Hormone and Metabolic Research最新文献

Thyrotropin receptor antibodies (TRAb) are specific for Graves' disease (GD) and play a crucial role in the pathogenesis of GD. TRAb assays have recently been greatly improved. This review discusses the clinical application of TRAb in the differential diagnosis of hyperthyroidism, the prognosis of GD, GD in gestation and pediatrics, and GD related ophthalmopathy (GO). In addition to the classical competition and bioassays, a new bridging assay has emerged for TRAb assays. TRAb is the main pathogenic mechanism of hyperthyroidism in GD. Treated GD still has a high rate of recurrence and even a short-term surge of TRAb, leading to rapid deterioration of GO. Fetal goiter may be associated with elevated maternal TRAb during pregnancy, overtreatment may lead to fetal hypothyroidism. Pediatric patients with GD have high TRAb, poor remission from treatment, and insignificant manifestations of GO. TRAb is significantly correlated with GO activity and severity. Currently, TRAb assay has high specificity and sensitivity and can be used directly to identify the cause of hyperthyroidism. TRAb can be used to predict recurrence of drug treated GD or progression of GO after RAI therapy. TRAb should be measured regularly for GD in gestation to guide anti-thyroid medication to avoid thyrotoxicosis or hypothyroidism in the fetus. Monitoring TRAb in pediatric GD may help control the progression of GO. TRAb assay is an important guide for the treatment of GO.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aims to evaluate the association between the triglyceride glucose (TyG) index, a novel marker reflecting insulin resistance, and the risk of developing DN in patients with T2DM. We conducted a comprehensive literature search in PubMed, Embase, and Web of Science databases up to May 12, 2024. Studies assessing the TyG index in relation to DN risk among T2DM patients were included. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. A total of eight longitudinal follow-up studies encompassing 15 889 patients with T2DM were included. The pooled analysis revealed a significant association between a higher TyG index and an increased risk of DN in patients with T2DM (RR=1.53, 95% CI: 1.37-1.71, p<0.001; I²=35%). The results of meta-regression analysis suggested that the cutoff of TyG index was positively associated with the RR for the association between TyG index and DN. Subgroup analyses demonstrated that the association was stronger in studies with cutoff of TyG index ≥9.5 as compared to those with the cutoff <9.5 (RR: 1.73 vs. 1.40, p for subgroup difference <0.05). The association was not significantly affected by study design, mean age of the patients, proportion of men, or follow-up durations. In conclusion, higher TyG index is significantly associated with an increased risk of DN in patients with T2DM.

The high cardiometabolic risk associated with polycystic ovary syndrome (PCOS) may be linked to central fat accumulation. This study compared fat distribution between women with PCOS and controls matched by body mass index. It also sought to determine if insulin resistance (IR), androgens, or inflammatory markers correlate with body composition parameters in PCOS patients. In total, thirty-five women with PCOS and 37 controls, aged 18-40 years, were included. Hormonal/metabolic profiles, inflammatory biomarkers [tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6)], anthropometry (waist circumference, waist-to-hip ratio, lipid accumulation product [LAP], visceral adiposity index [VAI]), and body composition assessed through dual-energy X-ray absorptiometry were assessed. The PCOS group exhibited significantly higher androgen levels and markers of IR. However, levels of TNF-α and IL-6 were comparable between the groups. Despite having similar total body fat mass (FM), the PCOS group had excessive central fat, including increased truncal FM and visceral adipose tissue (VAT). In PCOS, androgens were not associated with body fat or its distribution. IL-6 was positively correlated with total and truncal FM, while insulinemia and the homeostatic model assessment for IR were positively associated with VAT, as well as with total and truncal FM. Although anthropometric measurements and indices were positively associated with DXA-derived central FM parameters, our data suggest that LAP is the most effective tool for assessing central fat deposition and metabolic dysfunction in the PCOS patients studied herein. Furthermore, in this population, IR, rather than androgens or proinflammatory cytokines, is more closely associated with abdominal obesity.

The World Health Organization (WHO) predicted that patients with diabetes around the world will increase to 600 million by 2040, of which about 1/3 will develop diabetic nephropathy (DN). Therefore, the present study aimed to uncover therapeutic effect of HINT2 and determined its possible mechanisms. Patients with diabetes mellitus and normal volunteers were enrolled at our hospital. Male C57BL/6 mice were fed with a high fat diet and injected intraperitoneally with STZ for once (100 mg/kg body weight). Mouse podocytes (MPC5) cells were induced with 20 mmol/l D-glucose. Inhibition of HINT2 mRNA expression levels in patients with DN was observed, compared with normal group. The serum of HINT2 mRNA expression was negative in correlation with blood sugar, tubulo-interstitial damage, glomerular damage score or urine protein level in patients with DN. HINT2 expression in kidney tissue of mice with DN were downregulated. HINT2 presented reduced DN and inflammation and ROS-induced oxidative stress in model of DN. HINT2 promoted ferroptosis in model of DN by mitochondrial membrane potential. HINT2 suppressed MCU expression in model of DN. HINT2 protein combined with MCU protein increased MCU protein ubiquitination. HINT2 triggers mitochondrial Ca2+ influx to increase ROS production level by MCU. Taken together, these findings demonstrated that HINT2 reduced ROS-induced Oxidative stress and ferroptosis by MCU, suggesting that HINT2 may be a feasible strategy to treat DN.

Interleukin-18 (IL-18) is a proinflammatory cytokine that primarily stimulates the Th1 immune response. IL-18 exhibits anticancer activity and has been evaluated in clinical trials as a potential cancer treatment. However, evidence suggests that it may also facilitate the development and progression of some cancers. So far, the impact of IL-18 on papillary thyroid cancer (PTC) has not been investigated. In this study, we found that the expression of IL-18 was significantly increased in PTC compared to normal thyroid tissue. Elevated IL-18 expression was closely associated with lymphovascular invasion and lymph node metastases. Furthermore, compared to PTC patients with no nodal metastasis, serum IL-18 levels were slightly increased in patients with 1-4 nodal metastases and significantly elevated in patients with 5 or more nodal metastases. The pro-metastatic effect of IL-18 may be attributed to the simultaneous increase in the expression of S100A10, a known factor that is linked to nodal metastasis in PTC. In addition, the activation of several pathways, such as the intestinal immune network for lgA production and Staphylococcus aureus infection, may be involved in the metastasis process. Taken together, IL-18 may trigger pro-metastatic activity in PTC. Therefore, suppressing the function of IL-18 rather than enhancing it appears to be a reasonable strategy for treating aggressive PTC.

Peptic ulcers, recognized for their erosive impact on the gastrointestinal mucosa, present a considerable challenge in gastroenterology. Epidemiological insights underscore the global prevalence of peptic ulcers, affecting 5-10+% of individuals, with a yearly incidence of 0.3 to 1.9 cases per thousand. Recent decades have witnessed a decline in complications, attributed to improved diagnostics and therapeutic advancements. The review deepens into H. pylori-associated and NSAID-induced ulcers, emphasizing their distinct prevalence in developing and industrialized nations, respectively. Despite advancements, managing peptic ulcers remains challenging, notably in H. pylori-infected individuals facing recurrence and the rise of antibiotic resistance. The pathophysiology unravels the delicate balance between protective and destructive factors, including the intricate molecular mechanisms involving inflammatory mediators such as TNF-α, ILs, and prostaglandins. Genetic and ethnic factors, rare contributors, and recent molecular insights further enhance our understanding of peptic ulcer development. Diagnostic approaches are pivotal, with upper gastrointestinal endoscopy standing as the gold standard. Current treatment strategies focus on H. pylori eradication, NSAID discontinuation, and proton pump inhibitors. Surgical options become imperative for refractory cases, emphasizing a comprehensive approach. Advances include tailored H. pylori regimens, the emergence of vonoprazan, and ongoing vaccine development. Challenges persist, primarily in antibiotic resistance, side effects of acid suppressants, and translating natural compounds into standardized therapies. Promising avenues include the potential H. pylori vaccine and the exploration of natural compounds, with monoterpenes showing therapeutic promise. This review serves as a compass, guiding healthcare professionals, researchers, and policymakers through the intricate landscape of peptic ulcer management.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

The aim of the work was to systematically evaluate the efficacy and safety of Vandetanib in the treatment of advanced medullary thyroid carcinoma (MTC). MeSH entries to search for randomized controlled trials and clinical research literature on the application of Vandetanib in the treatment of medullary thyroid cancer from PubMed, Chinese national knowledge infrastructure (CNKI), and Web of Science databases since their establishment until March 2023 were used. In terms of efficacy, the analysis results showed that Vandetanib had a significantly higher objective response rate compared to the control group using placebo (OR=2.13, 95% CI: 1.38, 3.29). In terms of side effects, Vandetanib significantly increases the incidence of hypertension, rash, and diarrhea, and has statistical significance (p+<+0.05). Vandetanib has a better therapeutic effect on MTC, but it also increases the incidence of hypertension, rash, and diarrhea. Attention should be paid to the relief of side effects when using it.

The aim of the study was to investigate whether the biomarkers for bone turnover could rapidly recover during the period of diabetic ketoacidosis (DKA). Bone turnover biomarkers, including 25-hydroxyvitamin D3, N-terminal middle molecular fragment of osteocalcin (NMID), and β-C terminal cross-linking telopeptide of type 1 collagen were evaluated using in-patient data (n=627) from Shanghai Pudong Hospital from 2018-2022. The comparison was performed between type 2 diabetes (T2D only) (n=602) and DKA (n=25), in which we checked the bone turnover markers at pre-treatment and recovery. After matching by body mass index (BMI), we found that except for 25-OH-VitD3, the age difference, indices of glucose metabolism, and bone turnover were significant between the 2 groups (p<0.05). We found only a significant restoration of NMID (p<0.001). NMID and β-CTX, when compared with T2D, showed overt distinction between recovery and T2D (p<0.05). In addition, the investigations demonstrated a substantial difference between 25-OH-VitD3 in males and NMID in females, regardless of age (p<0.05). Multilinear regression analysis revealed that 2 hours postprandial plasma C-peptide was an independent predictor of the NMID in both pre-treatment (β=0.58, p=0.003) and recovery (β=0.447, p=0.025), although sex was significant in pre-treatment (β=-0.444, p=0.020). Finally, we found that only age variation affected DKA's fasting plasma glucose level (p<0.05). The study revealed that the bone turnover of DKA is significantly different in pre-treatment and recovery; however, NMID might recover quickly if the patients received appropriate treatment. Importantly, pancreatic function plays a critical role in changing bone turnover biomarkers.

Thyroglobulin (Tg) is an important tool to evaluate the persistence and recurrence risk in differentiated thyroid cancer (DTC). We aimed to evaluate the correlation between pre-radioiodine therapy stimulated Tg (pre-RAI Tg) levels and the first response to treatment evaluation, and to establish a cut-off pre-RAI Tg threshold for predicting an initial excellent response. Retrospective cohort study of DTC patients who underwent total thyroidectomy and radioiodine therapy. Response to therapy was evaluated 6 to 24 months after initial therapy, and patients were classified as: excellent response (ER); indeterminate response (IndR) and incomplete response (IncR). Total patients: 166 among which 85.5% female with mean age of 47.6 ± 13 years. The ER had a significantly lower pre-RAI Tg in comparison to IndR (p<0.001) and IncR (p<0.001), and pre-RAI Tg were different between the IndR and IncR (p=0.02). A cut-off pre-RAI Tg value at 7.55ng/ml was obtained by receiver operating characteristics curve for differentiating ER from IndR and IncR. The area under curve was 0.832 (95% CI 0.76-0.91). In multivariate analysis, ATA low-risk (RR 1.61, 95% CI 1.06-2.43, p=0.025) and Tg below 7.55ng/ml (RR 2.17, 95% CI 1.52-3.10, p<0.001) were associated with ER. After a median of 7.4-year follow-up, 124 (74.7%) patients were allocated into ER, 22 (13.2%) into IndR, and 20 (12%) into IncR. In conclusion, pre-RAI Tg predicts first evaluation of treatment response. Pre-RAI Tg cut-off was a key predictor of initial excellent response to therapy and may be an important tool in the follow-up of DTC patients.