Increased maternal leptin levels may be an indicator of subclinical hypothyroidism in a newborn

BackgroundSeveral factors may influence newborn thyroid-stimulating hormone (TSH) concentrations and cause subclinical hypothyroidism in a newborn. A sufficient level of leptin signalling is needed for the normal production of TSH and thyroid hormones by the thyroid gland. Our study aimed to investigate the correlation between maternal serum leptin concentration during the third trimester of pregnancy and newborn screening-TSH levels.MethodsThis prospective cross-sectional study was conducted in obstetrics and gynaecology clinics of a state hospital between June and August 2013. Maternal venous blood samples were collected from 270 healthy pregnant women in the third trimester just before delivery. Measurements of maternal fT3, fT4, TSH, anti-thyroid peroxidase (TPO), and anti-thyroglobulin (anti-Tg) antibodies from serum samples were performed by chemiluminescence immunoassay. Maternal serum leptin levels were determined by ELISA. Dried capillary blood spots were used to measure newborn TSH levels.ResultsSubjects were divided into two groups according to the neonatal TSH levels using a cut-point of 5.5 mIU/L. Median maternal serum leptin levels were significantly higher in newborns whose TSH levels were higher than >5.5 mIU/L [13.2 μg/L (1.3 - 46.5) vs 19.7 μg/L (2.4 - 48.5), p<0.05]. Serum leptin levels showed a negative correlation with maternal fT4 (r=0.32, p<0.05), fT3 (r=0.23, p<0.05), and a positive correlation with BMI (r=0.30, p<0.05).ConclusionsOur results suggest that high leptin levels in the third trimester of pregnancy influence maternal thyroid functions and might cause an increase in newborn TSH levels. Detection of high maternal serum leptin levels may be a reason for subclinical hypothyroidism.     

Exposure to p,p′-DDE: A Risk Factor for Type 2 Diabetes

Background

Persistent organic pollutants (POPs), such as PCBs, DDT and dioxins have in several cross-sectional studies shown strong associations with type 2 diabetes mellitus. Reversed causality can however not be excluded. The aim of this case-control study was to evaluate whether POPs concentration is a risk factor for type 2 diabetes.

Methodology/Principal Findings

A case-control study was performed within a well-defined cohort of women, age 50–59 years, from the Southern part of Sweden. Biomarkers for POP exposure, 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p′-DDE) were analyzed in stored serum samples, which were collected at the baseline examination when the cohort was established. For 107 out of the 371 cases, serum samples were stored at least three years before their type 2 diabetes was diagnosed. In this data set, CB-153 and p,p′-DDE were not associated with an increased risk to develop type 2 diabetes. However, when only the cases (n = 39) that were diagnosed more than six years after the baseline examination and their controls were studied, the women in the highest exposed quartile showed an increased risk to develop type 2 diabetes (OR of 1.6 [95% 0.61, 4.0] for CB-153 and 5.5 [95% CI 1.2, 25] for p,p′-DDE).

Conclusions/Significance

The results from the present case-control study, including a follow-up design, confirms that p,p′-DDE exposure can be a risk factor for type 2 diabetes.     

Circulating Thyroxine,Thyroid-Stimulating Hormone,and Hypothyroid Status and the Risk of Prostate Cancer

Background

Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

Methods

Within the ATBC Study, a randomized controlled trial of α-tocopherol and β-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2∶1 to cases on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG), and by categories of thyroid status.

Results

Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1–4: OR = 0.70, 95% CI: 0.51–0.97, p = 0.03). When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28–0.81, p = 0.006). We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9).

Conclusions

In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.     

Association of Alcohol Consumption with Markers of Prostate Health and Reproductive Hormone Profiles: A Multi-Center Study of 4535 Men in China

Background

The effect of alcohol consumption on prostate health and reproductive hormone profiles has long been investigated and currently, no consensus has been reached. Additionally, large studies focusing on this topic are relatively rare in China.

Purpose

To investigate the association of alcohol consumption with prostate measurements and reproductive hormone profiles in Chinese population; and to examine the relationship between hormone levels and prostate measurements.

Methods

This cross-sectional study included 4535 men from four representative provinces of China. Demographic details, family history of prostate disease, tobacco and alcohol consumption, as well as International Prostate Symptom Score (I-PSS) were collected through a questionnaire. Total prostate specific antingen (total PSA), free PSA, free PSA/total PSA ratio (f/tPSA), and reproductive hormones were measured in serum. Multi-variable regression models were used to test for association of alcohol consumption with markers of prostate health, used to test for association of alcohol consumption with reproductive hormones, and reproductive hormones with markers of prostate health.

Results

Alcohol consumption had no obvious impact on total PSA concentration and I-PSS. Current drinkers had lower level of free PSA (β = -0.11, p = 0.02) and f/tPSA (β = -0.03, p = 0.005), former drinkers also had lower level of free PSA (β = -0.19, p = 0.02) when compared with never drinkers. Lower Luteinizing hormone (LH) (β = -1.05, p = 0.01), sex hormone-binding globulin (SHBG) (β = -4.71, p = 0.01) and higher estradiol (β = 7.81, p = 0.01) was found in current drinkers than never drinkers, whereas higher LH (β = 1.04, p = 0.04) and free testosterone (FT) (β = 0.03, p = 0.02) was detected in former drinkers than never drinkers. Furthermore, LH was positively associated with f/tPSA (β = 0.002, p = 0.006), SHBG was also positively related with free PSA (β = 0.003, p = 0.003) and f/tPSA (β = 0.0004, p = 0.01). Both total testosterone (TT) and FT were inversely related with I-PSS (OR = 0.97, 95% CI, 0.95–0.98; OR = 0.23, 95% CI, 0.11–0.45, respectively).

Conclusions

Alcohol consumption could affect serum free PSA concentration and also f/tPSA ratio, and also acts as an endocrine disruptor on the male reproductive hormone profiles. LH and SHBG were positively related with fPSA and f/tPSA, and higher level of TT and FT may be helpful for improving participants'' subjective symptoms.     

Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective

The Institute of Medicine recommends that lactating women ingest 290 μg iodide/d and a nursing infant, less than two years of age, 110 μg/d. The World Health Organization, United Nations Children’s Fund, and International Council for the Control of Iodine Deficiency Disorders recommend population maternal and infant urinary iodide concentrations ≥ 100 μg/L to ensure iodide sufficiency. For breast milk, researchers have proposed an iodide concentration range of 150–180 μg/L indicates iodide sufficiency for the mother and infant, however no national or international guidelines exist for breast milk iodine concentration. For the first time, a lactating woman and nursing infant biologically based model, from delivery to 90 days postpartum, was constructed to predict maternal and infant urinary iodide concentration, breast milk iodide concentration, the amount of iodide transferred in breast milk to the nursing infant each day and maternal and infant serum thyroid hormone kinetics. The maternal and infant models each consisted of three sub-models, iodide, thyroxine (T4), and triiodothyronine (T3). Using our model to simulate a maternal intake of 290 μg iodide/d, the average daily amount of iodide ingested by the nursing infant, after 4 days of life, gradually increased from 50 to 101 μg/day over 90 days postpartum. The predicted average lactating mother and infant urinary iodide concentrations were both in excess of 100 μg/L and the predicted average breast milk iodide concentration, 157 μg/L. The predicted serum thyroid hormones (T4, free T4 (fT4), and T3) in both the nursing infant and lactating mother were indicative of euthyroidism. The model was calibrated using serum thyroid hormone concentrations for lactating women from the United States and was successful in predicting serum T4 and fT4 levels (within a factor of two) for lactating women in other countries. T3 levels were adequately predicted. Infant serum thyroid hormone levels were adequately predicted for most data. For moderate iodide deficient conditions, where dietary iodide intake may range from 50 to 150 μg/d for the lactating mother, the model satisfactorily described the iodide measurements, although with some variation, in urine and breast milk. Predictions of serum thyroid hormones in moderately iodide deficient lactating women (50 μg/d) and nursing infants did not closely agree with mean reported serum thyroid hormone levels, however, predictions were usually within a factor of two. Excellent agreement between prediction and observation was obtained for a recent moderate iodide deficiency study in lactating women. Measurements included iodide levels in urine of infant and mother, iodide in breast milk, and serum thyroid hormone levels in infant and mother. A maternal iodide intake of 50 μg/d resulted in a predicted 29–32% reduction in serum T4 and fT4 in nursing infants, however the reduced serum levels of T4 and fT4 were within most of the published reference intervals for infant. This biologically based model is an important first step at integrating the rapid changes that occur in the thyroid system of the nursing newborn in order to predict adverse outcomes from exposure to thyroid acting chemicals, drugs, radioactive materials or iodine deficiency.     

Interaction of Copper with Iron, Iodine, and Thyroid Hormone Status in Goitrous Patients

In many developing countries, men and women are at high risk of goiter and iron deficiency. The aim of the recent study is to assess the interaction of (Cu), with iron (Fe), iodine/iodide (I), and thyroid hormones in goitrous patients. Sixty goitrous male (GMPs) and 72 female patients (GFPs) were evaluated for the Cu, Fe, I, and thyroid hormones status in biological samples (serum and urine), and compared to non-goitrous subjects of both genders (M?=?106, F?=?120). The biological samples were analyzed for Cu and Fe concentration using atomic absorption spectrometer, while I was measured by the potentiometric method, prior to microwave-assisted acid digestion (MD). Quality control for the method was established with certified samples. Significantly higher mean values of Cu in serum, and urine samples of GMPs and GFPs, while lower value of Fe and I were observed as compared to control subjects (p?<?0.015), respectively. The mean values of free triiodothyronine (FT3) and free thyroxin (FT4) were found to be lower in goitrous patients of both genders than in the age-matched healthy controls (p?<?0.006 and 0.002), respectively, in contrast high mean values of thyroid-stimulating hormone (TSH) were detected in patients (p?<?0.009), as compared to non-goitrous subjects. It was observed that the deficiencies of Fe, I, and thyroid hormone in goitrous patients could be influenced by efficiency of Cu.     

Thyroid Hormone Upregulates Zinc-α2-glycoprotein Production in the Liver but Not in Adipose Tissue

Overproduction of zinc-α₂-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α₂-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α₂-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α₂-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α₂-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α₂-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α₂-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α₂-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α₂-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α₂-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α₂-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α₂-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α₂-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α₂-glycoprotein expression in adipose tissue could be the reason why zinc-α₂-glycoprotein is not related to weight loss in hyperthyroidism.     

A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants in Relation to Risk of Type 1 Diabetes

Background

The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes.

Methodology/ Principal Findings

The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p′-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p′-DDE (OR 0.56, 95% CI 0.29, 1.08).

Conclusions

The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes.     

Thyroid Hormone Signaling In Vivo Requires a Balance between Coactivators and Corepressors

Resistance to thyroid hormone (RTH), a human syndrome, is characterized by high thyroid hormone (TH) and thyroid-stimulating hormone (TSH) levels. Mice with mutations in the thyroid hormone receptor beta (TRβ) gene that cannot bind steroid receptor coactivator 1 (SRC-1) and Src-1^−/− mice both have phenotypes similar to that of RTH. Conversely, mice expressing a mutant nuclear corepressor 1 (Ncor1) allele that cannot interact with TRβ, termed NCoRΔID, have low TH levels and normal TSH. We hypothesized that Src-1^−/− mice have RTH due to unopposed corepressor action. To test this, we crossed NCoRΔID and Src-1^−/− mice to create mice deficient for coregulator action in all cell types. Remarkably, NCoR^ΔID/ΔID Src-1^−/− mice have normal TH and TSH levels and are triiodothryonine (T₃) sensitive at the level of the pituitary. Although absence of SRC-1 prevented T₃ activation of key hepatic gene targets, NCoR^ΔID/ΔID Src-1^−/− mice reacquired hepatic T₃ sensitivity. Using in vivo chromatin immunoprecipitation assays (ChIP) for the related coactivator SRC-2, we found enhanced SRC-2 recruitment to TR-binding regions of genes in NCoR^ΔID/ΔID Src-1^−/− mice, suggesting that SRC-2 is responsible for T₃ sensitivity in the absence of NCoR1 and SRC-1. Thus, T₃ targets require a critical balance between NCoR1 and SRC-1. Furthermore, replacement of NCoR1 with NCoRΔID corrects RTH in Src-1^−/− mice through increased SRC-2 recruitment to T₃ target genes.     

Statistical Evaluation of Trace Metals,TSH and T<Subscript>4</Subscript> in Blood Serum of Thyroid Disease Patients in Comparison with Controls

The present study is based on the measurement of concentrations of selected trace metals (Fe, Zn, Cu, Co, Mn, Ni, Cr, Cd and Pb) and thyroid hormones (TSH and T₄) in blood serum of hypothyroid and hyperthyroid patients in comparison with healthy donors/controls in order to establish the imbalances of the trace metals in diseased subjects. The serum samples were digested in HNO₃-HClO₄ mixture and quantification of the metals was performed by flame atomic absorption spectrometry. Average levels of Fe, Ni, Cu, Cr, Pb and TSH were found to be significantly higher (p < 0.05) in the serum of hypothyroid patients compared with other donor categories, while mean concentrations of Mn, Cd and T₄ were significantly elevated in the serum of hyperthyroid patients compared with other donor groups (p < 0.05). The correlation pattern of trace metals in the serum of patient groups revealed significantly different mutual associations compared with the controls. PCA and CA pointed out the interferences of the toxic metals with essential metals in the serum of both patient groups compared with the controls. Most of the metals exhibited noticeable disparities in their concentrations based on gender, food habits and tobacco use for all donor groups. Thus, the pathogenesis of thyroid diseases is significantly affecting the essential trace and toxic metals balance in both patients groups.     

Relationship between paired cord blood and milk POPs levels as a tool for assessing perinatal exposure,a pilot study

The long-term health threats posed to humans exposed to pollutants acting as endocrine disruptors (EDs) is yet to be quantified. There is insufficient knowledge about the sources and magnitude of exposure to selected polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) during the most sensitive period of fetal development, suggesting the need for a study. Organochlorine pesticides, classified as being persistent organic pollutants (POPs) and potential EDs, were also included in this analysis. Xenobiotics were measured in paired fetal cord blood and maternal breast milk samples. There were no significant differences in the concentrations of PCB-101, PBDE-47, and PBDE-99 between maternal milk and cord blood according to the Wilcoxon test, and the Spearman tests demonstrated significant correlations in β-HCH, γ-HCH, p,p'-DDE, and PCB-118 between maternal milk and cord blood from the same subjects. All others tested (HCB, β-HCH, γ-HCH, p,p'-DDE, p,p'-DDD, p,p'-DDT, PCB-101, PCB-138, PCB-153, PCB-170, PCB-180, PBDE-153) demonstrated significant differences in the same subject women with concentrations significantly higher in maternal milk than in cord blood. The presence of these compounds found in cord blood and maternal milk indicates that both are a source of perinatal exposure to these pollutants. This study opens up the opportunity for new research in estimating a prenatal exposure based on breast milk concentrations of organohalogen compounds.     

Tg in Adults as a Sensitive Biomarker of Iodine Status: A 5-Year Follow up Population Study in Different Levels of Iodine Intake Regions

This study was to evaluate the usefulness of serum thymoglobulin (Tg) in adults to assess iodine status through a 5-year cohort study which was conducted in three regions with different levels of iodine intake: mild deficiency, more than adequate, and excess, from 1999 to 2004 in China. A total of 3099 subjects over 14 years old with normal serum levels of Tg in 1999 were eligible, of whom 2448 were followed in 2004. Serum levels of thyroid hormones and thyroid autoantibodies as well as urine iodine were measured, and B-mode ultrasonography of the thyroid was performed. A general linear model was performed to determine the determinant factors of serum Tg. Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the baseline levels of serum Tg were substantially different (7.5μg/L, 5.9μg/L, and 6.8μg/L respectively, P<0.01), which were associated with age, sex, the rate of positive TgAb, abnormal thyroid volume, abnormal TSH, and positive personal history of thyroid diseases. The data from 1856 subjects with normal range of thyroid parameters but no personal history of thyroid diseases were analyzed to clarify the effect of iodine intake on Tg. Among these three regions, the serum Tg levels were substantially different in both 1999 and 2004, with a similar pattern for increased Tg (ΔTg) (3.1μg/L, 2.5μg/L and 3.5μg/L respectively, P<0.01). The general linear model analysis revealed that age, Tg, and baseline TSH levels were the determinants of ΔTg besides iodine intake. In conclusion, serum Tg in adults, resulting from a time-accumulative effect of iodine exposure, is a useful biomarker of regional iodine intake.     

Iodine Deficiency and Excess Coexist in China and Induce Thyroid Dysfunction and Disease: A Cross-Sectional Study

Background

In spite of the salt iodization, iodine deficiency disorders (IDD) have not been sustainably eliminated in China. There are coastal areas with low iodized salt coverage rates (iodine nutrition is inadequate) and other areas with excessive amounts of iodine in the drinking water.

Objective

This study aimed to clarify the association of iodine deficiencies resulting from a low coverage rate of iodized salt, excess iodine intake from drinking water with thyroid function and disease in adults.

Design

A cross-sectional study was conducted in adults in different iodine nutrition areas in three provinces in China.

Results

The prevalence of thyroid nodules was 15.52%, 8.66% and 22.17% in the iodine excess, sufficient and deficient groups, respectively. The prevalence of subclinical hypothyroidism was 20.09%, 10.41%, and 2.25% in the excess, sufficient and deficient iodine groups, respectively. The prevalence of subclinical hyperthyroidism and overt hyperthyroidism in the iodine deficient group was higher than that in the iodine excess group ( = 9.302, p = 0.002) and iodine sufficient group ( = 7.553, p = 0.006). Thyroid-stimulating hormone (TSH) was significantly correlated with excess iodine intake (β = 1.764,P = 0.001) and deficient iodine intake (β = −1.219, P = 0.028).

Conclusions

Thyroid nodules are more likely to be present in the iodine excess and deficient areas than in the iodine sufficient areas. Subclinical hyperthyroidism and overt hyperthyroidism are more likely to be prevalent in the iodine deficient areas than in the iodine excess or sufficient areas. Subclinical hypothyroidism is more likely to be prevalent in the high iodine intake areas than in the iodine deficient or sufficient areas. Median TSH may be deemed as an alternative indicator for monitoring the iodine nutrition status of the adult population in iodine excess and deficient areas.     

The Association of Thyroid Hormones and Tsh with the Metabolic Syndrome in Euthyroid Taiwanese Individuals

Objective: There are conflicting studies in euthyroid males and females regarding associations between thyroidrelated hormones and parameters of the metabolic syndrome (MetS). We investigated the association between serum thyroid hormones and thyroid-stimulating hormone (TSH) concentrations and MetS in euthyroid men and women.Methods: Taiwanese subjects aged 20 to 65 years who had undergone a voluntary health examination at a preventive examination agency in Taipei were enrolled in this cross-sectional study. The definition of MetS was suggested by the Bureau of Health Promotion, Department of Health, Taiwan. Euthyroidism was defined as TSH and free thyroxine (FT4) levels within the normal reference ranges while not taking any thyroid medication. We conducted multiple logistic regression to identify the ability of serum triiodothyronine (T3), FT4, and TSH concentrations to identify the relative risk for the presence of MetS and components of the MetS in euthyroid Taiwanese individuals.Results: A total of 8,207 Taiwanese subjects (mean age: men, 45.3 ± 9.9 years; women, 43.5 ± 9.3 years) were enrolled in this study. A total of 1,672 subjects (20.4%) were defined as having MetS; these subjects had significantly higher (P<.0001) mean age (48.4 ± 9.1 years vs. 43.6 ± 10.7 years), prevalence of men (78.7% vs. 53.4%), and smoking (16.8% vs. 11.6%) than those without MetS. The median TSH, FT4, and T3 levels in all subjects were 1.70 mIU/L, 1.41 ng/dL, and 1.20 ng/mL, respectively. Higher T3 and lower FT4 values rather than TSH increased the odds ratio for MetS in men and women after adjusting for smoking and age, particularly for the association of T3 and MetS in women (uppermost quartile versus lowermost quartile: odds ratio, 2.4; 95% confidence interval, 1.6 to 3.5; P for trend <.0001).Conclusion: In euthyroid Taiwanese men and women, relatively high serum T3 concentrations was most strongly associated with the presence of the MetS; relatively low serum T4 was less strongly related, and serum TSH levels were not associated with the MetS. It is not known if the relationship of serum T3 and T4 to the MetS is causal.Abbreviations:BMI = body mass indexFT4 = free thyroxineMetS = metabolic syndromeOR = odds ratioT3 = triiodothyronineTSH = thyroid-stimulating hormoneWC = waist circumference     

Maternal thyroid hormone trajectories during pregnancy and child behavioral problems

There is ample evidence demonstrating the importance of maternal thyroid hormones, assessed at single trimesters in pregnancy, for child cognition. Less is known, however, about the course of maternal thyroid hormone concentrations during pregnancy in relation to child behavioral development. Child sex might be an important moderator, because there are sex differences in externalizing and internalizing behavioral problems. The current study examined the associations between maternal thyroid hormone trajectories versus thyroid assessments at separate trimesters of pregnancy and child behavioral problems, as well as sex differences in these associations. In 442 pregnant mothers, serum levels of TSH and free T4 (fT4) were measured at 12, 24, and 36 weeks gestation. Both mothers and fathers reported on their children's behavioral problems, between 23 and 60 months of age. Latent growth mixture modeling was used to determine the number of different thyroid hormone trajectories. Three trajectory groups were discerned: 1) highest and non-increasing TSH with lowest fT4 that decreased least of the three trajectories; 2) increasing TSH and decreasing fT4 at intermediate levels; 3) lowest and increasing TSH with highest and decreasing fT4. Children of mothers with the most flattened thyroid hormone trajectories (trajectory 1) showed the most anxiety/depression symptoms. The following trimester-specific associations were found: 1) lower first-trimester fT4 was associated with more child anxiety/depression, 2) higher first-trimester TSH levels were related to more attention problems in boys only. A flattened course of maternal thyroid hormone concentrations during pregnancy was a better predictor of child anxiety/depression than first-trimester fT4 levels.     

Associations of Circulating Gut Hormone and Adipocytokine Levels with the Spectrum of Gastroesophageal Reflux Disease

Objective

The pathogenesis of gastroesophageal reflux disease (GERD) is complex and poorly understood. We aim to investigate the association of various circulating peptide hormones with heterogenous manifestations of GERD.

Methods

One hundred and four patients that had experienced typical GERD symptoms (heartburn and/or acid regurgitation) for at least 3 episodes per week in the past 3 months were enrolled. All patients received a baseline assessment of symptom severity and frequency with the Reflux Disease Questionnaire and an upper endoscopy to classify GERD into erosive esophagitis (EE, n = 67), non-erosive esophagitis (NE, n = 37), and Barrett’s esophagus (BE, n = 8). Fifty asymptomatic subjects with an endoscopically normal esophagus were recruited as the control group. Complete anthropometric measures and blood biochemistry were obtained and fasting serum levels of adipocytokines (adiponectin and leptin) and gut hormones (ghrelin and peptide YY (PYY)) were determined by enzyme-linked immunosorbent assay in all subjects.

Results

All circulating peptide hormone levels were not statistically different between the GERD and control groups. However, GERD patients appeared to have lower PYY levels [median (25^th-75^th percentile), 80.1 (49.8–108.3) vs. 99.4 (65.8–131.9) pg/ml, p = 0.057] compared with control subjects. Among the GERD patients, ghrelin levels were inversely associated with the frequency and severity of acid regurgitation. In male GERD patients, EE was associated with significantly higher PYY levels [107.0 (55.0–120.8) vs. 32.8 (28.7–84.5) pg/ml, p = 0.026] but lower adiponectin levels [6.7 (5.6–9.3) vs. 9.9 (9.6–10.6) μg/ml, p = 0.034] than NE. Patients with BE had significantly lower adiponectin levels [6.0 (5.1–9.2) vs. 9.2 (7.1–11.2) μg/ml, p = 0.026] than those without BE.

Conclusions

Humoral derangement of circulating peptide hormones might participate in inflammation and symptom perception in patients suffering from GERD. Further studies to clarify the exact role of these hormones in the pathogenesis of GERD are warranted.     

Increased Pro-Inflammatory Cytokines,C-Reactive Protein and Nerve Growth Factor Expressions in Serum of Patients with Interstitial Cystitis/Bladder Pain Syndrome

Objective

The etiology and pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) are unclear. Chronic inflammation is considered the main pathology of IC/BPS. This study measured the serum c-reactive protein (CRP), nerve growth factor (NGF) and pro-inflammatory cytokine/chemokine interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8 expression in patients with IC/BPS to elucidate the involvement of systemic inflammation in IC/BPS.

Methods

Serum samples were collected from 30 IC/BPS patients and 26 control subjects. The concentrations of serum nerve growth factor (NGF), IL-1β, IL-6, TNF-α, and IL-8 were quantified using a bead-based, human serum adipokine panel kit. Serum C-reactive protein (CRP) was also assessed. Differences of serum CRP, NGF, IL-1β, IL-6, TNF-α, and IL-8 levels between the IC/BPS patients and controls were compared, and correlations between CRP and pro-inflammatory cytokines and chemokine were also evaluated.

Results

The results showed that CRP level (p = 0.031), NGF (p = 0.015) and pro-inflammatory cytokines/chemokine IL-1β, IL-6, TNF-α, and IL-8 levels were significantly higher in the patients with IC/BPS than among controls (all p<0.001). Significant associations were observed between IL-1β and IL-8 (p<0.001), IL-6 and CRP (p = 0.01), IL-6 and IL-8 (p = 0.02), and IL-6 and TNF-α (p = 0.03).

Conclusion

Increased pro-inflammatory cytokines/chemokine (IL-1β, IL-6, TNF-α, and IL-8) expression in the sera of IC/BPS patients implies not only mast cell activation, but also that other inflammatory mediators play important roles in the pathogenesis of IC/BPS. Thus, for some patients, IC/BPS is considered a chronic inflammatory disease.     

p,p′-Dichlorodiphenyldichloroethylene Induces Colorectal Adenocarcinoma Cell Proliferation through Oxidative Stress

p, p′-Dichlorodiphenyldichloroethylene (DDE), the major metabolite of Dichlorodiphenyltrichloroethane (DDT), is an organochlorine pollutant and associated with cancer progression. The present study investigated the possible effects of p,p′-DDE on colorectal cancer and the involved molecular mechanism. The results indicated that exposure to low concentrations of p,p′-DDE from 10⁻¹⁰ to 10⁻⁷ M for 96 h markedly enhanced proliferations of human colorectal adenocarcinoma cell lines. Moreover, p,p′-DDE exposure could activate Wnt/β-catenin and Hedgehog/Gli1 signaling cascades, and the expression level of c-Myc and cyclin D1 was significantly increased. Consistently, p,p′-DDE-induced cell proliferation along with upregulated c-Myc and cyclin D1 were impeded by β-catenin siRNA or Gli1 siRNA. In addition, p,p′-DDE was able to activate NADPH oxidase, generate reactive oxygen species (ROS) and reduce GSH content, superoxide dismutase (SOD) and calatase (CAT) activities. Treatment with antioxidants prevented p,p′-DDE-induced cell proliferation and signaling pathways of Wnt/β-catenin and Hedgehog/Gli1. These results indicated that p,p′-DDE promoted colorectal cancer cell proliferation through Wnt/β-catenin and Hedgehog/Gli1 signalings mediated by oxidative stress. The finding suggests an association between p,p′-DDE exposure and the risk of colorectal cancer progression.