Journal of Endocrinological Investigation最新文献

Purpose: Hypo- and hyper-prolactinemia have deleterious effects on male reproduction, yet there is a dearth of information regarding the underlying mechanisms. The aim of this study was to delineate the molecular mechanisms by which hypo- and hyper-prolactinemia affects spermatogenesis and fertility in male rats.

Methods: In vivo male rat models for hypo- and hyper-prolactinemia were established using dopamine receptor agonist, Bromocriptine (Brm), and antagonist, Fluphenazine (Flu), respectively. Effects on fertility and spermatogenesis were assessed by studying pre- and post-implantation loss, litter size, sperm parameters, hormonal profile, testicular histology, testicular cell population, and testicular transcriptome in rats.

Results: Treatment with Brm and Flu for 60 days led to subfertility, which was indicated by an increase in pre- and post-implantation loss and decrease in litter size, when mated with control female rats. Decreased sperm count was observed after both treatments, whereas reduced sperm motility was noted in Flu group. Serum FSH was unaffected, and LH was decreased by Flu treatment. Testosterone was decreased in both the groups, whereas estradiol was decreased in the Flu group. An arrest in spermatogenic cycle beyond round spermatids was observed in the Flu group. Additionally, testicular apoptosis in germ cells, mostly spermatocytes of Stage IX-XIV was noted in both the groups. Further, testicular RNA-Seq analysis revealed a total of 1539 and 824 differentially expressed genes/DEGs in Brm and Flu, respectively (Sequence Read Archive/SRA Database accession number: PRJNA1150513). Gene ontology and pathway analysis of DEGs highlighted enrichment of steroid metabolic pathway and ribosomal biogenesis pathway. Hub genes identified from the DEGs were validated by qPCR and the results showed that Uba52, Rps27a, Rpl23, Rps5, Rps16 were significantly down-regulated by Brm, whereas Rps27a, Rps29, Rps15, Rps27, Faul1 were significantly down-regulated by Flu.

Conclusion: Hypo- and hyper-prolactinemia leads to subfertility and decreased sperm parameters possibly through an effect on steroid metabolism and ribosomal biogenesis pathway. Therefore, maintaining prolactin levels in physiological range is crucial.

Purpose: Aging plays an important role in type 2 diabetes mellitus (T2DM). But the association between accelerated biological age and T2DM, and the mechanisms underlying this association remains unclear. Thus, this study aimed to examine the associations of biological aging with T2DM, and explore the potential mediation effect of amino acids.

Methods: This prospective cohort study included 95,773 participants in the UK Biobank who were free of diabetes at baseline. Biological age was measured from clinical traits using PhenoAgeAccel. Cox proportional hazard models were used to estimate the hazard ritios (HRs) and 95% confidence intervals (CIs), and mediation analysis was used to explore the mediation effect of amino acids.

Results: During a median follow-up of 14.02 years, 6,347 incident T2DM cases were recorded. After multivariable adjustment for sociodemographic characteristics, lifestyle factors, and other risk factors of T2DM, participants with older biological age were at increased risk of incident T2DM (30% increase per standard deviation of PhenoAgeAccel, 95% CI: 28.0-33.0%). Additionally, higher branched chain amino acids (BCAAs) including isoleucine and leucine, aromatic amino acids (AAAs) including phenylalanine and tyrosine, were associated with increased PhenoAgeAccel and risk of incident T2DM; while glutamine and glycine were inversely associated. Alanine, glutamine, glycine, phenylalanine, tyrosine, isoleucine, leucine, and total concentration of branched-chain amnio acids could partially explain the associations between PhenoAgeAccel and T2DM.

Conclusion: Accelerated biological aging was associated with increased risk of incident T2DM independent of chronological age and may be a risk factor of T2DM, partially mediated by several amino acids.

Purpose: We aimed to identify differentially expressed spliceosome components in growth hormone (GH)-secreting pituitary tumors and investigate their roles in pathogenesis.

Methods: We performed transcriptome analysis of 20 somatotroph adenomas and 6 normal pituitary tissues to select dysregulated spliceosome components. Clinical characteristics were analyzed based on gene expression in 64 patients with acromegaly. Proliferation, invasion, and hormonal activity of GH secreting pituitary adenoma cells were investigated.

Results: TCERG1 expression was significantly higher in somatotroph adenomas than in normal pituitaries (log2 fold change 0.59, adjusted P = 0.0002^*). Genotype-phenotype analysis revealed that patients with higher TCERG1 expression had lower surgical remission rates than those with lower expression (63.64% vs. 95.45%, P = 0.009^*). TCERG1 expression was significantly higher in groups with cavernous sinus (CS) invasion or Ki67 index over 3 (all P>0.05^*). TCERG1 overexpression led to a 29.60% increase in proliferation (P<0.001^*) and a 249.47% increase in invasion after 48 h in GH3 cells (P = 0.026^*). Conversely, TCERG1 silencing significantly decreased cell proliferation (25.76% at 72 h, P<0.001^*) and invasion (96.87% at 48 h, P = 0.029^*). E-cadherin was decreased, but vimentin was increased in both TCERG1 overexpressed GH3 cells and somatotroph adenomas. And TCERG1 silence reversed the expression of the genes (CDH2, SNAI1, ZEB2, and VIM) in GH3 cells.

Conclusions: Spliceosome machinery provide novel insights into the pathogenesis of GH-secreting pituitary tumor and highlight the potential role of TCERG1 as a biomarker for tumor aggressiveness.

Objective: To analyze the risk factors associated with the development of severe hypocalcemia (SH) in patients who have undergone parathyroidectomy (PTX).

Methods: This research involved patients with chronic kidney disease-secondary hyperparathyroidism who underwent PTX between June 1, 2021, and May 31, 2023. SH was characterized by a serum total calcium (tCa) level below 1.8 mmol/L. This study aimed to analyze differences in preoperative laboratory findings and clinical manifestations between patients with and without SH. Logistic regression analysis was used to identify potential risk factors associated with the development of SH.

Results: The incidence of SH was 23% (n = 176). Significant differences were observed in free thyroxine (FT4), free triiodothyronine, alanine aminotransferase, osteocalcin, tCa, alkaline phosphatase (ALP), C-terminal cross-linked telopeptide of type I collagen, and parathyroid hormone between the SH and non-SH groups. The three independent risk factors for SH were tCa [odds ratio (OR) 0.063, 95% confidence interval (95% CI) 0.006-0.663], ALP (OR 1.003, 95% CI 1.001-1.005), and FT4 (OR 0.439, 95%CI 0.310-0.621). The area under the curve, sensitivity, specificity, and overall accuracy of this model were 0.904 (95% CI 0.856-0.952), 46.3%(95% CI 32.0%-61.3%), 94.8% (95% CI 89.7%-97.5%), and 83.5% (95% CI 77.3%-88.3%), respectively.

Conclusion: The preoperative level of FT4 plays a crucial role in predicting the risk of SH after PTX. The combined FT4-ALP-tCa model demonstrates the ability to predict SH risk, providing valuable insights for customizing calcium supplementation strategies and improving clinical decision-making.

Background: Cognitive impairment is known to occur in patients with prolactinoma, but the underlying mechanism is unclear.

Objective: To evaluate cognitive function in patients with prolactinoma and to investigate the basis of possible cognitive impairment in brain white matter changes using diffusion tensor imaging (DTI).

Methods: 37 consecutive patients with prolactinoma and 37 healthy controls of similar age, sex, and education were enrolled in the study. Hormone levels were determined in all participants, comprehensive neuropsychological testing was performed, and DTI was used to reconstruct and evaluate white matter tracts.

Results: In patients with prolactinoma, short- and long-term visual and verbal memory, attention, concentration, and executive and language functions were impaired compared to the healthy group. When comparing the DTI results, lower fractional anisotropy (FA) values were found in the patients' right uncinate fasciculus (R-UF), indicating neuronal damage. After applying the Bonferroni correction, the two groups had no significant difference in 42 tracts (p > 0.0012 for all). A positive correlation was found between poor FA scores on the R-UF and low scores on long-term memory, category and letter fluency tests. In addition, patients with hypoprolactinemia had the worst short-term memory scores, while normoprolactinemia had the best scores. Also, the poorer R-UF FA values were found in the patients with hypoprolactinemia and the highest in those with normoprolactinemia.

Conclusion: This study is the first to investigate reasons for cognitive dysfunction in patients with prolactinoma by DTI. No significant structural changes were found in brain tracts of patients with prolactinoma. Still, there may be a link between potential damage in the R-UF and cognitive dysfunction, and further research is needed. In addition, the results showed that the development of hypoprolactinemia is associated with cognitive dysfunction and emphasized that overtreatment should be avoided.

Skeletal comorbidities are frequent and clinically relevant findings in Cushing's syndrome (CS) since an uncoupled suppressed bone formation and enhanced bone resorption leads to a marked skeletal damage with a rapid increase of fracture risk. Reduced Bone Mineral Density (BMD) has been consistently reported and osteopenia or osteoporosis are typical findings in patients with CS. Vertebral Fractures (VFs) are frequently reported and may occur even in patients with an only mild reduction of BMD. Since CS is diagnosed late due to often difficult biochemical and radiological confirmation as well as to signs and symptoms common in other much more frequent diseases an approach suggested for overcoming underdiagnosis is to screen patients with manifestations which may overlap with those of CS such as arterial hypertension, diabetes mellitus and osteoporosis. Our review will focus on the rationale and best practice for screening osteoporotic patients for CS.

Purpose: Fine needle aspiration biopsy (FNAB) is currently the gold standard for diagnosis and treatment of thyroid nodules, but the growing need for anatomic pathology services in small communities is becoming a challenge. Telecytology (TC) is defined as the electronic transmission of cytological digital images, and allows for the collection of samples, primary diagnosis, and other applications without the physical presence of a pathologist. Our aim is to systematically report, summarize, and critically analyze the most up to date applications of TC to thyroid nodules FNAB evaluation.

Methods: We performed a systematic literature review by searching PubMed, Embase, and Cochrane Library databases. Only studies published in peer-reviewed scientific journals were included. Data were extracted using the PICO framework and critically analyzed. PRISMA guidelines were applied, and the risk of bias in the included studies was assessed using the ROBINS-I tools. The methodological quality was assessed following GRADE criteria.

Results: We included 13 observational studies, resulting in a total of 3856 evaluated FNAB specimens. The majority of studies (63.6%) showed an excellent concordance rate of diagnosis via TC and conventional cytology. TC can be used to perform preliminary assessment of samples with a concordance rate ranging from 74 and 100%, showing a significant reduction of the non-diagnostic rate. Image quality was referred to as perfect or nearly perfect in most cases, regardless of telecytology technique.

Conclusion: Telecytology could be a valuable implementation for thyroid FNAB evaluation both for primary diagnosis and preliminary assessment of samples.

Purpose: This study was designed to assess the pituitary functions of patients with traumatic maxillofacial fractures and compare the results with healthy controls.

Methods: Thirty patients (mean age, 38.14 ± 14.15 years; twenty-six male, four female) with a traumatic maxillofacial fracture at least 12 months ago (mean 27.5 ± 6.5 months) and thirty healthy controls (mean age, 42.77 ± 11.36 years; twenty-five male, five female) were included. None of the patients were unconscious following head trauma, and none required hospitalization in intensive care. Basal pituitary hormone levels of the patients were evaluated. All patients and controls had a glucagon stimulation test and an ACTH stimulation test to evaluate the hypothalamic-pituitary-adrenal axis and the GH-IGF-1 axis.

Results: Five of thirty patients (16.6%) had isolated growth hormone (GH) deficiency based on a glucagon stimulation test (GST). The mean peak GH level after GST in patients with hypopituitarism (0.54 ng/ml) was significantly lower than those without hypopituitarism (7.01 ng/ml) and healthy controls (11.70 ng/ml) (P < 0.001). No anterior pituitary hormone deficiency was found in the patients, except for GH.

Conclusion: Our study is the first to evaluate the presence of hypopituitarism in patients with traumatic maxillofacial fractures. Preliminary findings suggest that hypopituitarism and GH deficiency pose significant risks to these patients, particularly during the chronic phase of their trauma. However, these findings need to be validated in larger scale prospective studies with more patients.

Purpose: No consensus exists as the gold standard for Cushing's Syndrome (CS) screening. This study aimed to evaluate the diagnostic accuracy and utility of late-night salivary cortisol (LNSC) and cortisone (LNSE), overnight dexamethasone suppression test (ODST), and urinary free cortisol (UFC) in developing a screening algorithm for CS.

Methods: A retrospective, single-centre analysis on 93 adult patients referred to the Oxford Centre for Diabetes, Endocrinology, and Metabolism for CS evaluation (2017-2022). Data were analysed using binomial logistic regression and area under the receiver-operating curve (AUROC).

Results: Fifty-three patients were diagnosed with CS. LNSC (sensitivity 87.5%, specificity 64.9%, AUC 0.76), LNSE (sensitivity 72.4%, specificity 85.7%, AUC 0.79), and ODST (sensitivity 94.7%, specificity 52.1%; AUC 0.74) demonstrated comparable effectiveness for CS diagnosis. Their combined application increased diagnostic accuracy (AUC 0.91). UFC was not statistically significant. Pre-test clinical symptom inclusion improved screening test performance (AUC LNSC: 0.83; LNSE: 0.84; ODST: 0.82). For CD diagnosis, LNSE + LNSC (AUC 0.95) outperformed ODST. Combining these with ACTH levels < 12.6 pmol/L perfectly distinguished MACS (AUC 1.00). ODST (AUC 0.76) exhibited superior performance (sensitivity 100.0%, specificity 52.2%) in MACS detection.

Conclusions: LNSC, LNSE, and ODST are robust tools for CS screening, with their combined use offering the highest diagnostic precision. LNSE, especially when used with LNSC, is highly effective for CD diagnosis, exceeding ODST accuracy. ODST is preferable for MACS identification. Integrating ACTH levels markedly improves differentiation between CD and MACS. Conversely, UFC shows limited diagnostic utility.

Purpose: While males have dominated the physician lines over the last decades the recent female doctors' number increasing might progressively reduce this gender gap. This might be not fully true in the academic/research area. We aimed to analyze the gender distribution of first/senior Italian authors on neuroendocrine neoplasm papers published on peer reviewed journals.

Methods: Publications from January 2019 to September 2023 were reviewed; only papers with first and/or senior Italian authors were included. First/senior author gender, type of article, co-authorship with foreign authors were the variable analyzed.

Results: 742 papers with Italian first and/or senior authors were retrieved, 449 (60.5%) multicentric, 285 (38.4%) original articles. A female author was first and senior author in 386/742 (52%) and in 228/742 (31%) papers, respectively. 150 (20.2%) papers included foreign coauthors, being an Italian female researcher first author in 50 papers (33%), senior author in 28 (18.6%). The number of Italian female first/senior authors has been increasing over the years (22 in 2019, 113 in 2022; 16 in 2019, 62 in 2022, respectively). The first/senior female authors were mainly Oncologists/Endocrinologists/Pathologists rather than Gastroenterologists/Nuclear Medicine doctors/Surgeons/Radiologists.

Conclusion: There has been an increase in the prevalence of female authorship of published research in the neuroendocrine setting over the last 5 years, which partially reflects the current distributions in this field, taking into account that several specialties with different gender distribution are involved. However, senior authorship continues to be primarily men. Efforts should be made to improve proportionate gender representation in both clinical and academic/research setting.