Minerva endocrinology最新文献

Background: Serum uric acid (UA), the end product of purine metabolism, has been implicated in metabolic and cardiovascular diseases. While obesity, particularly visceral fat accumulation, is related with hyperuricemia, limited studies have explored the association between serum UA levels and the visceral-to-subcutaneous fat ratio as a novel marker of cardiometabolic risk. This study investigates the relationship between serum UA levels and abdominal fat distribution, focusing on the visceral-to-subcutaneous fat ratio in Korean men.

Methods: This retrospective, cross-sectional study analyzed 5114 male participants who underwent serum UA measurement and abdominopelvic computed tomography (CT) as part of health examinations from 2014 to 2019. Visceral and subcutaneous fat areas were quantified using CT imaging, and the visceral-to-subcutaneous fat ratio was calculated. Participants were stratified into quartiles based on serum UA levels. Univariate and multivariate analyses were performed to assess the association between serum UA levels and abdominal fat area and visceral fat/subcutaneous fat ratio were evaluated using univariate and multivariate analyses.

Results: Higher serum UA levels were significantly associated with increased visceral fat area, subcutaneous fat area, and visceral-to-subcutaneous fat ratio in both univariate and multivariate analyses. Participants in the highest UA quartile demonstrated the greatest visceral fat accumulation and the highest visceral-to-subcutaneous fat ratios. Multivariate analyses revealed that the association between serum UA and the visceral-to-subcutaneous fat ratio remained significant after adjusting for covariates.

Conclusions: This study demonstrated a positive correlation between serum UA levels and both visceral fat area and subcutaneous fat areas in Korean men. Furthermore, higher serum UA levels were positively correlated with the visceral-to-subcutaneous fat ratio, offering insights into its potential contribution to elevated cardiometabolic and cardiovascular risk.

Premature ovarian insufficiency (POI) is a critical condition affecting young women before the median age of menopause and consisting of spontaneous oligo-amenorrhea for at least four months associated with follicle stimulating hormone (FSH) levels ≥25 UI/L detected before 40 years of age. Several causes like genetic abnormalities, autoimmune diseases, drugs and/or pelvic surgery may favor this condition that is associated with a deeper clinical impact on women's health compared to physiological menopause. Specifically, cardiovascular and musculoskeletal systems as well as brain could be especially affected by the early loss of ovarian hormones. Therefore, appropriate treatment is necessary to adequately narrow the biological gap with the average age of menopause. Hormone replacement therapy (HRT) is the treatment of choice, regardless of the presence of neurovegetative symptoms. Transdermal high dosage of natural estradiol is generally preferred to guarantee the preservation of cardio-metabolic and bone health. When contraception is required, oral estroprogestins (EPs) maybe considered. A referral to reproductive experts for fertility preservation techniques should be considered case by case.

Background: Diabetic kidney disease (DKD) is a common and serious complication of diabetes mellitus, marked by a multifactorial pathogenesis and the absence of sensitive diagnostic biomarkers. Identifying novel molecular targets and therapeutic options is essential to improve early diagnosis and treatment outcomes.

Methods: To uncover potential biomarkers and therapeutic candidates, we performed an integrated genomic analysis using microarray and RNA-seq datasets from the Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA) databases. Differentially expressed genes (DEGs) were identified and subjected to protein-protein interaction (PPI) network analysis. Key genes were further explored through virtual screening of an FDA-approved compound library using molecular docking techniques. Drug-likeness was assessed via Lipinski's rule of five.

Results: A total of 40 DEGs were identified, among which ISCU (downregulated; involved in iron-sulfur cluster biogenesis) and AP1S2 (upregulated; associated with vesicular trafficking) emerged as potential biomarkers. PPI analysis revealed their involvement in critical DKD-related pathways, such as extracellular matrix remodeling and oxidative stress. Virtual screening identified six FDA-approved compounds with high binding affinity (≤-7.96 kcal/mol) to ISCU, notably ZINC000001576020, all of which complied with Lipinski's rule.

Conclusions: This in-silico study nominates ISCU and AP1S2 as candidate diagnostic biomarkers for DKD and identifies computationally prioritized inhibitors targeting ISCU. These findings require experimental validation but provide a molecular framework for precision diagnosis and therapeutic development. These findings offer new molecular insights that could inform precision diagnosis and personalized treatment strategies for diabetic kidney disease.

Glucagon-like peptide-1 (GLP-1) receptor agonists are used in diabetes management and can have a potential application in cancer therapy. While their involvement in cancer treatment is still being studied, recent research suggests they may have benefits in cancer therapy. A comprehensive literature search was conducted using search engines like Google Scholar, Scopus, and PubMed to explore the effects of GLP-1 receptor agonists in tumor suppression and regression. Mostly in-vitro studies on GLP-1 receptor agonists have shown promising effects in inhibiting cancer cell growth, inducing apoptosis, and modulating angiogenesis and have been reported to be beneficial in colon, prostate, gall bladder, ovarian, and endometrial carcinomas. However, concerns have been raised about potential tumorigeneses, as liraglutide has been reported to be associated with increased incidence of breast, thyroid, and pancreatic carcinomas. Whereas combination therapy of exendin-4 with gemcitabine may be beneficial in pancreatic cancer. GLP-1 receptor agonists may have significant potential in oncology, due to their various mechanisms of action and favorable safety profiles. Limited clinical application, lack of awareness, and the need for further research are current barriers. Future studies should focus on optimal dosage, patient selection, and interdisciplinary collaboration to integrate GLP-1 receptor agonists into routine oncological practice for improved outcomes, warranting large randomized clinical trials in this field.

Hypophosphatasia (HPP) is a rare and highly variable genetic disorder of metabolism characterized by markedly reduced serum alkaline phosphatase (ALP) activity as a result of defective production of tissue-non-specific alkaline phosphatase (TNSALP). HPP is known to affect fetuses in utero and also neonates, children, and adults. Severity ranges significantly, from lethal to mild and clinical presentations include rickets or osteomalacia, osteoporosis, respiratory failure and seizures. Odontohypophosphatasia has only dental manifestations. Low total ALP in serum is the hallmark of HPP, whereas elevated serum concentrations of pyridoxal-5-phosphate and phosphoethanolamine levels represent sensitive and specific biomarkers for HPP. Several pathognomonic radiographic changes are suggestive of HPP. Recently, asfotase alfa, a bone targeted recombinant TNSALP has been used to treat HPP with significant success, highlighting the importance of early diagnosis and intervention. This review describes our current knowledge of HPP, reporting on the epidemiology, classification, clinical presentation and main diagnostic features of the disease, as well as more recent therapeutic approaches.

Background: The vast majority of erectile dysfunction (ED) treatments are currently symptomatic and do not influence disease progression. Regenerative medicine may potentially reverse or stop the progression of complicated ED by restoring erectile capacity. We aimed to evaluate potential safety and effectiveness and the clinical correlates of platelet function before platelet-rich plasma (PRP) injection in men with vascular ED unresponsive to phosphodiesterase-5 inhibitors (PDE-5is).

Methods: A number of 150 patients with vascular ED were enrolled in an open-label, single arm, multicenter, prospective, interventional, non-randomized study. After 1-month pharmacological washout from PDE-5is, the 5-item International Index of Erectile Function (IIEF-5) questionnaire was administered and dynamic penile duplex ultrasound (d-PDU) was performed. Patients then underwent intracavernous PRP injection. One month after treatment, IIEF-5 and d-PDU were evaluated. Primary aim of the study was to assess efficacy and safety of PRP treatment by evaluating the proportion of patients achieving minimal clinically important differences (MCID) in the IIEF-5 questionnaire. Secondary endpoint was to determine whether MPV could correlate with improvement in d-PDU parameters.

Results: Most patients (80%) had a significant improvement in ED symptoms (IIEF-5 Score: 12±2.6 vs. 19±3.0; P<0.0001) and in PSV (32±3.5 cm/s vs. 42±7.6 cm/s; P<0.0001) after d-PDU evaluation. The ROC curve analysis showed a significant accuracy (72.1%, CI: 64.0-80.2, P≤0.0001) for MPV in identifying men clinically responding to PRP with favorable MCID≥5 at 1 month follow-up. The MPV<8.95 fL was identified as the best predictor of success rate with a sensitivity of 90% and a specificity of 54.1%.

Conclusions: This study provides the first evidence that PRP could represent an effective and safe option for patients poorly responding to PDE-5is. MPV higher than 8.95 fL may identify patients with poor response to treatment that might benefit of successive re-challenge with PRP.

Background: Acromegaly (ACRO) is a chronic rare disease caused by a pathological increase in growth hormone (GH) secretion. In ACRO an increased prevalence of psychiatric disorders has been demonstrated, in particular depressive disorders, associated to a significant deterioration of the quality of life, independently from disease control. In addition, anger feelings, often detected in subjects affected by chronic disease, have not yet been investigated, in pituitary patients. Aim of the study was to evaluate in ACRO patients with a controlled disease, compared to patients suffering for non-functioning pituitary adenoma (NFPA) 1) prevalence of depressive and anxiety disorders, and 2) expression and control of anger feelings. The second purpose was to evaluate the correlation between psychiatric disorders, anger feelings and the "activity of disease," that is active ACRO that needs medical treatment versus cured ACRO.

Methods: This is a cross-sectional, observational study, which included 53 patients enrolled at the Neuroendocrinology Outpatient Clinic of "Città della Salute e della Scienza di Torino". Of the 53 enrolled patients (24 male and 29 female), 34 had ACRO, while 19 had NFPA, as control group. All subjects went through the following self-administered, validated psychological tools: SF-36 (Short-Form 36 Item); STAXI - 2; BDI-II (Beck Depression Inventory -II); STAI (State-Trait Anxiety Inventory). Only in ACRO group, patients completed PASQ (Patient-Assessed Acromegaly Symptom Questionnaire) and ACROQoL (Acromegaly Quality of Life Questionnaire) questionnaires. In addition 45 patients underwent the International Neuropsychiatric Short Interview to assess the presence of a psychiatric disorder. For each patient, anthropometric, clinical and biochemical information was collected.

Results: A higher frequency of psychiatric anxiety and mood disorders (not reported in the medical history) was observed in patients with controlled ACRO. In the SF-36 questionnaire, a lower score was found in the "emotional well-being" items in ACRO compared to NFPA, particularly in those with cured ACRO. Cured acromegalic patients had a worse score in "emotional well-being," "energy/fatigue" and "general health" items. Finally, subjects in ACRO group obtained a lower score in the ability to control anger and a higher score in the physical expression of it, demonstrating a tendency to more aggressive behaviors.

Conclusions: This study showed that psychiatric illness is often hidden in patient suffering from ACRO, despite normal IGF-I levels. Recovery from the disease do not necessarily improve QoL scores, in fact in cured patients the quality of life can be even worse.

Hidradenitis suppurativa (HS) is a chronic inflammatory, immune-mediated, debilitating skin disease, characterized by subcutaneous nodules, with a still not clear pathophysiology. Although the prevalence is rather low (about 1% in Europe), its clinical complications, as well as the disabling symptomatology, make it necessary multidisciplinary therapeutic approaches. Not recently several authors described the involvement of the well-known gut-skin axis in both pathogenesis and progression of dermatological diseases. In particular, a high frequency of intestinal disorders (such as irritable bowel syndrome and inflammatory bowel disease) has been reported in HS patients, leading to speculate the existence of a relationship between such gut and skin diseases. The keystone in this relationship seems to be an impairment of the physiological gut mucosal barrier structure, resulting in the so-called leaky gut. The leaky gut, thus, might be responsible for a dietary compound-caused activation of the local immune system, with consequent trigging of both local and systemic inflammation, resulting in exacerbation of skin symptoms in HS patients. The current literature suggests the use of a low fermentable, oligo-, di, mono-saccharides and polyols (FODMAP) diet as a valid nutritional strategy in leaky gut. In light of this, we want to evaluate and consider the potential use of low-FODMAP diet in HS patient.

Background: The clinical management of repeatedly non-diagnostic thyroid nodules (RNDNs) via fine needle aspiration cytology (FNAc) is a matter of debate because current recommendations and clinical practice are not based on high-quality evidence. Our purpose was to characterize RNDNs and evaluate their clinical management in our centers.

Methods: This retrospective observational study included 319 consecutive patients who underwent ultrasound (US-)guided FNAc in two Italian academic hospitals between 2016 and 2020 and had previous cytology non-diagnostic result (TIR1). Clinical management and anamnestic data were retrieved, and the cytological specimens and US exams were double-blindly reviewed by two pathologists and endocrinologists.

Results: The risk of RNDNs was significantly greater in hypoechogenic nodules (Odds Ratio [OR]=1.727, 95% confidence Interval [CI]: 1.090-2.735, P=0.02) and lower in nodules that had been recognized less than 10 years before (OR=0.349, 95% CI: 0.153-0.796, P=0.01). Clinicians chose to directly perform surgery on multinodular, intermediate-risk nodules (as per AACE/AME guidelines and EUTIRADS class 4), while larger (P<0.0001) and uninodular (P=0.03) lesions were further investigated with a third FNAc. Only 16 RNDNs were sent to surgery. Twelve nodules turned out to be benign goiters with a high rate of fibrosis, while only 3 were definitively malignant. However, retrospectively, all the malignant ones exhibited higher-risk ultrasound features and had an undetermined result (TIR3B) at the third cytological evaluation.

Conclusions: In a real-life context, RNDNs exhibited a very low rate of malignancy and were mostly long-known goiters with regressive changes, as suggested by a hypoechoic pattern. Consequently, a clinical-US surveillance approach could be cautiously hypothesized, while greater attention could be given to larger and higher-US-risk (both as EUTIRADS 4-5 and AACE/AME intermediate- and high-risk classes) nodules.