Gestational TSH and FT4 Reference Intervals in Chinese Women: A Systematic Review and Meta-Analysis

Background: Serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) change dynamically during pregnancy. Differences in geographic regions, populations, and manufacturer's methodologies can affect the reference intervals for thyroid function tests. The 2017 guidelines of the American Thyroid Association (ATA) recommended 4.0 mU/L as the cut-off point for the upper limit of serum TSH in early pregnancy. A systematic review is called for to establish practical, gestational-specific TSH and FT4 reference intervals for pregnant Chinese women and to explore whether the criteria are suitable for China.Methods: English and Chinese articles published from inception to Aug 2017 were searched in the PubMed, EMBASE, and SCIE English-language databases and the CNKI, WanFang, and CQVIP Chinese databases. The relative descent or ascent rates of serum TSH and FT4 were calculated, after which Comprehensive Meta-Analysis V2.0 software was used to analyze the data.Results: Eleven studies (6 in English and 5 in Chinese), five kits and 11,629 Chinese women from nine cities were considered in this meta-analysis. Compared with the reference ranges provided by manufacturers, serum TSH decreased in the first trimester, with the upper limit declining by 21.7% (5.0–36.6%), to a value close to 4.0 mU/L, and the lower limit declining by 85.7% (73.5–97.1%). It continued decreasing in the second trimester, with the upper limit declining by 24.0% (6.4–40.9%) and the lower limit declining by 40.7% (9.0–85.7%). For FT4, the upper limit fluctuated slightly, and the lower limit increased by 6.8% (1.0–14.6%) in the first trimester. Serum FT4 dropped gradually, with the upper limit declining by 21.8% (2.5–31.8%) and the lower limit declining by 12.7% (2.6–19.6%) in the second trimester. During the third trimester, the upper limit decreased by 25.1% (12.7–35.0%), while the lower limit decreased by 20.9% (14.8–27.3%).Conclusions: Various regions, kits and test methods affect the gestational TSH and FT4 levels. The non-pregnant serum TSH upper limit minus 22% is very close to 4.0 mU/L, which can be used as a sub-optimal approach to represent the cut-off value for pregnant Chinese women in the first trimester

IL-34 Expression Is Reduced in Hashimoto's Thyroiditis and Associated With Thyrocyte Apoptosis

Hashimoto's thyroiditis (HT) is a common autoimmune disease accompanied by lymphocyte infiltration and thyroid tissue destruction. IL-34 was first described in 2008, and its involvement in the development of many autoimmune diseases has been recently identified. However, whether IL-34 is a regulatory factor in HT is unclear. Here, we demonstrate that IL-34 is expressed on thyroid follicular epithelial cells and that IL-34 expression is significantly reduced in thyroid tissue in patients with HT and spontaneous autoimmune thyroiditis (SAT) models. Serum IL-34 levels in patients with HT are also significantly reduced. In addition, IL-34 is associated with thyroid autoantibodies in both thyroid tissue and serum. Furthermore, our data show that IL-34 participates in the apoptosis resistance of thyrocytes in HT induced by CSF-1R and may be a potential indicator for evaluating thyrocyte damage

Estrogen Induces Metastatic Potential of Papillary Thyroid Cancer Cells through Estrogen Receptor α

Estradiol (E2) promotes metastatic propensity. However, the detailed mechanism remains largely unknown. E-cadherin, vimentin, and MMP-9 play a dominant role in the metastatic process. We aimed to investigate the effects of E2 on metastatic potential of PTC cell line BCPAP and on E-cadherin, vimentin, and MMP-9 protein expression. PTC cell line BCPAP was evaluated for the presence of estrogen receptor (ER) by western blot analysis. The effects of E2, PPT (a potent ERα-selective agonist), and DPN (a potent ERβ-selective agonist) on modulation of metastatic phenotype were determined by using in vitro scratch wound assay and invasion assay. In addition, the effects on E-cadherin, vimentin, and matrix metalloproteinase-9 (MMP-9) protein expression were evaluated by Western blot analysis. We found that BCPAP cells expressed ERα and ERβ. E2 and PPT enhanced, but DPN inhibited, the migration and invasion of BCPAP cells in an in vitro experimental model system that is modulated by E-cadherin, vimentin, and MMP-9. These findings indicate that E2 induces the metastatic potential of BCPAP cells through ERα and ERβ. The two ER subtypes play differential roles in modulation of BCPAP cell metastasis and the related molecule expressions including E-cadherin, vimentin, and MMP-9

The Correlation between Thyrotropin and Dyslipidemia in a Population-based Study

This study investigated the relationship between serum thyrotrophin levels and dyslipidemia in subclinical hypothyroid and euthyroid subjects. A total of 110 subjects with subclinical hypothyroidism and 1,240 euthyroid subjects enrolled in this study. Patients with subclinical hypothyroidism had significantly lower high density lipoprotein cholesterol (HDL-C) levels than those who were euthyroid. The lipid profiles were each categorized and mean thyrotrophin levels were higher in subjects in the dyslipidemia subclasses than subjects in the normal subclasses. Thyrotrophin was positively associated with serum triglyceride and negatively associated with serum HDL-C in women. Thyrotrophin was also positively associated with total cholesterol (TC) in the overweight population along with TC and LDL-C in overweight women. In the euthyroid population, thyrotrophin was positively associated with TC in the overweight population. In conclusion, serum thyrotrophin was correlated with dyslipidemia in subclinical hypothyroid and euthyroid subjects; the correlation was independent of insulin sensitivity

Glutamic acid decarboxylase autoantibodies are dominant but insufficient to identify most Chinese with adult-onset non-insulin requiring autoimmune diabetes: LADA China study 5.

AIMS: Adult-onset autoimmune diabetes is prevalent in China, in contrast to childhood-onset type 1 diabetes mellitus. Islet autoantibodies are the most important immune biomarkers to diagnose autoimmune diabetes. We assayed four different islet autoantibodies in recently diagnosed adult non-insulin-requiring diabetes Chinese subjects to investigate the best antibody assay strategy for the correct diagnosis of these subjects. METHODS: LADA China study is a nation-wide multicenter study conducted in diabetes patients from 46 university-affiliated hospitals in China. Non-insulin-treated newly diagnosed adult diabetes patients (n = 2388) were centrally assayed for glutamic acid decarboxylase autoantibody (GADA), protein tyrosine phosphatase-2 autoantibody (IA-2A), and zinc transporter 8 autoantibody (ZnT8A) by radioligand assay and insulin autoantibody (IAA) by microtiter plate radioimmunoassay. Clinical data were determined locally. RESULTS: Two hundred and six (8.63 %) subjects were autoantibody positive, of which GADA identified 5.78 % (138/2388) of the total, but only 67 % (138/206) of the autoimmune cases. IA-2A, ZnT8A, and IAA were found in 1.51, 1.84, and 1.26 % of the total study subjects, respectively. When assaying three islet autoantibodies, the most effective strategy was the combination of GADA, ZnT8A, and IAA, which could identify 92.2 % (190/206) autoimmune diabetes patients. The clinical data showed that those subjects with positive GADA had lower random C-peptide than autoantibody negative subjects (P < 0.05). CONCLUSIONS: As with Europeans, GADA is the dominant autoantibody in this form of autoimmune diabetes in China, but in contrast to Europeans, screening should include other diabetes-associated autoantibodies

Lumbar Scheuermann’s disease found in a patient with osteogenesis imperfecta (OI) caused by a heterozygous mutation in COL1A2 (c.4048G > A): a case report

Abstract Background Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by increased bone fragility and a series of extraskeletal manifestations. Approximately 90 % of OI cases are caused by type I collagen variants encoded by the collagen type I alpha 1 (COL1A1) or type I alpha 2 (COL1A2) gene. Lumbar Scheuermann’s disease is an atypical type of Scheuermann’s disease accompanied by Schmorl’s nodes and irregular endplates but without pronounced kyphosis. Although the etiology of Scheuermann’s disease is unclear, genetic and environmental factors are likely. Case presentation Here, we report a 32-year-old male patient who experienced multiple brittle fractures. Gene sequencing revealed a heterozygous mutation, c.4048G > A (p.G1350S), in the COL1A2 gene, and the patient was diagnosed with OI. Magnetic resonance imaging of his thoracolumbar spine revealed multiple Schmorl’s nodes. Conclusions This is the first reported case of OI coexisting with the spinal presentation of Scheuermann’s disease. It is speculated that the COL1A2 gene mutation might be an underlying novel genetic cause of Scheuermann’s disease. In conclusion, this case demonstrates the relationship between Scheuermann’s disease and OI for the first time and enriches the genotype-phenotype spectrum of OI