Hasil untuk "Diseases of the endocrine glands. Clinical endocrinology"

Yonggeun Cho, Hanmil Jang, Hyun-June Nam et al.

BackgroundFibroblast growth factor 23 (FGF23) is a bone-derived phosphaturic hormone that is essential for phosphate homeostasis. Elevated FGF23 levels underlie FGF23-related hypophosphatemic rickets and tumor-induced osteomalacia. Despite its clinical importance, population-based reference intervals (RIs) for intact FGF23 using the widely deployed LIAISON XL automated chemiluminescent immunoassay platform (DiaSorin) are lacking for East Asian populations.MethodsWe established method-specific RIs for intact FGF23 (iFGF23) in 386 healthy Korean adults (193 males and 193 females; age, 20–79 years) following the Clinical and Laboratory Standards Institute EP28-A3c guidelines. After the Box–Cox transformation and Horn’s outlier detection, the RIs were derived using nonparametric methods (2.5th–97.5th percentiles). The necessity for partitioning was assessed using the Harris–Boyd method. Associations between iFGF23 levels and demographic, anthropometric, and biochemical parameters were examined using Pearson’s correlation coefficients.ResultsThe overall nonparametric RI was 28.04–100.33 pg/mL (90% CI: 25.77–31.91 to 96.29–109.20). Age emerged as the primary determinant requiring partitioning, with young adults (20–29 years) exhibiting significantly lower concentrations than older adults (≥30 years): 25.73–78.76 versus 32.01–107.00 pg/mL. A sex-stratified analysis confirmed that this age effect persisted independently in both males and females. Although males had higher median iFGF23 than females (65.03 vs. 51.98 pg/mL, p < 0.001), Harris–Boyd analysis did not support sex-based partitioning (z = 5.17, z* = 5.38). Intact FGF23 was significantly correlated with age (r = 0.278), estimated glomerular filtration rate (r = –0.254), and alkaline phosphatase (r = 0.143; all p ≤ 0.005), but not with traditional mineral metabolism parameters (phosphate, calcium, parathyroid hormone, and 25-hydroxyvitamin D).ConclusionsThis study provides the first population- and method-specific RIs for intact FGF23 in an East Asian population and establishes critical age-stratified benchmarks for clinical interpretation. The distinct RI in young adults underscores the necessity of age-appropriate reference standards for diagnosing and monitoring phosphate homeostasis disorders. These findings highlight the importance of population-specific reference data in the absence of assay harmonization.

Xiaofeng Zhu, Xiaoyang Deng, Li Li et al.

Objective To evaluate the effect of intrauterine infusion of platelet-rich plasma (PRP) on luteal support and pregnancy outcomes in patients with thin endometrium undergoing frozen-thawed embryo transfer (FET).Methods A total of 160 patients with thin endometrium undergoing FET from March 2023 to March 2024 were assigned to the observation group (PRP infusion, n = 80) or the control group (conventional treatment, n = 80). All patients underwent hormone replacement therapy cycles, with PRP infused on days 9, 11, and 13 in the observation group. Outcomes included endometrial thickness, uterine hemodynamic parameters (PI, RI), PBAC-assessed menstrual volume, pregnancy outcomes, and embryology-related variables. Logistic regression identified independent factors associated with clinical pregnancy. Adverse events were also recorded.Results Post-treatment, the observation group had greater endometrial thickness and lower PI and RI values than the control group. PBAC scores, clinical pregnancy rate (36.25% vs. 21.25%), and live birth rate (25.00% vs. 12.50%) were significantly higher, while preterm birth rate did not differ. Embryo transfer–related variables were comparable between groups. Multivariate analysis identified PRP infusion and endometrial thickness at transfer as independent protective factors for clinical pregnancy, whereas advanced age was an unfavorable factor. No obvious adverse events occurred.Conclusion PRP infusion enhances endometrial receptivity by improving thickness and blood perfusion, thereby increasing pregnancy and live birth rates in thin endometrium patients undergoing FET. It is safe and may be used as an effective adjunct in endometrial preparation.

Yuqin Cai, Meijie Yang, Shuting Ma et al.

BackgroundHeart failure (HF) is a serious cardiovascular disorder with a poor prognosis, which affects the quality of life and survival in patients. The triglyceride-glucose (TyG) index, a new biomarker for insulin resistance (IR) in the body, has attracted widespread attention from researchers investigating cardiovascular disease (CVD). This study was aimed at assessing the prognostic value of the TyG index in HF patients by a meta-analysis, thereby providing clinicians with a new predictive tool.MethodsPubMed, Cochrane, EMBASE, and Web of Science were searched for studies (from inception to March 2025) on the association of the TyG index with the prognosis of HF. Meta-analysis was conducted using Stata15. Such association was assessed using a random effects model in conjunction with the hazard ratio (HR) and its 95% confidence interval (CI). In addition, subgroup analysis, publication bias analysis, and sensitivity analysis were performed.ResultsNineteen studies were included with 44275 HF patients. A significant association was found between an increase in the TyG index and an increase in the risk of all-cause death (ACD) in HF patients (HR=1.70, 95% CI: 1.40-2.08, P<0.001). Increased TyG index predicted major adverse cardiovascular events (MACEs) (HR=2.37, 95% CI: 1.80-3.13, P<0.001) and cardiovascular death (CV death) (HR=1.63, 95% CI: 1.01-2.61, P<0.001). Subgroup analysis showed an association of increased TyG index with a poor prognosis regardless of ejection fraction, and the presence or absence of diabetes. Dose-response analysis showed no linear dose-response relationship (DRR) of the index with ACD, MACEs or CV death.ConclusionThe TyG index is closely associated with the prognosis of HF. Therefore, it can be used as a prognostic tool for the assessment of HF. A high TyG index may indicate a high risk of ACD and CV events. Therefore, monitoring of the TyG index is significant for risk assessment and management of HF patients. Future studies on the use of the TyG index in therapeutic decision-making for HF are needed.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024562063.

Feiyan Zhang, Jie Lv, Maidinaimu Aibibula et al.

BackgroundKidney stones (KS) are a prevalent urological condition with high recurrence rates and substantial treatment costs. Hypertension has been identified as an independent risk factor for KS. The waist-to-hip ratio (WHR) has also been associated with KS; however, its relationship with KS in the hypertensive population remains unexplored. Through a population-based cross-sectional study, this study aimed to assess the association between WHR and KS risk in the hypertension population.MethodsData from the National Health and Nutrition Examination Survey (NHANES) 2007 to 2020 were analyzed, comprising 1,572 hypertensive patients. Logistic regression and restricted cubic splines analysis were performed to examine the association between WHR and KS. Receiver operator characteristic (ROC) analyses were performed to assess the diagnostic ability of several human obesity-related indices for KS.ResultsA total of 1,572 hypertensive patients were included in the final study, with a mean age of 54.87 years and a prevalence of KS of 12.28%. The study found a significant association between WHR and KS, even after adjusting for confounding factors, with higher WHR associated with a higher likelihood of KS occurrence (OR = 1.63, 95%CI: 1.13, 2.34). This positive association is linear (non-linear p >0.05). ROC curve results showed that WHR had the highest AUC. Subgroup analysis showed consistent associations in almost all populations, with no significant interaction effects (p for interaction > 0.05). Finally, sensitivity analysis further confirmed the stability of the results.ConclusionIn the hypertensive population, WHR is positively associated with the likelihood of KS. These findings highlight the importance of considering WHR as a risk factor for KS in hypertensive individuals, providing valuable insights for managing KS in this population.

Giovanna Caparello, Fabrizio Ceraudo, Francesca Meringolo et al.

Objective: The promotion of a healthy diet, such as the Mediterranean Diet (MD), among childhood is of a particular importance, since eating behaviors learned early in life have been shown to be maintained into adolescence and adulthood. The most efficient intervention in childhood is the active involvement of the schools. Design: The aim of this study was to evaluate the adherence to the MD model and the skin carotenoid levels among children divided by their school lunch attendance. Methods: This cross-sectional study involved 132 pupils (64 girls and 68 boys), divided between children who ate lunch at school (44%) and at home (56%). The children who had meals provided by the school participated in activities promoting the health benefits of fruits and vegetables. All participants underwent anthropometric measurements and assessment of the MD adherence and the physical activity using KIDMED and PAQ-C questionnaires, respectively, and skin carotenoid content using the Veggie Meter®. Results: We found mean KIDMED and PAQ-C scores, while skin carotenoid content was below the normal range in our population sample. Interestingly, children who ate lunch provided by the school had significantly higher carotenoid scores with respect to those who had lunch at home (p = 0.005). In multiple regression analyses, we found that carotenoid scores were positively influenced by gender (p = 0.03), school lunch attendance (p = 0.01) and daily vegetable consumption (p = 0.0002) in our children population sample. Conclusions: Our results suggest the importance of promoting a healthy lifestyle at the school to improve eating habits during childhood as a strategy for disease prevention across the lifespan.

Junwei Liu, Weiqiang Zhu, Lingjin Xia et al.

IntroductionCapping actin protein, gelsolin-like (CAPG) is a potential therapeutic target in various cancers. However, the potential immunotherapeutic effects and prognostic value of CAPG in uterine corpus endometrial carcinoma (UCEC) remain unclear.MethodsThe characterization, methylation effects, prognostic value, targeted miRNAs of CAPG, and the correlation of CAPG with immune cell infiltration and ferroptosis in UCEC were investigated using multiple public databases and online tools. Furtherly, we explored the potential physiological function of CAPG using EdU and Transwell migration assays, identified the cell localization and expression of CAPG and GPX4 by immunofluorescence, and detected the intracellular Fe2+ levels using a FerroOrange fluorescent probe in Ishikawa cells. Additionally, the OncoPredict package was used to analyze the potential chemotherapeutic drugs for UCEC.ResultsCAPG showed generally high expression in tumor group. The overall survival rate of the high-risk group was significantly lower than that of the low-risk group. Enrichment analysis indicated that CAPG is involved in immune-related pathways and is closely associated with the tumor microenvironment. CAPG expression levels were affected by abnormal DNA methylation and/or targeted miRNAs, infiltration levels and marker genes of various immune cells, thereby impacting immune response, ferroptosis, and patient prognosis. Ferroptosis analysis indicated that ALOX5 and VLDLR were the top CAPG-related ferroptosis markers; glutathione metabolism levels in tumor group were generally high, and decitabine was a ferroptosis inducer. CAPG-siRNA suppressed the cell proliferation and invasion, and markedly elevated the expression levels of immune-related genes IL8, TNF, TLR4 and the intracellular Fe2+ levels. CAPG co-located with GPX4 in nucleus and co-regulated ferroptosis and metabolism in Ishikawa cells. Moreover, four chemotherapy drugs showed better sensitivity to UCEC patients in the low-risk cohort.ConclusionsCAPG may serve as a potential biomarker of UCEC owing to its role in modulating the immune response and ferroptosis, providing novel perspectives for combined immunotherapy of UCEC.

Xitong Liu, Juanzi Shi

Introduction Obesity has been associated with an increased risk of reproductive failure, especially preterm birth. As preimplantation genetic testing for aneuploidies (PGT-A) is increasingly used worldwide, however, it is still unclear whether body mass index (BMI) has an effect on the preterm birth rate in patients undergoing in vitro fertilization (IVF) with PGT-A when transferring a single euploid blastocyst.Materials and methods This retrospective, single-center cohort study included 851 women who underwent the first cycle of frozen-thawed single euploid blastocyst transfer with PGT-A between 2015 and 2020. The primary outcome was the preterm birth rate. Secondary outcomes were clinical pregnancy, miscarriage, ectopic pregnancy, pregnancy complications, and live birth.Results Patients were grouped by World Health Organization (WHO) BMI class: underweight (<18.5, n = 81), normal weight (18.5–24.9, n = 637), overweight (25–30, n = 108), and obese (≥30, n = 25). There was no difference in the clinical pregnancy, miscarriage, ectopic pregnancy, pregnancy complication, and live birth by BMI category. In multivariate logistic regression analysis, preterm birth rates were significantly higher in women with overweight (adjusted odds ratio [aOR] 3.18; 95% confidence interval [CI], 1.29–7.80, p = .012) and obese (aOR 1.49; 95% CI, 1.03–12.78, p = .027) compared with the normal weight reference group.Conclusion Women with obesity experience a higher rate of preterm birth after euploid embryo transfer than women with a normal weight, suggesting that the negative impact of obesity on IVF and clinical outcomes may be related to other mechanisms than aneuploidy.

Qiaochu Wang, Nanxi Huang, John B. Psaltis et al.

ObjectiveEstrogen-related receptor γ (ERRγ) is a metabolic regulator with no identified physiological ligands. This study investigates whether calcium is an ERRγ ligand that mediates the effects of glucagon and whether cadmium, which mimics the effects of calcium, disrupts metabolism through ERRγ.MethodHepG2, MCF-7, and HEK293T transfected with ERRγ were treated with glucagon, calcium, cadmium, ERRγ agonist, or ERRγ inhibitor. Cells were then collected for in vitro assays including real-time qPCR, Western blot, ChIP, immunofluorescence, mutational analysis, or gene set enrichment analysis. Molecular dynamics simulations were performed to study mutation sites.ResultsIn HepG2 cells, treatment with glucagon, calcium, or cadmium re-localized ERRγ to the cell nucleus, recruited ERRγ to estrogen-related response elements, induced the expression of ERRγ-regulated genes, and increased extracellular glucose that was blocked by an ERRγ antagonist. In MCF-7 cells and HEK293T cells transfected with ERRγ, similar treatments induced the expression of metabolic genes. Mutational analysis identified S303, T429, and E452 in the ligand-binding domain as potential interaction sites. Molecular dynamics simulations showed that calcium induced changes in ERRγ similar to ERRγ agonist.ConclusionThe results suggest that calcium is a potential ligand of ERRγ that mediates the effects of glucagon and cadmium disrupts metabolism through ERRγ.

Mahya Mehri Hajmir, Atieh Mirzababaei, Cain C. T. Clark et al.

Abstract Background Previous studies have shown that the minor allele (C allele) for melanocortin 4 receptor (MC4R) rs17782313 may be associated with depressed mood. Moreover, dietary patterns have potentially adverse effects on depression. This study investigates the interactions between the MC4R gene variant (rs17782313) and dietary patterns on depression among Iranian obese and overweight women. Methods A total of 289 Iranian overweight and obese women, aged 18–50 years, were enrolled in this cross-sectional study. Biochemical, anthropometric, and body composition indices were assessed in all participants. Moreover, MC4R rs17782313, by the restriction fragment length polymorphism (PCR-RFLP) method, and depression, using the 21-item Depression Anxiety Stress Scales (DASS) questionnaire, were assessed. Food intakes were assessed by completing a 147-item semi-quantitative food frequency questionnaire (FFQ). Results By the use of factor analysis, 2 major dietary patterns were extracted: healthy dietary pattern (HDP) and unhealthy dietary pattern (UDP). Binary logistic analysis showed that individuals with minor allele risk (CC) with high adherence to the unhealthy pattern increased odds for depression (OR: 8.77, 95%CI: -0.86-18.40, P: 0.07), after controlling for confounders. Also, a logical inverse relationship was observed between CT genotype and HDP on depression in the crude and adjusted models (OR: -0.56, 95% CI: -3.69-2.57, P: 0.72) (OR: -4.17, 95% CI: -9.28-0.94, P: 0.11), although this interaction was not statistically significant. Conclusion According to the above findings, adherence to unhealthy food intake pattern increases odds of depression in MC4R risk allele (C allele) carriers. To confirm these findings, more studies are needed in the form of clinical trials and prospective studies with higher sample sizes.

Bettina Bongiovanni, Bettina Bongiovanni, Bettina Bongiovanni et al.

Dehydroepiandrosterone (DHEA) is an androgen synthesized by the adrenal cortex, which is an intermediary in the biosynthesis of sex hormones, such as testosterone and estradiol. DHEA mostly circulates as a conjugated ester, in the form of sulfate (DHEA-S). There exist several endogenous factors able to influence its synthesis, the most common ones being the corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), growth factors, and proinflammatory cytokines, among others. Like other steroid hormones, DHEA, can alter the functioning of immune cells and therefore the course of diseases exhibiting an immune-inflammatory component, mostly from autoimmune or infectious nature. We herein review the role played by DHEA during a major infectious disease like tuberculosis (TB). Data recorded from TB patients, mouse models, or in vitro studies show that DHEA is likely to be implied in better disease control. This provides a stimulating background for carrying out clinical studies aimed at assessing the usefulness of DHEA as an adjuvant in TB patients.

Breanna McSweeney, Rachel B. Campbell, Eshleen K. Grewal et al.

IntroductionPersons with lived experience of homelessness face many challenges in managing diabetes, including purchasing and storing medications, procuring healthy food and accessing healthcare services. Prior studies have found that pharmacy-led interventions for diabetes improved A1C, and lowered blood pressure and cholesterol in general populations. This study evaluated how select pharmacists in Canada have tailored their practices to serve persons with lived experiences of homelessness with diabetes.MethodsWe conducted a qualitative descriptive study using open-ended interviews with inner-city pharmacists in select Canadian municipalities (Calgary, Edmonton, Vancouver, and Ottawa). We used NVivo qualitative data analysis software to facilitate thematic analysis of the data, focusing on how pharmacists contributed to diabetes care for persons with lived experience of homelessness.ResultsThese pharmacists developed diabetes programs after discovering an unmet need in the population. Pharmacists have the unique ability to see patients frequently, allowing tailored education and hands-on assistance with diabetes management. These pharmacists provided extra-ordinary care like financial and housing resources and many of them were uniquely embedded within other services for persons with lived experience of homelessness (i.e. housing and social work supports). Pharmacists reported struggling with balancing optimal medical care for individuals with the financial constraints of running a business.ConclusionPharmacists are vital members of the diabetes care team for persons with lived experience of homelessness. Government policies should support and encourage unique models of care provided by pharmacists to improve diabetes management for this population.

Camila Viecceli, Camila Viecceli, Ana Carolina Viana Mattos et al.

ObjectiveThe first-line treatment for Cushing’s disease is transsphenoidal surgery, after which the rates of remission are 60 to 80%, with long-term recurrence of 20 to 30%, even in those with real initial remission. Drug therapies are indicated for patients without initial remission or with surgical contraindications or recurrence, and ketoconazole is one of the main available therapies. The objective of this study was to evaluate the safety profile of and the treatment response to ketoconazole in Cushing’s disease patients followed up at the endocrinology outpatient clinic of a Brazilian university hospital.Patients and methodsThis was a retrospective cohort of Cushing’s disease patients with active hypercortisolism who used ketoconazole at any stage of follow-up. Patients who were followed up for less than 7 days, who did not adhere to treatment, or who were lost to follow-up were excluded.ResultsOf the 172 Cushing’s disease patients who were followed up between 2004 and 2020, 38 received ketoconazole. However, complete data was only available for 33 of these patients. Of these, 26 (78%) underwent transsphenoidal surgery prior to using ketoconazole, five of whom (15%) had also undergone radiotherapy; seven used ketoconazole as a primary treatment. Ketoconazole use ranged from 14 days to 14.5 years. A total of 22 patients had a complete response (66%), three patients had a partial response (9%), and eight patients had no response to treatment (24%), including those who underwent radiotherapy while using ketoconazole. Patients whose hypercortisolism was controlled or partially controlled with ketoconazole had lower baseline 24-h urinary free cortisol levels than the uncontrolled group [times above the upper limit of normal: 0.62 (SD, 0.41) vs. 5.3 (SD, 8.21); p &lt; 0.005, respectively] in addition to more frequent previous transsphenoidal surgery (p &lt; 0.04). The prevalence of uncontrolled patients remained stable over time (approximately 30%) despite ketoconazole dose adjustments or association with other drugs, which had no significant effect. One patient received adjuvant cabergoline from the beginning of the follow-up, and it was prescribed to nine others due to clinical non-response to ketoconazole alone. Ten patients (30%) reported mild adverse effects, such as nausea, vomiting, dizziness, and loss of appetite. Only four patients had serious adverse effects that warranted discontinuation. There were 20 confirmed episodes of hypokalemia among 10/33 patients (30%).ConclusionKetoconazole effectively controlled hypercortisolism in 66% of Cushing’s disease patients, being a relatively safe drug for those without remission after transsphenoidal surgery or whose symptoms must be controlled until a new definitive therapy is carried out. Hypokalemia is a frequent metabolic effect not yet described in other series, which should be monitored during treatment.

Xiao-cong Liu, Yu Huang, Kenneth Lo et al.

ObjectiveMeasuring the body mass index (BMI) or waist circumference (WC) alone is insufficient for assessing possible health risks due to obesity. This study aimed to investigate whether the quotient of WC and BMI can be used as a proxy of the high-risk phenotype of obesity.MethodsData for analysis were derived from the National Health and Nutrition Examination Survey (NHANES 1999-2014). The Waist-BMI Ratio was defined as WC divided by BMI. The associations between Waist-BMI Ratio and mortality were estimated using Cox regression models. Restricted cubic spline and two-piecewise linear regression models were used to identify non-linear relationships. The discriminative abilities of different anthropometric measures were compared using receiver operating characteristic curves (ROC).ResultsThis study is based on data from 35557 adults (51.1% female, mean age 44.9 years). During an average follow-up of 101.8 months, 3680 participants died, including 807 of cardiovascular causes. In fully adjusted models, Waist-BMI Ratio was independently associated with overall (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.48-2.13) and cardiovascular (HR, 1.77; 95% CI, 1.25-2.52) mortality. Spline analyses revealed that dose-response relationships existed between Waist-BMI Ratio and death. The mortality risk rises dramatically above the cut-off point of the Waist-BMI Ratio (HR, 3.22; 95% CI, 2.43-4.26 for overall mortality and HR, 3.07; 95% CI, 1.71-5.52 for cardiovascular mortality). ROC curve analysis suggested that Waist-BMI Ratio was a better discriminator of mortality (AUC 0.637 for overall and 0.639 for cardiovascular mortality) than BMI, WC, and waist-to-height ratio (Delong’s test all P &lt;0.001).ConclusionsWaist-BMI Ratio was independently associated with overall and cardiovascular mortality in a J-shaped pattern, offering an immense potential risk marker for obesity in the clinical setting.

Amy Creecy, John G. Damrath, Joseph M. Wallace

Osteocytes make up 90–95% of the cellular content of bone and form a rich dendritic network with a vastly greater surface area than either osteoblasts or osteoclasts. Osteocytes are well positioned to play a role in bone homeostasis by interacting directly with the matrix; however, the ability for these cells to modify bone matrix remains incompletely understood. With techniques for examining the nano- and microstructure of bone matrix components including hydroxyapatite and type I collagen becoming more widespread, there is great potential to uncover novel roles for the osteocyte in maintaining bone quality. In this review, we begin with an overview of osteocyte biology and the lacunar–canalicular system. Next, we describe recent findings from in vitro models of osteocytes, focusing on the transitions in cellular phenotype as they mature. Finally, we describe historical and current research on matrix alteration by osteocytes in vivo, focusing on the exciting potential for osteocytes to directly form, degrade, and modify the mineral and collagen in their surrounding matrix.

Yu.M. Urmanova, M.Yu. Shakirova, N.T. Rikhsieva et al.

Background. Nowadays, a search for diagnostically significant markers of aggressiveness of non­functioning pituitary adenomas remains relevant for further prognosis in the postoperative period. Non­functioning pituitary adenomas without pituitary hypersecretion are the forms of adenohypophysis tumors. In the general population, frequency of non­functioning pituitary adenomas is 50 cases per 1 million people. The purpose of the study is to determine the clinical diagnostic markers of tumor aggressiveness in patients with non­functio­ning pituitary adenomas and growth hormone deficiency, as well as their role in the severity of the neuroendocrine symptoms of the disease. Materials and methods. Under our supervision, there were 87 patients (44 men, 43 women), of them 31 with a verified diagnosis of non­functioning pituitary adenomas after transnasal hypophysectomy. Follow­up was from 1 to 3 years. Results. When patients were distributed in groups depending on histological description of non­functioning pituitary adenomas, those with chromophobe pituitary adenoma prevailed (77.5 %). Non­functioning pituitary ade­nomas in women were associated with obesity, primary and secondary hypothyroidism, secondary hypogonadism, syndrome of persistent galactorrhea­amenorrhea (symptomatic and idiopathic forms), diabetes insipidus, empty sella syndrome and others. In men, non­functioning pituitary adenomas was accompanied by obesity, primary and secondary hypothyroidism, secondary hypogonadism, diabetes insipidus, gynecomastia. The scale developed to determine the markers of aggressiveness of non­functioning pituitary adenomas allowed identifying factors by 3 degrees and developing a set of measures to prevent the recurrence of tumor growth. Conclusions. Markers of aggressiveness of non­functioning pituitary adenomas are: young age of the patient, first symptoms of the disease, large tumor sizes, asymmetry and deformation of the pituitary gland, signs of tumor invasion into adjacent tissues/arteries/cavernous sinus, small cell and/or dark cell chromophobe adenomas, panhypopituitarism.

Vania Nosé

Mohamad Maghnie, José I. Labarta, Ekaterina Koledova et al.

The “360° GH in Europe” meeting, which examined various aspects of GH diseases, was held in Lisbon, Portugal, in June 2016. The Merck KGaA (Germany) funded meeting comprised three sessions entitled “Short Stature Diagnosis and Referral,” “Optimizing Patient Management,” and “Managing Transition.” Each session had three speaker presentations, followed by a discussion period, and is reported as a manuscript, authored by the speakers. The first session examined current processes of diagnosis and referral by endocrine specialists for pediatric patients with short stature. Requirements for referral vary widely, by country and by patient characteristics such as age. A balance must be made to ensure eligible patients get referred while healthcare systems are not over-burdened by excessive referrals. Late referral and diagnosis of non-GH deficiency conditions can result in increased morbidity and mortality. The consequent delays in making a diagnosis may compromise the effectiveness of GH treatment. Algorithms for growth monitoring and evaluation of skeletal disproportions can improve identification of non-GH deficiency conditions. Performance and validation of guidelines for diagnosis of GH deficiency have not been sufficiently tested. Provocative tests for investigation of GH deficiency remain equivocal, with insufficient information on variations due to patient characteristics, and cutoff values for definition differ not only by country but also by the assay used. When referring and diagnosing causes of short stature in pediatric patients, clinicians need to rely on many factors, but the most essential is clinical experience.

Yukihiro Bando, Hitomi Tohyama, Keiko Aoki et al.

Aims: This preliminary randomized, parallel-group comparative study evaluated the efficacy of ipragliflozin for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). Methods: Sixty-two patients with T2DM (age, 56 ± 8 years; hemoglobin A1c levels, 8.1 ± 0.9%; BMI, 27.5 ± 3.3 kg/m2) were randomly assigned in a 2:1 ratio to receive ipragliflozin (50 mg/day) (treatment group; n = 40) or continued treatment (control group; n = 22) for 12 weeks. The primary endpoints were changes in sd LDL-C levels detected using the LipoPhor AS® system; the secondary endpoints included changes in the sd LDL-C/large buoyant LDL-C (lb LDL-C) ratio, a surrogate marker for LDL particle size, and percent changes in routine lipid parameters. Results: The treatment group exhibited a statistically significant reduction from baseline for LDL-C levels (−0.37 mg/dL vs. 14.4 mg/dL, p = 0.038), sd LDL-C levels (−1.28 mg/dL vs. 2.81 mg/dL, p = 0.012), and sd LDL-C/lb LDL-C ratio (−3.20% vs. 4.58%, p = 0.040) compared with the control group. Multiple regression analysis among all subjects revealed change in TG levels (p = 0.011) and LDL-C levels (p = 0.024) as well as change in body weight (p = 0.006) as independent factors contributing to the reduction in sd LDL-C. Conclusions: Ipragliflozin may have a potential for lowering sd LDL-C levels associated with increasing LDL particle size in Japanese patients with T2DM.

Anna Lih, Lorraine Pereira, Ramy H. Bishay et al.

Introduction. Obesity and diabetes are difficult to treat in public clinics. We sought to determine the effectiveness of the Metabolic Rehabilitation Program (MRP) in achieving long-term weight loss and improving glycaemic control versus “best practice” diabetes clinic (DC) in obese patients using a retrospective cohort study. Methods. Patients with diabetes and BMI > 30 kg/m2 who attended the MRP, which consisted of supervised exercise and intense allied health integration, or the DC were selected. Primary outcomes were improvements in weight and glycaemia with secondary outcomes of improvements in blood pressure and lipid profile at 12 and 30 months. Results. Baseline characteristics of both cohorts (40 MRP and 40 DC patients) were similar at baseline other than age (63 in MRP versus 68 years in DC, P=0.002). At 12 months, MRP patients lost 7.65 ± 1.74 kg versus 1.76 ± 2.60 kg in the DC group (P<0.0001) and 9.70 ± 2.13 kg versus 0.98 ± 2.65 kg at 30 months (P<0.0001). Similarly, MRP patients had significant absolute reductions in %HbA1c at 30 months versus the DC group (−0.86 ± 0.31% versus 0.12% ± 0.33%, P<0.038), with nonsignificant improvements in lipids and blood pressure in MRP patients. Conclusion. Further research is needed to establish the MRP as an effective strategy for achieving sustained weight loss and improving glycaemic control in obese patients with type 2 diabetes.

Shan-Shan Wu, Qiu-Hua Liang, Yuan Liu et al.

It has been presumed that adipokines deriving from adipose tissue may play important roles in bone metabolism. Omentin-1, a novel adipokine, which is selectively expressed in visceral adipose tissue, has been reported to stimulate proliferation and inhibit differentiation of mouse osteoblast. However, little information refers to the effect of omentin-1 on human osteoblast (hOB) proliferation. The current study examined the potential effects of omentin-1 on proliferation in hOB and the signal pathway involved. Omentin-1 promoted hOB proliferation in a dose-dependent manner as determined by [3H]thymidine incorporation. Western blot analysis revealed that omentin-1 induced activation of Akt (phosphatidylinositol-3 kinase downstream effector) and such effect was impeded by transfection of hOB with Akt-siRNA. Furthermore, LY294002 (a selective PI3K inhibitor) and HIMO (a selective Akt inhibitor) abolished the omentin-1-induced hOB proliferation. These findings indicate that omentin-1 induces hOB proliferation via the PI3K/Akt signaling pathway and suggest that osteoblast is a direct target of omentin-1.