Context The association between serum thyrotropin (TSH) and obesity traits has been investigated previously in several epidemiological studies. However, the underlying causal association has not been established. Objective This work aimed to determine and analyze the causal association between serum TSH level and obesity-related traits (body mass index [BMI] and obesity). Methods The latest genome-wide association studies (GWASs) on TSH, BMI, and obesity were searched to obtain full statistics. Bidirectional 2-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 single-nucleotide variation (formerly single-nucleotide polymorphism). Based on the preliminary MR results, free thyroxine (fT4) and free 3,5,3′-triiodothyronine (fT3) levels were also set as outcomes to further analyze the impact of BMI on them. 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 IVW and MR-Egger results both 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 = .038, SE = 0.013, P = .004). In further MR analysis, the IVW method indicated that BMI could causally increase the fT3 (β = 10.123, SE = 2.523, P < .001) while not significantly affecting the fT4 level. Conclusion Together with fT3, TSH can be significantly elevated by an increase in genetically driven BMI.

Background: Metabolic disorders (MDs) and the metabolic syndrome (MetS) may be associated with thyroid diseases. The aim of this study was to investigate the relationship between MDs and various types of thyroid nodules (TNs), according to gender. Methods: We analyzed cross-sectional data from the Thyroid Disorders, Iodine Status, and Diabetes Epidemiological (TIDE) survey in China. A total of 56,729 subjects ≥18 years of age were included. Thyroid gland morphology was assessed by thyroid standardized ultrasonography. A multivariate logistic regression model was used to explore the odds ratio (OR) and confidence intervals [CIs] for any associations between MDs and TNs. Subgroup analyses were conducted according to gender and TN type (solitary, S-TN; multiple, M-TNs). Results: The prevalence of TNs was increased in several MDs, and was higher in women than men regardless of whether they suffered from MDs (22.0%, CI [21.6–22.5%] vs. 15.7%, CI [15.3–16.7%], p < 0.001). TNs were associated with the presence of MDs (OR = 1.189, CI [1.107–1.278], p < 0.001), hypercholesterolemia (OR = 1.235, CI [1.177–1.296], p < 0.001), high low-density lipoprotein cholesterol (LDL-C; OR = 1.249, CI [1.186–1.316], p < 0.001), and hyperuricemia (OR = 1.206, CI [1.126–1.293], p < 0.001). MDs and MetS were, respectively, significantly associated with TNs, S-TNs, and M-TNs in men, while MDs were significantly associated with the three TN profiles in women. With respect to dyslipidemia, hypercholesterolemia and high LDL-C had the strongest association with TNs, whereas hypertriglyceridemia had no effect. Conclusions: TNs (especially M-TNs) may be associated with MDs and their various components, and there appear to be some gender-specific associations.

Objective: Gestational diabetes mellitus (GDM) is characterized by glucose intolerance during gestation. It is associated with a series of maternal and foetal complications. Interleukin (IL)-34 is a recently discovered pro-inflammatory cytokine that functions as a ligand for colony-stimulating factor-1 receptor (CSF-1R). The contribution of IL-34 in the development of multiple chronic inflammatory diseases and autoimmune diseases has been recently discovered. The aim of this study was to evaluate whether IL-34 participates in the pathogenesis of GDM. Method: A total of 120 women were enrolled in this study, which included 60 GDM patients and age- and sex-matched healthy pregnant women. The expression of IL-34 in serum, cord blood and placental tissues was analysed by ELISA and Western blot assays. The association between IL-34 levels and clinical features was also studied. We additionally evaluated the effect of recombinant mouse IL-34 (rmIL-34) on apoptosis and pancreatic β cell function. Results: We found that IL-34 expression is highly increased in serum, cord blood and placental tissues in patients with GDM. In addition, there was a positive association between serum IL-34 and insulin resistance and glucose concentrations. Our data also revealed that IL-34 contributes to the apoptosis of pancreatic β cells in GDM caused by CSF-1R. Furthermore, functional studies found that IL-34 inhibited pancreatic β cell function and cell viability, while CSF-1R inhibitor blocked this effect. Conclusion: IL-34 plays a crucial role in the development of GDM by targeting CSF-1R, insulin production and β cell function.

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 (PRDM1, TGFBR3, E2F1, FGF1, ADAM12, ALPL, RET, AL928654.2, AC128688.2). 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 ALPL (alkaline phosphatase) and hsa-miR-204-5p were significantly correlated and that ALPL 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 ALPL 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.

Objective: The aim of our study was to compare the reference intervals (RIs) [median (2.5^th-97.5^th 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^th percentile in the iodine-sufficient subgroup were both lower than the iodine-deficient or more-than-adequate subgroup, while the 97.5^th 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^th percentile but higher 2.5^th 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^th percentile TSH in the iodine-sufficient population were the lowest among the different iodine status subgroups, while the 97.5^th percentile of TSH showed an upward trend with increasing iodine sufficiency.

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^NTR) 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-T₄) treatment for SCH from gestational day 17 (E17). In contrast, expression of apoptosis-related proteins [pro-NGF, p75^NTR, phospho-C-Jun N-terminal kinase (p-JNK), p53, Bax and cleaved caspase-3] was increased. The two groups with treatment with L-T₄for SCH from E10 and E13, respectively, showed no significant difference compared with the CON group. L-T₄treatment enhanced relative expression of NGF by increasing NGF/proNGF ratio in offspring from maternal SCH rats. In conclusion, L-T₄treatment for SCH from early pregnancy dramatically ameliorated cognitive impairment via TrkA/p75^NTRsignaling, which involved activation of the neuronal proliferation and inhibition of neuronal apoptosis in SCH rats’ offspring.