Endocrine最新文献

Purpose: Early diagnosis and immediate treatment of Cushing's syndrome (CS) are critical for a better prognosis but remain a challenge. However, few comprehensive reports have focused on this issue or investigated whether patient-reported manifestations are consistent with physician-assessed symptoms of CS. This study aimed to clarify the differences in patient-reported and physician-assessed manifestations of signs and symptoms of CS that prevent early diagnosis.

Methods: This single-center retrospective study included 52 patients with CS (16 with Cushing's disease and 36 with adrenal CS). Upon clinical diagnosis, medical records were used to independently review the patient-reported and physician-assessed manifestations of typical (such as purple striae and proximal myopathy) and nonspecific features (such as hirsutism and hypertension). The correlations and differences between the patient-reported and physician-assessed manifestations were then analyzed.

Results: We observed a positive correlation between the total number of manifestations of nonspecific features reported by patients and those assessed by physicians, but not for typical features. Moreover, manifestations reported by the patients were less frequent than those assessed by physicians for typical features, leading to discrepancies between the two groups. In contrast, there were no differences in most nonspecific features between the patient-reported and physician-assessed manifestations. Notably, the concordance between patient-reported and physician-assessed manifestations of typical features was not associated with urinary free cortisol levels.

Conclusion: Regardless of disease severity, patients often do not complain of the typical features of CS that are crucial for formulating a diagnosis.

Introduction: Micro- and macrovascular complications are common among persons with type 2 diabetes. Recently there has been growing interest to investigate the potential of circulating small non-coding RNAs (sncRNAs) as contributors to the development of diabetic complications. In this study we investigate to what extent circulating sncRNAs levels associate with prevalent diabetic kidney disease (DKD) in persons with type 2 diabetes.

Methods: Plasma sncRNAs levels were determined using small RNA-seq, allowing detection of miRNAs, snoRNAs, piRNAs, tRNA fragments, and various other sncRNA classes. We tested for differentially expressed sncRNAs in persons with type 2 diabetes, with DKD (n = 69) or without DKD (n = 405). In secondary analyses, we also tested the association with eGFR, albuminuria (UACR), and the plasma proteome.

Results: In total seven sncRNAs were negatively associated with prevalent DKD (all P_FDR ≤ 0.05). Including one microRNA (miR-143-5p), five snoRNAs (U8, SNORD118, SNORD24, SNORD107, SNORD87) and a piRNA (piR-019825 | DQ597218). Proteomic analyses showed that the seven sncRNAs, and especially the piRNA piR-019825, were associated with plasma levels of 24 proteins of which several have known associations with kidney function including TNF sR-I (TNFRFS1A), DAN (NBL1) and cystatin C (CST3).

Conclusion: We have identified novel small non-coding RNAs, primarily from classes other than microRNAs, that are associated with diabetic kidney disease. Our results show that the involvement of small non-coding RNAs in DKD goes beyond the already known microRNAs and also involves other classes of sncRNA, in particular snoRNAs and the piRNA piR-019825, that have never been studied before in relation to kidney function.

Purpose: Pheochromocytoma is a rare neuroendocrine tumor. Despite the low incidence, these tumors are of indisputable importance. This study aimed to analyze the management of pheochromocytoma in a referral center, with an emphasis on the minimally invasive adrenalectomy, which is the preferred therapeutic approach.

Methods: A retrospective analysis was performed on a cohort of patients diagnosed with pheochromocytoma who underwent adrenalectomy between January 2013 and December 2022. Clinical data including demographics, timelines, symptomatology, comorbidities, biochemical markers, genetic testing, surgical details, and follow-up outcomes, were collected and analyzed.

Results: The cohort included 44 patients, predominantly women (52.27%), with a median age of 53.39 years (range 13-83). Most of patients exhibited paroxysmal symptoms suggesting catecholamine excess. Documented hypertension was the most frequent (86.36%), along with glucose anomalies (40.01%) and anxiety disorder (31.82%). Genetic testing was performed in 36 (81.81%) patients and 14 (38.88%) revealed a positive result, predominantly RET pathogenic variant. Laparoscopic surgery was performed in 34 (79.07%) patients, showing significantly shorter operative time (2.5 h vs. 4.25 h, t-test p < 0,001) and fewer complications (23.53% vs 77.78%, p = 0.008). Postoperative complications occurred in 36.36% of the patients, mostly mild (grade I, 56.25%), with no mortality. SDHB pathogenic variant correlated with both recurrent and metastatic disease (p = 0.006). One-year follow-up reported 9.09% recurrence and 6.82% metastasis.

Conclusions: Adrenalectomy demonstrated a high safety and effectiveness. This study exhibited a higher rate of genetic testing referral than other studies. Despite past advances, there is still a need for further studies to establish protocols and evaluate new techniques.

Purpose: Considering the prevalence of type 2 diabetes (T2D), osteoporosis should be considered a serious complication. However, an effective tool for the assessment of low bone mass mineral density (BMD) in T2D patients is not currently available. Therefore, the aim of our study was to establish a simple-to-use risk assessment tool by exploring risk factors for low BMD in T2D patients.

Methods: This study included 436 patients with a low BMD and 381 patients with a normal BMD. Multiple logistic regression analysis was performed to evaluate risk factors for low BMD in T2D patients. A nomogram was then developed from these results. A receiver operating characteristic (ROC) curve, calibration plot, and goodness-of-fit test were used to validate the nomogram. The clinical utility of the nomogram was also assessed.

Results: Multivariate logistic regression indicated that age, sex, education, body mass index (BMI), fasting C-peptide, high-density cholesterol (HDL), alkaline phosphatase (ALP), estimated glomerular filtration rate (eGFR), and type I collagen carboxy terminal peptide (S-CTX) were independent predictors for low BMD in T2D patients. The nomogram was developed from these variables using both the unadjusted area under the curve (AUC) and the bootstrap-corrected AUC (0.828). Calibration plots and the goodness-of-fit test demonstrated that the nomogram was well calibrated.

Conclusions: The nomogram-illustrated model can be used by clinicians to easily predict the risk of low BMD in T2D patients. Our study also revealed that common factors are independent predictors of low BMD risk. Our results provide a new strategy for the prediction, investigation, and facilitation of low BMD in T2D patients.

Selpercatinib, a selective RET kinase inhibitor, has demonstrated remarkable efficacy in treating patients with advanced medullary (MTC) and differentiated thyroid cancer with RET alterations. Primary resistance to selpercatinib is a very uncommon situation, and its underlying mechanisms are poorly understood. We report the case of a 42-year-old female with advanced MTC harboring a somatic M918T RET mutation who exhibited a primary resistance to selpercatinib. Despite prompt treatment initiation after the diagnosis of progressive disease, the patient continued experiencing rapid spread of disease, characterized by the appearance of new metastatic lesions and increased tumor burden. Genomic analysis revealed no additional mutations associated with on-target or off-target resistance. This case highlights a rare clinical scenario of primary resistance to selpercatinib in advanced MTC. While secondary resistance mechanisms have been well-documented, primary resistance remains poorly understood. Possible explanations include tumor heterogeneity and activation of alternative signaling pathways that stills need to be elucidated. Emerging therapies targeting resistance mechanisms and next-generation RET inhibitors offer promising avenues for further investigation.

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.

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.

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.

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.