Effects of Maternal Marginal Iodine Deficiency on Interactions between Cerebellar Bergmann Glia Cells and Purkinje Cells in Rat Offspring.

Iodine deficiency (ID) during early pregnancy has an adverse effect on children's psychomotor and motor function but the mechanism has not been clarified. Therefore, our aim was to study the effect of maternal marginal ID on cerebellar neurodevelopment and the underlying mechanism. After obtaining marginal ID rats, we examined interactions between Bergmann glia cells (BGs) and Purkinje cells (PCs) using immunofluorescence and expression of the glutamate transporter and receptor by western blot. Our results showed that marginal ID reduced the number of contacted points between BGs and PCs, and disturbed expression of the glutamate transporter and receptor. Our results support the hypothesis that marginal ID inhibits interactions of BGs-PCs, which may be involved in abnormal regulation of the glutamate transporter and receptor.

Widespread expression of zinc transporter ZnT (SLC30) family members in mouse endocrine cells.

Zinc is abundant in most endocrine cell types, and plays a pivotal role in the synthesis and secretion of many hormones. Recent studies have demonstrated the expression of numerous zinc transporter (ZnT) family members in the pancreas, thyroid, and adrenal glands, suggesting a role for ZnTs in regulating cellular zinc homeostasis in endocrine cells. However, the cellular distribution of ZnTs in the endocrine organs has not been well established. In the present study, the mRNA expression level, cellular distribution of ZnTs as well as liable zinc ions were examined in the mouse pituitary, adrenal glands, thyroid, and pancreas. In general, ZnT1-10 mRNA was expressed to various degrees in the detected endocrine organs, with no detectable ZnT10 mRNA in the pancreas. In the anterior pituitary, both the acidophilic and basophilic cells were immunopositive to ZnT1-5, 7, 8, except for ZnT10. In the adrenal cortex, the immunoreactivity of all the tested ZnTs, including ZnT1-5, 7, 8, 10, was observed in the zona fasciculata, and some ZnTs were detected in the zona glomerulosa, zona reticularis, and the adrenal medulla. Both the follicle epithelial cells and parafollicular cells in the thyroid gland were immunostained with ZnT1-5, 7, 8, but not ZnT10. In the endocrine pancreas, the immunoreactivity of tested ZnTs was observed to various degrees except for ZnT10 in the cytoplasm of islet cells. Furthermore, autometallographic staining showed that liable zinc was observed in the endocrine cells, such as the adrenal cortical cells, thyroid follicle epithelial cells, and the pancreatic islet cells. All together, the wide distribution of liable zinc and the phenomenon that numerous ZnT family members are partially overlapped in a subset of endocrine cells suggest an important role for the ZnT family in controlling cellular zinc levels and subsequently regulating the synthesis and secretion of hormones in the endocrine system.

[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.

Development and validation of a risk assessment model for prediabetes in China national diabetes survey.

BACKGROUND: Prediabetes risk assessment models derived from large sample sizes are scarce. AIM: To establish a robust assessment model for prediabetes and to validate the model in different populations. METHODS: The China National Diabetes and Metabolic Disorders Study (CNDMDS) collected information from 47325 participants aged at least 20 years across China from 2007 to 2008. The Thyroid Disorders, Iodine Status and Diabetes Epidemiological Survey (TIDE) study collected data from 66108 participants aged at least 18 years across China from 2015 to 2017. A logistic model with stepwise selection was performed to identify significant risk factors for prediabetes and was internally validated by bootstrapping in the CNDMDS. External validations were performed in diverse populations, including populations of Hispanic (Mexican American, other Hispanic) and non-Hispanic (White, Black and Asian) participants in the National Health and Nutrition Examination Survey (NHANES) in the United States and 66108 participants in the TIDE study in China. C statistics and calibration plots were adopted to evaluate the model's discrimination and calibration performance. RESULTS: A set of easily measured indicators (age, education, family history of diabetes, waist circumference, body mass index, and systolic blood pressure) were selected as significant risk factors. A risk assessment model was established for prediabetes with a C statistic of 0.6998 (95%CI: 0.6933 to 0.7063) and a calibration slope of 1.0002. When externally validated in the NHANES and TIDE studies, the model showed increased C statistics in Mexican American, other Hispanic, Non-Hispanic Black, Asian and Chinese populations but a slightly decreased C statistic in non-Hispanic White individuals. Applying the risk assessment model to the TIDE population, we obtained a C statistic of 0.7308 (95%CI: 0.7260 to 0.7357) and a calibration slope of 1.1137. A risk score was derived to assess prediabetes. Individuals with scores ≥ 7 points were at high risk of prediabetes, with a sensitivity of 60.19% and specificity of 67.59%. CONCLUSION: An easy-to-use assessment model for prediabetes was established and was internally and externally validated in different populations. The model had a satisfactory performance and could screen individuals with a high risk of prediabetes.

[Sex hormone-binding globulin of gestational diabetes mellitus pregnant women with well-controlled glucose and pregnancy outcomes].

OBJECTIVE: To explore the relationship between sex hormone-binding globulin (SHBG) of gestational diabetes mellitus (GDM) pregnant women with well-controlled glucose and pregnancy outcomes. METHODS: Two hundred and fifty-one GDM pregnant women of 24 - 28 weeks in Shengjing Hospital of China Medical University were recruited from Mar. 2005 to Mar. 2010. Two hundred and sixteen cases of GDM with well-controlled glucose were defined as glycemic satisfied group, and they were treated by diet therapy (169 cases) or insulin therapy (47 cases). Thirty-five cases with unsatisfied glucose were defined as glycemic unsatisfied group. One hundred and ninety-two healthy pregnant women of 24 - 28 weeks were defined as healthy control group. Serum SHBG and homeostasis model analysis of insulin resistance (HOMA-IR) at 24 - 28 weeks and above 36 weeks were measured. GDM was diagnosed by "two-step" method according to the National Diabetes Data Group (NDDG) criteria. The pregnancy outcomes and complications of the three groups were recorded. RESULTS: (1) Comparison of pregnancy outcomes and complications:glycemic satisfied group was less likely to develop hypertensive disorders in pregnancy (10.6%), premature birth (8.3%), large for gestational age (LGA) (8.8%), neonatal asphyxia (3.7%) and neonatal hypoglycemia (2.3%) compared to glycemic unsatisfied group (42.9%, 34.3%, 31.4%, 22.9% and 11.4%, respectively). And the difference was statistically significant (P < 0.05 or P < 0.01). There was no significant difference for incidence of polyhydramnios, pueperal infection, postpartum hemorrhage, neonatal hyperbilirubinemia between the two groups (P > 0.05). When compared to healthy control group (7.3%, 2.1%, 4.2%, 2.1% and 1.6%), no significant difference was found for incidence of premature birth (8.3%), pueperal infection (3.2%), postpartum hemorrhage (5.1%), neonatal asphyxia (3.7%) and neonatal hypoglycemia (2.3%, P > 0.05). (2) Comparison of results of 24 - 28 weeks and above 36 weeks: serum SHBG of glycemic satisfied group [(384 ± 88), (457 ± 48) nmol/L] was significantly higher than that of glycemic unsatisfied group [(313 ± 45), (401 ± 73) nmol/L]; HOMA-IR of glycemic satisfied group (5.3 ± 1.1, 5.5 ± 1.1) was significantly lower than that of glycemic unsatisfied group (7.0 ± 1.3, 7.6 ± 1.7; P < 0.01). Serum SHBG of glycemic satisfied group was significantly lower than that of healthy control group [(492 ± 95), (565 ± 40) nmol/L]; and HOMA-IR of glycemic satisfied group (5.3 ± 1.1, 5.5 ± 1.1) was significantly higher than that of healthy control group (3.6 ± 0.6, 3.9 ± 0.5; P < 0.01). FPG of glycemic satisfied group [(5.84 ± 0.28), (5.16 ± 0.13) mmol/L] was significantly lower than that of glycemic unsatisfied group [(6.13 ± 0.16), (5.68 ± 1.14) mmol/L;P < 0.01]. FINS of glycemic satisfied group [(20.4 ± 2.1), (24.1 ± 4.2) mmol/L] was significantly lower than that of glycemic unsatisfied group [(24.7 ± 4.5), (29.9 ± 2.7) mmol/L; P < 0.01]. (3) Correlation analysis. Between 24-28 weeks, SHBG was negatively correlated with HOMA-IR in the three groups (r = -0.952, P < 0.01); and SHBG was negatively correlated with HOMA-IR in glycemic satisfied group (r = -0.903, P < 0.01). CONCLUSIONS: Well-controlled glucose can not completely improve maternal and fetal outcomes of GDM pregnant women. High insulin resistance and low serum SHBG can influence pregnancy outcomes.

Two-Years Prospective Follow-Up Study of Subacute Thyroiditis.

Purpose: The aim of the present prospective follow-up study was to explore the early indicators of hypothyroidism and the final changes in thyroid volume in subacute thyroiditis (SAT) patients. Methods: We enrolled 61 SAT patients and followed them up for 2 years to assess the incidence of hypothyroidism and changes in thyroid volume. Binary logistic regression and receiver operating characteristic (ROC) curves were used for data analysis. Results: During the 2 years follow-up period, we found that the volumes of the thyroid gland in SAT patients at 1 and 2 years were significantly smaller than those in the healthy control group, which were significantly smaller compared to the initial thyroid volumes after SAT onset (p < 0.001). Also, the thyroid volumes of SAT patients with hypothyroidism were significantly smaller than those of SAT patients without hypothyroidism. The early maximum thyroid-stimulating hormone (TSH) values (within 3 months after SAT onset) were closely related to the incidence of hypothyroidism at 2 years. The OR value was 1.18 (95% CI = 1.01-1.38, p = 0.032). The early maximum TSH value had a maximum area under the ROC curve (AUC) of 0.866 for the development of hypothyroidism 2 years after SAT onset vs. euthyroidism (p < 0.001). Conclusions: The thyroid volumes of patients increased significantly after the onset of SAT, while during the follow-up these volumes decreased; the thyroid volumes at 1 and 2 years were significantly smaller than those of normal healthy subjects, especially in SAT patients with hypothyroidism. Furthermore, the early maximum TSH value could be used as an effective indicator of the development of hypothyroidism 2 years after the onset of SAT.

[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.

Association between iron deficiency and prevalence of thyroid autoimmunity in pregnant and non-pregnant women of childbearing age: a cross-sectional study.

BACKGROUND: Thyroid autoimmunity (TAI) is prevalent among women of reproductive age and associated with adverse pregnancy outcomes. This study aimed to investigate the association between iron nutritional status and the prevalence of TAI in women during the first trimester of pregnancy and in non-pregnant women of childbearing age. METHODS: Cross-sectional analysis of 7463 pregnant women during the first trimester of pregnancy and 2185 non-pregnant women of childbearing age nested within the sub-clinical hypothyroid in early pregnancy study, a prospective collection of pregnant and non-pregnant women's data, was conducted in Liaoning province of China between 2012 and 2015. Serum thyrotropin, free thyroxine, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), serum ferritin, and urinary iodine were measured. Iron deficiency (ID) was defined as serum ferritin <15 µg/L and iron overload (IO) was defined as ferritin >150 µg/L. TPOAb-positive was defined as >34 U/mL and TgAb-positive was defined as >115 U/mL. Multilevel logistic regression was conducted to examine the association between TAI and different iron nutritional status after adjusting for potential confounders. RESULTS: The prevalence of isolated TPOAb-positive was markedly higher in women with ID than those without ID, in both pregnant and non-pregnant women (6.28% vs. 3.23%, χ = 10.264, P = 0.002; 6.25% vs. 3.70%, χ = 3,791, P = 0.044; respectively). After adjusting for confounders and the cluster effect of hospitals, ID remained associated with TPOAb-positive in pregnant and non-pregnant women (odds ratio [OR]: 2.111, 95% confidence interval [CI]: 1.241-3.591, P = 0.006; and OR: 1.822, 95% CI: 1.011-3.282, P = 0.046, respectively). CONCLUSION: ID was associated with a higher prevalence of isolated TPOAbs-positive, but not with isolated TgAb-positive, in both pregnant women during the first trimester of pregnancy and non-pregnant women of childbearing age, while IO was not associated with either isolated TPOAb-positive or isolated TgAb-positive. CLINICAL TRIAL REGISTRATION: ChiCTR-TRC-13003805, http://www.chictr.org.cn/index.aspx.

Novel frameshift mutation causes early termination of the thyroxine-binding globulin protein and complete thyroxine-binding globulin deficiency in a Chinese family: A case report.

BACKGROUND: Thyroxine-binding globulin (TBG; the gene product of SERPINA7) is the main transporter of thyroid hormones in humans. Mutations in the TBG gene may lead to inherited TBG deficiency. There have been 28 reported mutations that associate with complete TBG deficiency (TBG-CD). Here we identified a novel frameshift mutation causing early termination of the TBG protein and TBG-CD in a Chinese family. CASE SUMMARY: A 46-year-old Chinese man was referred to our hospital with normal free thyroxine, free triiodothyronine, thyrotropin, but lower total thyroxine and total triiodothyronine, and undetectable serum TBG, indicative of TBG-CD. Blood samples were obtained from the patient's family members and thyroid function and serum TBG were evaluated. Genomic DNA from peripheral blood was sequenced to detect possible TBG mutation(s). Quantitative PCR high-resolution melting curve analysis was used to screen TBG-Poly (L283F) among 117 Chinese men. A novel mutation of TBG (p.Phe135Alafs*21), a 19-nucleotide insertion in exon 1, was identified, which resulted in a truncated TBG protein product and caused TBG-CD. The other mutation, identified in the proband's father, is a known polymorphism, TBG-Poly (L283F). The frequency of the TBG-Poly allele among 117 unrelated Han Chinese men from northeast China was 21.37%. CONCLUSION: A novel mutation in the TBG gene associated with the TBG-CD phenotype was identified in a Chinese family. Additionally, it was found that 21.37% of Chinese males had TBG-Poly (L283F).

[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.

[Distribution and significance of IgG subclasses of serum antithyroglobulin antibody in Hashimoto thyroiditis].

OBJECTIVE: To evaluate the distribution and significance of IgG subclasses of antithyroglobulin antibody in sera from patients with Hashimoto thyroiditis. METHODS: Sera from 112 patients with Hashimoto thyroiditis were collected and patients were divided into 3 groups, i. e. hypothyroidism, subclinical hypothyroidism and euthyroidism. Antigen specific ELISA was used to detect the distribution of IgG subclasses of antithyroglobulin antibody. RESULTS: The positive rates of IgG subclasses of TgAb were IgG1 90.2%, IgG2 58.0%, IgG3 19.6% and IgG4 87.5% respectively. The mean geometric titers of IgG1 in sera from patients with hypothyroidism and subclinical hypothyroidism were 1: 450.8 and 1: 245.5 respectively, both being significantly higher than that with euthyroidism (1:8.7, P < 0.01). The mean geometric titers of IgG2 in sera from patients with hypothyroidism and subclinical hypothyroidism were 1: 37.3 and 1: 3.2 respectively, both being also significantly higher than that with euthyroidism (1: 0.2, P < 0.01 and P < 0.05 respectively) and that with hypothyroidism was significantly higher than that with subclinical hypothyroidism (P < 0.05). CONCLUSION: The distribution of IgG subclasses of antithyroglobulin antibody in sera from patients with Hashimoto thyroiditis was predominantly IgG1, IgG2 and IgG4. High titers of IgG1 and IgG2 implicated the possibility of development from subclinical hypothyroidism to overt hypothyroidism.

[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.

Intralesional and topical glucocorticoids for pretibial myxedema: A case report and review of literature.

Pretibial myxedema (PTM), an uncommon manifestation of Graves' disease (GD), is a local autoimmune reaction in the cutaneous tissue. The treatment of PTM is a clinical challenge. We herein report on a patient with PTM who achieved complete remission by multipoint subcutaneous injections of a long-acting glucocorticoid and topical glucocorticoid ointment application for a self-controlled study. A 53-year-old male presented with a history of GD for 3.5 years and a history of PTM for 1.5 years. Physical examination revealed slight exophthalmos, a diffusely enlarged thyroid gland, and PTM of both lower extremities. One milliliter of triamcinolone acetonide (40 mg) was mixed well with 9 mL of 2% lidocaine in a 10 mL syringe. Multipoint intralesional injections into the skin lesions of the right lower extremity were conducted with 0.5 mL of the premixed solution. A halometasone ointment was used once daily for PTM of the left lower extremity until the PTM had remitted completely. The patient's PTM achieved complete remission in both legs after an approximately 5-mo period of therpy that included triamcinolone injections once a week for 8 wk and then once a month for 2 mo for the right lower extremity and halometasone ointment application once daily for 8 wk and then once 3-5 d for 2 mo for the left lower extremity. The total dosage of triamcinolone acetonide for the right leg was 200 mg. Our experience with this patient suggests that multipoint subcutaneous injections of a long-acting glucocorticoid and topical glucocorticoid ointment application are safe, effective, and convenient treatments. However, the topical application of a glucocorticoid ointment is a more convenient treatment for patients with PTM.

[The relationship between serum thyroid autoantibodies, iodine intake, development and prognosis of Graves' disease].

OBJECTIVE: To investigate the relationship of thyroid autoantibodies including serum thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody (TSBAb) and iodine intake with the development and prognosis of Graves' hyperthyroidism. METHODS: A total of 63 subjects with overt hyperthyroidism were screened out from 3 Chinese rural communities with different iodine intakes at first survey. Serum TSAb, TSBAb, thyrotropin binding inhibitory immunoglobulin (TBII), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were detected. The patients were followed up 2 years later. TSAb and TSBAb were measured with recombinant human thyrotropin receptor (rhTSHR)-Chinese hamster ovary cell (rhTSHR-CHO cell) bioassay. RESULTS: At the first survey, the prevalences of positive TSAb, TBII and TSBAb were found in 80.9%, 61.7% and 6.4% of the patients with Graves' disease respectively. TSAb and/or TBII were positive in 91.5% of the patients. The consistent rate of TSAb and TBII was 59.6% in the cases. All indexes mentioned above were higher in the patients than in healthy controls. Positive correlations were found between TSAb and TBII (r = 0.407), TSAb and thyroglobulin (r = 0.301), TSAb and thyroid volume (r = 0.317) respectively. The prevalence of positive TSAb (91.7%) in Graves' patients in iodine excessive area are significantly higher than those in iodine mildly deficient area (66.7%). The positive rates and the titers of TBII, TPOAb and TGAb were not different statistically among the patients in the three communities. At follow-up, the patients with Graves' hyperthyroidism were classified into euthyroid group (G1) and hyperthyroid group (G2) according to their outcomes of the disease. The TSAb titers and the thyroid volume in the cases of G1 decreased significantly, whereas the patients with highly positive TPOAb titers in the first survey and the follow-up were hard to become euthyroid and TSAb may be the secondary factor influencing the thyroid as compared with TPOAb. CONCLUSION: TSAb is more significant than TBII in diagnosing and predicting the outcomes of Graves' hyperthyroidism. The application of both TSAb and TBII could raise the positive rates of thyrotrophin receptor antibody tests. TSAb, TPOAb titers and thyroid volume were factors influencing the prognosis of Graves' hyperthyroidism.

[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.

[Effect of chronic mild and moderate iodine excess on thyroid anti-oxidative ability of iodine deficiency and non-iodine deficiency Wistar rats].

OBJECTIVE: To investigate the effects of chronic mild and moderate iodine excess on thyroid oxidative injury and anti-oxidative ability of iodine deficiency and non-iodine deficiency Wistar rats. METHODS: Four-week-old Wistar rats were fed with iodine deficient diet for three months to make iodine deficient goiter models, then divided randomly into three groups: iodine deficient control group (Group IDC) fed with double distilled water, iodine-supplement group I (Group IS I) fed with potassium iodate solutions with the iodine concentrations of 100 microg/L, and iodine-supplement group II (Group IS II), fed with potassium iodate solution with the iodine concentrations of 330 microg/L. Another four-week-old Wistar rats were fed with normal diet for three months, and then divided randomly into three groups: normal control group (NC) fed with double distilled water, iodine-excess group I (IEI) fed with potassium iodate solution with the iodine concentration of 300 microg/L, and iodine-excess group II (Group IEII), fed with potassium iodate solution with the iodine concentration of 660 microg/L. 1, 2, 4, 8, and 24 weeks after treatment samples of urine were collected to detect the median urine iodine (MUI), samples of plasma were collected from the hearts of 8-14 rats from each group and then rats were killed. Their thyroid glands were taken out to measure the wet weight and made into homogenate. Biochemical method was used to measure the activities of glutathione-peroxidase (GSH-P(X)) and superoxide dismutase (SOD) as well as the contents of malonyldialdehyde (MDA) and H2O2 in the homogenates of thyroid glands. RESULTS: The GSH-P(X) activity 2 weeks after treatment of Group IS II was significantly lower than that of Group IDC (P < 0.05), and the GSH-P(X) activity 4 weeks after treatment of Group IS I was significantly lower than that of Group IDC (P < 0.001). The activities of GSH-P(X) 4, 8, and 24 weeks after treatment of Groups IS I and IS II were all lower than those of Group C at the same time points significantly (P < 0.001, < 0.01, and < 0.05 respectively). The activities of SOD were decreased gradually in Groups IS I and IS II and were significantly lower than those of Group IDC since 8 weeks after treatment (P < 0.001 or < 0.05). The SOD activities in thyroid glands of Groups IEI and IEII since 8 weeks after treatment decreased significantly in comparison with Group NC (all P < 0.01 or < 0.001). The contents of H2O2 in thyroid glands of Groups IS I and IS II were significantly lower than those of Group IDC at different time points (P < 0.001, < 0.01, or < 0.05), and were significantly lower than those of Group NC 8 and 24 weeks after treatment (P < 0.001 or < 0.01). The contents of MDA in thyroid glands since 2 weeks after treatment of Group IEI were all significantly lower than those of Group IDC at the same time points (all P < 0.05), and the content of MDA in thyroid glands since 1 week after treatment of Groups IS II were all significantly lower than those of Group IDC at the same time points (all P < 0.05). CONCLUSION: Supplementation of 100 microg/L and 330 microg/L iodine on iodine deficiency Wistar rats may alleviate the oxidative injury but weaken the anti-oxidative protection of thyroid. The anti-oxidative protection of thyroid glands of non-iodine deficiency Wistar rats may also be weakened by supplementation of 300 microg/L and 660 microg/L iodine.

[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.

[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.