Endocrine Connections最新文献

Background: Semen analysis is the standard test for evaluating male fertility. However, it may not address all aspects of male infertility. This review explores the role of leukocyte elastase (LE) as a possible biomarker for male fertility by evaluating 28 corresponding studies.

Objectives: We aimed to explore how leukocyte elastase levels in semen relate to sperm quality and pregnancy outcomes.

Methods: This systematic review followed PRISMA guidelines and included studies from PubMed, Medline, EMBASE, and Scopus (March 22-25, 2024) using the keywords "Elastase," "Sperm," and "Semen." Out of 897 identified articles, 334 were screened, leading to 90 full-text reviews. We included 28 studies reporting sperm parameters linked to LE and excluded non-English articles, reviews, and animal studies. Data collected included study details, methods, population, LE levels, sperm characteristics, and pregnancy outcomes. A narrative synthesis was used due to differing study designs. Quality assessment, using the National Heart, Lung, and Blood Institute tool, rated 21 studies medium quality, 6 high, and 1 low.

Results: Only a limited number of studies reported a correlation between leukocyte elastase levels and sperm parameters, with no significant link to sperm concentration. Overall, we did not identify a strong association between LE levels and pregnancy or fertilization rates.

Conclusions: While LE serves as a marker for seminal leukocyte concentration, its link to sperm quality and fertility outcomes remains weak and inconsistent. Based on current evidence, LE does not appear to be a reliable diagnostic marker for male infertility. Future studies should focus on standardizing LE measurement techniques and exploring its interaction with other semen parameters to clarify its role in male fertility.

Acquired hypothalamic obesity (HO) is a rare type of obesity caused by acquired disease-related and/or treatment-related damage to the hypothalamus, most commonly craniopharyngiomas. Effective management of HO is critical due to its significant impact on quality of life and resistance to conventional treatments. This systematic review and meta-analysis aims to evaluate the 12-month, 24-month and 60-month outcomes of bariatric surgery for HO caused by CPs compared with patients with common obesity (CO). Relevant studies were identified in MEDLINE and EMBASE databases until May 2024. A total of four matched case-control studies were included. The results indicated that bariatric surgery significantly reduced weight in patients with HO (22.98 ± 14.22/21.47 ± 9.61/19.07 ± 16.12% total weight loss, 12/24/60 months after surgery), but the effect was significantly less than that in CO controls (-6.17/-6.41/-7.72% total weight loss 12/24/60 months after surgery). Bariatric surgery can significantly reduce body weight in craniopharyngiomas-related HO, but the effect is less than that in matched patients with common obesity. Further studies are necessary to determine the best surgical or multidisciplinary approach to the treatment of acquired HO.

Aim: Incretin therapies, including dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), are crucial for type 2 diabetes treatment. Evidence of their association with gallbladder, biliary diseases, and liver injury remains inconsistent. This study evaluated the association between incretin therapies and hepatobiliary adverse events using the FDA's Adverse Event Reporting System (FAERS) data.

Methods: Case reports involving incretin therapies and hepatobiliary events from January 2006 to December 2023 were extracted from FAERS. The association between these agents and hepatobiliary adverse events (hAEs) was analyzed using reporting odds ratios and empirical Bayesian geometric means. Descriptive analyses were conducted to characterize the demographic and clinical features of the hAE cases. Additionally, subgroup analyses calculated reporting odds ratios to evaluate the strength of the association between specific incretin drugs and hAEs.

Results: Among 68,351 case reports associated with incretin-based therapies, 1327 (1.941%) involved hepatobiliary adverse events. DPP-4 inhibitors demonstrated statistically significant associations with multiple hepatobiliary events, like cholelithiasis, chronic cholecystitis, and biliary diseases. In contrast, GLP-1 receptor agonists showed weaker associations, primarily linked to gallbladder and biliary disease risks. Subgroup analyses revealed stronger positive correlations with hepatobiliary events for liraglutide and semaglutide among GLP-1 agonists, and for sitagliptin, linagliptin, and vildagliptin among DPP-4 inhibitors. The pooled reporting odds ratio of 2.85 indicated a positive correlation between these drugs and studied adverse events.

Conclusions: This study found statistically significant associations between DPP-4 inhibitors and hepatobiliary adverse events like cholelithiasis and cholecystitis. GLP-1 agonists showed weaker gallbladder/biliary disorder links but higher acute cholecystitis risk. Subgroup analyses revealed varying correlations among specific drugs, potentially dose-dependent. Further large-scale studies are needed to evaluate class effect differences and elucidate mechanisms for guiding clinical use.

Background: Gender-affirming hormone therapy (GAHT) is used in individuals with gender identity dysphoria to align an individual's secondary sexual characteristics with their affirmed gender. We conducted a systematic review of the literature to explore the mechanisms regarding the effects of GAHT on the vasculature.

Methods: A literature search using PUBMED, Embase, Scopus and Lilacs was performed using search terms for GAHT, cardiovascular disease (CVD) risk and transgender. Studies were screened by two independent reviewers. Comparison to a cohort of transgender individuals naïve or prior to GAHT or a cisgender population was required. Quality assessment was done using the relevant Critical Skills Appraisal Programme checklists.

Results: Out of 2,564 potentially eligible studies, 69 studies met the inclusion criteria. Studies provided evidence of beneficial changes in CVD risk profile including reduced haemoglobin and pro-inflammatory markers, and atheroprotective changes in lipids in transgender women. In transgender men there was evidence of negative changes in CVD risk profile including atherogenic changes in lipids and increased haemoglobin, arterial stiffness, and pro-inflammatory markers.

Conclusions: There is a paucity of research across non-traditional measures of CVD risk which in combination with heterogeneous study design, loss of follow-up, low sample sizes and lack of diversity in age and ethnicity requires the results to be interpreted with caution. More evidence is required to elucidate the mechanisms behind the increased risk of CVD in the transgender population and determine if GAHT is a contributing factor.

Objective: Increasing numbers of pregnancies are complicated by pregestational diabetes mellitus, especially type 2 diabetes (T2DM). Some studies have reported similar or greater risks of adverse pregnancy outcomes among women with T2DM relative to type 1 diabetes (T1DM). We aimed to compare the risk of four pregnancy complications: pre-eclampsia, preterm delivery, macrosomia, and perinatal mortality, in pregnant women with T2DM vs T1DM in high-income countries.

Design: Systematic review with meta-analyses.

Methods: Systematic literature searches in Medline and Embase were performed. We included observational studies with original data of outcome occurrence in both women with pregestational T2DM and T1DM. Two researchers independently evaluated full-text studies for inclusion and assessed the risk of bias using the Newcastle-Ottawa scale. Finally, we performed four meta-analyses.

Results: We included 35 publications in total. Meta-analyses demonstrated that, compared to T1DM, T2DM was associated with a lower risk of pre-eclampsia (risk ratio (RR): 0.76; 95% CI: 0.68-0.85), preterm delivery (RR: 0.69; 95% CI: 0.62-0.77), and macrosomia (RR: 0.75; 95% CI: 0.60-0.94). Perinatal mortality was more likely in pregnancies with T2DM (RR: 1.26; 95% CI: 1.06-1.50).

Conclusion: A summation of the research literature demonstrated that, compared to T1DM, women with T2DM had a lower risk of pre-eclampsia, preterm delivery, and macrosomia, but a higher risk of perinatal mortality.

Significance statement: Our review of pregnant women with diabetes suggests a higher risk of perinatal mortality for cases with maternal type 2 diabetes, even though the risks of pre-eclampsia, preterm delivery, and macrosomia were higher in cases with type 1 diabetes. Hence, the prevention of the development of type 2 diabetes and focus on improved gestational and diabetic care could be beneficial for fetal health.

Background: Signal transducer and activator of transcription 6 (STAT6) is an important nuclear transcription factor. Previous studies demonstrated that blocking STAT6 can ameliorate thyroid function by reducing serum T3 and T4. Sodium/iodide symporter (NIS) is a key protein that mediates active iodine uptake and plays an important role in regulating thyroid function. This study explored the interaction between STAT6 and NIS.

Methods: Immunohistochemical staining was performed for detecting the expression of NIS in different tissues. RT-PCR was performed for evaluating the mRNA level of NIS when Nthy-ori 3-1 cells were incubated with IL4, thyroid stimulating hormone (TSH), or monoclonal thyroid-specific stimulatory autoantibody (TSAb) for 24 h. Quantitative RT-PCR, western blot, and immunofluorescence analysis were performed for detecting NIS expression after inhibiting STAT6 phosphorylation by AS1517499. Finally, we used luciferase reporter assays to explore the ability of STAT6 to regulate the promoter activity of the NIS-coding gene.

Results: NIS was highly expressed in thyroid epithelial cells of EAGD mice or Graves' disease (GD) patients, and TSAb increased the expression of NIS. We show that a STAT6 phosphorylation inhibitor can attenuate the effect of TSAb on increasing NIS protein and mRNA levels. Finally, we confirm that transcription factor STAT6 can mediate NIS transcription and co-activator P100 protein can enhance STAT6-dependent transcriptional activation.

Conclusion: In GD, TSAb induces STAT6 signaling to upregulate NIS expression, and STAT6 blockade ameliorates thyroid function via downregulation of the NIS. Our study furthers understanding of the effects of STAT6 on thyroid function and reveals new avenues for GD treatment.

Childhood cancer survivors are at increased risk of developing (long-term) skeletal adverse effects, such as osteonecrosis, impaired bone mineral density, and fractures. This paper provides an overview of the current understanding of bone health in these survivors, examining whether it represents a significant concern. It focusses on the challenges of assessing and managing bone health in childhood cancer survivors, highlighting diagnostic pitfalls, methods for accurately identifying those at high risk, and suggested strategies for the surveillance and management of osteonecrosis and impaired bone mineral density. The need for improved surveillance strategies, particularly for high-risk survivors, alongside potential prevention and management options, including pharmacological and lifestyle interventions, is emphasised. Given the lack of consensus on optimal prevention and treatment strategies, the paper emphasises the need for further research to optimise care and improve long-term outcomes for childhood cancer survivors with bone health impairments.

Introduction: Incidental uptake within or adjacent to the thyroid gland is occasionally observed on somatostatin receptor-targeted PET imaging in patients with neuroendocrine neoplasms (NENs). The reported prevalence and clinical relevance of such findings are not well established.

Materials and methods: We reviewed PET scan reports for all patients undergoing [68Ga]Ga-DOTA-TOC PET/CT or [64Cu]Cu-DOTA-TATE PET/CT in our department from 2018 to 2022. Scans reporting incidental uptake within or adjacent to the thyroid gland were reviewed post hoc to extract semi-quantitative scores of tracer uptake for the incidental lesions. We further extracted data from electronic patient charts, including cytology and histology.

Results: A total of 3692 PET scans were performed on 1808 unique patients. Incidental abnormal thyroid uptake was reported in 42 of the 1808 patients, with thyroid malignancy identified in five of these 42 patients. Two patients had medullary thyroid cancers, two had neuroendocrine tumor metastases, and one had a renal clear cell carcinoma metastasis. Focal uptake in close relation to the thyroid gland, suggestive of parathyroid adenoma, was reported in another 13 of the 1808 patients, with biochemical hyperparathyroidism found in six of these 13 patients.

Conclusion: In patients undergoing somatostatin receptor-targeted PET scans for evaluation of NENs, the prevalence of reported abnormal uptake within or adjacent to the thyroid gland was low. However, the rates of thyroid malignancy and parathyroid adenomas were substantial. Prospective studies are needed to determine the optimal diagnostic and therapeutic strategies for these incidental findings.

Objectives: The incidence of congenital hypothyroidism (CH) has increased worldwide over the last decades, mainly due to the lowering of screening thresholds, resulting in the increased identification of newborns with transient CH. Several studies have reported the prevalence and the predictive parameters of transient CH, but reports on the long-term outcome are rare. This study aimed to assess the long-term course of neonates with transient CH.

Design: Neonates diagnosed with transient and permanent CH between the years 1998 and 2018 at the Pediatric Endocrine Institute of Ha'Emek Medical Center were enrolled in the study. Data were retrieved retrospectively from medical files.

Results: A total of 76 newborns (45M, 59%) with transient CH and 53 (25M, 47%) with permanent CH were included in the study. The major causes of transient CH were prematurity (29%) and subclinical hypothyroidism (30%). During retrospective follow-ups of up to 23 years, reinitiation of levothyroxine therapy was not required, apart from four patients with underlying syndromic etiologies. Neurodevelopmental impairment occurred in 16% of children with transient CH compared with 29.4% in the permanent CH group.

Conclusions: Transient CH is frequent among preterm infants but is generally limited to infancy. Subclinical hypothyroidism frequently presents as overt hypothyroidism at birth, but in most cases, the requirement for levothyroxine supplemental therapy is limited to the first years of life, suggesting that long-term follow-up of thyroid function tests may be unnecessary for non-syndromic children. The high rate of neurodevelopmental impairment in newborns with transient CH emphasizes the need for neurodevelopmental monitoring in these patients.

Significance statement: A high rate of transient CH has been identified over the past decades following the lowering of TSH screening thresholds. The long-term outcome of transient CH has been evaluated in a few studies with inconclusive results. In the current study, we assessed the long-term outcomes of transient CH for up to 23 years. We found that 29% of cases were attributed to prematurity and 30% to subclinical hypothyroidism. No morphological anomalies were identified. Only syndromic patients (three with Down syndrome and one with Coffin-Lowry syndrome) required levothyroxine supplemental therapy at the time of the study, indicating that long-term thyroid function monitoring may be unnecessary. The high prevalence of neurodevelopmental impairment suggests the need for close neurodevelopmental monitoring in this population.

Background: Collagen type VIII α 1 chain (COL8A1), a collagen type VIII protein, has been suggested to exert various functions in progression of multiple cancers. However, the effect of COL8A1 in papillary thyroid cancer (PTC) has not been elucidated.

Methods: The Cancer Genome Atlas (TCGA) databases were applied to investigate the COL8A1 expression and its clinical significance in PTC. The COL8A1 expression level was further validated using Gene Expression Omnibus (GEO) data and clinical paired PTC tissues. Additionally, the Kaplan-Meier curve was used to analyze the prognosis. The cell's migrative and invasive abilities were evaluated by wound healing assay and Transwell assay. CCK8 assays were used to evaluate the proliferation of PTC cells. Western blotting was conducted to explore the potential mechanisms involved in the pro-tumor role of COL8A1. The correlation between immune cell infiltration and COL8A1 was analyzed using the Tumor Immune Estimation Resource (TIMER) database and the single-sample GSEA (ssGSEA) method.

Results: We found that COL8A1 was upregulated in PTC (P < 0.05). High COL8A1 expression level was significantly associated with advanced T stage (P < 0.01), N stage (P < 0.001) and poor prognosis (P = 0.0142) in PTC. Furthermore, cell migration and invasion were significantly reduced following COL8A1 knockdown (P < 0.001). Mechanistic studies demonstrated that the epithelial-to-mesenchymal transition (EMT) related proteins (FN1, MMP9, MMP7, ZEB2 and Twist1) and phosphorylation of AKT and ERK were obviously down-regulated after COL8A1 knockdown (P < 0.01). Moreover, COL8A1 expression was correlated with immune cell infiltration.

Conclusion: Our study demonstrates that COL8A1 may function as an oncogene and a potential prognostic biomarker for PTC patients.