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Open access

The effect of radioactive iodine treatment for differentiated thyroid cancer on male gonadal function: a meta-analysis

Yanling Cai, Yan Yang, Xiao Pang, and Suping Li

Purpose

The aim was to investigate the effect of radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) on male gonadal function.

Methods

PubMed, Embase, Web of Science, OVID, Scopus, and Wanfang databases were searched up to June 10, 2022, to identify published studies related to RAI and male gonadal function. ReviewManager version 5.4.1 software was used to calculate mean differences (MDs) with 95% CIs.

Results

Initially, 1958 articles were retrieved from the databases, and 6 articles were included in the quantitative analysis. The meta-analysis results showed that follicle-stimulating hormone (FSH) increased when the follow-up duration was ≥12 months after RAI, but the difference was not statistically significant (MD = −2.64, 95% CI = (−5.61, 0.33), P = 0.08). But the results of the subgroup analysis showed that when the follow-up time was ≤6 months, FSH levels were significantly higher after RAI (MD = −7.65, 95% CI = (−13.95, −1.34), P = 0.02). The level of inhibin B was significantly lower at ≥12 months and ≤6 months after RAI (MD = 66.38, 95% CI = (8.39, 124.37), P = 0.02) and (MD = 116.27, 95% CI = (43.56, 188.98), P = 0.002). Additionally, luteinizing hormone (LH) and testosterone have similar results – that is, LH and testosterone levels were higher after RAI, but the difference was not statistically significant (MD = –0.87, 95% CI = (−2.04, 0.30), P = 0.15) and (MD = −1.69, 95% CI (−7.29, 3.90), P = 0.55).

Conclusions

Male gonadal function may be temporarily impaired within 6 months after RAI but may return to normal levels afterward.

Open access

Association between isolated hypothyroxinaemia in early pregnancy and perinatal outcomes

Xiujuan Su, Yan Zhao, Zhijuan Cao, Yingying Yang, Tony Duan, and Jing Hua

Background

The effect of isolated maternal hypothyroxinaemia (IMH) on pregnancy complications and neonatal outcomes in human beings is still controversial.

Methods

This was a retrospective cohort study based on the electronic medical register system. The records of women with a singleton pregnancy who sought antenatal examination between January 2014 and December 2015 at Shanghai First Maternity and Infant Hospital were extracted from the electronic medical records system. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and anti-thyroperoxidase autoantibody (TPO-Ab) was measured before 20 gestational weeks, and a multiple logistic regression model was used to estimate the odds ratios of pregnancy complications and neonatal outcomes between euthyroid women and those with isolated hypothyroxinaemia.

Results

A total of 8173 women were included in this study, of whom 342 (4.18%) were diagnosed with IMH. Regression analysis showed that IMH diagnosed in the second trimester (13–20 weeks) was associated with an increased risk of hypertensive disorders of pregnancy (OR = 2.66, 95% CI: 1.38–5.10) and placenta abruption (OR = 3.64, 95% CI: 1.07–12.41), but not with preterm delivery (OR = 1.09, 95% CI: 0.50–2.40), small or large gestational age of infant (OR = 0.91, 95% CI: 0.39–2.12; OR = 1.16, 95% CI: 0.72–1.86), macrosomia (OR = 1.71, 95% CI: 0.95–3.07), gestational diabetes mellitus (OR = 1.36, 95% CI: 0.86–2.15) and placenta previa (OR = 1.62, 95% CI: 0.39–7.37).

Conclusion

IMH could be a risk factor for hypertensive disorders of pregnancy.

Open access

Autoimmune thyroid disease correlates to islet autoimmunity on zinc transporter 8 autoantibody

Yun Cai, Jieni Yan, Yong Gu, Heng Chen, Yang Chen, Xinyu Xu, Mei Zhang, Liping Yu, Xuqin Zheng, and Tao Yang

Objective

The most common coexisting organ-specific autoimmune disease in patients with type 1 diabetes mellitus (T1DM) is autoimmune thyroid disease (AITD). However, there have been few clinical reports based on a large population about the prevalence of zinc transporter 8 autoantibody (ZnT8A) and other islet autoantibodies in AITD patients. We aimed to explore the presence of islet autoantibodies, ZnT8A, glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen 2 autoantibodies (IA-2A) compared with thyroid autoantibodies, thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TGAb) and thyrotropin receptor autoantibodies (TRAb) in patients with Graves’ disease (GD), Hashimoto’s thyroiditis (HT) and T1DM patients with AITD.

Methods

Totally, 389 patients with GD, 334 patients with HT, 108 T1DM patients with AITD and 115 healthy controls (HC) were recruited in the study. Islet autoantibodies (ZnT8A, GADA and IA-2A) were detected by radioligand binding assay. Thyroid autoantibodies, TPOAb and TGAb were detected by chemiluminescence assay, and TRAb was detected by RIA.

Results

The prevalence of ZnT8A, GADA and IA-2A was higher in GD and HT patients than that of HC (ZnT8A: GD 8.48%, HT 10.8% vs HC 1.74%; GADA: GD 7.46%, HT 7.74% vs HC 0.870%; IA-2A: GD 4.88%, HT 3.59% vs HC 0%; All P < 0.05) but lower than that of T1DM subjects with AITD (ZnT8A: 42.6%; IA-2A: 44.4%; GADA: 74.1%; all P < 0.0001).

Conclusions

An increased prevalence of ZnT8A as well as GADA and IA-2A was found in both GD and HT patients, indicating that there is a potential link between thyroid autoimmunity and islet autoimmunity.

Open access

Metformin improves glycemic variability in adults with type 1 diabetes mellitus: an open-label randomized control trial

Xiuzhen Zhang, Dan Xu, Ping Xu, Shufen Yang, Qingmei Zhang, Yan Wu, and Fengyi Yuan

Introduction

Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM.

Objectives

In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored.

Patients and methods

A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests, and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000–2000 mg metformin daily add-on insulin (MET group, n = 34) or insulin (non-MET group, n = 31). After, baseline measurements were repeated.

Results

The mean amplitude of glycemic excursions was substantially reduced in MET group, compared with non-MET group (–1.58 (–3.35, 0.31) mmol/L vs 1.36 (–1.12, 2.24) mmol/L, P = 0.004). In parallel, the largest amplitude of glycemic excursions (–2.83 (–5.47, –0.06) mmol/L vs 0.45 (–1.29, 4.48) mmol/L, P = 0.004), the s.d. of blood glucose (–0.85 (–1.51, 0.01) mmol/L vs –0.14 (–0.68, 1.21) mmol/L, P = 0.015), and the coefficient of variation (–6.66 (–15.00, 1.50)% vs –1.60 (–6.28, 11.71)%, P = 0.012) all demonstrated improvement in the MET group, compared with the non-MET group. Significant reduction in insulin dose, BMI, and body weight was observed in patients in MET, not those in non-MET group.

Conclusion

Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as an adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.

Open access

Evaluation of lipid profile and its relationship with blood pressure in patients with Cushing’s disease

Lang Qin, Xiaoming Zhu, Xiaoxia Liu, Meifang Zeng, Ran Tao, Yan Zhuang, Yiting Zhou, Zhaoyun Zhang, Yehong Yang, Yiming Li, Yongfei Wang, and Hongying Ye

Introduction

The purpose of the study was to describe lipid profile and explore pathogenetic role of LDL-c on hypertension in patients with Cushing’s disease (CD). Hypertension is a common feature in patients with CD. Previous study found low-density lipoprotein cholesterol (LDL-c) uptake in vascular cells might be involved in vascular remodeling in patients with CD. Therefore, we evaluated the relationship between lipid profile and the blood pressure in patients with CD.

Methods

This retrospective study included 84 patients referred to Huashan Hospital for the evaluation and diagnosis of CD from January 2012 to December 2013. All subjects had detailed clinical evaluation by the same group of endocrinology specialists to avoid subjective influences.

Results

We found that high LDL-c patients had significant higher body mass index (BMI), systolic blood pressure (SBP), cholesterol (CHO), triglyceride (TG), and apolipoproteinB (apoB) (P < 0.05). An association was detected between SBP values and lipids profile including CHO, TG, LDL-c, apolipoproteinA (apoA), apoB and lipoprotein(a) (LP(a)). After adjustment for all covariates, the LDL-c remained positively associated with SBP. In patients with or without taking statins, patients with LDL-c ≥3.37 mmol/L had higher SBP than patients with LDL-c <3.37 mmol/L. Then, LDL-c was coded using restricted cubic splines (RCS) function with three knots located at the 5th, 50th and 95th percentiles of the distribution of LDL-c. Compared to individuals with 3.215 mmol/L of LDL-c, individuals with 4.0, 4.5 and 5.0 mmol/L of LDL-c had differences of 3.86, 8.53 and 14.11 mmHg in SBP, respectively.

Conclusions

An independent association between LDL-c and SBP was found in patients with CD. We speculate that LDL-c may be a pathogenic factor for hypertension in those patients.

Open access

Prevalence of antibodies targeting ubiquitin-conjugating enzyme 2L3 and eukaryote translation elongation factor 1 α1 in Chinese Han and American Caucasian populations with type 1 diabetes

Li Qian, Yuxiao Zhu, Yan Luo, Mu Zhang, Liping Yu, Yu Liu, and Tao Yang

We assessed the prevalence of two novel islet autoantibodies, those targeting ubiquitin-conjugating enzyme 2L3 (UBE2L3) and eukaryote translation elongation factor 1 α1 (eEF1A1), in type 1 diabetes mellitus (T1DM) to evaluate their utility in T1DM diagnosis with comparison to other islet autoantibodies. We also aimed to determine whether age and ethnicity impacted their diagnostic value. Electrochemiluminescence assay was used to detect UBE2L3-Ab and eEF1A1-Ab in 193 Chinese Han and 570 American Caucasian subjects with T1DM, and 282 Chinese Han and 199 American Caucasian controls. In Chinese and American cohorts, the UBE2L3-Ab cut-off indices were 0.039 and 0.038, and the eEF1A1-Ab cut-off indices were 0.048 and 0.050, respectively. The prevalence of UBE2L3-Ab was significantly higher in the Chinese (9.33%) and American (3.86%) subjects with T1DM than in the controls (P < 0.05). The prevalence of UBE2L3-Ab in T1DM was significantly higher in Chinese than in American (P < 0.05). Albeit not statistically significant, the prevalence of UBE2L3-Ab in T1DM was slightly higher in children than in adults of both ethnicities. The differences in eEF1A1-Ab levels between subjects with T1DM and controls were not significant. Meanwhile, all American subjects with UBE2L3-Ab also harbored glutamic acid decarboxylase autoantibody (GADA) or insulin autoantibody (IAA). In contrast, 2.07% of the Chinese subjects with UBE2L3-Ab positive were previously classified as autoantibody-negative based on GADA and IAA. So the prevalence of UBE2L3-Ab in T1DM patients was significantly higher than in controls and was variable according to ethnicity as well as tended to be higher in children than adults. However, UBE2L3-Ab and eEF1A1-Ab may not be reliable diagnostic biomarkers forT1DM.

Open access

Sexually dimorphic distribution of kiss1 and kiss2 in the brain of yellowtail clownfish, Amphiprion clarkii

Yan-yu Zhang, Xian Zhang, Shao-yang Bu, Wei-wei Zhang, Tian-xiu Li, De-cai Zheng, Ze-xiang Huang, and Qian Wang

Kisspeptin system was shown to be a key factor in mediating social stress and reproduction. Yellowtail clownfish, Amphiprion clarkii, is a hermaphrodite fish, whose sex determination and gonadal development are affected by the social status of individuals. The yellowtail clownfish is a fantastic animal model to explore sex determination, but the social status and precise distribution of kiss mRNAs in the brain of this species are unknown. Hererin, a novel in situ hybridization technique, RNAscope, was used to investigate the distribution of kiss1 and kiss2 expressions in the brain of yellowtail clownfish. The coronal planes of brain showed that the kiss1 signal was mainly present in dorsal habenular nucleus (NHd) and kiss2 mRNA was widely expressed in telencephalon, midbrain, and hypothalamus, especially in dorsal part of the nucleus of the lateral recess (NRLd). Additionally, kiss1 and kiss2 signals have sexually dimorphic distribution. The kiss1 mRNA was distributed in NHd, the telencephalon, and lateral part of the diffuse nucleus of the inferior lobe (NDLIl) of females but in NHd and NDLIl of males. kiss2 signals were stronger in females than that in males. The distribution of kiss1 and kiss2 neurons in NHd of habenula and NRLd of hypothalamus may suggest that kiss genes associate environmental signaling and reproductive function in yellowtail clownfish.

Open access

Serum levels of ghrelin and LEAP2 in patients with type 2 diabetes mellitus: correlation with circulating glucose and lipids

Jiaxi Li, Pu Huang, Jing Xiong, Xinyue Liang, Mei Li, Hao Ke, Chunli Chen, Yang Han, Yanhong Huang, Yan Zhou, Ziqiang Luo, Dandan Feng, and Chen Chen

Objective

Ghrelin regulates body weight, food intake, and blood glucose. It also regulates insulin secretion from pancreatic islet cells. LEAP2 is a newly discovered endogenous ligand of the growth hormone secretagogue’s receptor (GHSR). It not only antagonizes the stimulation of GHSR by ghrelin but also inhibits the constitutive activation of GHSR as an inverse agonist. Type 2 diabetes (T2D) patients have endocrine disorders with metabolic imbalance. Plasma levels of ghrelin and LEAP2 may be changed in obese and T2D patients. However, there is no report yet on circulating LEAP2 levels or ghrelin/LEAP2 ratio in T2D patients. In this study, fasting serum ghrelin and LEAP2 levels in healthy adults and T2D patients were assessed to clarify the association of two hormones with different clinical anthropometric and metabolic parameters.

Design

A total of 16 females and 40 males, ages 23–68 years old normal (n  = 27), and T2D patients (n  = 29) were enrolled as a cross-sectional cohort.

Results

Serum levels of ghrelin were lower but serum levels of LEAP2 were higher in T2D patients. Ghrelin levels were positively correlated with fasting serum insulin levels and HOMA-IR in healthy adults. LEAP2 levels were positively correlated with age and hemoglobin A1c (HbA1c) in all tested samples. Ghrelin/LEAP2 ratio was negatively correlated with age, fasting blood glucose, and HbA1c.

Conclusions

This study demonstrated a decrease in serum ghrelin levels and an increase in serum LEAP2 levels in T2D patients. LEAP2 levels were positively correlated with HbA1c, suggesting that LEAP2 was associated with T2D development. The ghrelin/LEAP2 ratio was closely associated with glycemic control in T2D patients showing a negative correlation with glucose and HbA1c.

Open access

Elevated circulating Gpnmb levels are associated with hyperthyroidism

Jiayang Lin, Peizhen Zhang, Yan Huang, Xueyun Wei, Dan Guo, Jianfang Liu, Deying Liu, Yajuan Deng, Bingyan Xu, Chensihan Huang, Xiaoyu Yang, Yan Lu, Lijing Jia, and Huijie Zhang

Background:

Glycoprotein non-metastatic protein B (Gpnmb) has been identified as a new cytokine secreted by hepatocyte that plays an important role in balancing lipid homeostasis and development of obesity and metabolic disorders. However, information is not available regarding the association between circulating Gpnmb and hyperthyroid in humans.

Methods:

We measured serum Gpnmb in 180 hyperthyroid patients and 82 healthy subjects that were recruited from the clinic. Of them, 46 hyperthyroid patients received thionamide treatment for 3 months.

Results:

Hyperthyroid subjects had higher levels of circulating Gpnmb than healthy controls (47.8 ± 10.1 ng/mL vs 31.0 ± 4.9 ng/mL, P < 0.001). Subjects with higher levels of serum free triiodothyronine (T3) and free thyroxine (T4) had higher levels of circulating Gpnmb. After thionamide treatment, levels of circulating Gpnmb in hyperthyroid subjects remarkably declined with significant improvement of thyroid function (P < 0.001). Furthermore, the change of circulating Gpnmb levels was significantly associated with basal metabolic rate (BMR) and thyroid hormones, including free T3 and free T4, adjusting for age, gender, smoking and BMI before thionamide treatment. In multivariable logistic regression analyses, circulating Gpnmb was significantly associated with risks of hyperthyroidism (OR (95% CI): 1.44 (1.20–1.74), P < 0.001), adjusted for age, gender, BMI, fasting glucose, HOMA-IR, LDL-cholesterol, ALT and AST.

Conclusions:

These findings indicate that circulating Gpnmb concentrations are independently associated with hyperthyroid, suggesting that circulating Gpnmb may be a predictor of risk for hyperthyroidism and can be used for therapeutic monitoring.

Open access

Preliminary evidence of the association between DNAm and orbital volumetry in GO

Ya-Fen Hu, Lin Hua, Xiu Tuo, Ting-Ting Shi, Yi-Lin Yang, Yun-Fu Liu, Zhong-Yu Yan, and Zhong Xin

Background

The pathogenesis underlying the alterations of orbital architecture in Graves’ orbitopathy (GO) is not yet fully understood. The present study aimed to investigate the association of DNA methylation in peripheral blood and orbital volumetry in Chinese patients with GO.

Methods

A total of 35 GO subjects (70 orbits) were subjected to CT scan. The total cross-sectional area of the extraocular muscles (orbital muscles, OM), total orbit area (TOA), and the exophthalmometry were measured and OM/TOA ratio was calculated. Targeted bisulfite sequencing was performed on seven candidate genes.

Results

No significant correlation was established between the DNA methylation levels of these genes and exophthalmometry. The MBP methylation level was found to be correlated with OM/TOA ratio (P < 0.05). Multiple linear regression analysis on parameters including age, sex, TRAb, duration of GO, and DNA methylation levels of seven genes with OM/TOA ratio confirmed that MBP and OM/TOA ratio had a significant correlation (P < 0.05). The partial least squares analysis showed that the top three genes with the highest loadings were MBP, BOLL, and BECN1 and that OM/TOA ratio affected the DNA methylation block than exophthalmometry.

Conclusions

This study provided preliminary evidence that MBP is a potential gene associated with OM enlargement in GO patients according to the combination of DNA methylation sequencing and orbital CT measurement.