Publications by authors named "Weiping Teng"

227 Publications

Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway.

Front Endocrinol (Lausanne) 2021 4;12:659738. Epub 2021 Jun 4.

Department of Endocrinology and Metabolism, The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China.

Background: Hashimoto's thyroiditis (HT) is an autoimmune disease that features activation of thyroid antigen-specific helper T cells. HT patients have increased Th1 and Th17 T cell subsets. Glycolysis supports chronic activation of Th1 and Th17 T cells, but how this contributes to HT remains unknown.

Methods: The metabolism of CD4+ T cells from 30 HT patients and 30 healthy controls was evaluated by determining the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). Mice in a subacute thyroiditis (SAT) model were treated with 2DG, metformin, or combination. Metrics of mTOR/HIF-1α/HK2/glycolysis were measured by western blot and Seahorse assay methods. The severity of SAT was measured by flow cytometry and HE staining.

Results: CD4+ T cells from HT patients had enhanced ECAR and OCR. Levels of Glut1, HK2, PKM2, and LDHA in cultured HT CD4+ T cells were elevated. The expression of HK2 and PKM2 in cultured SAT CD4+ T cells was elevated compared with the control group. Activation of the mTOR and HIF-1α pathways was significant in SAT mice, and expression of HIF-1α in the 2DG treated group was reduced. Treatment with 2DG and/or metformin significantly decreased the ratio of Th17 and Th1 T cells.

Conclusions: Thyroiditis results in elevation of the mTOR/HIF-1α/HK2/glycolysis pathway in CD4+ T cells. The activation of this pathway is reduced by treatment with 2DG and metformin, which also reverted imbalances in CD4+ T cell differentiation.
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http://dx.doi.org/10.3389/fendo.2021.659738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211914PMC
June 2021

Using Tumor-Infiltrating Immune Cells and a ceRNA Network Model to Construct a Prognostic Analysis Model of Thyroid Carcinoma.

Front Oncol 2021 1;11:658165. Epub 2021 Jun 1.

Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China.

Thyroid carcinoma is a solid malignant tumor that has had a fast-growing incidence in recent years. Our research used thyroid carcinoma gene expression profiling from TCGA (The Cancer Genome Atlas) database to identify differentially expressed ceRNAs. Using the gene expression profiling from 502 carcinoma thyroid tissues and 58 normal thyroid tissues from the TCGA database, we established the thyroid carcinoma-specific competitive endogenous RNA (ceRNA) network and found nine overall survival (OS)-associated genes (). We quantified the proportions of immune cells using the algorithm "CIBERSORT", found three OS-associated immune cells (memory B cells, M0 macrophages, and activated dendritic cells), and established a thyroid carcinoma-specific immune cell network based on that. The good reliabilities AUC (area under the curve) of 10-year survival (0.955, 0.944, respectively) were accessed from the nomograms of genes and immune cells. Subsequently, by conducting co-expression analyses, we found a potential regulation network among ceRNAs and immune cells. Besides, we found that (alkaline phosphatase) and hsa-miR-204-5p were significantly correlated and that was related to activated dendritic cells. We took advantage of multi-dimensional databases to verify our discovery. Besides, immunohistochemistry (IHC) assays were conducted to detect the expression of a dendritic cell marker (CD11c) and ALPL in thyroid carcinoma (TC) and paracancerous tissues. In summary, our study found a potential mechanism in which hsa-miR-204-5p regulated in activated dendritic cells, which may allow them to play a critical role in thyroid carcinoma. These findings provide potential prognostic biomarkers and therapeutic targets for thyroid carcinoma.
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http://dx.doi.org/10.3389/fonc.2021.658165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204697PMC
June 2021

Inhibition of MicroRNA-326 in a NOD.H-2 Mouse Model of Autoimmune Thyroiditis.

Front Immunol 2021 1;12:620916. Epub 2021 Jun 1.

Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Previous studies reported that various miRNAs participate in autoimmune diseases, but the potential regulatory mechanism of miRNAs in autoimmune thyroiditis (AIT) needs further exploration.

Objective: This study aimed to further verify that miR-326 contributes to AIT by regulating Th17/Treg balance through Ets-1 using lentiviral gene delivery through tail vein and thyroid injection in NOD.H-2 mice.

Materials And Methods: Five-week-old NOD.H-2 mice were divided randomly into tail vein and thyroid injection groups, and each received either mmu-miR-326 sponge (LV-sponge) or lentiviral vector control. Mice were divided for tail vein injection: the therapeutic LV-ctrl, therapeutic LV-sponge, prophylactic LV-ctrl, and prophylactic LV-sponge groups. The control group was fed high-iodine water without vein injection. The thyroid infiltration of lymphocytes and serum TgAb value were investigated by thyroid hematoxylin and eosin (HE) staining and ELISA, respectively. Ets-1 and lymphocyte counts were measured by RT-PCR, western blotting, and flow cytometry. The thyroid CD4IL-17a cells and CD4Ets-1 cells were detected by immunofluorescence, and the serum cytokines were tested by ELISA.

Results: In the tail vein injection groups, the thyroid inflammatory score and serum TgAb titer were significantly lower in the LV-sponge groups than in the control and LV-ctrl groups while Ets-1 protein expression in mouse spleens was increased in the LV-sponge groups. Moreover, Th17/Treg ratio declined in the LV-sponge group and decreased significantly in the prophylactic LV-sponge group ( = 0.036) tested by flow cytometry. Immunofluorescence showed that, in LV-sponge groups, CD4IL-17a cells were decreased significantly ( = 0.001), while CD4Ets-1 cells were increased significantly in the LV-sponge group ( = 0.029). The serum IL-17/IL-10 was decreased significantly in the LV-sponge group ( < 0.05). In the thyroid injection groups, the thyroid inflammatory score and serum TgAb titer in the LV-sponge group decreased significantly compared with those in the LV-ctrl group ( < 0.05). In addition, in LV-sponge groups, CD4IL-17a cells were decreased, while CD4Ets-1 cells were increased significantly in the inhibition group evaluated by immunofluorescence. Moreover, tail vein injection of LV-sponge resulted in much lower TgAb levels in thyroiditis compared with thyroid injection.

Conclusion: MiR-326 targeted therapy may be a promising approach for AIT. In addition, tail vein injection may achieve a better intervention effect than thyroid injection.
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http://dx.doi.org/10.3389/fimmu.2021.620916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205278PMC
June 2021

Reference Intervals for Serum Thyroid-Stimulating Hormone Based on a Recent Nationwide Cross-Sectional Study and Meta-Analysis.

Front Endocrinol (Lausanne) 2021 1;12:660277. Epub 2021 Jun 1.

Department of Endocrinology and Metabolism and the institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China.

Objective: The aim of our study was to compare the reference intervals (RIs) [median (2.5-97.5 percentiles)] for thyroid-stimulating hormone (TSH) between subgroups stratified by ethnicity and iodine status in a global context.

Design And Methods: Primary data were derived from a recently published cross-sectional study in mainland China. Secondary data were obtained from online databases. The RIs for TSH were calculated in the reference population according to the National Academy of Clinical Biochemistry (NACB) standard and in the disease-free population. A meta-analysis of ethnicity- and iodine status-specific TSH RIs was performed.

Results: The primary data showed that the TSH RI (mU/L) in the disease-free population was 2.33 (0.67, 7.87), which is wider than the published RI [2.28 (0.74, 7.04)] in the reference population. The meta-analysis showed that whether in the reference or disease-free population, the RIs in Yellows were much higher than those in Caucasians. In the reference population, the median and 2.5 percentile in the iodine-sufficient subgroup were both lower than the iodine-deficient or more-than-adequate subgroup, while the 97.5 percentile showed a positive trend with increasing sufficiency of iodine. However, in the disease-free population, the iodine-sufficient subgroup had a lower median and 97.5 percentile but higher 2.5 percentile than the iodine-deficient subgroup.

Conclusion: Yellows have a higher TSH RI than Caucasians. In the reference population, both the median and 2.5 percentile TSH in the iodine-sufficient population were the lowest among the different iodine status subgroups, while the 97.5 percentile of TSH showed an upward trend with increasing iodine sufficiency.
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http://dx.doi.org/10.3389/fendo.2021.660277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204855PMC
June 2021

Hyperthyroidism Prevalence in China After Universal Salt Iodization.

Front Endocrinol (Lausanne) 2021 28;12:651534. Epub 2021 May 28.

Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, China.

Background: Universal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination.

Methods: Data were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015-2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured.

Results: After two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves' disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% . 0.64%, P<0.001; GD: 0.65% . 0.37%, P<0.001).Prevalence was significantly decreased after 60 years-of-age compared with 30-39 years-of-age (OH:0.61% . 0.81%, P<0.001; GD: 0.38% . 0.57%, P<0.001).Excessive iodine(EI) and deficient iodine(DI) were both related to increased prevalence of OH (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.68-2.59; OR1.35, 95%CI 1.07-1.72, respectively); however, only deficient iodine was associated with increased prevalence of GD (OR1.67, 95%CI 1.30-2.15). Increased thyroid peroxidase antibody and thyroglobulin antibody levels were significantly associated with prevalence of OH and GD, but not severe SCH and mild SCH. Although hyperthyroidism was more prevalent in women, the association disappeared after adjusting for other factors such as antibody levels.

Conclusion: OH and GD prevalences in mainland China are stable after two decades of USI. Iodine deficiency, elevated thyroid antibody levels, and middle age are the main risk factors for OH and GD. The severe SCH population, rather than the mild SCH population, shows similar characteristics to the OH population.
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http://dx.doi.org/10.3389/fendo.2021.651534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194401PMC
May 2021

Maternal Subclinical Hypothyroidism in Rats Impairs Spatial Learning and Memory in Offspring by Disrupting Balance of the TrkA/p75 Signal Pathway.

Mol Neurobiol 2021 May 8. Epub 2021 May 8.

Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, 110001, China.

Maternal subclinical hypothyroidism (SCH) during pregnancy can adversely affect the neurodevelopment of the offspring. The balance of nerve growth factor (NGF)-related tropomyosin receptor kinase A/p75 neurotrophin receptor (TrkA/p75) signaling in the hippocampus is important in brain development, and whether it affects cognitive function in maternal SCH's offspring is not clear. In this study, we found that compared with the control (CON) group, expression of proliferation-related proteins [NGF, p-TrkA, phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) and phospho-cAMP response element-binding protein (p-CREB)] decreased in the hippocampus of the offspring in the SCH group, overt hypothyroidism (OHT) group, and the group with levothyroxine (L-T) treatment for SCH from gestational day 17 (E17). In contrast, expression of apoptosis-related proteins [pro-NGF, p75, phospho-C-Jun N-terminal kinase (p-JNK), p53, Bax and cleaved caspase-3] was increased. The two groups with treatment with L-T for SCH from E10 and E13, respectively, showed no significant difference compared with the CON group. L-T treatment enhanced relative expression of NGF by increasing NGF/proNGF ratio in offspring from maternal SCH rats. In conclusion, L-T treatment for SCH from early pregnancy dramatically ameliorated cognitive impairment via TrkA/p75 signaling, which involved activation of the neuronal proliferation and inhibition of neuronal apoptosis in SCH rats' offspring.
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http://dx.doi.org/10.1007/s12035-021-02403-zDOI Listing
May 2021

The Relationship Between Thyroid Function and Metabolic Syndrome and Its Components: A Cross-Sectional Study in a Chinese Population.

Front Endocrinol (Lausanne) 2021 31;12:661160. Epub 2021 Mar 31.

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Objective: The present study examined the relationship between thyroid function status and the prevalence of metabolic syndrome in a Chinese population.

Methods: Cross-sectional data were obtained from the Thyroid Disease, Iodine Nutrition and Diabetes Epidemiology (TIDE) Survey. A total of 62,408 subjects aged ≥18 years were enrolled. Differences in metabolic indicators and the prevalence of metabolic syndrome according to sex and thyroid function status were compared. Logistic regression was used to analyze the influence of thyroid function on metabolic syndrome and its components.

Results: The prevalence of metabolic syndrome was generally higher in men than women. Overt hyperthyroidism and subclinical hypothyroidism had a significant effect on metabolism in men. Body mass index (BMI), waist circumference, and triglycerides (TGs) were significantly lower in men in the overt hyperthyroidism group, and BMI, waist circumference, systolic blood pressure (SBP) and TGs were higher in men in the subclinical hypothyroidism group than men in the normal group. Overt and subclinical hypothyroidism had significant impacts on metabolic components in women. BMI, waist circumference, TGs, SBP and DBP in the subclinical and overt hypothyroidism groups were significantly higher than the euthyroid group in women. The relative risk of abdominal obesity and hypertriglyceridemia was increased in women with hypothyroidism. Thyroid dysfunction had different effects on metabolic syndrome and its components before and after menopause.

Conclusion: Thyroid function had important effects on the prevalence of metabolic syndrome. Women with hypothyroidism, especially post-menopausal women, had a higher risk of metabolic syndrome than men.
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http://dx.doi.org/10.3389/fendo.2021.661160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044548PMC
March 2021

The Iodine Status and Prevalence of Thyroid Disorders among Women of Childbearing-age in China: National Cross-sectional Study.

Endocr Pract 2021 Apr 7. Epub 2021 Apr 7.

Department of Endocrinology and Metabolism and the Institute of Endocrinology, First Hospital of China Medical University, 155 Nanjing Bei Street, Shenyang, 110001, Liaoning, China. Electronic address:

Objective: Mandatory universal salt iodization in China was implemented 20 years ago; however, the current iodine status and prevalence of thyroid disorders among childbearing-age women are unknown.

Methods: A nationally representative cross-sectional study with 26166 enrolled participants aged 18 to 49 years from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum concentrations of thyroid hormones and thyroid antibodies and the urine iodine concentration (UIC) were measured.

Results: The median UIC was 178.7 μg/L, which is indicative of adequate iodine status; however, 19.04% and 19.87% of the participants were classified as having iodine deficiency and excessive iodine, respectively. The weighted prevalences of thyroid disorders were as follows: 1.08% had overt hyperthyroidism, 0.58% had subclinical hyperthyroidism, 0.76% had Graves' disease, 1.28% had overt hypothyroidism, 14.28% had subclinical hypothyroidism, 13.53% were positive for TPOAb, and 14.55% were positive for TgAb. Excessive iodine and overweight were associated with higher odds of subclinical hypothyroidism. A family history of thyroid disorders and an age between 40-49 years were significantly associated with higher odds of positivity for TPOAb and positive TgAb.

Conclusion: Iodine deficiency, excessive iodine, subclinical hypothyroidism, and positivity for thyroid autoantibodies are still prevalent among women of childbearing age in China. Women of childbearing age who are relatively older, are overweight, or have a family history of thyroid disorders are encouraged to undergo active screening of their UIC and thyroid function when planning a pregnancy.
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http://dx.doi.org/10.1016/j.eprac.2021.03.017DOI Listing
April 2021

MicroRNA expression profiles of the thyroid after goiter formation and involution in rats under different iodine regimens.

Endocrine 2021 Mar 25. Epub 2021 Mar 25.

Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China.

Background: Thyroid damage occurs during experimental iodine-deficient goiter and involution with iodine supplementation. This study investigated the dynamic microRNAs (miRNAs) expression profiles in iodine-deficient thyroids during adequate and excessive iodine supplementation.

Methods: Twenty-four female Wistar rats were randomly divided into control, low-iodine (LI), LI-1I, and LI-2I groups. The LI-1I and LI-2I groups were fed a LI diet for 12 weeks, followed by a onefold (adequate) or twofold (excessive) physiological dose of iodine for 4 weeks to induce involution. The miRNA expression profiles were evaluated and the potential functions of the differentially expressed miRNAs identified were explored.

Results: In the LI group, 20 miRNAs were downregulated and 8 were upregulated. After involution, 21 miRNAs recovered to the control group levels in the LI-1I group, which was more than the 17 that recovered in the LI-2I group. In addition, 8 new differentially expressed miRNAs were identified in the LI-1I group, which was less than the 13 found in the LI-2I group. Bioinformatics analyses indicated that all differentially expressed miRNAs were involved in different processes and pathways, such as autoimmune thyroid disease and the Ras signaling pathway.

Conclusion: Differentially expressed miRNAs are involved in iodine-deficient goiter formation and involution. Supplementation with adequate, not excessive, iodine may be more beneficial to restore homeostasis.
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http://dx.doi.org/10.1007/s12020-021-02679-0DOI Listing
March 2021

Causal Association between Serum Thyroid-Stimulating Hormone and Obesity: A Bidirectional Mendelian Randomization Study.

J Clin Endocrinol Metab 2021 Mar 23. Epub 2021 Mar 23.

Department of Endocrinology and Metabolism and the institute of Endocrinology, The First Hospital of China Medical University, Shenyang, Liaoning, P.R. China.

Context: The association between serum thyroid-stimulating hormone (TSH) and obesity traits has been investigated previously in several epidemiological studies. However, the underlying causal association has not been established.

Objective: To determine and analyze the causal association between serum TSH level and obesity-related traits (BMI and obesity).

Design, Setting, Participants: The latest genome-wide association studies (GWASs) on TSH, BMI and obesity were searched to obtain full statistics. Bidirectional two-sample Mendelian randomization (MR) was performed to explore the causal relationship between serum TSH and BMI and obesity. The inverse variance-weighted (IVW) and MR-Egger methods were used to combine the estimation for each SNP. Based on the preliminary MR results, free thyroxine (fT4) and free triiodothyronine (fT3) levels were also set as outcomes to further analyze the impact of BMI on them.

Main Outcome Measures: BMI and obesity were treated as the outcomes to evaluate the effect of serum TSH on them, and TSH was set as the outcome to estimate the effect of BMI and obesity on it.

Results: Both IVW and MR-Egger results indicated that genetically driven serum TSH did not causally lead to changes in BMI or obesity. Moreover, the IVW method showed that the TSH level could be significantly elevated by genetically predicted high BMI (β=0.038, se=0.013, p=0.004). In further MR analysis, the IVW method indicated that BMI could causally increase the fT3 (β=10.123, se=2.523, p<0.001) while not significantly affecting the fT4 level.

Conclusion: Together with fT3, TSH can be significantly elevated by an increase in genetically driven BMI.
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http://dx.doi.org/10.1210/clinem/dgab183DOI Listing
March 2021

Circulating Exosomes From Patients With Graves' Disease Induce an Inflammatory Immune Response.

Endocrinology 2021 Mar;162(3)

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China.

Exosomes are extracellular vesicles that can participate in autoimmune diseases. The purpose of this study was to explore whether circulating exosomes are involved in Graves' disease (GD) pathogenesis. In this study, serum exosomes were extracted from 26 healthy controls (HC-EXO), 26 GD patients (GD-EXO), and 7 Graves' ophthalmopathy patients (GO-EXO). For each group, the total protein content was detected, and thyrotropin receptor, insulin-like growth factor 1 receptor (IGF-1R), heat shock protein 60 (HSP60), and cluster of differentiation (CD) 63 expression were analyzed by Western blotting (WB). Healthy volunteer-derived peripheral blood mononuclear cells (PBMCs) and HC-EXO or GD-EXO were cocultured for 24 h, and immunofluorescence was used to observe the locations of the exosomes and toll-like receptor (TLR) 2/3. CD11c+TLR2+ and CD11c+TLR3+ cell percentages were determined by flow cytometry. Myeloid differentiation factor 88 (MyD88), toll/interleukin (IL)-1 receptor domain-containing adaptor inducing interferon-β (TRIF) and p-P65 expression were analyzed by WB. IL-6 and IL-1β supernatant levels were detected using enzyme-linked immunosorbent assay. The results showed that the total protein concentration was similar among GD-EXO, GO-EXO, and HC-EXO. IGF-1R and HSP60 expression was significantly higher in GD-EXO and GO-EXO than in HC-EXO. After coculturing PBMCs with GD-EXO or HC-EXO for 24 h, GD-EXO could bind to TLR2/3. GD-EXO significantly increased CD11c+TLR2+ and CD11c+TLR3+ cell percentages; MyD88, TRIF, and p-P65 protein expression; and IL-6 and IL-1β levels. In conclusion, we first demonstrated that GD-EXO and GO-EXO highly expressed IGF-1R and HSP60. GD-EXO may induce an inflammatory response through the TLR/NF-κB signaling pathway and be involved in the pathogenesis of GD.
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http://dx.doi.org/10.1210/endocr/bqaa236DOI Listing
March 2021

Estimated change in prevalence of abnormal thyroid-stimulating hormone levels in China according to the application of the kit-recommended or NACB standard reference interval.

EClinicalMedicine 2021 Feb 28;32:100723. Epub 2021 Jan 28.

Department of Endocrinology and Metabolism and the Institute of Endocrinology, First Hospital of China Medical University, 155 Nanjing Bei Street, Shenyang 110001, Liaoning, China.

Background: Both the kit-recommended and United States National Academy of Clinical Biochemistry (NACB) standard thyroid-stimulating hormone (TSH) reference intervals (RIs) are used to determine thyroid dysfunction in clinical practice and epidemiological surveys in China. However, a number of kit-recommended RIs were derived from the European or United States reference population.

Methods: A nationally representative cross-sectional study with 78,470 enrolled participants aged 18 years or older from China was performed. Serum concentrations of thyroid hormones, TSH, thyroid antibodies (by Roche Diagnostics), and urine iodine concentration (UIC) were measured.

Findings: The abnormal TSH weighted prevalence was 15.33% (95% CI, 14.24% to 16.49%) according to the kit-recommended RI and 6.89% (6.46% to 7.34%) according to the NACB standard RI. The NACB standard prevalence of abnormal TSH was associated with an absolute change in abnormal TSH prevalence of -11.20% (-12.23% to -10.18%) among women. When estimating the proportion of supranormal TSH levels according to background characteristics, the NACB standard definition decreased the prevalence by more than 10% in some categories, with the highest absolute difference of -13.92% (-15.52% to -12.33%) observed among the elderly, -12.85% (-13.68% to -12.02%) among those with UIC ≥300 μg/L, and -12.15% (-13.02% to -11.28%) among non-smokers. For subnormal TSH, with the highest absolute difference of 3.17% (2.74% to 3.61%) observed among regular smokers, 3.11% (2.49% to 3.74%) among the elderly, and 2.53% (2.29% to 2.77%) among those with BMI <25.

Interpretation: For adults in China, the NACB standard RI of TSH reveals a lower estimated prevalence of supranormal TSH levels than the kit-recommended RI. Because of the public health significance of overt and subclinical hypothyroidism and the very large population base in China, the TSH RI should be further assessed.

Funding: National Health Commission of the People's Republic of China and National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/j.eclinm.2021.100723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848757PMC
February 2021

The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study.

Endocr Pract 2020 Aug;26(8):869-882

Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, P.R. China.

Objective: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid auto-antibodies in euthyroid subjects.

Methods: Data were obtained from the Thyroid Diseases and Diabetes Mellitus project survey of 55,891 subjects from 31 provinces in China. The body mass index (BMI), waist circumference (WC), blood pressure, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyroid-stimulating hormone (TSH), urinary iodine concentration, blood glucose, lipid profile, and uric acid levels were evaluated. Free thyroxine and free triiodothyronine levels were measured in patients with abnormal serum TSH levels.

Results: In males, the BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2-hour post-glucose oral glucose tolerance test results of the TPOAb-/TgAb-positive group were significantly higher than those of the TPOAb-/TgAb-negative group. In females, the BMI, WC, SBP, DBP, total cholesterol, and low-density-lipoprotein cholesterol (LDL-C) in the TPOAb-/TgAb-positive group were significantly increased compared to the TPOAb-/TgAb-negative group. Multivariate analysis showed that in males, the odds ratio (OR) of positive TgAbs in the abdominal obesity group was 1.175 (95% confidence interval [CI], 1.016 to 1.359; P = .03), and the OR of positive TPOAbs in the hyperuricemia group was 1.195 (95% CI, 1.041 to 1.372; P = .011). In females, the OR of positive TgAbs was 1.19 (95% CI, 1.068 to 1.326; P = .002) in the high LDL-C group.

Conclusion: Obesity, high LDL-C, and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner.

Abbreviations: AIT = autoimmune thyroiditis; BMI = body mass index; CI = confidence interval; DBP = diastolic blood pressure; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HbA1c = glycated hemoglobin; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OGTT2hPG = oral glucose tolerance test 2-hours post-glucose; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference.
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http://dx.doi.org/10.4158/EP-2020-0008DOI Listing
August 2020

Association between Urinary Iodine Concentration and Thyroid Nodules in Adults: A Cross-Sectional Study in China.

Biomed Res Int 2020 17;2020:4138657. Epub 2020 Dec 17.

Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Background: Associations between iodine intake and thyroid nodules (TNs) were not consistent. We aimed to illustrate the relationship between urinary iodine concentration (UIC) and TNs.

Methods: A total of 12,698 participants were enrolled in analysis. All of the participants filled out questionnaires and underwent physical examinations, laboratory tests, and thyroid ultrasonography. UIC, serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) were measured in the central laboratory.

Results: The prevalence of TNs was 16.00%, and the median UIC was 206.1 g/L. TNs and UIC were negatively related when UIC was less than 527 g/L (adjusted OR = 0.87; 95% CI, 0.80, 0.94), and the relationship between UIC and TNs was not statistically significant when UIC was greater than 527 g/L (adjusted OR = 1.25; 95% CI, 0.98, 1.60). In women, UIC was negatively associated with risk for TNs (adjusted OR 0.95; 95% CI, 0.91, 0.99).

Conclusion: The relationship between TNs and UIC differed between men and women. The risk of TNs decreased with the elevation of UIC in men when UIC was lower than 527 g/L, while UIC and the presence of TNs were negatively correlated in women. In the future, cohort studies or other studies that can explain causality must be conducted to explore the relationship between iodine status and TNs.
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http://dx.doi.org/10.1155/2020/4138657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762642PMC
May 2021

Circulating Exosomes From Patients With Graves' Disease Induce an Inflammatory Immune Response.

Endocrinology 2021 Mar;162(3)

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China.

Exosomes are extracellular vesicles that can participate in autoimmune diseases. The purpose of this study was to explore whether circulating exosomes are involved in Graves' disease (GD) pathogenesis. In this study, serum exosomes were extracted from 26 healthy controls (HC-EXO), 26 GD patients (GD-EXO), and 7 Graves' ophthalmopathy patients (GO-EXO). For each group, the total protein content was detected, and thyrotropin receptor, insulin-like growth factor 1 receptor (IGF-1R), heat shock protein 60 (HSP60), and cluster of differentiation (CD) 63 expression were analyzed by Western blotting (WB). Healthy volunteer-derived peripheral blood mononuclear cells (PBMCs) and HC-EXO or GD-EXO were cocultured for 24 h, and immunofluorescence was used to observe the locations of the exosomes and toll-like receptor (TLR) 2/3. CD11c+TLR2+ and CD11c+TLR3+ cell percentages were determined by flow cytometry. Myeloid differentiation factor 88 (MyD88), toll/interleukin (IL)-1 receptor domain-containing adaptor inducing interferon-β (TRIF) and p-P65 expression were analyzed by WB. IL-6 and IL-1β supernatant levels were detected using enzyme-linked immunosorbent assay. The results showed that the total protein concentration was similar among GD-EXO, GO-EXO, and HC-EXO. IGF-1R and HSP60 expression was significantly higher in GD-EXO and GO-EXO than in HC-EXO. After coculturing PBMCs with GD-EXO or HC-EXO for 24 h, GD-EXO could bind to TLR2/3. GD-EXO significantly increased CD11c+TLR2+ and CD11c+TLR3+ cell percentages; MyD88, TRIF, and p-P65 protein expression; and IL-6 and IL-1β levels. In conclusion, we first demonstrated that GD-EXO and GO-EXO highly expressed IGF-1R and HSP60. GD-EXO may induce an inflammatory response through the TLR/NF-κB signaling pathway and be involved in the pathogenesis of GD.
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http://dx.doi.org/10.1210/endocr/bqaa236DOI Listing
March 2021

Beta-elemene inhibits differentiated thyroid carcinoma metastasis by reducing cellular proliferation, metabolism and invasion ability.

Ann Transl Med 2020 Oct;8(19):1232

Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, China.

Background: Accelerated glycolysis is a characteristic of carcinoma. The herb-derived compound, beta (β)-elemene, has shown promising anticancer effects against various tumors by inhibiting aerobic glycolysis. However, its activity against thyroid carcinoma and the mechanism is still unknown.

Methods: Differentiated thyroid carcinoma (DTC) cell lines, including papillary thyroid carcinoma (PTC) cell lines (IHH-4, TPC-1, K1), and follicular thyroid carcinoma (FTC) cell line (FTC133) were treated with different concentration of β-elemene. The viability of DTC cells was analyzed using the CCK8 method. Cell cycle and apoptosis analysis were performed by flow cytometry and western blotting. The cell invasion ability was evaluated in Transwell assays. Energy metabolism in living cells was measured using a Seahorse XF analyzer. The antitumor effects of β-elemene were analyzed in a nude mouse xenograft tumors model.

Results: CCK8 assays showed β-elemene significantly inhibited DTC cell proliferation in a dose- and time-dependent manner. β-elemene promoted cell apoptosis, with increased expression of cleaved caspase-9 and decreased BCL-2 expression. Transwell assays showed that β-elemene significantly inhibited the invasion ability of DTC cells. β-elemene also reduced angiogenesis by decreasing VEGF expression in DTC cells. β-elemene reduces the basal oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and maximal glycolytic capacity as well as maximal respiration and ATP production. Moreover, β-elemene inhibited tumor growth in a mouse xenograft model .

Conclusions: In this study, we have provided the first evidence of the antitumor effects of β-elemene, which was shown to inhibit cell proliferation, promote apoptosis, induce cell cycle arrest, inhibit cell invasion ability and reduce angiogenesis. Furthermore, we showed that β-elemene significantly inhibits the respiratory and glycolytic ability of human DTC cells. Thus, our findings show the potential of β-elemene as a novel treatment for DTC.
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http://dx.doi.org/10.21037/atm-20-4460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607100PMC
October 2020

Exposure to the Chinese Great Famine in Early Life and Thyroid Function and Disorders in Adulthood: A Cross-Sectional Study.

Thyroid 2021 04 23;31(4):563-571. Epub 2020 Dec 23.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Malnutrition in early life may permanently change the structure and function of the body, which lead to a number of diseases in adulthood. The effect of famine exposure during the early life on thyroid function and disorders remains unclear. This study investigated the association between exposure to the Great Chinese Famine (1959-1961) in early life and thyroid function and disorders in adulthood. Nine thousand eight hundred eighty-one subjects with appropriate birth dates derived from the Thyroid disorders, Iodine status, and Diabetes Epidemiological survey were included. Thyroid function and disorders were defined by the test results of blood sample and ultrasonography of all participants. Associations between famine exposure in early life and thyroid function and disorders in adulthood were assessed with binary logistic regression and linear regression. Participants exposed to the Great Chinese Famine during the fetal stage was associated with a higher thyrotropin (TSH) level in adulthood ( = 0.024;  = 0.038), compared with the nonexposed participants. The association was significant among rural participants ( = 0.039;  = 0.02) but not in urban participants ( = 0.005;  = 0.77). Fetal-exposed group did not show a higher risk of thyroid disorders than the age-matched balanced control group, including overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and thyroid nodules ( > 0.05). Famine exposure during the fetal stage was associated with a higher TSH level in adulthood. The fetal stage could be the critical period for programming the pituitary-thyroid axis.
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http://dx.doi.org/10.1089/thy.2020.0325DOI Listing
April 2021

Concentration-dependent Differences in Urinary Iodine Measurements Between Inductively Coupled Plasma Mass Spectrometry and the Sandell-Kolthoff Method.

Biol Trace Elem Res 2021 Jul 9;199(7):2489-2495. Epub 2020 Oct 9.

Department of Endocrinology and Metabolism and the Institute of Endocrinology, First Hospital of China Medical University, No.155 Nanjing Bei Street, Shenyang, 110001, Liaoning, China.

A large amount of historical data regarding urinary iodine concentration (UIC) were measured with the Sandell-Kolthoff (S-K) method for iodine nutrition surveillance. The congruence in urinary iodine measurements between inductively coupled plasma mass spectrometry (ICP-MS) and the S-K method has been debated. A total of 2064 adult urine samples were included in the present study. The UIC measurement results obtained simultaneously by standardized ICP-MS and the S-K method were analyzed. The UIC obtained with ICP-MS was significantly higher than that obtained with the S-K method (158 μg/L vs. 148 μg/L, p < 0.001). The Bland-Altman difference plot showed a small but significant mean difference of 6.12 μg/L between the two methods. The stratified analysis showed that the correlation coefficient was higher in the UIC < 300 μg/L group than the UIC ≥ 300 μg/L group (0.93 vs. 0.88, p = 0.0001). The mean difference between the S-K and ICP-MS methods was positively correlated with the UIC. The ICP-MS and S-K methods were comparable when the UIC was less than 300 μg/L; however, UIC values between 300 and 600 μg/L should be compared with caution after considering the research objective. We do not suggest comparing UICs obtained from the ICP-MS and S-K methods in iodine monitoring studies if the UIC is greater than 600 μg/L.
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http://dx.doi.org/10.1007/s12011-020-02381-8DOI Listing
July 2021

Generation and Characterization of a New Resistance to Thyroid Hormone Mouse Model with Thyroid Hormone Receptor Alpha Gene Mutation.

Thyroid 2021 04 23;31(4):678-691. Epub 2020 Oct 23.

Department of Endocrinology and Metabolism, Endocrine Institute, and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, China.

In humans, resistance to thyroid hormone (RTH) caused by mutations in the thyroid hormone receptor alpha () gene, RTHα, manifests as tissue-specific hypothyroidism and circulating thyroid hormone levels exhibit hypothyroid-like clinical features. Before the identification of patients with RTHα, several Thrα1 knock-in mouse models were generated to clarify the function of TRα1. However, the phenotypes of these mice were not consistent with the clinical presentation of RTHα in humans. For the present study, we generated an RTHα mouse model that carries the mutation found in human RTHα patients. Here, we report the gross phenotypes of this mouse RTHα model. Traditional homologous recombination gene targeting techniques were used to introduce a mutation ( in the mouse gene. The phenotypes of the resulting mice were studied and compared with clinical features observed for RTHα with . Thrα1 homozygous mice exhibited severe neurological phenotypes, such as spasticity and motor ataxia, which were similar to those observed in endemic cretinism. Thrα1 heterozygous mice reproduced most clinical manifestations of patient with RTHα, such as a normal survival rate and male fertility, as well as delayed postnatal growth and development, neurological and motor coordination deficits, and anemia. The mice had typical thyroid function with a modest increase in serum triiodothyronine (T3) levels, a low thyroxine (T4)/T3 ratio, and low reverse T3 (rT3) levels. The Thrα1 mice faithfully recapitulate the clinical features of human RTHα and thus can provide a useful tool to dissect the role of TRα1 in development and to determine the pathological mechanisms of RTHα.
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http://dx.doi.org/10.1089/thy.2019.0733DOI Listing
April 2021

Dynamic Changes in Antithyroperoxidase and Antithyroglobulin Antibodies Suggest an Increased Risk for Abnormal Thyrotropin Levels.

Front Endocrinol (Lausanne) 2020 4;11:521. Epub 2020 Aug 4.

Department of Endocrinology and Metabolism, The Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China.

Antithyroperoxidase (TPOAb) and antithyroglobulin (TgAb) antibodies are associated with abnormal thyrotropin (TSH) levels. However, the effect of dynamic changes in TPOAb and TgAb on incident abnormal TSH is unknown. A total of 2,387 euthyroid participants aged 18 years or older from three rural areas in northern China were enrolled in this cohort study. Questionnaire interviews and laboratory measurements were performed at baseline in 1999 and at follow-up in 2004. Multinomial logistic regression was used to examine the relationship between changes in thyroid antibodies and incident abnormal TSH levels. In this 5 year follow-up study, TPOAb tier gain was significantly associated with an increased risk of subnormal TSH levels (adjusted RR, 1.535; 95% CI: 1.357-1.736) and supranormal TSH levels (adjusted RR, 1.378; 95% CI: 1.196-1.587), and TgAb tier gain was significantly associated with an increased risk of supranormal (adjusted RR, 1.090; 95% CI: 1.007-1.179) TSH levels. Both thyroid antibody-positive seroconversion and persistent positivity were significantly associated with an increased risk of incident abnormal TSH levels. Thyroid antibody positive seroconversion was associated with a higher risk of incident subnormal TSH than incident supranormal TSH, whereas persistent positive thyroid antibody was associated with a higher risk of incident supranormal TSH than incident subnormal TSH. Dynamic thyroid antibody changes may be related to incident abnormal TSH levels. Those with persistent positive thyroid antibody were more likely to have supranormal TSH than subnormal TSH, and those with positive seroconversion were more likely to have subnormal TSH than supranormal TSH. Further studies are needed to confirm this conclusion and to explore this association mediated by TSH receptor antibodies.
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http://dx.doi.org/10.3389/fendo.2020.00521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417360PMC
June 2021

The combination of ATA classification and FNA results can improve the diagnostic efficiency of malignant thyroid nodules.

Endocr Connect 2020 Sep;9(9):903-911

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Purpose: To determine the diagnostic efficiency of the ATA classification and ultrasound-guided fine-needle aspiration (FNA) results in identifying the risk factors of malignancy, we analyzed the thyroid nodules of patients who underwent thyroidectomy and compared preoperative ATA classifications with FNA results.

Methods: We retrospectively analyzed 274 nodules of 196 patients who underwent ultrasonography, FNA and thyroidectomy. Histopathological findings of thyroid nodules were considered as the Au standard in the analysis of the diagnostic efficiency of the ATA classification and FNA results. Univariate analysis and binary multivariate logistic regression analysis were applied to identify the ultrasound features associated with malignancy.

Results: The overall malignancy rate of 274 nodules was 41.6%. The areas under the ROC curves (AUCs) for the ATA classification and FNA results were 0.88 and 0.878, respectively (P < 0.001). The sensitivity and specificity of the ATA classification were 86 and 86.9%, whereas those of FNA results were 68.5 and 91.4%, respectively. The specificity (98.7%) and sensitivity (94.3%) increased after the combined use of the ATA classification and FNA results. Taller-than-wide shape, microcalcifications, hypoechogenicity and irregular margins were independent risk factors for malignancy. Microcalcifications had the highest OR (7.58), and taller-than-wide shape had the highest specificity in BSRTC I, II, III and IV cytology.

Conclusion: The diagnostic efficiency of the ATA classification and FNA results in identifying malignant nodules was high, and the use of both criteria improved the diagnostic accuracy. Taller-than-wide shape, microcalcifications, hypoechogenicity and irregular margins were independent risk factors for malignancy.
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http://dx.doi.org/10.1530/EC-20-0303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583133PMC
September 2020

The Effect of Increased Iodine Intake on Serum Thyrotropin: A Cross-Sectional, Chinese Nationwide Study.

Thyroid 2020 12 21;30(12):1810-1819. Epub 2020 Sep 21.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Data were acquired from a Chinese nationally representative cross-sectional study of 78,470 participants (TIDE study). The total study population were participants from the TIDE program, and the reference population was a subset of the total population defined by the National Academy of Clinical Biochemistry (NACB) guidelines. Serum concentrations of thyroid hormones, TSH, thyroid antibodies, and urine iodine concentration (UIC) were measured. The geometric mean serum TSH (2.5th-97.5th) for the reference population (defined by the NACB) and total population was 2.28 mIU/L (0.74-7.04 mIU/L) and 2.34 mIU/L (0.61-8.33 mIU/L), respectively. In the reference population, increase in UIC was significantly associated with increase in the 50th and 97.5th centiles and decrease in the 2.5th centile of TSH. The median TSH was significantly higher in women than in men (2.41 mIU/L vs. 2.16 mIU/L, -value <0.001). Increased age was significantly associated with an increased TSH, 97.5th centile. For each 10-year increase in the population age, the TSH 97.5th centile increased by 0.534 mIU/L. The prevalence of subclinical hypothyroidism diagnosed according to the assay-recommended interval (Roche 0.27-4.2 mIU/L) and NACB standard interval in the TIDE study (0.74-7.04 mIU/L) differed significantly (Roche 13.61% vs. TIDE 3.00%,  < 0.05). However, there was no significant difference in future cardiovascular disease, reflected by the Framingham risk score, between the 0.27-4.2 and 4.2-7.04 mIU/L TSH groups. Serum TSH concentration significantly increased with increase in iodine intake. Thus, iodine intake must be considered in establishing TSH reference intervals. To avoid overdiagnosis and overtreatment of subclinical hypothyroidism, different areas should use individual serum TSH reference intervals.
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http://dx.doi.org/10.1089/thy.2019.0842DOI Listing
December 2020

An Inverse Relationship Between Iodine Intake and Thyroid Antibodies: A National Cross-Sectional Survey in Mainland China.

Thyroid 2020 11 23;30(11):1656-1665. Epub 2020 Jul 23.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Iodine intake is associated with thyroid autoimmunity. In this study, we evaluated the changes in thyroid autoimmunity after 20 years of universal salt iodization (USI) in China. A total of 78,470 subjects (18 years or older) from 31 provincial regions of mainland China participated in the study. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), TSH receptor antibody, thyrotropin (TSH), and urinary iodine concentration (UIC) were measured. Positive TPOAb and TgAb were detected in 10.19% [CI 9.80-10.59] and 9.70% [CI 9.28-10.13] of the subjects, respectively. The prevalence of positive isolated TPOAb (i-TPOAb), positive isolated TgAb (i-TgAb), and double positive TPOAb and TgAb (d-Ab) was 4.52%, 4.16%, and 5.94%, respectively. The prevalence of thyroid antibody positivity was the highest in the iodine-deficient (UIC <100 μg/L) groups. The prevalence of i-TPOAb was inversely associated with more than adequate iodine intake (MAI) and excessive iodine intake (EI); the odds ratio (OR) was 0.89 [CI 0.81-0.98] for MAI and 0.90 [CI 0.81-0.99] for EI. We observed that i-TgAb, like i-TPOAb, was a high-risk factor for subnormal TSH levels (OR = 3.64 [CI 2.62-5.05]) and elevated TSH levels (OR = 1.62 [CI 1.49-1.77]). The prevalence of thyroid antibody positivity varied among five ethnic groups. After two decades of USI, the prevalence of thyroid antibody positivity has remained low. MAI and EI had an inverse relationship with TPOAb positivity, which reveals that UIC between 100 and 299 μg/L is optimal and safe for thyroid autoimmunity. These conclusions need to be confirmed in a follow-up study because this study was a cross-sectional study.
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http://dx.doi.org/10.1089/thy.2020.0037DOI Listing
November 2020

Serum CA125 Level Is Associated with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes.

Diabetes Metab Syndr Obes 2020 22;13:1803-1812. Epub 2020 May 22.

Department of Ophthalmology, The First Hospital of China Medical University, Shenyang 110001, People's Republic of China.

Background: To investigate the association between serum carbohydrate antigen 125 (CA125) and the presence as well as severity of diabetes retinopathy (DR) in Chinese adult patients with type 2 diabetes.

Methods: A hospital-based cross-sectional study was conducted from February 2012 to November 2018. DR was assessed using Early Treatment Diabetic Retinopathy Study criteria. Vision-threatening DR (VTDR) was diagnosed if subjects had severe non-proliferative DR (NPDR), proliferative DR (PDR), or clinically significant macular edema (CSME). Multivariate logistic regression models were applied to explore the associations.

Results: Among the 2696 participants, the overall prevalence of DR was 25.1%, of which the prevalence of mild NPDR, moderate NPDR, and VTDR was 10.8%, 4.5%, and 9.9%, respectively. Serum CA125 level was significantly higher in participants with DR and increased with the severity of DR ( = 0.013). After accounting for age, gender, smoking, drinking, duration of diabetes, anti-diabetic agents use, systolic blood pressure, pulse pressure, weight, hemoglobin A1c and fasting plasma glucose levels, CA125 level was significantly associated with subjects in any-severity DR (odds ratio [OR] 1.006 [95% confidence interval CI: 1.002-1.010], = 0.006) and VTDR (1.008 [1.003-1.013], = 0.001). When CA125 was treated as categorized variables, the prevalence of VTDR might increase as improving CA125 quartiles ( value for trend = 0.017).

Conclusion: In this study, serum CA125 level was associated with the presence and severity of DR in Chinese patients with type 2 diabetes. Further prospective studies should be warranted to validate the feasible role of CA125 as well as other biomarkers.
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http://dx.doi.org/10.2147/DMSO.S250928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250309PMC
May 2020

Experimental evidence for alpha enolase as one potential autoantigen in the pathogenesis of both autoimmune thyroiditis and its related encephalopathy.

Int Immunopharmacol 2020 Aug 19;85:106563. Epub 2020 May 19.

Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China.

Alpha-enolase (ENO1) is a ubiquitous protein. Patients with autoimmune thyroiditis-associated encephalopathy have high serum ENO1Ab titers. We aimed to explore whether ENO1Ab was the pathogenic antibody in the thyroid and brain. The serum ENO1Ab titers were significantly increased in the mice immunized with Thyroglobulin (Tg). And in the mice immunized with ENO1, serum levels of both TgAb and thyroid-stimulating hormone (TSH) were significantly increased. Obvious CD16 cell infiltration, IgG deposit and cleaved caspase-3 were observed in the thyroid of ENO1-immunized mice. Spatial learning and memory abilities and synaptic functions were impaired in ENO1-immunized mice. Furthermore, the expression levels of Iba-1, GFAP, interlukin-6, CDK5, and phosphorylated tau were increased, and endothelial tight junction proteins were decreased in the brain of ENO1-immunized mice. These results suggest that ENO1Ab can cause thyrocyte damage via ADCC effect and impair cerebral function by disrupting the blood-brain barrier.
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http://dx.doi.org/10.1016/j.intimp.2020.106563DOI Listing
August 2020

Functional analysis of thyroid peroxidase gene mutations resulting in congenital hypothyroidism.

Clin Endocrinol (Oxf) 2020 10 8;93(4):499-507. Epub 2020 Jun 8.

Department of Endocrinology and Metabolism, Institute of Endocrine, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, China.

Objective: Thyroid peroxidase (TPO) is essential for thyroid hormone biosynthesis. TPO mutations might lead to congenital hypothyroidism. In the present study, we analysed the function of a compound heterozygous TPO mutation in a Chinese family.

Design: We studied a 23-year-old Chinese girl with a history of growth retardation and severe constipation from the age of 3 months, who was diagnosed as having congenital hypothyroidism.

Methods: Genomic DNA was extracted from peripheral blood samples obtained from the patient's family members. The genomic DNA was sequenced to detect mutations in a panel of genes associated with congenital hypothyroidism. Bioinformatic analysis and structural modelling predicted the potential disease-causing potential mutant genes and the microstructure of the mutant protein, respectively. Western blotting and ELISA were used to measure protein expression, and guaiacol oxidation assay measured the TPO activity of the mutant protein.

Results: We identified a compound heterozygous mutation (c.C1993T, c.T2473C) in the TPO gene. Bioinformatic analysis predicted that the TPO mutations were potentially disease causing. Structural modelling predicted damage to the microstructure of the mutant TPO protein. Western blotting and ELISA showed reduced protein levels of the mutant TPO protein compared with that of the wild-type protein. The mutant TPO protein showed weaker activity compared with that of the wild-type protein.

Conclusions: A novel compound heterozygous mutation of TPO gene was identified in a Chinese family. This mutation might alter the extracellular microstructure of TPO, and decrease its expression and the activity, resulting in congenital hypothyroidism.
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http://dx.doi.org/10.1111/cen.14253DOI Listing
October 2020

Maternal Thyroid Dysfunction and Gestational Anemia Risk: Meta-Analysis and New Data.

Front Endocrinol (Lausanne) 2020 15;11:201. Epub 2020 Apr 15.

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, China.

Previous studies indicate the effects of thyroid dysfunction on adverse obstetric outcomes and fetal neurodevelopment, of which the results on gestational anemia are controversial. Here, we evaluated the influence of thyroid dysfunction on gestational anemia via published epidemiological articles and a new prospective study conducted by our team, respectively. We searched studies on the PubMed, Embase, MEDLINE, and Cochrane databases as of November 2019, and conducted a prospective study in which participants underwent thyroid function and blood routine testing throughout pregnancy. The meta-analysis showed that pregnancies with overt hypothyroidism [OH; odds ratio (OR) = 3.74, 95% confidence interval (CI): 1.95-7.15] or that were thyroid peroxidase antibody (TPOAb)-positive (OR = 1.97, 95%CI: 1.19-3.26) had increased anemia risk, but similar results were not found in pregnancies with subclinical hypothyroidism (SCH) and hyperthyroidism. In the prospective study from our new data, the hypothyroid group had significant reductions in hemoglobin (Hb) ( = 0.048) and increased anemia risk (OR = 6.384, 95%CI: 2.498-16.311) during the second half of pregnancy. From the first to second half of pregnancy, the longitudinal reductions in Hb, erythrocyte (RBC), and hematocrit (Hct) levels were significantly increased in hypothyroid group. Our meta-analysis indicates that untreated OH or TPOAb-positive pregnant women have increased risk of anemia. In addition, our new data showed that treated hypothyroidism is also a risk factor for anemia in the second half of pregnancy rather than in the first half. The results may guide strengthening of Hb monitoring in pregnancies with thyroid dysfunction.
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http://dx.doi.org/10.3389/fendo.2020.00201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174567PMC
April 2021

Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study.

BMJ 2020 04 28;369:m997. Epub 2020 Apr 28.

Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, China.

Objective: To assess the prevalence of diabetes and its risk factors.

Design: Population based, cross sectional study.

Setting: 31 provinces in mainland China with nationally representative cross sectional data from 2015 to 2017.

Participants: 75 880 participants aged 18 and older-a nationally representative sample of the mainland Chinese population.

Main Outcome Measures: Prevalence of diabetes among adults living in China, and the prevalence by sex, regions, and ethnic groups, estimated by the 2018 American Diabetes Association (ADA) and the World Health Organization diagnostic criteria. Demographic characteristics, lifestyle, and history of disease were recorded by participants on a questionnaire. Anthropometric and clinical assessments were made of serum concentrations of fasting plasma glucose (one measurement), two hour plasma glucose, and glycated haemoglobin (HbA).

Results: The weighted prevalence of total diabetes (n=9772), self-reported diabetes (n=4464), newly diagnosed diabetes (n=5308), and prediabetes (n=27 230) diagnosed by the ADA criteria were 12.8% (95% confidence interval 12.0% to 13.6%), 6.0% (5.4% to 6.7%), 6.8% (6.1% to 7.4%), and 35.2% (33.5% to 37.0%), respectively, among adults living in China. The weighted prevalence of total diabetes was higher among adults aged 50 and older and among men. The prevalence of total diabetes in 31 provinces ranged from 6.2% in Guizhou to 19.9% in Inner Mongolia. Han ethnicity had the highest prevalence of diabetes (12.8%) and Hui ethnicity had the lowest (6.3%) among five investigated ethnicities. The weighted prevalence of total diabetes (n=8385) using the WHO criteria was 11.2% (95% confidence interval 10.5% to 11.9%).

Conclusion: The prevalence of diabetes has increased slightly from 2007 to 2017 among adults living in China. The findings indicate that diabetes is an important public health problem in China.
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http://dx.doi.org/10.1136/bmj.m997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186854PMC
April 2020

THE CORRELATION BETWEEN METABOLIC DISORDERS AND TPOAB/TGAB: A CROSS-SECTIONAL POPULATION-BASED STUDY.

Endocr Pract 2020 Apr 27. Epub 2020 Apr 27.

Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, P.R. China, 550004.

Objectives: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid autoantibodies in euthyroid subjects.

Methods: Data were obtained from a TIDE project survey of 55,891 subjects from 31 provinces in China. The body mass index(BMI), waist circumference(WC), blood pressure(BP), TPOAb, TgAb, TSH, UIC, blood glucose, lipid profile, uric acid(UA) levels were evaluated. FT4 and FT3 levels were measured in patients with abnormal serum TSH levels.

Results: In males, the BMI, WC, SBP, DBP, and OGTT2hPG of the TPOAb/TgAb-positive groups were significantly higher than those of the TPOAb/TgAb-negative groups. In females, the BMI, WC, SBP, DBP, TC, and LDL-C in the TPOAb/TgAb-positive groups were significantly increased compared to those in the TPOAb/TgAb-negative groups. Multivariate analysis showed that, in males, the OR of positive TgAb in the abdominal obesity group was 1.175 (95% CI 1.016-1.359, P for difference= 0.03), and the OR of positive TPOAb in the hyperuricemia group was 1.195 (95% CI 1.041-1.372, P for difference = 0.011). In females, the OR of positive TgAb was 1.19 (95% Cl 1.068-1.326, P for difference= 0.002) in the high LDL-C group.

Conclusions: Obesity, high LDL-C and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner.
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http://dx.doi.org/10.4158/EP-2020-0008DOI Listing
April 2020

The Presence of Serum TgAb Suggests Lower Risks for Glucose and Lipid Metabolic Disorders in Euthyroid General Population From a National Survey.

Front Endocrinol (Lausanne) 2020 18;11:139. Epub 2020 Mar 18.

Department of Endocrinology, Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China.

The expressions of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) are very common in the sera of patients with autoimmune thyroid diseases (AITD). The relationship between thyroid autoantibodies and the occurrence of glucose and lipid metabolic disorders remains unclear. This study was performed to investigate the correlation between the presence of serum TPOAb/TgAb and those metabolic disorders in euthyroid general population. The data of this study were derived from the Thyroid Disease, Iodine status, and Diabetes National epidemiological (TIDE) survey from all 31 provinces of mainland China. A total of 17,964 euthyroid subjects including 5,802 males (4,000 with TPOAbTgAb and 1,802 with TPOAb/TgAb) and 12,162 females (8,000 with TPOAbTgAb and 4,162 with TPOAb/TgAb) were enrolled in this study. The blood glucose and lipid levels were compared between individuals with TPOAbTgAb and those with TPOAbTgAb, TPOAbTgAb, TPOAbTgAb. Both fasting blood glucose (FBG) concentration and the proportion of individuals with impaired FBG (IFG) showed the decreased trends in TPOAbTgAb males as compared with TPOAbTgAb men. There were significantly lower FBG and higher HDL-C levels as well as tendencies toward decreased incidences of IGT and hypertriglyceridemia in TPOAbTgAb females when compared with TPOAbTgAb women. Binary logistic regression analysis further showed that serum TgAb single positivity in males was an independent protective factor for IFG with an OR of 0.691 (95% CI, 0.503-0.949). For females, serum TgAb single positivity was an independent protective factor for hypertriglyceridemia with an OR of 0.859 (95% CI, 0.748-0.987). Trend test showed that with the increase of serum TgAb level, there were significant decreases in the prevalence of IFG among the men with TSH ≤ 2.5 mIU/L and that of hypertriglyceridemia in the women, especially among non-obese females. Serum TgAb single positivity may imply a reduced risk of IFG in euthyroid men and that of hypertriglyceridemia in euthyroid women. The mechanisms for the independent protective roles of TgAb await further investigation.
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http://dx.doi.org/10.3389/fendo.2020.00139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093715PMC
February 2021