that were from non-smokers turning to smokers and 2.9% in those whose smoking behavior did not change. Logistic analysis indicated that the shifting from non-smoking to smoking was independent risk factor for the increase on high incidence of positive TPOAb. CONCLUSION: Smoking cigarette was a independent risk factor of goiter. Smoking was also a risk factor of increasing TPOAb positive rate. Shifting from not smoking to smoking was an independent risk factor of increasing high incidence of positive TPOAb.

[Thyroid function and thyroid autoimmunity at the late pregnancy: data from 664 pregnant women].

OBJECTIVE: To study the prevalence of thyroid diseases, as well as characteristics of the disease spectrum and thyroid autoimmunity in women at the end of pregnancy. METHODS: Six hundred and sixty-four pregnant women (pregnancy group) and 276 non-pregnant women (control group) were enrolled in the study. Serum thyrotropin (TSH), thyroid peroxidase antibody (TPOAb), free T(3) (FT(3)) and free T(4) (FT(4)) were measured by high-sensitive immunochemiluminescent assay, and urinary iodine was also examined at the end of pregnancy. Overt hyperthyroidism was diagnosed when both TSH < 0.3 mU/L and FT(4) and/or FT(3) levels were elevated. Subclinical hyperthyroidism was diagnosed when TSH < 0.3 mU/L with normal FT(4) and FT(3) levels. The diagnostic criteria for overt hypothyroidism was TSH > 4.8 mU/L accompanied by decreased FT(4), and for subclinical hypothyroidism was TSH > 4.8 mU/L with normal FT(4) and FT(3) levels. RESULTS: (1) The median urinary iodine (MUI) of pregnancy group was 201.5 microg/L, and that of control group was 196.0 microg/L (P > 0.05). Women in the two groups were iodine-adequate. (2) The overall prevalence of thyroid diseases in pregnancy group and control group was 7.8% (52/664) and 6.9% (19/276), respectively (P > 0.05). (3) As for the diseases pattern, there were obvious differences between the two groups. In pregnancy group, the prevalence of hyperthyroidism was lower than that of hypothyroidism (1.1% vs 6.8%, P < 0.01). In control group, the prevalence of hyperthyroidism and hypothyroidism was 4.7% and 2.2%, respectively (P > 0.05). Compared with control group, the prevalence of hyperthyroidism in pregnancy group was much lower (1.1% vs 4.7%, P < 0.01), mainly due to the decrease of overt hyperthyroidism; whereas, the increment of subclinical hypothyroidism resulted in the higher prevalence of hypothyroidism in pregnancy group (6.8% vs 2.2%, P = 0.01). (4) The median TSH level of the healthy women in pregnancy group was significantly higher than that in control group (2.50 vs 1.54 mU/L, P < 0.01). The positive rate of TPOAb in pregnancy women was lower than that in non-pregnancy women (3.3% vs 9.4%, P < 0.01). CONCLUSION: At the end of pregnancy, hypothyroidism accounts for most thyroid diseases. Thyroid autoimmunity is suppressed.

[The dynamic changes of serum Th1 and Th2 cytokines in postpartum thyroiditis].

OBJECTIVE: To investigate the dynamic changes of serum Th1 and Th2 cytokines in patients with postpartum thyroiditis (PPT) during the first postpartum year. METHODS: 21 patients diagnosed as clinical PPT and 11 healthy postpartum women were enrolled in the study. Blood samples were taken before delivery and every 3 months postpartum for testing serum IFNgamma, IL-2, IL-4 and IL-10, which were measured with ELISA method. RESULTS: In patients with PPT, the detection rate of IFNgamma and IL-2 at 6th month postpartum were 19.0% (4/21) and 14.3% (3/21), respectively, being lower than those before delivery [52.4% (11/21) and 61.9% (13/21), respectively, P < 0.05]. The detection rate of IL-4 and IL-10 in patients were 71.4% (15/21) and 95.2% (20/21), respectively. A significant raise when compared with that before delivery (61.9%, 13/21) was seen in IL-10 (P < 0.05). Although Th1 cytokines (IFNgamma, IL-2) declined gradually post-parturition both in healthy postpartum women and PPT patients, yet Th2 cytokines (IL-4, IL-10) showed different tendency in healthy postpartum women and PPT patients. Th2 cytokines declined gradually in healthy postpartum women, while it kept at high level until the 12th month postpartum in the PPT patients. CONCLUSION: In PPT patients, Th2 cytokines show higher levels after delivery. Th2 cells are dominant and protected thyroids from Th1 cells during the course of PPT; this might be helpful to the recovery from disturbance of thyroid autoimmunity.

[Long-term effects of high iodine intake: inhibition of thyroid iodine uptake and organification in Wistar rats].

OBJECTIVE: To investigate the effects of chronic iodine excess on thyroid function, thyroid peroxidase (TPO) activity, and expression of sodium-iodide symporter (NIS). METHODS: 500 Wistar rats were randomly exposed to 4 doses of iodine 4 microg/d (G0, control), 6 microg/d (G1), 12 microg/d (G2), and 24 microg/d (G3) for 1, 2, 4 and 8 months. The urine iodine and tissue iodine was determined by arsenic/cerium catalyzing spectrophotograph. Radioimmunoassays were used to detect thyrotropin (TSH), free thyroxin (FT4), free triiodothyronine (FT3), total thyroxin (TT4), and total triiodothyronine (TT3). Guaiacol reaction method and potassium iodide oxygenation method were used to determine the activity of TPO. Suspension of single cells from thyroid tissue was made and the positive rate of NIS was determined by flow cytometry. The expression of NIS protein was assayed by immunohistochemistry. RESULTS: The urine iodine levels of G1, G2, and G3 were 1.5, 3, and 6 times of G0 respectively. FT4, FT3, and total iodine were found progressively accumulated in thyroid tissue with the elevation of iodine intake. The TPO activities of G2 and G3 at the 8th month were 0.17 +/- 0.04 and 0.15 +/- 0.03 respectively, both significantly lower than that of G0 (0.4 +/- 0.23, P < 0.05). The levels of iodine intake at different time points of G1-3 were significantly reduced in a iodine-dose dependent manner (r = -0.63 to -0.78, P < 0.01). The 131I intake at month 8 of G1, G2, and G3 were 56%, 49%, and 39% that of G0 respectively. At month 8 the NIS positive rates of G2 and G3 were significantly lower than that of G0 (both P < 0.05). The NIS protein positive rate was positively correlated with NIS protein expression intensity (r = 0.7-0.72, P < 0.01). The iodine content of thyroid tissue was negatively correlated with TPO activity, iodine intake rate, NIS protein positive rate and expression intensity (r = -0.62 to -0.88, P < 0.05). CONCLUSION: Moderate iodine excess continuously suppresses the thyroid iodine uptake and organification, which presents a mechanism for iodine-induced thyroid failure.

Association of cyclooxygenase-2 expression with Hp-cagA infection in gastric cancer.

AIM: To observe the expression of cyclooxygenase-2 (COX-2) and to investigate the association between COX-2 expression and infection with cytotoxic-associated gene A (cagA) positive strain Helicobacter pylori (Hp) in human gastric cancer, and subsequently to provide fresh ideas for the early prevention of gastric cancer. METHODS: 32 Specimens of gastric cancer and corresponding adjacent normal gastric mucosa were obtained from patients who had undergone surgical operations of gastric cancer. All the samples including 1 case of stomach malignant lymphoma and 31 cases of gastric adenocarcinoma were confirmed by pathology diagnosis. The expression of COX-2 in 32 specimens of gastric cancer and corresponding adjacent normal gastric mucosa was quantitatively determined and analyzed with Flow Cytometry, and the levels of COX-2 protein were compared between specimens with cagA(+) Hp infection and those without cagA(+) Hp infection. The cagA gene in 32 specimens of gastric cancer was detected by polymerase chain reaction (PCR) method. RESULTS: Twenty-seven of 32 (84 %) specimens of gastric cancer showed over-expression of COX-2, compared with the adjacent normal gastric mucosa. cagA(+) gene were detected from 19 specimens of gastric cancer, but not from the other 13 specimens. The levels of COX-2 protein in 19 specimens of gastric cancer with cagA(+) Hp infection (the number of positive cells was 73.82+/-18.2) were significantly higher than those in the 13 specimens without cagA(+) Hp infection (the number of positive cells was 35.92+/-22.1). CONCLUSION: COX-2 is overexpressed in gastric cancer and cagA(+) Hp infection could up-regulate the expression of COX-2 in gastric cancer in human. There may also exist another way or channel to regulate the expression of COX-2 in gastric cancer in addition to cagA(+) Hp infection. Therefore, applying COX-2 selective inhibitors could be an effective and promising way to prevent gastric cancer.