Acromegaly is associated with increased risk of diffuse or nodular goiter and possibly of thyroid cancer. The aim of this study was to verify whether these findings persist in the current scenario of improved disease control. A two-steps protocol was carried out:. In the first (retrospective), clinical and laboratory data (including 969 IGF-I measurements), and the frequency of thyroid cancer were recorded for 92 acromegaly patients over a 28-year period. The annual control percentage was defined as the average of the ratios between each of the 969 IGF-I measurements over the total follow-up period and the respective upper age limit (IGF-I/ULN) less than 1.Acromegaly activity was determined at the last visit. In the second step (cross-sectional), 74 of the 92 acromegaly patients underwent thyroid ultrasound and were subjected to a two-stage cluster analysis, with the aim of grouping them into homogeneous clusters. 70% of the 92 patients had inactive disease, with a median control rate of 50%, with four cases of thyroid cancer (4.3%), only one in a patient with active disease. Two-thirds of the 74 patients (evaluated by ultrasound) had nodules, and 27% had diffuse thyroid hyperplasia. Three clusters were segregated with high significant differences in sex and echotextural alterations (p < 0.0001 in both cases). Age, number of nodules, thyroid volume and follow-up time were similar between the clusters. No inherent thyroid changes were apparently identified in a large cohort of acromegaly patients. Better control during follow-up may attenuate thyroid manifestations in acromegaly.
In recent years, the key role of the gut microbiota (GM) in the diagnosis, prognosis, and treatment of thyroid cancer (TC) has become increasingly clear. This review examines the complex interactions between gut dysbiosis and the occurrence and development of TC; focuses on changes in specific microbiotas that are directly related to tumor stage, lymph node metastasis, and drug resistance; and evaluates the potential of these microbiotas as novel biomarkers for treating TC. To elucidate the underlying molecular mechanisms, this review systematically evaluates the pathways through which the GM regulates the host immune response through metabolites (such as short-chain fatty acids and lipopolysaccharides) and reveals the core role of chronic inflammation in the formation of the microenvironment and the immune escape of TC. Furthermore, by exploring the effects of the microbiota on the hypothalamic-pituitary-thyroid axis and the peripheral thyroid hormone conversion, this review elucidates the profound role of the GM in the regulation of thyroid homeostasis. Based on this evidence, this review highlights the clinical applications of intervention strategies targeting the microbiota, including probiotics, dietary adjustments, and fecal microbiota transplantation, as adjuvant approaches for TC management.
Endolysosomal two-pore channels (TPCs) are non-selective cation channels that control the release of Ca2+ and Na+ from the endolysosomal lumen. TPCs also reportedly play a role in autophagy. Interestingly, autophagy regulates bone cell differentiation and function. This study aimed to provide an in-depth insight into TPC2's action in the autophagy pathway to control osteoblast differentiation and function. Primary human mesenchymal stem cells (hMSCs) and human osteoblast-like cells (Saos-2) were used to assess osteoblastogenesis and bone mineralization, respectively. MSCs were treated with different pharmacological TPC2 inhibitors including naringenin, tetrandrine, MT-8 and SG-094 during their differentiation process. Finally, formation of osteoblasts and in vitro bone mineralization were evaluated by alkaline phosphatase, alizarin red S and Von Kossa staining. Western blot analysis was performed to investigate the expression of autophagy-related molecules. The inhibition of TPC2 activity stimulates osteoblast differentiation from hMSCs and bone mineralization by Saos-2 cells. Interestingly, TPC2 inhibition reduces beclin-1 and LC3-II expression while that of the mammalian target of rapamycin (mTOR), the master regulator of autophagy, increases. Inhibition of mTOR activity by rapamycin reverses osteoblast differentiation induced by TPC2 inhibitor SG-094. Inhibition of TPC2 channel activity increases osteoblast differentiation and bone mineralization in vitro and interferes with the completion of autophagy, upregulating phosphorylated mTOR.
Dyslipidemias are highly prevalent metabolic disturbances and represent a major driver of atherosclerotic cardiovascular disease. Beyond primary forms, numerous endocrine diseases induce secondary dyslipidemias that substantially modify lipid metabolism and contribute to cardiometabolic risk. This Position Statement of the Nutrition Hormones and Metabolism Club of the Italian Society of Endocrinology (SIE) aims to provide an updated, evidence-based synthesis of the pathophysiology, biochemical profile, and clinical impact of dyslipidemias associated with endocrine disorders. A comprehensive review of current literature was performed, integrating epidemiological, mechanistic, and clinical data on lipid alterations across major endocrine diseases. Expert consensus was used to interpret evidence and formulate recommendations for clinical practice. Distinct and disease-specific dyslipidemic patterns were identified across conditions involving the hypothalamic-pituitary, thyroid, adrenal, gonadal, and GH/IGF-1 axes. Disorders such as acromegaly, growth hormone deficiency, hypothyroidism, hyperthyroidism, Cushing's syndrome, male and female hypogonadism, congenital adrenal hyperplasia, and polycystic ovary syndrome exhibit characteristic lipid abnormalities driven by hormonal dysregulation. These alterations contribute to increased cardiometabolic risk yet are frequently underrecognized and suboptimally managed. Early identification and tailored intervention may significantly improve outcomes. Endocrine-related dyslipidemias represent a clinically relevant but often overlooked contributor to cardiovascular risk. By summarizing current evidence and expert perspectives, this Position Statement aims to support clinicians in improving diagnosis, risk stratification, and management of lipid disorders associated with endocrine diseases, fostering a multidisciplinary approach to cardiometabolic prevention.
BACKGROUND: Prevention of progression into type 2 diabetes (T2D) in patients with prediabetes is a key goal of obesity management. In SURMOUNT-5, once weekly tirzepatide at the maximum tolerated dose (MTD 10 mg or 15 mg) compared with semaglutide (MTD 1.7 mg or 2.4 mg) resulted in significantly greater body weight reduction in adults living with obesity without T2D. PURPOSE: Assess changes in glycemia outcomes with tirzepatide (MTD 10 mg or 15 mg) compared with semaglutide (MTD 1.7 mg or 2.4 mg) in participants with obesity and prediabetes from SURMOUNT-5. METHODS: Participants (N = 425) with baseline prediabetes, defined as having ≥ 1 fasting lab-based value of either FSG 100–125 mg/dL or HbA1c 5.7–6.4%, were included in this analysis. Change from baseline in HbA1c, proportion of participants achieving normoglycemia (i.e., HbA1c < 5.7% and FSG < 100 mg/dL), percent change from baseline in body weight, fasting insulin, estimates of insulin sensitivity (HOMA2-IR), and proportion of participants achieving body weight reduction thresholds (≥ 10% to ≥ 30%) at Week 72 were assessed using MMRM or logistic regression for categorical measures using the efficacy analysis set. RESULTS: Mean baseline age was 47 years, 63% were female, BMI was 40 kg/m2, and HbA1c was 5.86%. At Week 72, mean HbA1c reduction was significantly greater with tirzepatide vs semaglutide (-0.60% vs -0.48%; estimated treatment difference [ETD; 95% CI] -0.12% [−0.18, −0.06]; p < 0.001). A greater proportion of tirzepatide-treated participants reverted to normoglycemia (89.9%) vs semaglutide (76.2%). Mean percent body weight reduction was significantly greater with tirzepatide (−21.5% vs -14.5%; ETD −7.1% [−9.1, −5.0]; p < 0.001). Greater improvements in fasting insulin and HOMA2-IR were observed with tirzepatide vs semaglutide (p < 0.001). CONCLUSION: In this post hoc analysis of SURMOUNT-5, a greater proportion of tirzepatide-treated participants with obesity and prediabetes at baseline reverted to normoglycemia compared with semaglutide. Greater improvements in glycemia, estimates of insulin sensitivity and body weight were also observed with tirzepatide.
Gynecomastia, defined as thebenign proliferation of male breast glandular tissue, is a common condition in both adolescence and adulthood, often associated with physical discomfort and psychological distress. Despite its high prevalence, clinical management is frequently inconsistent and lacks standardized, evidence-based recommendations. The Italian Society of Andrology and Sexual Medicine (SIAMS) convened a multidisciplinary expert panel to develop updated clinical practice guidelines for the evaluation and management of gynecomastia. Recommendations were formulated based on a systematic review of the available literature and developed through expert consensus according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. The document was critically reviewed and approved by the SIAMS Executive Committee. The guidelines address physiological, pharmacological, pathological, congenital, and genetic forms of gynecomastia, providing a structured diagnostic and therapeutic approach. Clinical assessment, including detailed history and examination, is the cornerstone of diagnosis, and should be complemented by targeted hormonal and imaging investigations when appropriate. Observation is recommended for physiological or recent-onset cases. Pharmacological therapy may be considered in selected idiopathic or painful forms, whereas testosterone replacement should be restricted to men with proven hypogonadism. Surgery is indicated for long-standing fibrotic gynecomastia or significant psychological distress. Psychological support is also advised, especially for adolescents. These SIAMS Guidelines provide an evidence-based, standardized framework for the diagnosis and management of gynecomastia, promoting individualized, multidisciplinary care and identifying priorities for future research.
Gonadotropin-releasing-hormone (GnRH) stimulation test is used for assessment of gonadotropic activation in patients with central precocious puberty (CPP). However, it is invasive and GnRH preparation is not available in all countries. Depot-leuprolide acetate (dLA), used for the treatment of CPP, stimulates gonadotropins briefly before suppressing them. This study aimed to evaluate the utility of luteinizing hormone (LH) level measured 40-minutes after dLA injection for assessing gonadotropic activation compared to GnRH stimulation test. In this prospective study, girls with idiopathic CPP were randomized to receive dLA 3.75 mg/4 weeks IM, 11.25 mg/12 weeks SC or 11.25 mg/12 weeks IM. A standard GnRH test was performed before (baseline) and after 6 months of treatment. Forty minutes after the first dLA injection, LH and follicle-stimulating hormone (FSH) levels were measured, and the same measurements were repeated after 6 months of treatment. The study recruited 132 girls. Peak LH on the GnRH test did not differ from the 40-minute-post-dLA LH levels [11.0(6.8-17.1) vs. 9.4(5.8-16.6); p = 0.06]. There were no significant differences between the treatment groups. Using the GnRH test peak of LH ≥ 5 IU/L as the gold-standard, ROC analysis identified the optimal cut-off of post-dLA injection LH ≥ 5.4 IU/L on initial measurement (sensitivity = 86%, specificity = 90% and AUC = 0.91). At 6 months, peak LH levels in treatment groups were similarly suppressed (2.1 ± 1.6, 2.5 ± 1.8, 2.2 ± 0.9; p = 0.2011). Furthermore, post- dLA LH cut-off of < 3.07 IU/L yielded an AUC = 0.83, sensitivity = 80.8% and specificity = 75.5%. The 40-minute post-dLA LH provided clinically useful information concerning gonadotropic activity for both diagnosis and treatment monitoring and may provide a practical and clinically informative alternative in selected settings, particularly when standard GnRH testing is not readily available.
To investigate the association of testosterone levels on ovarian stimulation response in PCOS patients-stratified by serum LH/FSH ratio-undergoing IVF-ET. A total of 1,354 PCOS patients who underwent fresh embryo transfer were ultimately included in the study. we analyzed and classified it according to the basal LH/FSH ratio values into the following groups: the LH/FSH ≥ 2 group (412 cases) and the LH/FSH < 2 group (942 cases). According to the value of basal serum T level, there were 488 cases in the high T group (> 0.75 ng/ml) and 866 cases in the non-high T group (≤ 0.75 ng/ml), and the outcomes of embryo transfer cycles were compared among the patients in each group. Based on the LH/FSH ratio and testosterone (T) levels, patients were divided into four groups: Group A (LH/FSH < 2, T ≤ 0.75 ng/ml), Group B (LH/FSH < 2, T > 0.75 ng/ml), Group C (LH/FSH ≥ 2, T ≤ 0.75 ng/ml), and Group D (LH/FSH ≥ 2, T > 0.75 ng/ml). There were no statistically significant differences in embryo quality among the four groups (P > 0.05). Regarding pregnancy outcomes, Group B had the lowest live birth rate (51.56%), which was significantly lower than those of Group A (61.87%), Group C (59.79%), and Group D (68.10%)(P ≤ 0.05). Meanwhile, Group B had the highest miscarriage rate (22.38%), significantly higher than the other three groups (10.98%, 12.43%, and 12.90%) (P ≤ 0.05). After adjusting for confounding factors, logistic regression analysis using Group A as the reference showed that Group B had a significantly increased risk of miscarriage (OR = 2.200, 95% CI = 1.325-3.653, P = 0.002) and a significantly lower live birth rate (OR = 0.719, 95% CI = 0.520-0.994, P = 0.046). In patients with PCOS, a high LH/FSH ratio accompanied by elevated testosterone levels was not strongly associated with the likelihood of achieving a live birth. However, in the subgroup with an LH/FSH ratio ≤ 2, elevated testosterone levels may be associated with a reduced likelihood of live birth and an increased risk of miscarriage.
BACKGROUND: Chronic hypoparathyroidism (HypoPT) is a rare endocrine disorder associated with lifelong treatment and a wide spectrum of long-term complications. Potential gender differences in disease-related complications remain poorly defined. This systematic review aimed to evaluate sex-related differences in long-term complications of chronic HypoPT and to explore the impact of disease etiology on these outcomes. METHODS: A systematic search of PubMed, Scopus, EMBASE, and the Cochrane Library was conducted for English-language studies published from January 1980 to July 2025. Eligible studies included randomized controlled trials, cohort studies, case-control studies, and case series involving both women and men with chronic HypoPT and reporting long-term complications. Study selection and data extraction were performed independently by two reviewers according to PRISMA guidelines. Outcomes of interest included renal, skeletal, neurological, cardiovascular, neuropsychiatric complications, and quality of life. RESULTS: Forty-two studies were included. Renal complications showed sex-related patterns, with hypercalciuria more frequently reported in women and chronic kidney disease more commonly observed in men. Skeletal complications, particularly vertebral fractures, were more prevalent in postmenopausal women, while bone mineral density and turnover markers showed minimal sex differences. Neurological complications, including basal ganglia calcifications, did not consistently differ by sex, although women more frequently reported cognitive and neuropsychiatric symptoms. Cardiovascular risk appeared higher in women in some cohorts. Quality of life impairment and symptom burden were consistently greater in women, especially when assessed using disease-specific instruments. CONCLUSIONS: Available evidence suggests gender-related trends in long-term complications of chronic HypoPT, but data are limited by heterogeneity and lack of sex-stratified analyses. Gender-informed research is needed to support personalized management strategies.
To evaluate the short- and mid-term volume reduction rate(VRR) after percutaneous ethanol injection(PEI), at 1,3 and 6 months, in patients with cystic or predominantly cystic thyroid nodules(CNs/pCNs, respectively), conducting a systematic review and meta-analysis of published data on VRR outcomes across these intervals. A systematic search of articles published up to October 30,2025 identified studies reporting PEI treatment for CNs/pCNs.Characteristics of the study design, CNs/pCNs cohorts, and outcomes of interest(VRR at 1,3 and 6 months of follow up)were extracted.Statistical analysis included a random-effects meta-analysis, assessment of heterogeneity with use of the I2 statistic, and meta-regression and subgroup analyses to explore potential sources of heterogeneity. Six studies comprising 431 CNs/pCNs were included.The pooled VRRs at 1,3 and 6 months post-PEI were 85.18%(95% CI: 80.72-89.64),91.50%(95% CI: 88.88-94.12) and 93.11%(95% CI: 90.91-95.31),respectively. Stratifying by nodule cystic composition, the VRR at consecutive follow-up time points was significantly different between the 1- and 3-month intervals in both subgroups [CN: VRRs at 1, 3 and 6 months were 91.16% (88.38-93.93), 95.69% (94.16-97.22) and 96.02% (94.16-97.87), respectively; pCN: VRRs at 1,3 and 6 months were respectively 80.19% (77.04-83.33), 87.08% (84.95-89.2) and 90.01%(88.83-91.19)].A secondary meta-regression analysis with baseline mean volume as covariate demonstrated a significant inverse association with VRR at 1 and 3 months in pCN(p = 0.02). By providing pooled VRRs for the short- and mid-term follow-up, this meta-analysis should be regarded as an initial step, paving the way for larger, high-quality studies aimed at standardizing the PEI procedure and supporting its incorporation into future dedicated guidelines.
To investigate the associations of baseline high-sensitivity C-reactive protein (hs-CRP), hs-CRP trajectories, and cumulative hs-CRP (CumCRP) exposure with the risk of incident heart failure (HF) in individuals with diabetes. We analyzed 18,269 patients with diabetes from the Kailuan Study who were free of HF and cancer at baseline (2006-2012). Baseline hs-CRP was categorized into quartiles (Q1-Q4), with a separate group for hs-CRP values > 20 mg/L. Repeated measurements were used to identify long-term trajectories via group-based trajectory modelling and calculate time-weighted cumulative hs-CRP after excluding participants with hs-CRP > 20 mg/L. Fine-Gray subdistribution hazard models were employed to estimate adjusted hazard ratios (HRs) for incident HF. Over a mean follow-up of 9.66 ± 2.85 years, 826 HF occurred. Compared with baseline hs-CRP quartile (Q1), the HRs for HF increased across higher quartiles and in the > 20 mg/L group were 1.22 (95% CI 0.98-1.52) for Q2, 1.25 (1.00-1.55) for Q3, 1.42 (1.15-1.76) for Q4, and 1.68 (1.24-2.28) for hs-CRP > 20 mg/L group. In longitudinal analyses, the high-decreased (HR:1.65; 95% CI:1.32-2.06) and moderate-fluctuated (HR:1.48; 95% CI:1.07-2.04) trajectories were associated with significantly higher HF risk than the low-stable pattern. Similarly, the highest CumCRP quartiles were associated with increased HF risk with HR (95% CI) of 1.33 (1.08-1.64) for Q3, and 1.47 (1.19-1.82) for Q4 compared to Q1. In this large cohort of patients with diabetes, higher baseline hs-CRP, greater cumulative hs-CRP exposure, and hs-CRP trajectories characterized by earlier elevation were independently associated with increased risk of incident HF. These findings highlight the importance of monitoring long-term inflammatory burden for HF risk stratification in diabetes.
Cyclic Cushing's syndrome (CCS), a rare and atypical form of endogenous hypercortisolism, remains a very relevant problem from a diagnostic point of view. To confirm this disease, it is necessary to record two episodes of hypercortisolism alternating with period of normocortisolism. Intercyclic phase is characterized not only by negative laboratory test results but also by the absence of pronounced symptoms, making the pathology hidden and, presumably, undiagnosed in certain cases. Some causes remain undetermined and require further investigation. The process of diagnosing and verifying CCS is often lengthy and requires repeated testing at certain intervals. However, none of the currently available methods are 100% accurate. Therefore, a step-by-step approach with confirmation by several highly sensitive tests is recommended for the differential diagnosis of ACTH-dependent and ACTH-independent cyclic hypercortisolism. The risk of false results cannot be ruled out even when the most reliable methods available today are used. Thus, the diagnostic algorithm for each individual case will be specific and will depend on the phase of the disease, the patient's condition, and concomitant pathology. Our review summarizes current data on the mechanisms of cyclic hypercortisolism known to date and provides a comparative and critical analysis of modern diagnostic methods that help identify this pathology and indicate its origin.
Adult Growth Hormone Deficiency (AGHD) is a complex and under-recognized condition, mainly managed in outpatient settings and characterized by fragmented and heterogeneous clinical data. Population registries provide high-quality evidence but require long timeframes and substantial resources. The aim of this study was to design and validate an artificial intelligence (AI)-driven methodology for the construction of a disease-specific AGHD Data Mart from routine clinical data within a single high-volume center, to support real-world evidence generation and future advanced analytics. A standardized Data Science framework, based on automated extraction from hospital data warehouses and electronic medical records, integrating structured data and unstructured clinical narratives through natural language processing, was implemented. AGHD patients were identified using a combination of ICD-9 codes and text-mining applied to outpatient reports. A multidisciplinary workflow ensured clinical validation of extracted data. The Data Mart described patient identification from first hospital access (T0) and included diagnostic modality, etiology, biochemical data, comorbidities, and growth hormone replacement therapy. Among 210 identified patients, 188 were validated as AGHD after expert review. Diagnoses were based on dynamic testing (28.2%), panhypopituitarism with low IGF-1 (54.3%), or AI-assisted identification (17.6%). Etiology was retrieved in 87.8% of cases, with post-surgical causes being the most frequent. 37.8% of patients were receiving rhGH therapy. Specific trends for IGF-1 values for single patients were described. This study represents the first AI-driven AGHD Data Mart and demonstrates the feasibility of constructing the Data Mart from routine clinical data. This approach offers a complementary framework for structured RWD extraction and may support future longitudinal analyses and AI-based clinical support in AGHD.
Anemia, inflammation and iron deficiency are linked to Fibroblast growth factor 23 (FGF23). Aim of this study was to explore the dynamics of FGF23 in Hereditary Hemochromatosis type-I (HH1). Twenty-six consecutive patients with genetically confirmed and uncomplicated HH1 and nineteen healthy age-matched voluntary blood donors (CTR) were enrolled for the study. Intact (iFGF23) and C-terminal (cFGF23) FGF23 and iron status markers were evaluated at baseline (T0) and seven days (T7) after phlebotomy/voluntary blood donation (VBD). Bone mineral density (BMD) and vertebral fracture assessment (VFA) were also evaluated at T0. Cross-sectional and longitudinal analyses failed to reveal significant differences in iFGF23 in both HH1 (T0: 54.27 ± 14.42 pg/mL; T7: 54.70 ± 15.48 pg/mL) and CTR (T0: 52.77 ± 17.63 pg/mL; T7: 53.27 ± 15.88 pg/mL) groups. Absence of significant difference was also observed for cFGF23 at baseline between the two groups (HH1, T0: 0.98 ± 0.39 pmol/L; CTR, T0: 1.18 ± 0.91 pmol/L) but not at T7 when the values (HH1, T7: 01.20 ± 0.89; CTR, T7: 1.84 ± 1.11 pmol/L) were significantly increased in CTR compared to T0 (p = 0.0003) and to HH1 (p = 0.0240). After phlebotomy/VBD, in both HH1 and CTR groups, serum levels of phosphate were unchanged from baseline while serum iron, ferritin and transferrin saturation and erythrocyte-related parameters (red blood cells, hemoglobin and hematocrit) were significantly reduced (all p  <  0.0001). Serum iron, ferritin, and transferrin saturation were significantly higher in HH1 than in CTR (p = 0.0002 for serum iron and p  <  0.0001 for both ferritin and transferrin saturation) at T7. In the CTR group, these parameters showed a trend toward iron deficiency whereas in HH1 they remained near the upper limit of the normal range, suggesting a persistent mild iron overload. Correlation and regression analyses did not show significant associations between circulating FGF23 (both iFGF23 and cFGF23) and iron status markers. BMD and VFA were not significantly different between HH1 and CTR. Furthermore, BMD and Trabecular Bone Score values were not associated with circulating FGF23 levels. This pilot study indicates that the serum levels of iFGF23 and cFGF23 and skeletal health evaluated through BMD and VFA do not differ between patients with uncomplicated HH1 and healthy subjects at baseline. The absence of changes in the serum levels of iFGF23 and cFGF23 in HH1 patients with uncomplicated HH1 after phlebotomy may reflect the persistence of iron overload which could counteract the physiological hypoxia-driven stimulation of FGF23 production and cleavage observed in healthy subjects after VBD.
Hypoparathyroidism (HypoPT) is a rare endocrine disorder frequently associated with impaired quality of life. Disease-specific patient-reported outcome measures may help to better characterize symptom burden in Hypoparathyroid patients. The Hypoparathyroidism Patient Questionnaire-28 (HPQ-28) was originally developed in German and subsequently validated French. The aim of this study was to validate the Italian version of the HPQ-28 in a multicenter cohort. In this cross-sectional study, adult participants were recruited from two tertiary referral centres in Italy. The study population were divided in three groups: patients with chronic postsurgical HypoPT (Group 1), patients with hypothyroidism without HypoPT (Group 2), and healthy controls (Group 3). Structural validity was assessed using confirmatory factor analysis with a weighted least squares mean- and varianceadjusted estimator. Internal consistency was evaluated using Cronbach's alpha and McDonald's omega coefficients. Test-retest reliability was assessed using intraclass correlation coefficients in a subgroup of patients. Construct validity was examined by comparing HPQ-28 scores across clinical groups. A total of 163 participants were included (69 HypoPT patients, 60 hypothyroid patients, and 34 controls). Confirmatory factor analysis supported the original six-factor structure of the HPQ-28, with acceptable goodness-of-fit indices (CFI = 0.933, TLI = 0.924, RMSEA = 0.075, SRMR = 0.081). Internal consistency was satisfactory across domains, with Cronbach's alpha ranging from 0.70 to 0.89 and McDonald's omega from 0.75 to 0.93. Test-retest reliability demonstrated good temporal stability. Patients with HypoPT reported significantly higher symptom burden compared with both hypothyroid patients and healthy controls across several domains. The Italian version of the HPQ-28 demonstrates good psychometric properties and represents a reliable disease-specific instrument for assessing symptom burden in patients with hypoparathyroidism in both clinical practice and research settings.
Osteosarcopenia (OSP) is defined as the coexistence of osteoporosis (OP) and sarcopenia (SP), and is associated with increased risks of falls, fractures, and frailty. Postmenopausal women are particularly susceptible due to estrogen deficiency, however, its overall prevalence in this population remains unclear. This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251142908). PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to 15 October 2025. Eligible studies reported OSP prevalence (or data enabling its calculation) in postmenopausal women, with OP and SP defined by recognized criteria (WHO, EWGSOP, AWGS or equivalents). Two reviewers independently performed study selection, data extraction, and quality assessment using the JBI checklist. Pooled prevalence was estimated using generalized linear mixed models and random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment. Heterogeneity, influence analyses, publication bias, and exploratory subgroup analyses by diagnostic criteria, economic level, geographic region, and population source were conducted. Meta-regression evaluated the effect of mean age. Sixteen studies involving 7,631 postmenopausal women and 1,421 OSP cases were included. The pooled prevalence of OSP was 15.6% (95% CI: 9.6-24.3%; I²=97.1%). Using consistent criteria, prevalence was 20.1% (95% CI: 10.7-34.4%) for WHO + AWGS 2019 and 12.7% (95% CI: 2.3-47.5%) for WHO + EWGSOP 2018. Exploratory subgroup analyses showed higher prevalence estimates in developing versus developed regions (18.0% vs. 12.7%), Asian versus non-Asian countries (18.7% vs. 8.2%), and hospital-based versus community-based populations (26.4% vs. 8.7%). No significant study-level association between mean age and OSP prevalence was observed in meta-regression analyses based on the 14 studies with available mean age data. Most studies were of high quality, and no significant publication bias was detected. This meta-analysis found a pooled OSP prevalence of 15.6% among postmenopausal women across included studies. Given high heterogeneity, this estimate should be interpreted with caution, as it reflects diverse settings and diagnostic approaches. Exploratory subgroup analyses suggested higher prevalence in developing regions, Asian populations, and hospital‑based settings. Standardized criteria and integrated bone‑muscle assessment may improve early identification and management of OSP in this high-risk population.
Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with various metabolic disturbances, including calcium metabolism disorders and acid-base imbalances. Emerging evidence suggests a potential link between PA and urolithiasis; however, previous studies have been limited by small sample sizes and inconsistent findings. This study aims to investigate the association between PA and urinary stone formation using a large-scale real-world dataset. We conducted a retrospective cohort study using the TriNetX database, which includes de-identified electronic health records from over 250 million individuals. Patients diagnosed with PA were identified based on ICD-10-CM and ICD-9-CM codes, and a propensity score-matched (PSM) cohort of PA and non-PA patients with hypertension was created. The primary outcome was the incidence of urolithiasis (kidney and urinary tract stones), identified using ICD-10-CM codes (N20-N23). Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analyses were conducted based on sex, metabolic disorders, and renal function (eGFR ≥ 60 vs. <60 mL/min/1.73 m²). A total of 10,578 PA patients and 7,897,605 non-PA patients were identified, with 10,577 matched pairs included in the final analysis after 1:1 propensity score matching. PA was associated with a significantly higher risk of urolithiasis compared to non-PA patients at 1-year (HR: 1.524, 95% CI: 1.238-1.877), 3-year (HR: 1.312, 95% CI: 1.120-1.537), 5-year (HR: 1.303, 95% CI: 1.130-1.502), and 7-year (HR: 1.269, 95% CI: 1.107-1.456) follow-ups. Subgroup analyses revealed that the increased risk of urolithiasis persisted across both sexes and was more pronounced in patients without metabolic disorders (HR: 1.826, 95% CI: 1.452-2.295). Our findings demonstrate a significant association between PA and increased urolithiasis risk, independent of sex. These results highlight the clinical importance of urinary stone screening in patients with PA, particularly those with hypertension or unexplained metabolic abnormalities. Further prospective studies are needed to elucidate the underlying mechanisms and evaluate whether targeted PA treatment could mitigate stone risk in this population.
PURPOSE: Varicocele is a recognized male factor of infertility. Surgical/microsurgical correction represents a therapeutical option to improve fertility outcomes but predictive parameters for the identification who can actually benefit from varicocele correction are under investigated. Here we aimed to identify baseline predictors of semen outcome improvement after varicocele treatment by scleroembolization approach. METHODS: 85 patients receiving varicocele treatment by anterograde scleroembolization (ASE, N = 42) or retrograde scleroembolization (RSE, N = 43) were retrospectively recruited. Basal and 6-months follow-up evaluation of semen, hormonal and ultrasound parameters (US) were performed to address the respective effect of varicocele treatment. In addition, basal parameters were assessed as clinical outcome predictors. RESULTS: Varicocele grade reduction was observed in more than 90% of patients (P < 0.001). Compared to basal, significant increase of sperm concentration (10.0 ± 9.2 × 106cells/mL vs. 23.4 ± 26.9 × 106cells/mL; P < 0.001), total sperm count (TSC 39.0 ± 54.5 × 106cells vs. 70.3 ± 90.6 × 106cells, P < 0.001) and total motile sperm count (TMS, 9.8 ± 12.8 × 106cells vs. 36.7 ± 58.1 × 106cells, P < 0.001), was observed, with no differences between RSE or ASE. All US parameters were also improved (all P < 0.001). Logistic regression analysis of basal semen and ultrasound parameters showed that basal sperm motility and left testis-mean transit time (L-MTT) were associated with TSC and TMS doubling at follow-up. However, Receiver Operating Characteristic curve analysis showed that only basal L-MTT basal sperm was consistently associated with TSC and TMS doubling at follow-up (respectively: AUC = 0.834, CI: 0.747–0.921 and AUC = 0.805, CI: 0.708–0.901; both P < 0.001). CONCLUSION: Baseline sperm count and US parameters represent useful clinical descriptors to address those subjects eligible for varicocele correction.
This study aimed to investigate the associations between composite inflammatory indicators and the presence of osteoporosis (OP) and sarcopenia in patients with type 2 diabetes mellitus (T2DM), and to explore the potential mediating role of inflammation in the relationship between sarcopenia and OP. In this cross-sectional study, 756 adults with T2DM were enrolled. Osteoporosis was defined as a Bone Mineral Density (BMD) T-score ≤ -2.5 at the hip or lumbar spine. Sarcopenia was diagnosed according to Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Composite inflammatory indicators, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), pan-immune inflammation value (PIV), platelet-to-lymphocyte ratio (PLR), advanced lung cancer inflammation index (ALI), neutrophil-to-albumin percentage ratio (NPAR), platelet-to-neutrophil ratio (PNR), and neutrophil-lymphocyte-platelet ratio (NLPR) were calculated from routine blood parameters. Associations between composite inflammatory indicators and OP as well as sarcopenia were assessed using restricted cubic splines (RCS) and multivariate logistic regression analysis. The ability of composite inflammatory indicators to identify sarcopenia was evaluated using receiver operating characteristic (ROC) curves. Mediation analysis to assess the indirect effect of inflammation on the sarcopenia and osteoporosis relationship. In this study, the prevalence of osteoporosis was 31.1%, and the prevalence of sarcopenia was 34.0%. RCS analysis revealed that ALI exhibited a linear negative correlation with osteoporosis, and SII, SIRI, NLR, PIV, PLR, NLPR, NPAR exhibited linear positive correlations with sarcopenia (all P for nonlinearity > 0.05). PNR and ALI demonstrated a negative nonlinear association with sarcopenia (all P for nonlinearity < 0.05). Logistic regression analysis indicated that sarcopenia was positively associated with osteoporosis (P< 0.05). However, ALI (aOR 0.99, 95% CI 0.98-1.00) showed inverse association with osteoporosis (P < 0.05). Logistic regression analysis also indicated that osteoporosis was positively associated with sarcopenia (P < 0.05). The multivariable regression analysis showed hs-CRR (aOR 1.03, 95% CI 1.01-1.05), SII (aOR 1.00, 95% CI 1.00-1.00), SIRI (aOR 1.46, 95% CI 1.13-1.93), PIV (aOR 1.00, 95% CI 1.00-1.00), NPAR (aOR 1.11, 95% CI 1.04-1.19), and NLR (aOR 1.20, 95% CI 1.05-1.38) showed positive associations with sarcopenia. Conversely, ALI (aOR 0.98, 95% CI 0.97-0.99) exhibited a inverse association with sarcopenia (P < 0.05). The area under the ROC curve (AUC) for ALI in identifying sarcopenia was 0.68. Mediation analysis showed that ALI mediated the statistical association between sarcopenia and osteoporosis with proportions (%) of 19.58. Sarcopenia is positively associated with osteoporosis in patients with T2DM, and this relationship is partially mediated by systemic inflammation, as captured by the ALI. The ALI may serve as a useful and accessible clinical indicator to identify T2DM patients at higher risk for sarcopenia and osteoporosis, who may benefit from targeted screening and multimodal interventions.
To evaluate shifts in waist-to-height ratio (WHtR) categories among adults with obesity or overweight, with or without prediabetes, treated with tirzepatide in the SURMOUNT-1 study. This post hoc analysis included 2,538 participants from the SURMOUNT-1 Phase 3, double-blind, randomized, placebo-controlled trial. Adults with BMI ≥ 30 or ≥ 27 kg/m² and at least one obesity-related complication (ORC), excluding diabetes, were randomized to receive once-weekly tirzepatide (5, 10, or 15 mg) or placebo, alongside a reduced-calorie diet and increased physical activity. Participants were grouped by baseline WHtR (≤ 0.49, > 0.49 to ≤ 0.59, > 0.59) according to the National Institute for Health and Care Excellence (NICE) framework. Participants with prediabetes at baseline had additional follow-up data beyond week 72, and shifts in their WHtR categories at week 176 were also included. Change from baseline in WHtR was analyzed using a mixed model for repeated measures (MMRM). Shift tables were used to summarize changes from baseline to post-baseline WHtR category levels. At baseline, 89.8% of participants had a WHtR > 0.59, 10.1% had > 0.49 to ≤ 0.59, and 0.1% had ≤ 0.49. After 72 weeks of tirzepatide (10/15 mg), 16.7% of participants achieved a WHtR ≤ 0.49, and 54.7% improved their baseline WHtR category compared to 9.6% with placebo. At 176 weeks, among participants with prediabetes, 12.2% achieved WHtR ≤ 0.49, and 46.4% improved their category with tirzepatide versus 9.3% with placebo. Tirzepatide treatment was associated with sustained improvements in WHtR categories, with a greater proportion of participants shifting to a better WHtR category compared to participants treated with placebo. Improved WHtR may be suggestive of lower future cardiometabolic risk. Further analyses of this nature will enhance the understanding and application of WHtR in obesity management across diverse populations.