Endocrine最新文献

Introduction: Diabetes and neuronal loss in the hippocampus have been observed to be correlated in several studies; however, the exact causality of this association remains uncertain. This study aims to explore the potential causal relationship between diabetes and the hippocampal nervous system.

Methods: We utilized the two-sample Mendelian randomization (MR) analysis to investigate the potential causal connection between diabetes and the hippocampal nervous system. The summary statistics of Genome-wide association study (GWAS) for diabetes and hippocampus neuroimaging measurement were acquired from published GWASs, all of which were based on European ancestry. Several two-sample MR analyses were conducted in this study, utilizing inverse-variance weighted (IVW), MR Egger, and Weight-median methods. To ensure the reliability of the results and identify any horizontal pleiotropy, sensitivity analyses were undertaken using Cochran's Q test and the MR-PRESSO global test.

Results: Causal associations were found between diabetes and the nervous system in the hippocampus. Type 1 and type 2 diabetes were both identified as having adverse causal connections with the right hippocampal nervous system. This was supported by specific ranges of IVW-OR values (P < 0.05). The consistency of the sensitivity analyses further reinforced the main findings, revealing no significant heterogeneity or presence of horizontal pleiotropy.

Conclusions: This study delved into the causal associations between diabetes and the hippocampal nervous system, revealing that both type 1 and type 2 diabetes have detrimental effects on the right hippocampal nervous system. Our findings have significant clinical implications as they indicate that diabetes may play a role in the decline of neurons in the right hippocampus among European populations, often resulting in cognitive decline.

Purpose: To explore the relationship between glucose management indicator (GMI) and HbA1c and find the affecting factors in adult T2D patients with good glycemic control.

Methods: Adult T2D patients with both HbA1c < 7% and time in range (TIR) > 70% were retrospectively analyzed. A significant difference between GMI and HbA1c was defined as an absolute value of hemoglobin glycation index (|HGI|, HbA1c minus GMI) ≥ 0.5%. Factors associated with high |HGI| were determined by logistic regression analysis. The performance of possible factors in predicting high |HGI| was verified by ROC curve analysis. And the linear relationship between GMI and HbA1c was also investigated.

Results: Of all the 94 patients (median HbA1c 6.18%, mean GMI 6.34%) included, 28.72% had an |HGI | ≥ 0.5% and only 15.96% had an |HGI | < 0.1%. Standard deviation of blood glucose (SDBG), a glycemic variability index, affected |HGI| (OR = 3.980, P = 0.001), and showed the best performance in predicting high |HGI| (AUC = 0.712, cutoff value = 1.63 mmol/L, P = 0.001). HbA1c was linearly correlated with GMI (β = 0.295, P = 0.004). Their correlation weakened after further adjusting for SDBG (β = 0.232, P = 0.012). Linear correlation between them was closer in patients with smaller SDBG ( < 1.63 mmol/L) than those with larger SDBG (P = 0.004).

Conclusions: Even in adult T2D patients with good glycemic control, the discrepancy between GMI and HbA1c existed. Their relationship was affected by glycemic variability. SDBG mainly accounted for this consequence.

Trial registration: Chinese clinical trial registry ( www.chictr.org.cn ), ChiCTR2000034884, 2020-07-23.

Purpose: An improvement in iodine status in the Veneto region (Italy) in the last decade has been documented. Our aim was to estimate the incidence of autoimmune thyroiditis (AT) in this region over the period 2012-2022.

Methods: A retrospective population-based study conducted in Veneto using the population registry and administrative health databases. We documented incident hyperthyroidism from 2013 to 2022 to exclude prevalent cases and calculated standardised incidence rates (IR) per 10,000 person-years by age and sex.

Results: We identified 65,379 incident cases (IR: 13.38), 5.44-fold higher in females than in males. IR decreased from 15.86 (95% CI: 15.50, 16.21) in 2013 to 12.35 (95% CI: 12.04, 12.67) in 2022. The decline was evident only in females, with a documented reduction in IR from 27.26 (95% CI: 26.61, 27.91) in 2013 to 20.49 (95% CI: 19.92, 21.07) in 2022 (P = 0.002). The decrease was sharper in females aged 15-54 years (IR from 37.86 (95%CI: 36.79, 38.94) in 2013 to 27.40 (95% CI: 26.44, 28.36) in 2022; P < 0.001) than in those aged ≥55 years (IR from 20.06 (95% CI: 19.13, 20.99) in 2013 to 16.56 (95% CI: 15.78, 17.35) in 2022; P = 0.034). In 2020, an out-of-trend decrease in AT incidence was documented, corresponding with the SARS-CoV-2 pandemic, with a realignment to the trend in the subsequent years.

Conclusions: A decline in AT was documented in the Veneto region in the last decade, paralleling improvement in the iodine status. The reduction was significant only among females, particularly in reproductive age.

Objective: This study aims to investigate the role of TRAb in the angiogenesis associated with Graves' disease (GD) and to elucidate its underlying mechanisms.

Methods: Human thyroid follicular epithelial cells (Nthy-ori 3-1) and human umbilical vein endothelial cells (HUVECs) were treated with the monoclonal thyroid-stimulating antibody M22 and thyroid-stimulating hormone (TSH) at various concentrations. Cell viability, migration, and tube formation were evaluated using CCK-8, wound healing, and tube formation assays, respectively. Protein expressions of TSHR receptor (TSHR) and phosphorylated AKT (p-AKT) in M22-induced HUVECs were quantified via Western blotting. Proteomic analysis was employed to identify changes in protein expression profiles and relevant signaling pathways in GD specimens. Immunofluorescence assays were conducted to detect and localize the expressions of CD34 and PROX1 in GD specimens and normal thyroid tissues.

Results: M22 stimulated the proliferation of Nthy-ori 3-1 cells and HUVECs in a dose-dependent manner, while TSH exhibited an inverted U-shaped dose-response effect. M22 also dose-dependently promoted angiogenesis, and more effectively induced tube formation in HUVECs compared to TSH, although the difference was not statistically significant. A total of 16 proteins were significantly upregulated and 24 were downregulated in M22-induced HUVECs. Notably, PROX1, the most significantly upregulated protein, is closely associated with angiogenesis. Immunofluorescence confirmed that PROX1 was significantly more expressed in thyroid tissues from GD patients compared to normal tissues adjacent to papillary thyroid cancer (PTC), and it co-localized with CD34.

Conclusion: TRAb enhances angiogenesis and upregulates PROX1 expression in HUVECs, suggesting a novel possible mechanism for goiter formation in GD.

Hypothyroidism is typically treated with levothyroxine monotherapy. However, despite normalized serum thyroid-stimulating hormone levels, 5-10% of patients continue to experience persistent symptoms, raising concerns about the adequacy of thyroxine monotherapy. Combination therapy with levothyroxine and liothyronine has been proposed as an alternative, but it presents practical challenges, including dosing complexity, the short half-life of triiodothyronine, increased monitoring requirements, and potential adverse effects. Moreover, there is no clear consensus within the medical community regarding the superiority of combination therapy over levothyroxine monotherapy, although some studies indicate potential benefits in specific patient populations. Genetic factors, such as polymorphisms in the DIO2 gene, may influence individual responses to therapy, further complicating treatment. To address the limitations of combination therapy, we propose a novel approach: TTCombo. This digital health technology delivers personalized doses of levothyroxine and liothyronine, improving treatment adherence and optimizing outcomes. By providing individualized, physiologically tailored hormone replacement, TTCombo has the potential to revolutionize hypothyroidism management and enhance patient quality of life.

Background: The types of growth hormone-secreting pituitary adenomas are diverse, we have found that there are significant differences in clinical features and prognosis between PIT-1 single-cell spectrum growth hormone adenomas and growth hormone phenotypic polyhormonal adenomas.

Methods: This study examined a cohort of 193 patients with growth hormone-secreting pituitary adenoma (GHPA), stratifying them into two groups: PIT-1 single transcription factor positive growth hormone adenoma (STF-GHPA) and Multiple transcription factor-positive growth hormone-secreting adenomas (MTF-GHPA). The objective was to compare these two groups' clinical characteristics. Within the MTF-GHPA group, we further subtyped them based on transcription factors to evaluate potential variations in clinical manifestations. Logistic regression analyses were employed to develop a risk factor model for investigating factors influencing hormone remission.

Results: There were no statistically significant differences in terms of age, gender, serum GH, and IGF-1 levels between patients diagnosed with MTF-GHPA and STF-GHPA. However, patients with MTF-GHPA exhibited a higher proportion of hypopituitarism compared to those with STF-GHPA. Furthermore, MTF-GHPA were characterized by smaller tumor size and less invasiveness, as indicated by lower Knosp classes. However, patients with MTF-GHPA have a lower rate of hormonal remission (30.8%) and more postoperative complications (31.0%), which means that STF-GHPA (hormonal remission:71.6%; postoperative complications:13.4%) has a better endocrine outcome than MTF-GHPA patients. Between the PIT-1 + SF-1+ and PIT-1 + TPIT+ subtypes within MTF-GHPA, significant differences were also observed in tumor size, endocrine outcomes, and postoperative complications. Risk factors influencing hormonal remission for GHPA included preoperative GH level, primary/recurrent, extent of resection, and transcription factor expression.

Conclusion: Co-expression of multiple transcription factors is an important factor associated with clinical behavior and endocrine outcomes in patients with GHPA.

Purpose: We aimed to investigate the value of the neutrophil-lymphocyte ratio (NLR) in predicting the all-cause and cardiovascular mortality risk of individuals with prediabetes.

Methods: A total of 11,504 prediabetic patients from the National Health and Nutrition Examination Survey (NHANES) 2003-2016 were included in the present study. Mortality and the underlying cause of death were ascertained by linkage to National Death Index records through December 31, 2019. Restricted cubic spline (RCS) analysis was conducted to visualize the association between the NLR and mortality risk. The optimal NLR cutoff value corresponding to the most significant correlation with survival outcomes was calculated by the maximally selected rank statistics method (MSRSM). Weighted multivariable Cox regression models and subgroup analyses were used to calculate HRs and 95% CIs for all-cause and cardiovascular mortality.

Results: During a median follow-up of 101 months (interquartile range, 64.0-138.0 months), 1654 (14.38%) deaths were documented, including 422 (3.67%) and 1232 (10.71%) due to cardiovascular and non-cardiovascular events, respectively. RCS regression analysis indicated that the NLR was positively associated with all-cause and cardiovascular mortality. Individuals were divided into lower (≤2.94) and higher (>2.94) NLR groups using the MSRSM. In the multivariable-adjusted model, compared with the lower NLR group, the higher NLR group had a HR of 1.63 (95% CI, 1.38-1.93) and 2.19 (95% CI, 1.55-3.01) for all-cause and cardiovascular mortality, respectively.

Conclusions: The NLR was a valuable marker for predicting all-cause and cardiovascular mortality risk in prediabetic patients.

Purpose: Pituitary apoplexy (PA) has been increasingly reported in association with both infection from and vaccination for COVID19. Our aim was to analyse the available published cases and compare the clinical characteristics in the two groups (infection vs vaccination).

Methods: We systematically reviewed the published literature for all cases of PA associated with COVID19 infection or vaccination. We also presented two cases managed at our Centre.

Results: Collectively, fortythree cases were analysed. Patients with PA after COVID19 vaccination (n = 7), compared with patients with PA after COVID19 infection (n = 36), were significantly younger (p = 0.009) and had a more abrupt onset of PA (p = 0.022), but showed a milder hormonal involvement (p = 0.008) and a lower rate of persistent hypopituitarism during follow-up (p = 0.001). Patients in the vaccination group did not have clinical risk factors for PA, although this difference did not reach statistical significance.

Conclusions: PA associated with COVID19 is a rare but clinically significant entity, although pathophysiological details of this association are lacking. Given the significantly different clinical presentation, we could speculate that PA induced by COVID19 vaccination might represent a distinct clinical entity, with different pathophysiological mechanism, compared to PA from COVID19 infection.

Background and aim: Phoenixin (PNX), a newly discovered neuropeptide associated with reproduction, has been speculated to be involved in precocious puberty. Therefore, we assessed serum PNX levels in girls with precocious puberty.

Methods: Serum phoenixin-14 (PNX-14) and phoenixin-20 (PNX-20) levels were determined in girls with central precocious puberty (CPP) and premature thelarche (PT) and in healthy controls (n = 58 per group). Spearman's correlation was used to analyze the correlations between variables. Receiver operating characteristic curves were used to evaluate the performance of PNX for the diagnosis of CPP. Significant predictors of serum PNX levels were determined using least absolute shrinkage and selection operator regression and multiple linear regression analyses.

Results: Serum PNX-14 and PNX-20 levels were significantly higher in girls with CPP than in the controls; however, no significant differences in serum PNX-14 and PNX-20 levels were observed between girls with PT and the controls. PNX-20 levels were positively correlated with basal luteinizing hormone (LH) levels, peak LH levels, the peak LH to follicle-stimulating hormone (FSH) ratio, and estradiol levels. No significant correlation was observed between PNX-14 levels and any of these parameters. Multivariate linear regression analysis revealed that PNX-20 levels exhibited the strongest correlation with peak LH/FSH values. The areas under the curve (AUCs) of PNX-14 and PNX-20 for predicting CPP were 0.628 (cut-off value, 100.12 pg/mL; sensitivity, 44.6%; specificity, 77.6%) and 0.775 (cut-off value, 360.03 pg/mL; sensitivity, 66.5%; specificity, 79.3%), respectively. When these two indicators were combined, the AUC was 0.785.

Conclusions: Serum PNX levels may be associated with precocious puberty in girls and can be used as an auxiliary CPP indicator. However, given the low sensitivity and specificity of PNX, it should not be used as a single diagnostic indicator of CPP.

Purpose: In polycystic ovary syndrome (PCOS), ectopic fat accumulation remains debatable. Therefore, intra-abdominal, hepatic, and epicardial fat were compared between PCOS women and body mass index (BMI)-matched controls and their associations with metabolic and hormonal parameters were explored. Furthermore, the performance of echocardiographic epicardial adipose tissue thickness (EATT) and hepatic steatosis measurement using transient elastography-based controlled attenuation parameter (TE-CAP) in screening abdominal visceral adipose tissue (VAT) was originally evaluated.

Methods: Women aged 18-39 years with BMI < 35 kg/m² were recruited. PCOS was defined by the Rotterdam criteria. All participants underwent clinical and laboratory exams, dual-energy X-ray absorptiometry (DXA), TE-CAP, and echocardiography. A receiver operating characteristic curve was applied to evaluate the accuracy and optimal cutoff values of TE-CAP and EATT in predicting DXA-measured VAT.

Results: The study included 35 women with PCOS and 37 controls. PCOS women exhibited higher levels of androgens, insulin resistance (IR) parameters, LDL-cholesterol, triglycerides, VAT, and EATT. VAT correlated with IR and triglycerides, whereas EATT correlated with HDL-cholesterol. In PCOS women aged 18-29, the cutoff values of CAP and EATT for VAT were 198.0 and 3.07, respectively, with CAP showing higher area under the curves (AUC). In PCOS women aged 30-39, the cutoff values were 209.5 and 3.36, respectively, with EATT showing higher AUC.

Conclusion: VAT correlates with more metabolic parameters in PCOS than TE-CAP or EATT. TE-CAP is useful for VAT screening in PCOS patients aged 18-39 years, whereas EATT is effective and outperforms CAP in those aged 30-39 years.