Journal of Endocrinological Investigation最新文献

Purpose: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by pathogenic variants in MEN1 tumor suppressor gene. Diagnosis is commonly based on clinical criteria and confirmed by genetic testing. The objective of the present study was to report on a MEN1 case characterized by multiple pancreatic glucagonomas, with particular concern on the possible predisposing genetic defects.

Methods: While conducting an extensive review of the most recent scientific evidence on the unusual glucagonoma familial forms, we analyzed the MEN1 gene in a 35-year-old female with MEN1, as well as her son and daughter, using Sanger and next-generation sequencing (NGS) approaches. We additionally explored the functional and structural consequences of the identified variant using in silico analyses.

Results: NGS did not show any known pathogenic variant in the tested regions. However, a new non-conservative variant in exon 4 of MEN1 gene was found in heterozygosity in the patient and in her daughter, resulting in an amino acid substitution from hydrophobic cysteine to hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from populations databases and was never reported in full papers: its characteristics, together with the high specificity of the patient's clinical phenotype, pointed toward a possible causative role.

Conclusion: Our findings confirm the need for careful genetic analysis of patients with MEN1 and establish a likely pathogenic role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 associated with glucagonomas.

Purpose: The aim of the present study is to evaluate the association of metabolic and glycemic variables with semen parameters in patients with type 1 diabetes (T1D) with and without erectile dysfunction (ED).

Methods: The study population included 88 adults with T1D using a continuous glucose monitoring, of whom 28 with ED (ED group) and 60 without it (NO ED group). All men completed the International Index of Erectile Function (IIEF-5) and underwent body composition analysis (BIA) and semen analysis.

Results: ED group showed worse HbA1c levels [median (IQR), 8.4 (7.7, 9.9) vs 7.4 (7, 8.2) %, P < 0.001)], higher insulin dose [60 (51, 65) vs 45 (38, 56) UI/die, P = 0.004)] and a higher total body water and intracellular water as compared with ED group. Men in the ED group presented higher semen volume [2.8 (2.6, 4.2) vs 2.5 (2.2, 2.7) mL, P < 0.001] and sperm concentration [24 (19, 29) vs 20 (12, 23) mil/mL, P = 0.010], but reduced sperm progressive motility [28 (25, 35) vs 35 (25, 36) %, P = 0.011], higher rate of non-progressive motility [15 (10, 15) vs 10 (5, 10) %, P < 0.001] and higher rate of typical morphology [7(5, 8) vs 5 (4, 5) %, P = 0.001]. Based on multivariate logistic regression analysis performed to assess the association between clinical variables and ED, intracellular water (OR 3.829, 95% CI 1.205, 12.163, P = 0.023) resulted as the only independent predictor of ED.

Conclusion: Men with T1D and ED showed worse metabolic profile which is associated with poor semen quality, as compared with those without ED.

Purpose: With the rise of medically assisted reproductive techniques (ART) the number of pregnancies complicated by gestational diabetes mellitus (GDM) has increased. The aim of this study was to evaluate retrospectively the outcomes of pregnancies complicated by GDM who conceive trough ART (cases) compared to those who conceived spontaneously (controls).

Methods: In 670 women with GDM, 229 cases and 441 controls, followed by the Diabetology of Padua, between 2010-2022, clinical-metabolic maternal characteristics and maternal-foetal outcomes were evaluated.

Results: As for the maternal clinical-metabolic characteristics, plasma glucose levels at 60' and 120' under oral glucose tolerance test (OGTT) at time of diagnosis were significantly higher in cases (177.4 ± 31.1 vs 170.9 ± 34.1 mg/dl, p = 0.016; 151.5 ± 32.2 vs 144.0 ± 33.4 mg/dl, p = 0.005 respectively). Furthermore, at diagnosis, cases show higher levels of total cholesterol (257 ± 53 mg/dl vs 246 ± 52 mg/dl; p = 0.012) and triglycerides (199.8 ± 83.2 mg/dl vs 184.9 ± 71.3 mg/dl; p = 0.02) compared to controls. As for maternal outcomes, thyroid disfunction, was recorded in a higher percentage in case (21.4% vs 14.3%; p = 0.008), as well as, the frequency of cesarean section (50.3% vs 41.2%; p = 0.038) and twin pregnancies (16.2% vs 2.5%; p < 0.001). As for neonatal outcomes, there were no statistically significant differences, except for the birth weight of the second twin, which was significantly lower in cases (2268 ± 536 vs 2822 ± 297 g; p = 0.002). No other significant differences were found.

Conclusion: This study showed no meaningful differences in the outcomes of GDM pregnancies who were conceived with ART compared to that arose spontaneously as the patients were promptly diagnosed and treated.

Purpose: The aim of this study was to evaluate changes in hip geometry parameters following treatment with teriparatide (TPD), denosumab (Dmab) and zoledronate (ZOL) in real-life setting.

Methods: We studied 249 patients with osteoporosis (OP) with mean [SD] age of 71.5 [11.1] years divided into 3 treatment groups; Group A received TPD; n = 55, Group B (Dmab); n = 116 and Group C (ZOL); n = 78 attending a routine metabolic bone clinic. Bone mineral density (BMD) was measured by DXA at the lumbar spine (LS), total hip (TH) and femoral neck (FN) prior to treatment and after 2 years (Group A), after a mean treatment duration of 3.3 [1.3] years (Group B) and after 1, 2 and 3 doses of ZOL (Group C) to assess treatment response. Hip structural analysis (HSA) was carried out retrospectively from DXA-acquired femur images at the narrow neck (NN), the intertrochanter (IT) and femoral shaft (FS).

Results: Changes in parameters of hip geometry and mechanical strength were seen in the following treatment. Percentage change in cross-sectional area (CSA): 3.56[1.6] % p = 0.01 and cross-sectional moment of inertia (CSMI): 4.1[1.8] % p = 0.029 increased at the NN only in Group A. Improvement in HSA parameters at the IT were seen in group B: CSA: 3.3[0.67]% p < 0.001, cortical thickness (Co Th): 2.8[0.78]% p = 0.001, CSMI: 5.9[1.3]% p < 0.001, section modulus (Z):6.2[1.1]% p < 0.001 and buckling ratio (BR): - 3.0[0.86]% p = 0.001 with small changes at the FS: CSA: 1.2[0.4]% p = 0.005, Z:1.6 [0.76]%, p = 0.04. Changes at the IT were also seen in Group C (after 2 doses): CSA: 2.5[0.77]% p = 0.017, Co Th: 2.4[0.84]% p = 0.012, CSMI: 3.9[1.3]% p = 0.017, Z:5.2[1.16]% p < 0.001 and BR: - 3.1[0.88]% p = 0.001 and at the NN (following 3 doses): outer diameter (OD): 4.0[1.4]% p = 0.0005, endocortical diameter(ED): 4.3[1.67% p = 0.009, CSA:5.2[1.8]% p = 0.003, CSMI: 9.3[3.8]% p = 0.019.

Conclusions: Analysis of the effect of OP therapies on hip geometry is useful in understanding the mechanisms of their anti-fracture effect and may provide additional information on their efficacy.

Purpose: Transition from pediatric to adult care is associated with significant challenges in patients with Turner syndrome (TS). The objective of the TRansition Age Management In Turner syndrome in Italy (TRAMITI) project was to improve the care provided to patients with TS by harnessing the knowledge and expertise of various Italian centers through a Delphi-like consensus process.

Methods: A panel of 15 physicians and 1 psychologist discussed 4 key domains: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders.

Results: A total of 41 consensus statements were drafted. The transition from pediatric to adult care is a critical period for patients with TS, necessitating tailored approaches and early disclosure of the diagnosis to promote self-reliance and healthcare autonomy. Fertility preservation and bone health strategies are recommended to mitigate long-term complications, and psychiatric evaluations are recommended to address the increased prevalence of anxiety and depression. The consensus also addresses the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS; regular screenings and interventions are advised to manage these conditions effectively. In addition, cardiac abnormalities, including aortic dissections, require regular monitoring and early surgical intervention if certain criteria are met.

Conclusions: The TRAMITI consensus statement provides valuable insights and evidence-based recommendations to guide healthcare practitioners in delivering comprehensive and patient-centered care for patients with TS. By addressing the complex medical and psychosocial aspects of the condition, this consensus aims to enhance TS management and improve the overall well-being and long-term outcomes of these individuals.

Purpose: To investigate how sleeve gastrectomy (SG), a typical operation of bariatric surgery, attenuated symptom, and progression of diabetic kidney disease (DKD).

Methods: DKD model was induced by high-fat diet (HFD) combined with streptozocin in Wistar rats. SG was performed, and the group subjected to sham surgery served as control. The animals were euthanized 12 weeks after surgery, followed by sample collection for the subsequent experiment. The HK-2, a renal proximal tubular epithelial cell line derived from human, was utilized to investigate the potential mechanisms.

Results: SG improved metabolic parameters and glucose homeostasis, and could alleviate DKD in terms of renal function indices as well as histological and morphological structures in DM rats, accompanied with a significant reduction in renal tubular injury. Compared with sham group, SG reduced the renal tubular ferroptosis. To further clarify the mechanism involved, in vitro experiments were performed. In the presence of high glucose, renal tubular TGF-β1 secretion was significantly increased in HK-2 cell line, which led to activation of ferroptosis through TGF-β1/Smad3 signaling pathway. Inhibition of TGF-β1 receptor and phosphorylation of Smad3 significantly ameliorated TGF-β1-mediated ferroptosis. In vivo experiments also found that SG improved the hyperglycemic environment, reduced renal TGF-β1 concentrations, and down-regulated the TGF-β1/Smad3 signaling pathway.

Conclusions: With the capacity to lower the glucose, SG could attenuate the ferroptosis by inhibiting TGF-β1/Smad3 signaling pathway in DKD rats, and eventually attenuated DKD.

Purpose: To evaluate the impact of high thyroid stimulating hormone (TSH) levels on human granulosa-luteal (hGL) cells.

Methods: hGL cells were isolated from follicular aspirates derived from patients undergoing IVF treatment without any thyroid disorder (serum TSH 0.5-2 mU/L). Cells were cultured at 37 °C in DMEM, supplemented with 5% FBS. The cells were treated with 1 nM LH and increasing concentrations of TSH. At the end of culture, conditioned medium and cells were collected to analyze progesterone production, cell viability, and mRNA levels of genes involved in the steroidogenesis process. Human ovarian tissues were analyzed for TSH receptor (TSHR) expression by IHC.

Results: The expression of TSHR was detected in human corpus luteum by IHC and in hGL by RT-PCR. In hGL cells, TSH treatment did not modulate progesterone production nor the expression of steroidogenic genes, such as p450scc and HSD3b 1/2. However, TSH induced a dose-dependent increase in cell death. Finally, TSH did not affect LH-induced p450scc and HSD3b1/2 expression while LH partially reverted TSH negative effect on cell death in hGL.

Conclusions: Elevated TSH levels in hypothyroid women may be associated with impaired CL functioning and maintenance. These findings open a new line of research for the importance of the treatment of women with thyroid dysfunction that could contribute to the onset of infertility.

Purpose: Asymptomatic primary hyperparathyroidism (aPHPT) has been recognized as a condition that can lead to renal complications. Timely identification of prognostic indicators for renal impairment holds the potential to facilitate proactive monitoring and treatment strategies in these patients. This study aims to investigate the utility of acoustic radiation force impulse (ARFI) imaging and renal resistive index (RRI), in identifying renal parenchymal and vascular changes in patients with aPHPT.

Methods: Forty-two patients with aPHPT and 42 controls matched for age, sex, and body mass index were included in the study. The presence of renovascular changes was evaluated by RRI measurement with Doppler ultrasonography, and the presence of renal parenchymal involvement was evaluated by ARFI quantification, given as shear wave velocity (SWV).

Results: In aPHPT patients, both the mean RRI and mean SWV values exhibited substantial elevation compared to the control group (P < 0.001 for both). Significant associations were observed between SWV values and serum calcium, parathyroid hormone (PTH), and adenoma size within the patient group (P < 0.001, P < 0.001, P = 0.016, respectively). Similarly, the mean RRI demonstrated positive correlations with serum calcium and PTH levels in the patient group (P< 0.001, P = 0.011, respectively). Multivariate linear regression analysis underscored the connection between mean RRI and mean SWV values with serum calcium levels within the patient group. In addition, serum PTH levels affected mean SWV positively and significantly.

Conclusion: The use of ARFI imaging and RRI measurements appears to hold potential in identifying renal involvement in patients with aPHPT.

Background: Polycystic ovary syndrome (PCOS) is the most common feminine endocrine disorder, characterized by androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. The negative impact of symptoms on the quality of life (QoL) of patients is still not clear.

Purpose: The present review aimed at studying the impact of the symptoms, the psychological symptoms, and brain alterations in women with PCOS.

Methods: A systematic search was undertaken for studies that assessed the impact of PCOS symptoms on QoL, psychological symptoms, and brain alterations in PCOS patients.

Results: Most of the information about QoL came from psychometric studies, which used culture-based questionnaires. Alterations of sleep quality, body image, and mood disorders can negatively affect the QoL of the patients. Sexual satisfaction and desire were affected by PCOS. Brain imaging studies showed functional alterations that are associated with impairments of visuospatial working memory, episodic and verbal memory, attention, and executive function.

Conclusions: Several factors can negatively influence the quality of life of the patients, and they are directly related to hyperandrogenism and the risk of infertility. In particular, obesity, hirsutism, acne, and the fear of infertility can have a direct impact on self-esteem and sexual function. Metabolic and psychiatric comorbidities, such as mood, anxiety, and eating disorders, can affect the well-being of the patients. Moreover, specific cognitive alterations, such as impairments in attention and memory, can limit PCOS patients in a series of aspects of daily life.

Purpose: Growth hormone deficiency (GHD) is a rare condition with a worldwide prevalence of 1 patient in 4000 to 10,000 live births, placing a significant economic burden on healthcare systems. The aim of this study is to generate evidence on the economic burden of children and adolescents with GHD treated with rhGH and their parents in Italy.

Methods: A cost of illness analysis, adopting the prevalence approach, has been developed, producing evidence on the total annual cost sustained by the Italian National Health System (NHS) and by the society. The study is based on original data collected from a survey conducted among Italian children and adolescents with GHD and their parents.

Results: 143 children/adolescents with GHD and their parents participated to the survey, conducted from May to October 2021. Patients had a mean age of 12.2 years (SD: 3.1) and were mostly males (68.5%). The average direct healthcare cost sustained by the NHS was € 8,497.2 per patient/year; adding the out-of-pocket expenses (co-payments and expenses for private healthcare service), the total expense was € 8,568.6. The indirect costs, assessed with the human capital approach, were € 847.9 per patient/year. The total of direct and indirect cost is € 9,345.1 from the NHS perspective, and € 9,416.5 from a social perspective. The total cost incurred by the Italian NHS for children with GHD (range: 5,708-8,354) was estimated in € 48.5-71.0 million, corresponding to 0.04-0.06% of the total Italian public health expense in the year 2020.

Conclusions: The total annual cost for GHD children is close to € 10,000, and is mainly due to the cost of rhGH treatment. This cost is almost entirely sustained by the NHS, with negligible out-of-pocket expenses. The economic burden on the Italian NHS for the health care of established GHD children is fourfold higher than the prevalence of the disease in the overall Italian population.