Endocrine最新文献

Background: High body mass index (BMI) is a risk factor for vitamin D deficiency. The rise in serum 25-hydroxyvitamin D [25(OH)D] concentrations following cholecalciferol supplementation is suboptimal, owing to adipose tissue sequestration and/or volumetric dilution. Calcifediol is a proven potent oral alternative for vitamin D supplementation, but whether BMI adversely affects its efficacy in raising 25(OH)D concentrations, is not well known.

Material and methods: Adults with serum concentrations of 25(OH)D < 30 ng/mL were recruited and stratified as normal, overweight, or obese using WHO criteria. Baseline evaluation included 25(OH)D, parathyroid hormone (PTH), and total 1,25-dihydroxyvitamin D [1,25(OH)₂D] based on BMI category (n = 883). A subset of participants was supplemented with 50 µg calcifediol (n = 193) and assessed for the rise in serum concentrations of 25(OH)D at 3- and 6-months following supplementation.

Results: Participants were stratified as obese (11.2%), overweight (32.1%), or normal weight (56.7%). There were no significant baseline differences in serum concentrations of 25(OH)D among the groups (13.1 ± 6.4 vs 12.8 ± 6.8 vs 11.6 ± 6.6 ng/mL, p = 0.62). Similarly, PTH or 1,25(OH)₂D concentrations were not different among the groups. On follow-up, 25(OH)D concentrations increased in all three groups at 3 and 6 months from baseline. The increase in 25(OH)D was 74.4 ng/mL (IQR 35.3-115.3) in obese, followed by overweight 62.2 ng/mL (18.1-98.7) and normal weight groups 47.1 ng/mL (17.5-89.7) at 3 months. 1,25(OH)₂D also increased in all groups, without any significant intergroup differences (p > 0.05).

Conclusion: BMI does not impede the rise in 25(OH)D concentrations following supplementation with calcifediol in young adults with vitamin D deficiency.

Purpose: Adropin is an emerging metabolic hormone that has a role in regulating energy homeostasis. The present study aimed to explore the impact of adropin on redox homeostasis and its possible role in testicular functions in adult mouse testis.

Methods: Western blot, flow-cytometry, and TUNEL assay were performed to explore the impact of intra-testicular treatment of adropin (0.5 μg/testis) on testicular functions of adult mice. Hormonal assay was done by ELISA. Further, antioxidant enzyme activities were measured.

Results: Adropin treatment significantly increased the sperm count and testicular testosterone by increasing the expression of GPR19 and steroidogenic proteins. Also, adropin treatment reduced the oxidative/nitrosative stress by facilitating the translocation of NRF2 and inhibiting NF-κB into the nucleus of germ cells. Enhanced nuclear translocation of NRF2 leads to elevated biosynthesis of antioxidant enzymes, evident by increased HO-1, SOD, and catalase activity that ultimately resulted into declined LPO levels in adropin-treated mice testes. Furthermore, adropin decreased nuclear translocation of NF-κB in germ cells, that resulted into decreased NO production leading to decreased nitrosative stress. Adropin/GPR19 signaling significantly increased its differentiation, proliferation, and survival of germ cells by elevating the expression of PCNA and declining caspase 3, cleaved caspase 3 expression, Bax/Bcl2 ratio, and TUNEL-positive cells. FACS analysis revealed that adropin treatment enhances overall turnover of testicular cells leading to rise in production of advanced germ cells, notably spermatids.

Conclusion: The present study indicated that adropin improves testicular steroidogenesis, spermatogenesis via modulating redox potential and could be a promising target for treating testicular dysfunctions.

Background: Our study aimed to investigate the prevalence and demographic characteristics of immune checkpoint inhibitor-associated hypophysitis (ICI-hypophysitis) using data from the FAERS, and the risk factors of prognosis were explored.

Methods: In this retrospective study, all cases of newly-diagnosed hypophysitis associated with FDA approved ICIs from 1st January 2007 to 31st December 2022 were accumulated using FAERS. Demographic data including age, sex, body weight, the prognosis of cases, and other co-occurred endocrinopathies induced by ICIs were analyzed and compared between different subgroups of immunotherapy.

Results: The reporting frequency of ICI-hypophysitis was 1.46% (2343/160089). Patients on the combination therapy had higher risk of hypophysitis reporting, followed by anti-CTLA-4 agent compared with other monotherapies (p < 0.001). Male subjects displayed higher reporting risk of ICI-hypophysitis (p = 0.015). Patients on anti-PD-1 therapy or the combination therapy showed higher occurrence rate of type 1 diabetes (anti-PD-1 vs. anti-PD-L1 vs. anti-CTLA-4 vs. combination therapy, 4.2% vs. 0.7% vs. 0.3% vs. 8.4%, p < 0.001). The occurrence rate of new-onset thyroid diseases in patients receiving combination therapy was higher than anti-PD-1 monotherapy (12.3% vs. 8.4%, p = 0.010). Elder age, lung cancer, and renal cancer emerged to be positively associated with severe clinical outcomes [>65 years, OR 1.042, 95%CI (1.022-1.063), p < 0.001; lung cancer, OR 1.400, 95%CI (1.019-1.923), p = 0.038; renal cancer, OR 1.667, 95%CI (1.153-2.412), p = 0.007]. Anti-CTLA-4 monotherapy was discovered to be a protective factor of severe outcomes [OR 0.433, 95%CI (0.335-0.558), p < 0.001]. Female sex and co-occurrence of ICI-related diabetes exhibited lower risk of death [female, OR 0.571, 95%CI (0.361-0.903), p = 0.017; diabetes, OR 0.090, 95%CI (0.016-0.524), p = 0.007].

Conclusions: ICI-induced hypophysitis is male-predominant irAE, most commonly seen in patients on anti-CTLA-4 mono- or combination therapy. Awareness among clinicians is critical when patients with elder age, lung or renal cancer develop hypophysitis, which indicates poor clinical outcomes. Female sex, anti-CTLA-4 monotherapy and co-occurrence of ICI-related diabetes are protective risk factors for poor prognosis.

Diabesity is a condition where an individual has both diabetes and obesity, which can lead to severe complications including cardiovascular disease, a leading cause of mortality. Recently, cancer has become a leading cause of excess hospitalizations, and both diabetes and obesity are associated with a higher risk of developing several types of cancer. In this review, we propose that chronic stress significantly increases this association. Managing diabetes and obesity is challenging as they both cause significant distress. The relationship between stress and cancer is interconnected, with anxiety and depression being common in cancer patients. Cancer diagnosis and treatment can cause lasting changes in the body's neuroendocrine system, with stress causing an excessive release of catecholamines and prostaglandins in patients undergoing cancer surgery, which promotes the spread of cancer to other parts of the body. Furthermore, stress could significantly increase the risk of cancer in patients with diabetes, obesity, or both.

Objectives: To assess the efficacy and tolerability of iGlarLixi-a novel, fixed-ratio, soluble combination of insulin glargine and lixisenatide-for the treatment of type 2 diabetes (T2D).

Methods: The PubMed, Embase, Cochrane Library and ClinicalTrials.gov databases were searched from inception to November 15, 2023 to identify randomized controlled trials (RCTs) comparing iGlarLixi with a placebo or any other antidiabetic agent in adults with T2D. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated to evaluate the outcomes.

Results: A total of 10 trials enrolling 6071 T2D patients were included. Compared with placebos or other antidiabetic agents, iGlarLixi exerted beneficial effects on changes in HbA1c, the percentage of patients who achieved an HbA1c < 7%, the percentage of patients who achieved an HbA1c < 6.5%, the percentage of patients who achieved an HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes, changes in fasting plasma glucose, and changes in self-measured plasma glucose. Regarding safety, iGlarLixi did not increase the incidence of severe hypoglycemia or serious adverse events but did increase the incidence of gastrointestinal adverse events, symptomatic hypoglycemia, and adverse events (e.g., nausea, vomiting, diarrhea).

Conclusions: iGlarLixi showed improved efficacy and safety in patients with T2D. Additional large, multicenter RCTs are warranted to obtain deeper insights into the efficacy and safety of iGlarLixi, thereby providing guidance for clinical treatment decisions.

Purpose: In a patient with elevated thyroid stimulating hormone (TSH, >50 µIU/ml) with sellar mass, it is crucial to differentiate isolated pituitary hyperplasia (IPH) from primary hypothyroidism coexisting with nonfunctioning pituitary adenoma (PHCNFPA) pre-operatively to avoid unwarranted surgery in the former condition. Here, we describe patients having pituitary mass/enlargement with markedly elevated TSH (>50 µIU/ml) and attempt to find the differentiating features between IPH and PHCNFPA.

Methods: This is a retrospective study conducted at a tertiary care center. Case records of patients presenting between January 2020 and December 2022 with elevated TSH (>50 µIU/ml) for whom magnetic resonance imaging (MRI) of the sella was available were reviewed. Demographic details, symptomatology, clinical examination findings, thyroid function tests, data on pituitary hormonal excess and deficiencies, MRI findings, and details regarding levothyroxine supplementation were noted. Based on the final diagnosis, the patients were categorized into two groups: PHCNFPA and IPH.

Results: Five and 11 patients were diagnosed with PHCNFPA and IPH, respectively. The median (IQR) age at presentation of patients with PHCNFPA was significantly higher than that of IPH patients [37 (28-60.5) vs. 21 (10-21.5) years, p: 0.002]. A longer duration of hypothyroid symptoms was noted in the IPH group whereas visual field defects and corticotropin deficiency were more frequent and the pituitary lesion size was greater in PHCNFPA. Thyroid function tests were not different between the two groups. The pituitary enlargement in IPH was initially an increase in pituitary height that progressed to symmetrical nipple-, dome- or tent-shaped enlargement. Besides this characteristic enlargement pattern, isointense appearance on T1-weighted and T2-weighted images, homogeneous contrast enhancement, and prompt regression of pituitary lesion with levothyroxine replacement were characteristic of IPH whereas heterogeneous enhancement, cystic/hemorrhagic change, and ≥Knosp III invasion were characteristic of PHCNFPA. Peripheral rim enhancement and Knosp I-II parasellar extension were not uncommon in patients with IPH and did not distinguish it from PHCNFPA.

Conclusions: The present study reports the radiological evolution of IPH and a unique series of PHCNFPA along with the distinguishing characteristics between them.

Background: Despite several epidemiological studies reporting a significant association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and the risk of diabetes mellitus, the results remain controversial. In this systematic review and meta-analysis, we aimed to summarize the existing evidence from published observational studies and evaluate the dose-response relationship between adherence to the DASH diet and diabetes mellitus risk.

Methods: We performed a systematic search for relevant articles published up to September 2023 using electronic databases of PubMed, Embase, Scopus, and China National Knowledge Infrastructure (CNKI). A random-effects model was applied to calculate the combined relative risks (RR) with 95% confidence intervals (CIs) for the highest compared to the lowest categories of DASH score in relation to diabetes mellitus risk. Heterogeneity among the included studies was assessed using the Cochran's Q test and I-squared (I²) statistic. Literature search, study selection, data extraction, and quality assessment were performed by two independent reviewers.

Results: Fifteen studies involving 557,475 participants and 57,064 diabetes mellitus cases were eligible for our analyses. Pooled analyses from included studies showed that high adherence to the DASH diet was significantly associated with a reduced risk of diabetes mellitus (RR: 0.82; 95% CI: 0.76-0.90, P < 0.001). Moreover, the dose-response meta-analysis revealed a linear trend between adherence to the DASH diet and diabetes mellitus (RR:0.99; 95%CI: 0.97-1.02, P_{dose-response} = 0.546, P_nonlinearity = 0.701). Subgroup analyses further revealed a significant inverse association between adherence to the DASH diet and diabetes mellitus risk in case-control studies (RR: 0.65; 95%CI: 0.29-1.43, P < 0.001), with a marginal inverse association in cohort studies (RR:0.83; 95%CI: 0.76-0.91, P < 0.001). Additionally, we conducted analyses separately by comparison and found a significant inverse association between DASH diet and diabetes mellitus risk in T3 vs T1 comparison studies (RR = 0.74; 95%CI: 0.64-0.86, P = 0.012).

Conclusion: The findings of this study demonstrate a protective association between adherence to the DASH diet and risk of diabetes mellitus. However, further prospective cohort studies and randomized controlled trials are needed to validate these findings.

Aim: The C-reactive protein to albumin (CRP/Alb) ratio has emerged as a novel biomarker for various inflammatory diseases. This study aimed to evaluate the association between the CRP/Alb ratio and incident metabolic syndrome (MetS) with a large-sample, community-based Korean cohort over a 12-year follow-up period.

Materials and methods: Among 10,030 participants, a total of 6205 participants aged 40-69 years without MetS were selected from the Korean Genome and Epidemiology Study (KoGES). The baseline CRP/Alb ratio was divided into quartiles. The definition of newly developed MetS was the one proposed by the 2009 Joint Interim Statement of Circulation. Hazard ratios (HRs) with 95% confidence intervals (CIs) for incident MetS were calculated using multivariable Cox proportional hazards regression models after adjusting for potentially confounding variables.

Results: During the 12-year follow-up period, MetS developed in 2535 subjects (40.9%, 2535/6205) with an incidence rate of 5.6-11.9 (over 2 years). Compared to the reference first quartiles, the HRs (95% CIs) of incident MetS in the second, third, and fourth quartiles increased in a dose-response manner. Compared to the reference quartile, the HRs (95% CIs) of the incidence of MetS for the second, third, and fourth quartiles of CRP/Alb ratio were 1.12 (0.99-1.27), 1.24 (1.11-1.40), and 1.51 (1.34-1.69) after adjusting for age, sex, smoking status, alcohol intake, physical activity, total cholesterol, mean arterial pressure, HOMA-IR, and total energy intake.

Conclusions: High CRP/Alb ratio at baseline may be a useful surrogate indicator of future incident MetS.

Background: Prostate cancer patients, undergo imaging procedures, with [⁶⁸Ga]Ga-PSMA-11 PET/CT (prostate-specific membrane antigen based positron emission tomography/computed tomography) utilized for primary and secondary staging. PSMA thyroid incidentalomas (PTI) are discovered in the thyroid gland while imaging prostate cancer patients with [⁶⁸Ga]Ga-PSMA-11 PET/CT.

Aims: The aim of the study was to determine the clinical significance of PTIs detected on [⁶⁸Ga]Ga-PSMA-11 PET/CT. Another goal was to identify a possible threshold for the maximum standardized uptake value (SUVmax), above which a malignant growth could be suspected.

Study design: A retrospective cross-sectional study.

Methods: 769 patients with prostat cancer who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT scans in the nuclear medicine department of a tertiary care hospital between January 2020 and December 2022 were retrospectively screened in this study. We analyzed 67 patients in whom PTI was detected. Patients who exceeded the inclusion criteria had their thyroid ultrasonography and ultrasonography -guided fine needle aspiration findings analyzed.

Results: PTI was discovered in 67 patients (8%). 42 patients who met the inclusion and exclusion criteria were included in the study. Of the 4 malignant patients (9.5%) in the study population, 2 were classified as TIRADS 3 and 2 were classified as TIRADS 4. The cut-off SUVmax value was found to be 5.6. With 100% sensitivity and 47.37% specificity, a cutoff SUVmax of 5.3 was determined through receiver-operator characteristic analysis in order to predict malignant cytology.

Conclusion: PTI is a significant clinical finding; most of diffuse and focal uptakes are frequently related to benign diseases. Each center should establish its own a possible SUVmax cut-off over which a malignant lesion should be suspected.

Background: The TNFRSF9 molecule is pivotal in thyroid carcinoma (THCA) development. This study utilizes Pathomics techniques to predict TNFRSF9 expression in THCA tissue and explore its molecular mechanisms.

Methods: Transcriptome data, pathology images, and clinical information from the cancer genome atlas (TCGA) were analyzed. Image segmentation and feature extraction were performed using the OTSU's algorithm and pyradiomics package. The dataset was split for training and validation. Features were selected using maximum relevance minimum redundancy recursive feature elimination (mRMR_RFE) and modeling conducted with the gradient boosting machine (GBM) algorithm. Model evaluation included receiver operating characteristic curve (ROC) analysis. The Pathomics model output a probabilistic pathomics score (PS) for gene expression prediction, with its prognostic value assessed in TNFRSF9 expression groups. Subsequent analysis involved gene set variation analysis (GSVA), immune gene expression, cell abundance, immunotherapy susceptibility, and gene mutation analysis.

Results: High TNFRSF9 expression correlated with worsened progression-free interval (PFI) and acted as an independent risk factor [hazard ratio (HR) = 2.178, 95% confidence interval (CI) 1.045-4.538, P = 0.038]. Nine pathohistological features were identified. The GBM Pathomics model demonstrated good prediction efficacy [area under the curve (AUC) 0.819 and 0.769] and clinical benefits. High PS was a PFI risk factor (HR = 2.156, 95% CI 1.047-4.440, P = 0.037). Patients with high PS potentially exhibited enriched pathways, increased TIGIT gene expression, Tregs infiltration (P < 0.0001), and higher rates of gene mutations (BRAF, TTN, TG).

Conclusions: The GBM Pathomics model constructed based on the pathohistological features of H&E-stained sections well predicted the expression level of TNFRSF9 molecules in THCA.