Endocrine最新文献

Purpose: Erythropoietin-producing hepatocellular (EPH) receptors are the largest known family of tyrosine kinases receptors (TKR) in humans, implicated in cell proliferation, adhesion, migration, tumor angiogenesis, invasion and metastasis. The aim of the present study is to assess the expression of EPHs in neuroendocrine neoplasms (NENs).

Methods: Immunohistochemical staining of specimens of 30 patients with gastroenteropancreatic and lung NENs was performed for EPH-A1, EPH-A2, EPH-A4, EPH-A5 protein expression, in addition to ki-67 multiplication index and programmed death-ligand 1. Additionally, we performed a systematic review of the available literature in three different databases reporting on the expression of EPH in all neuroendocrine neoplasms.

Results: Positive expression was seen in 16/19 (84%) specimens for EPH-A1, 15/23 (65%) for EPH-A2, 21/24 (88%) for EPH-A4, 24/26 (92%) for EPH-A5. EPH-A1 was expressed in 9/9 pancreatic, 3/4 small intestine, but not in one lung NEN, EPH-A2 in 5/10 pancreatic, 3/4 small intestine and lung, and in one of each of gastric, appendix, colorectal, and cervical NENs, respectively. EPH-A4 showed positive expression in 9/11 pancreatic, 4/4 small intestine, 3/3 lung specimens and EPH-A5 in 10/11, 4/4 and 4/4, respectively. Data retrieved from the systematic review of the literature in combination with the data from the present study are suggestive of a frequent EPH expression in pituitary, thyroid, lung and gastroenteropancreatic NENs, yet, with varying expressions of the single receptor subtypes.

Conclusion: EPHs may have a role in NEN tumorigenesis, prognosis as well as a role in the evolving molecular-targeted therapies.

Purpose: Mortality in pituitary adenomas (PAs) has been extensively compared to general population. However, direct comparisons between PA subtypes are scarce. We aimed to compare mortality in various subtypes of PA (acromegaly, Cushing's disease (CD), macroprolactinomas and non-functioning pituitary macroadenomas (MacroNFPA)), within a single referral center.

Methods: We retrospectively analyzed mortality and survival time in all 962 PAs admitted in our department between 2011 and 2023: acromegaly (n = 306), CD (n = 69), macroprolactinoma (n = 168) and MacroNFPA (n = 419).

Results: Median follow-up was 10.2 (5.2, 15.2) years. The overall survival probability was 90.9% and 78.1% after 10 and 20 years respectively with age at diagnosis as the only significant predictor. There were no significant differences in survival probability between various PA subtypes in the whole cohort. In patients over 45 years of age at diagnosis there was a significant difference in survival probability between the four groups (p = 0.01) in the first 15 years of follow-up. In head-to-head comparisons CD had a significantly higher mortality risk than patients with acromegaly (HR 3.38 [CI 95% 1.07 to 10.60]) even after adjusting for age and sex.

Conclusion: Patients diagnosed with CD after 45 years of age have a significantly lower survival probability than other PA subtypes in the first 15 years of follow-up. All other PA subtypes had a similar survival probability after adjusting for age and sex. Due to advances in medical treatment of hormone secreting tumors, mortality in patients with PAs might increasingly depend more on tumor mass than on hormonal hypersecretion.

Purpose: Data on the polar vessel sign (enlarged feeding vessel terminating in parathyroid lesions) on four-dimensional computed tomography (4D-CT) is limited. We performed a retrospective analysis to determine the prevalence, predictors, and adjunctive utility of polar vessel sign in pre-operative 4D-CT of patients with primary hyperparathyroidism (PHPT).

Methods: One radiologist blinded to the patients' details reported the 4D-CT of eighty-four operated patients with histopathology-proven single-gland PHPT. Two protocols were used to obtain arterial-phase images: timed via bolus tracking (n = 41) or fixed at 20 s after contrast injection (n = 43).

Results: Seventy-one patients were symptomatic for PHPT, with median serum calcium 12.1 mg/dL. On the arterial phase of 4D-CT, 88.1% of lesions had the polar vessel sign, including 7/9 asymptomatic patients, 6/6 parathyroid carcinomas, and 3/4 ectopic(1:mediastinum, 2:thyro-thymic ligament). Predictors of polar vessel sign were maximum lesion dimension (2.2 vs. 1.4 cm; P = 0.03), solid-cystic CT morphology (47.3% vs. none; P = 0.004), and bolus tracking-timed arterial phase (55.4% vs. none; P = 0.001). Of these, bolus tracking improved the polar vessel's visualization (100% vs. 76.7%; P = 0.001) independent of lesion dimension and solid-cystic morphology. The latter two predicted polar vessel sign in images obtained at a fixed interval (20 s). A significantly lower proportion of bolus tracking-timed scans had lesion percentage arterial enhancement (PAE) < 128.9% (2/41 vs. 9/43; P = 0.04). Even with suboptimal PAE, the polar vessel helped identify 9/11 lesions.

Conclusion: The polar vessel sign demonstrated an additive role to PAE during CT reporting. Bolus tracking is valuable in optimizing vessel and tumor arterial enhancement and is easily incorporated into parathyroid 4D-CT protocol.

Purpose: To study what adult women with congenital adrenal hyperplasia (CAH) thought about the timing of genital surgery.

Methods: As part of a larger follow-up study performed between the years 2002-2005 there were questionnaires concerning genital surgery, type of surgery, their thoughts about timing of genital surgery and experience of information about surgery. Early surgery was defined as ≤4 years of age and late ≥10 years. The medical and surgical files were reviewed.

Results: 62 women with CAH due to 21-hydroxylase deficiency, mean age 28 years (18-63) were included. The age at first genital surgery was 3 years (0-28 years) in the 52 patients (84%) who had had genital surgery, with 60% had early surgery (≤4 years) and 29% late (≥10 years). Almost half of the cohort had a positive experience of the information about surgery, a third had no opinion and a fifth had a negative experience. Of the women 39% thought that early surgery was good, while 19% thought it should be done during or after puberty and 42% had no opinion. Of those preferring early surgery 70% had early surgery themselves. Vaginal surgery was less common among those favoring early surgery. Age, phenotype, genotype, decade of surgery and experience of the information about surgery did not differ significantly between the three groups.

Conclusion: Equal numbers of women had no opinion regarding age at surgery or preferred early surgery while 19% thought it would be preferred to have surgery during or after puberty.

Purpose: Researches indicate that patients with papillary thyroid cancer (PTC) are prone to experiencing anxiety and depression. However, lacking of large-scale, prospective studies thoroughly examine the trajectory of these emotional states. Therefore, this study aims to investigate changes in anxiety and depression levels in PTC patients before and after operation and assess the impact of gender and menopausal states on emotional well-being.

Method: A prospective longitudinal study enrolled 320 PTC patients who completed the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) at pre- and post-operation. Paired-sample T-tests and logistic regression analysis were used to evaluate emotional changes and identify influencing factors.

Results: Anxiety and depression levels significantly increased (p = 0.028, p = 0.005) postoperatively, with incidence of 13.8% for anxiety and 26.9% for depression. Multivariate regression analysis showed that gender was a factor affecting depression (p = 0.041), and menopausal state significantly influenced emotions including anxiety and depression (p = 0.004, p = 0.031). Subgroup analysis showed that female patients exhibited higher levels of adverse emotions postoperatively compared to preoperatively (p = 0.003, p < 0.001). Postoperatively, female patients were more susceptible to anxiety and depression (p = 0.011, p = 0.029), and postmenopausal women were particularly at risk for depression (p = 0.017).

Conclusions: The study highlights the importance of postoperative psychological care, particularly for female and postmenopausal patients. Larger sample sizes and longer follow-up periods are needed for a comprehensive understanding of psychological changes in PTC survivors.

Purpose: Regenerating islet-derived protein 4 (REG4) is a secretory protein that belongs to the C-type lectin superfamily. This study aims to explore the diagnostic value of REG4 as a potential biomarker for metabolic syndrome by analyzing the correlation between serum REG4 levels and metabolic syndrome.

Methods: Serum REG4 levels were measured using enzyme-linked immunosorbent assay (ELISA). Bioinformatics analysis was conducted to investigate REG4-related genes and metabolic signaling pathways.

Results: Serum REG4 levels were significantly elevated in MetS patients compared to healthy controls (439.7 vs. 422.6 ng/L, p < 0.01). In addition, circulating REG4 levels showed a positive correlation with AUGg, HbA1c, VAI, BMI, WHR, TG, TC, LDL-C, while being inversely correlated with HDL-C in the study population. Serum REG4 levels were positively correlated with MetS score. Multiple linear regression analysis identified HOMA-IR and LDL-C as independent factors affecting serum REG4 concentration. Interventional studies have shown that OGTT can significantly increase serum REG4 levels in healthy individuals, but significantly reduce REG4 levels in MetS patients. Bioinformatics analysis suggested that REG4 is linked to several metabolism-related genes and is enriched in various metabolism-related signaling pathways.

Conclusion: REG4 may serve as a valuable biomarker and potential treatment target for insulin resistance (IR) and MetS.

Clinical trial registration number: ChiCTR2000032878.

Purpose: This review aims to provide updated information regarding the role of thyroid and leptin hormones and their crosstalk in affecting the male reproductive function in hypothyroid and obesity conditions.

Method: A wide literature search was made using online search engines on published articles using keywords including thyroid hormone, hypothyroidism, leptin hormone, hyperleptinemia, obesity, the relationship between thyroid and leptin hormones and male reproduction, and hypothyroidism, obesity, and male reproduction.

Results: All information pertaining thyroid and leptin hormone effects on male reproduction, hypothyroidism, hyperleptinemia, and obesity effect on male fertility as well as the related molecular mechanisms are obtained.

Conclusion: Thyroid and leptin hormones individually play a significant role in male reproduction. Alterations of these hormones' levels could adversely affect the male reproductive functions. PI3K/AKT signaling was found to be the major signaling pathway involved in mediating the effect of both hormones on male reproduction. Impaired crosstalk between the two hormones may occur in hypothyroidism with obesity which would contribute towards male reproductive dysfunction.

Background: Diabetic ketoacidosis (DKA) is often treated with intravenous regular insulin infusion (IVRII). Subcutaneous fast-acting insulin analogues (FAIAs); either alone or combined with subcutaneous long-acting insulin (LAI); might be useful to treat DKA. Our meta-analysis updated on their benefits and safety in DKA.

Methods: We searched major electronic databases for randomised trials on subcutaneous FAIAs ± subcutaneous LAI vs IVRII in DKA. Primary outcomes were all-cause in-hospital mortality, time to resolution of DKA and hyperglycemia, in-hospital DKA recurrence and hospital readmission for DKA post-discharge. Secondary outcomes included resource utilisation and patient satisfaction. Safety outcomes were adverse events. Reviewers assessed risk of bias and quality of evidence using GRADE. We performed a priori subgroup and trial sequential analyses on primary outcomes.

Results: Seven trials enrolled 351 mainly adult patients (255/351) with mild to moderate DKA. No trials studied subcutaneous FAIA and subcutaneous LAI. Their risk of bias was high or unclear in several domains. No all-cause in-hospital mortality and DKA recurrence were reported. No trial investigated hospital readmission for DKA post-discharge. There was no difference in mean time to resolution of DKA (mean difference = -0.70, 95% CI -2.18 to 0.79 h, p = 0.36) or hyperglycemia [blood glucose < 250 mg/dL (13.9 mmol/L)] (mean difference = -0.17, 95% CI -1.10 to 0.76 h, p = 0.72) between subcutaneous FAIA and IVRII groups. There were largely no subgroup effects. Both groups had similar secondary outcomes. Hypoglycemia was the most common adverse event. Quality of evidence was low to very-low for all outcomes. The only possible trial sequential analysis for time to resolution of DKA was inconclusive.

Conclusions: There was low- to very-low quality evidence that subcutaneous FAIA did not affect patient-centered outcomes in mainly adult patients with mild to moderate DKA compared to IVRII.

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia, which derives from either insufficient insulin production [type 1 diabetes mellitus (T1DM)] or both impaired insulin sensitivity along with inadequate insulin production [type 2 diabetes mellitus (T2DM)] and affects millions of people worldwide. In addition to the adverse effects of DM on classical target organs and tissues, skeletal health can also be adversely affected. There is considerable evidence linking DM with osteoporosis. The fracture risk in patients with DM differs upon the type of diabetes, and it appears to be related to the type of anti-diabetic treatment. Antidiabetic drugs may have various effects on bone health. Most of them have neutral or even favorable effects on bone metabolism with the exception of thiazolidinediones (TZDs). Some studies suggest that TZDs may have negative impact on bone health by decreasing bone formation and increasing the fracture risk. There are also limited studies linking the use of canagliflozin, a Sodium-glucose contransporter-2 inhibitor (SGLT2i), with increased fracture risk. On the other hand, therapies that are based on incretin effect, like Dipeptidyl peptidase-4 inhibitors (DPP-4i) and Glucagon-like peptide-1 receptor agonizts (GLP-1RAs) might have positive effects on bone health by promoting bone formation. Herein we review the impact of antidiabetic drugs on bone health, highlighting the potential benefits and risks associated with these medications in an attempt to contribute to the development of personalized treatment strategies for individuals with DM.

Objective: Polycystic Ovarian Syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age. Several candidate genes have been shown to be associated with PCOS. Previous studies have shown that variations in CYP11A1 and CYP19A1 genes are associated with hormonal dysregulation associated with PCOS in different ethnic populations. This study aims to investigate the genomic association between SNPs rs4077582 of CYP11A1 and rs700519 of CYP19A1 and the development of PCOS in Pakistani population.

Methods: A total of 280 subjects were recruited for the study, including 142 PCOS cases diagnosed based on Rotterdam criteria and 138 age-matched controls. The anthropometric, hormonal and biochemical parameters of all subjects were analyzed. Genomic DNA was extracted and genotyping of the selected SNPs was performed using Sanger sequencing. Further, we also examined the genotypic-phenotypic correlation analysis for various clinical and biochemical parameters for SNP rs4077582 of CYP11A1.

Results: We found significant differences in allele frequency (OR = 0.42, 95% CI = 0.30-0.60, χ² = 16.3693, p = 0.000052) and genotypic frequency (χ² = 26.4376, p = 0.00001) between PCOS women and controls for SNP rs4077582 of CYP11A1. Genotype-phenotype correlation analysis showed a significant difference in FAI (p = 0.005), testosterone (p = 0.001), androstenedione (p = 0.005) and urea (p = 0.049) levels between the three genotypes. No association between SNP rs700519 of CYP19A1 and PCOS was observed.

Conclusion: Our results suggest the role of SNP rs4077582 of CYP11A1 gene in the clinical manifestation of PCOS in Pakistani women.