Journal of Endocrinological Investigation最新文献

Purpose: Varicocele has been associated with reduced male fertility potential. Treatment modalities for varicocele improve semen parameters, yet more than 50% of cases remain infertile. Varicocele-induced heat and hypoxia stress may cause aberrant epigenetic modifications, possibly leading to abnormal sperm functions. This study aims to investigate the genome-wide sperm DNA methylation alterations in infertile men with clinical varicocele and evaluate the effect of varicocele treatment on methylation and fertility status.

Methods: This study includes 30 healthy fertile men and 50 infertile men with clinical varicocele. Whole genome bisulfite sequencing (WGBS) was employed to identify differentially methylated CpG (DMC) sites in sperm genomic DNA of the infertile men with varicocele compared to the fertile controls. DMCs located within genes associated with spermatogenesis and sperm functions were selected for validation in larger study population by pyrosequencing. Varicocele group were followed up after 3 months of either antioxidant treatment or varicocelectomy, and sperm DNA methylation changes were evaluated. Participants were monitored for 1 to 2 years following treatment to evaluate their fertility status.

Results: From WGBS analysis, a total of 6414 DMCs and 1484 differentially methylated genes (DMGs) were identified. Signalling pathways involved in spermatogenesis process and sperm functions were enriched in the pathway analysis. Selected DMC within gene H2AX was significantly hypermethylated, and CDKN1B and BCR were hypomethylated in varicocele study population. However, after 3 months of varicocele treatment (both modes), notable restoration could only be observed in H2AX and CDKN1B DMCs. 20% of the follow-up patients achieved fertility after varicocele treatment and demonstrated a reversal of DNA methylation alterations.

Conclusion: This study highlights the altered sperm DNA methylation landscape and its possible implications on altered spermatogenesis and sperm function in clinical varicocele cases. It also presents insights into the possibility of restoration of altered DNA methylation levels following varicocele treatment.

The sella turcica, a saddle-shaped depression of the sphenoid bone, serves as a critical anatomical structure housing the pituitary gland and holds significant evolutionary, clinical, and anthropological importance. This review traces the evolutionary origins of the sella turcica from early vertebrates through mammalian and primate evolution, emphasizing its role in the stabilization and protection of neuroendocrine functions. Morphological stability of the sella turcica across hominin evolution highlights strong selective pressures on cranial base anatomy, despite broader craniofacial diversification. Anthropologically, the sella turcica provides a durable landmark for craniometric analyses, forensic reconstructions, and paleoanthropological investigations, revealing patterns of sex-based dimorphism, population variation, and disease prevalence. Developmental anomalies such as empty sella syndrome and pituitary hypoplasia illustrate the evolutionary trade-offs between increased encephalization and cranial vulnerability. Integrating historical, paleopathological, and clinical perspectives, this article underscores the sella turcica's significance as a nexus of evolutionary innovation, structural resilience, and biological fragility.

Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders caused by numerous variants in several genes encoding enzymes involved in adrenal steroidogenesis. While 21-hydroxylase deficit is the most common and well-known form of CAH, accounting for 90%-95% of cases, there are six other forms of CAH, due to mutations in the genes of other key enzymes involved in adrenal steroidogenesis. These forms are less frequent and, consequently, clinician experience is extremely limited. These disorders are 11β-hydroxylase deficiency (11βOHD); 17α-hydroxylase/17,20-lyase deficiency (17OHD); 3β-hydroxysteroid dehydrogenase type 2 deficiency (3ΒHSD2D); P450 oxidoreductase deficiency (PORD); steroidogenic acute regulatory protein (StAR) deficiency, causing congenital lipoid adrenal hyperplasia and cholesterol side-chain cleavage enzyme (P450scc) deficiency. This narrative review therefore focuses on these rarer forms of CAH, providing an update on their clinical presentation, diagnosis, management, and treatment.

Purpose: To characterize, using real-life data, the clinical profile of men undergoing their first bone health evaluation at a tertiary academic center over a 14-year period.

Methods: Retrospective, observational, cross-sectional study including adult men referred to our center between 2007 and 2021 for bone health assessment. Fractures, comorbidities, risk factors for bone loss, and pharmacological treatments were collected.

Results: 536 men were enrolled (147 under 50, 385 over 50). At least one comorbidity associated with bone loss was found in 49.3% of patients, and 43.8% were receiving medications causing bone mineral density (BMD) reduction-mainly corticosteroids and androgen deprivation therapy. The prevalence of osteoporosis, osteopenia, and low BMD for age was 42.3%, 44.8%, and 48.6%, respectively. Osteoporosis-related fractures were found in 216 patients (40.8%), whose 34 men under 50 (15.7%). Up to 17.5% of men with fractures had normal BMD. A total of 181 patients (33.8%) had never received calcium/vitamin D supplementation or bone-active therapy; the prevalence of treatment-naïve patients was 20-23% even among men with fractures or receiving corticosteroids/androgen-deprivation therapy.

Conclusions: Male osteoporosis presents with a high rate of fractures in the real-life clinical practice at a tertiary academic center. The high prevalence of comorbidities associated with bone loss suggests that secondary forms of osteoporosis should be carefully investigated, even in presence of normal BMD. The significant proportion of untreated men-including those with known risk factors or fractures-highlights the urgent need to raise awareness and improve the management of male osteoporosis, especially in primary healthcare.

Purpose: The growth charts for individuals with Down syndrome (DS) available to-date were developed from a cohort of patients from the USA. As diet and environmental factors play a key role on auxological attainment, the growth of patients from the Mediterranean area should be assessed by means of dedicated centiles. Accordingly, we aimed to develop growth charts from a wide Italian population and to provide a metabolic validation for the BMI distribution outlined.

Methods: Retrospective, bicentric study. We gathered auxological and biochemical data from two cohorts of Italian children and adolescents with DS assessed every 6- to 12-months between 1992 and 2024.

Results: 526 patients were enrolled. We longitudinally retrieved the auxological data recorded in the setting of 2796 clinical evaluations. By assessing height, weight and BMI with reference to age, we outlined the age-dependent distribution of each parameter and developed syndrome-specific growth charts. When comparing our charts with the USA ones, the latter showed a statistically greater upward trendline in weight and BMI. Eventually, we assessed the distribution of triglycerides, cholesterol, glycated hemoglobin and uric acid with reference to the BMI. A higher BMI centile was statistically associated with greater triglycerides, cholesterol, and uric acid levels, and we identified the 90th centile of BMI as a risk threshold for dyslipidemia and hyperuricemia.

Conclusion: We developed DS-specific growth charts from a wide Italian population. The comparison with the USA percentiles outlined statistically significant differences in the distribution of weight and BMI, thus highlighting the need of dedicated charts for individuals from the Mediterranean area.

Purpose: DBLG1 is a hybrid closed-loop (CL) system interoperable with ViCentra Kaleido and Roche Insight pumps. The SP8 trial investigated the safety and glycemic outcomes of DBLG1 coupled to the DANA-i pump (DBLG1-DANAi) in adults and adolescents with type 1 diabetes mellitus (T1D).

Methods: The safety of DBLG1-DANAi (primary outcome of SP8) was evaluated using two criteria: (i) the incidence of serious adverse device events (SADEs) and (ii) the time spent in hypoglycemia (time below range 70 mg/dL [3.9 mmol/L], TBR70) with DBLG1-DANAi compared to an SAP (sensor-augmented pump) system. Secondary outcomes included non-serious adverse events and standard glycemic metrics. Five months after its start, the trial was halted due to the COVID-19 crisis. One hundred and forty (140) of the 148 planned adults had already been included in the study, as well as all planned adolescents (N = 36).

Results: The intention-to-treat (ITT) population included 105 adult and 36 adolescent participants in whom no SADE was observed with DBLG1-DANAi. The per-protocol (PP) population consisted of 73 adults and 18 adolescents who spent two weeks with SAP, followed by two weeks with DBLG1-DANAi. No increase in TBR70 was observed during the DBLG1-DANAi period. Furthermore, the time spent in the glucose level range of 70-180 mg/dL [3.9-10.0 mmol/L] (time in range, TIR70-180) ​​increased significantly with DBLG1-DANAi, both in adults (+ 10.5%; p < 0.0001) and adolescents (+ 16.0%; p < 0.0001).

Conclusion: During the two-week study period, DBLG1 was interoperable with the DANA-i pump. This result requires confirmation in future long-term studies.

Clinicaltrials:

Gov id: NCT04190277.

Purpose: This study aimed to evaluate the one-year metabolic and renal effects of combined therapy with SGLT-2 inhibitors and GLP-1 receptor (GLP-1R) agonists in patients with type 2 diabetes mellitus (T2DM), both with and without diabetic kidney disease (DKD). The primary objective was to assess changes in BMI, HbA1c, LDL-C, eGFR, and UACR in a real-world setting.

Methods: A retrospective analysis was conducted on 250 patients with type 2 diabetes mellitus (T2DM) treated with SGLT-2 inhibitors and GLP-1 receptor agonists at the Diabetology Service of CTO-Alesini Hospital, Rome, between 2022 and 2025. Metabolic and renal parameters were collected at baseline and after 12 months. Patients were stratified according to the presence of diabetic kidney disease (DKD). The primary outcomes included changes in BMI, HbA1c, LDL-C, eGFR, and UACR. Secondary analyses evaluated the impact of adding an SGLT-2 inhibitor to pre-existing GLP-1 receptor agonist therapy, or vice versa.

Results: After 12 months, we observed significant reductions in BMI (p = 0.03), HbA1c (p < 0.001), LDL-C (p < 0.01), and UACR (p < 0.001). In patients with DKD (46% of the cohort), UACR improved markedly (p < 0.001), while eGFR remained stable. Significant reductions in HbA1c (p < 0.001) and LDL-C (p < 0.01) were also observed. In non-DKD patients, HbA1c and LDL-C decreased after one year, with eGFR remaining within the normal range. Importantly, among DKD patients, the addition of an SGLT-2 inhibitor to GLP-1 receptor agonist therapy resulted in significant reductions in both HbA1c (p = 0.04) and UACR (p < 0.01), whereas the addition of a GLP-1 receptor agonist primarily reduced HbA1c (p < 0.01). In non-DKD patients, both treatment sequences improved HbA1c and LDL-C.

Conclusion: Dual therapy with SGLT-2 inhibitors and GLP-1 receptor agonists was associated with improvements in glycemic control, lipid profile, and albuminuria, particularly among patients with DKD. The sequence of drug addition appeared to influence outcomes, with the addition of SGLT-2 inhibitors providing superior renal benefits in DKD. These findings may provide support for early combined use of both agents in high-risk patients with T2DM.