Exercise interventions can improve parameters in offspring predisposed to metabolic issues. In this study, we investigate whether acute aerobic exercise in offspring can improve metabolism via miRNA modulation in mice programmed by maternal obesity. Female Swiss mice fed either a standard chow (C) or a high-fat diet (HF) during gestation and lactation were mated with C male mice. Offspring fed the C diet underwent swimming exercise protocols, consisting of water adaptation (14 days), a lactate minimum test, and an aerobic intensity exercise session or no exercise at 84 days of age. Offspring of obese dams (OHF) exhibited increased hepatic glycogen and triglyceride compared to offspring of control dams (OC). However, in offspring of obese dams subjected to an individualized aerobic session (OHF-E), these parameters did not differed from the other groups. Hepatic gene expression analysis showed that miR-122 was upregulated in OHF-E, inversely to Agpat levels. Additionally, OHF exhibited higher miR-370 and lower Cpt1a levels; exercise restored miR-370 and elevated Cpt1a levels in OHF-E. Regarding muscle tissue, exercise reduced Ptp1b expression in OHF-E and increased Hif1a and Pparg, despite no changes observed in miR-206 levels. A single session of exercise significantly affected miRNA and transcript levels related to hepatic lipid and muscle glucose metabolism, suggesting that even one bout of exercise can benefit offspring in the context of maternal metabolic programming. This highlights tissue responsiveness and adaptive capacity, warranting further investigation into its potential as a long-term, non-pharmacological intervention.
To evaluate the diagnostic performance and determine the optimal cutoff values of the triglyceride-to-high-density lipoprotein cholesterol ratio and lipid accumulation product index as predictors of metabolic syndrome among adults with obesity in Indonesia. This cross-sectional study analyzed secondary data from the 2023 Indonesia Health Survey, which included 3,988 samples (2,958 women). Descriptive statistics were used to characterize the sample. Receiver Operating Characteristic curve analysis and the Youden index were employed to assess diagnostic performance and determine the optimal cutoff values of the triglyceride-to-high-density lipoprotein cholesterol ratio and lipid accumulation product index. The associations between both predictors and the presence of metabolic syndrome were examined using multivariable logistic regression. The lipid accumulation product index exhibited greater predictive accuracy than the triglyceride-to-high-density lipoprotein cholesterol ratio, particularly among men. This result indicated the superior utility of the lipid accumulation product index as a clinical screening tool for metabolic syndrome, with area under the curve values of 0.842 (95% CI 0.817-0.866) for men and 0.737 (95% CI 0.720-0.755) for women, compared to that of the triglyceride-to-high-density lipoprotein cholesterol ratio, with area under the curve values of 0.810 (95% CI 0.784-0.837) for men and 0.728 (95% CI 0.710-0.746) for women. The optimal cutoff values of the triglyceride-to-high-density lipoprotein cholesterol ratio and lipid accumulation product index were 4.456 (sensitivity 64.8%, specificity 81.4%) and 45.752 (sensitivity 75.5%, specificity 81.2%) for men and 2.792 (sensitivity 59.2%, specificity 76.8%) and 41.285 (sensitivity 58.6%, specificity 75.8%) for women, respectively. The lipid accumulation product index demonstrated superior accuracy in predicting metabolic syndrome among adults with obesity, particularly among men. Sex-specific cutoff values enhance its reliability and practicality for early screening and intervention to prevent metabolic complications.
This study aimed to compare body composition measurements between patients with nonfunctional adrenal incidentalomas (NFAI) and mild autonomous cortisol secretion (MACS) using bioelectrical impedance analysis (BIA) and anthropometric methods. This cross-sectional study included patients diagnosed with MACS or NFAI. Body composition was assessed using BIA, anthropometric measurements, and the Durnin and Womersley (DW) method. Correlation and Bland-Altman analyses were performed to assess the relationship and agreement between the DW method and BIA. Fifty-seven patients (32 with MACS and 25 with NFAI) were included; those with MACS were older (p = 0.004). Post-dexamethasone suppression test cortisol levels (p < 0.001) and the incidence of bilateral tumors (p = 0.017) were higher in MACS patients. No significant differences in body composition parameters were observed between the MACS and NFAI groups. A strong correlation was observed between BIA- and DW-derived fat mass in MACS patients (r = 0.890, p < 0.001). Bland-Altman analysis revealed a slight mean bias for body fat mass of -0.4 kg (limits of agreement: -9.14-8.34 kg) and for body fat percentage of -0.83% (limits of agreement: -11.32-9.66%) between methods. A robust correlation and acceptable agreement was demonstrated between the DW method and BIA for estimating body fat. The DW equation may provide a practical and low-cost alternative for assessing body composition in MACS and NFAI cohorts. Limitations include the lack of a healthy control group and the inability to validate BIA and anthropometric estimates against gold-standard imaging techniques, potentially introducing accuracy bias.
To determine the frequency and types of breast calcif ication, the distribution of breast imaging-reporting and data system (BI-RADS) scores, and the association between calcif ication and biochemical/clinical findings in patients with primary hyperparathyroidism (PHPT). We recruited ≥ 40-year-old female patients with PHPT (n = 104) and age-matched healthy women (n = 107) as controls. Mammography was performed on all participants. Calcif ication, calcif ication type, and BI-RADS scores were recorded, and patients were divided into two groups based on PHPT duration and presence/absence of calcification. BI-RADS score distribution was indifferent between groups. The frequency of calcification and distribution of calcification types showed no difference between groups. Likewise, mammography findings were consistent among PHPT patients regardless of disease duration. There was no cutoff for disease duration that could predict the presence of calcification. Breast calcification was negatively correlated with parathyroid hormone (r = -0.220, p = 0.025) and 24-hour urine calcium levels (r = -0.195, p = 0.048), and positively correlated with age (r = 0.219, p = 0.025) in PHPT patients. Of the six patients who underwent cytological examination, one was found to be malignant (PHPT group). Female patients with PHPT do not have an increased incidence of breast calcification or higher BI-RADS scores compared to healthy women, and the calcification rates were unaffected by the duration of the disease. The presence of calcification does not appear to be associated with an increased risk of breast cancer in PHPT patients. Nonetheless, given the frequency of breast cancer and that the only patient with breast cancer was part of the PHPT group, it would be appropriate to screen these patients for breast cancer carefully.
This study aims to evaluate ultra-processed food consumption and eating behavior in adults with obesity. A cross-sectional study with 77 volunteers from São Paulo, Brazil. Food consumption was assessed using three 24-hour dietary recalls, classified by using the NOVA classification system, and the Diet Quality Index was also evaluated. Eating behavior and symptoms of binge eating and bulimia were assessed using the Bulimic Investigatory Test Edinburgh (BITE), the Dutch Eating Behaviour Questionnaire (DEBQ), and the Three Factor Eating Questionnaire (TFEQ-21). The average BMI of the sample was 39.14 kg/m² ± 5.57, and the median caloric intake was 1661 kcal (756.07-4774.40), with a macronutrient distribution of 48% carbohydrates, 32% fat, and 20% protein. Volunteers were divided into tertiles of calories ingested from ultra-processed foods (%): 1st < 24.10% (n = 25); 2nd between 24.10%-35.40% (n = 26); and the 3rd > 35.40% (n = 26). The sample showed intermediate diet quality (43.08 ± 10.17), while the 3rd tertile presented a low-quality diet (37 ± 10), differing from other groups (p = 0.001; p = 0.003). All groups showed intermediate BITE scores (19,6 ± 9,8), an indicator of unusual eating behavior. The third tertile had a higher symptom score than the first tertile (p = 0.008). In the association analysis, the consumption of ultra-processed foods was positively associated with the presence of binge eating and bulimia symptoms (p = 0.018), emotional (p = 0.001) and external eating (p = 0.001) as assessed by the DEBQ, and emotional (p = 0.008) and uncontrolled eating (p = 0.006) as assessed by the TFEQ-21. In contrast, diet quality was negatively associated with the consumption of ultra-processed foods (p < 0.001). Our findings suggest that higher consumption of ultra-processed foods by volunteers with obesity may be associated with higher scores for unusual eating behavior, symptoms of binge eating, and bulimia, in addition to augmented emotional, external and uncontrolled eating, and lower diet quality scores.
The Female Athlete Triad (Triad) and Relative Energy Deficiency in Sport (RED-S) are conditions associated with low energy availability (EA) that can lead to menstrual dysfunction, impaired bone health, and metabolic disturbances. This case report describes the remission of Triad in a professional triathlete during the COVID-19 pandemic. A 24-year-old female triathlete was evaluated in 2018. She reported bulimia nervosa from 12-15 years old and hypothalamic amenorrhea since she was 21 years old. Her training volume was approximately 20 hours per week (swimming, cycling, and running), and the amount of EA was critically low (< 10 kcal/fat free mass/day). The athlete had lower than expected BMD at DXA scan (lumbar spine Z-score -2.3 SD) and lower cortical and trabecular vBMD and trabecular number by comparison with HR-pQCT normative data for young Brazilian women. During the 2020 pandemic, training centers were closed, leading to a decrease in exercise volume and a more balanced energy intake. Menstrual cycles resumed and she conceived spontaneously in the same year. Pregnancy and postpartum recovery were uneventful. She returned to competitions post pandemic, but no longer as a professional athlete. Chronic energy deficiency significantly affects the hypothalamic-pituitary-gonadal axis and bone health. A forced reduction in training intensity and improved dietary intake were key factors in the restoration of menstrual function and reproductive health. This case highlights the potential reversibility of the Female Athlete Triad when energy balance is restored. Awareness and early intervention are essential for preventing long-term consequences in female athletes.
To describe Brazilian national and regional trends in type 2 diabetes mellitus (T2DM) prevalence, incidence, burden, and exposure to T2DM risk factors. We sourced the Global Burden of Diseases Study (GBD) 2021 to obtain estimates and trends of T2DM deaths, incidence, prevalence, Years of Life Lost (YLLs), Years Lived with Disability (YLDs), and Disability Adjusted Life Year (DALYs) in Brazil and its regions. We present crude and age-standardized metrics, as well as the exposure to T2DM risk factors between 1990 and 2021. The national age-standardized prevalence of T2DM increased by 37.4% (95% UI 32.7 to 42.6) and the incidence by 32.3% (95% UI 27.6 to 37.7) from 1990 to 2021. Age-standardized deaths by T2DM decreased by 18.0% (95% UI -21.4 to -15.3), and the accompanying YLLs by 22.8% (95% UI -25.8 to -20.2). YLDs increased by 35.4% (95% UI 29.1 to 41.3), while DALYs' rates reduced by 3.1% (95% UI -8.2 to 1.7) since 1990. The Northeast region showed higher age-standardized prevalence, incidence, YLLs, and YLDs in 2021, while the North region had the most pronounced increases. T2DM prevalence increased consistently, alongside rises in exposure to sugar-sweetened beverage consumption and high BMI. While smoking exposure declined in all regions, low physical activity and diets high in red and processed meat increased over time. T2DM burden in Brazil is growing due to the increasing exposure to T2DM risk factors. Greater emphasis on prevention and public policies focusing on reducing risk factors and inequalities can reduce T2DM burden in Brazil.
This study aimed to analyze preoperative, intraoperative, and postoperative factors that affect the surgical prognosis of non-functioning pituitary adenomas (NFPA) and to determine postoperative complication rates. We conducted a retrospective cohort study of patients with NFPA who underwent surgery between 1995 and 2024 at a tertiary public hospital in Brazil. Variables analyzed included tumor size, cavernous sinus invasion (Knosp classification), endocrinological status, preoperative clinical features, surgical complications, and outcomes. Statistical significance was set at p ≤ 0.05. Seventy-three patients were included, with a mean age of 53 years and a slight predominance of females. Tumors were classified as macroadenomas (59%) and giant adenomas (41%). The transsphenoidal approach was used in 81% of cases. Partial resection was achieved in 56%, subtotal in 16%, and total in 27%. Immediate postoperative complications included diabetes insipidus (30%), bleeding (11%), hydrocephalus (10%), ischemia (10%), meningitis (6%), and cerebrospinal fluid fistula (11%). Mortality was 9.6%, significantly associated with postoperative hydrocephalus, ischemia, and larger tumor size. Giant tumors were correlated with higher rates of preoperative neurological deficits and postoperative complications. Transcranial surgery was more frequently performed in cases of giant adenomas and was associated with increased rates of ischemia and neurological deficits. Tumor recurrence was observed in 33% of patients over a mean follow-up of 48 months. Tumor size and postoperative complications such as hydrocephalus and ischemia were associated with increased morbidity and mortality. Postoperative hydrocephalus, ischemia, and tumor size are key determinants of mortality in NFPA surgical treatment. Implementing preventive and management strategies targeting these complications could improve patient outcomes, albeit rigorous long-term follow-up is essential due to the high rates of recurrence and reoperation.
To investigate the impact of dietary intake profile on body composition, physical performance, and muscle strength in patients with acromegaly. Observational, cross-sectional study involving patients with acromegaly compared with age and sex-matched controls. Body composition, including total lean mass (TLM) and appendicular lean mass (ALM), was assessed using dual-energy X-ray absorptiometry (DXA). All participants completed a Food Frequency Questionnaire (FFQ) and underwent strength and performance testing. A total of 82 patients were included, 41 in the acromegaly group (AG) and 41 in the control group (CG). The AG comprised 23 women and 18 men, mean age 55.9 ± 11.8 years and mean BMI 31.1 ± 5.2 kg/m2. Muscle mass was increased in the AG, but strength and physical performance were worse compared to CG. AG exhibited a higher intake of carbohydrates, trans fats, and certain micronutrients, as omega-3, vitamin B9, and beta-carotene, compared to the CG. Niacin (R = -0.316, p = 0.004) and vitamin B6 (R = -0.320, p = 0.042) were associated with performance on the sit to stand test. Beta-carotene (R=-0.429, p=0.005), vitamin E (R = -0.321, p=0.041), and flavone (R = -0.313, p = 0.046) were associated with better time to get up and go (TUG) test performance, whereas caffeine intake (R = 0.344, p = 0.028) was associated with worse time. Additionally, niacin (R = 0.341, p = 0.029) and selenium (R = 0.317, p = 0.046) had a positive impact on the short physical performance battery (SPPB) test. Hand grip strength was positively correlated with monounsaturated fats (R = 0.387, p = 0.012) and selenium (R = 0.316, p = 0.044). Selenium, zinc, omega-6 fatty acids, calcium, and iron, were all positively associated with TLM, while caffeine and isoflavones showed a negative association. Patients with acromegaly exhibited increased muscle mass, but their functional capacity were compromised, potentially due to alterations in muscle composition. The intake of nutrients such as selenium, β-carotene, flavonoids, vitamin E and niacin, may improve physical performance and muscle strength.
Cushing's syndrome, characterized by chronic hypercortisolism, is associated with various health risks, including psychiatric symptoms and cognitive impairments. This systematic review of case studies aimed to map and categorize these symptoms. We hypothesized that a broader range of psychiatric and cognitive manifestations would be observed beyond anxiety, depression, and memory impairment. The review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024433186). We conducted searches in PsycINFO, Embase, PubMed, and Scopus, identifying 273 potentially relevant studies. After screening, 66 studies were included, comprising 74 cases (81% female; mean age 35.7 years, range 13-81). revealed that 93% of cases presented psychiatric complaints, including depression (39.2%), psychosis/schizophrenic symptoms (35.1%), suicidal ideation/attempts (20.3%), anxiety (17.5%), panic attacks (2.7%), and post-traumatic stress disorder (1.4%). Cognitive complaints were reported in 32% of cases, primarily as general cognitive complaints (18.9%), memory impairment (9.5%), and attentional deficits (5.4%). An overlap of psychiatric and cognitive symptoms was observed in 26% of cases. This review underscores the clinical relevance of symptoms such as mania, psychosis, and suicidal behavior in Cushing's syndrome, which are often underreported. Individualized clinical assessment informed by these case studies is crucial for comprehensive management that extends beyond the typical focus on depression and memory. Moreover, greater awareness of the full spectrum of neuropsychiatric manifestations in hypercortisolism is needed.
Pheochromocytomasand paragangliomas (PPGLs) are rare catecholamine-secreting tumors that can affect systemic physiology, including bone metabolism. Although they are typically associated with genetic syndromes such as MEN2 and von Hippel-Lindau disease, PPGLs are not commonly linked to primary bone tumors. However, recent findings suggest a novel cancer syndrome involving both PPGLs and giant cell tumor of bone (GCTB) through H3F3A mutations. We report a rare case of a 53-year-old woman with multicentric GCTB, initially diagnosed at age 24, who subsequently developed bilateral pheochromocytomas. Following multiple recurrences of skeletal tumors and eventual leg amputation, imaging and biochemical evaluation revealed bilateral adrenal tumors with markedly elevated catecholamine levels. Genetic analysis identified mosaicism for a pathogenic H3F3A (G35W) variant in both adrenal and bone tumors. Surgical resection of both adrenal glands normalized catecholamine levels and resolved hypertension. The patient has remained tumor-free and normotensive for five years following adrenalectomy. This case supports the existence of a shared pathogenic mechanism linking PPGLs and GCTBs, likely mediated by postzygotic H3F3A mutations. Recognition of this association is crucial for early diagnosis, genetic counseling, and management of similar cases.
This study aimed to evaluate body composition, quality of life, and depression risk in women with polycystic ovary syndrome (PCOS) compared to women without PCOS. This prospective, cross-sectional study assessed quality of life (QoL) and depressive symptoms in women with polycystic ovary syndrome (PCOS) compared with controls with and without overweight or obesity. Assessments included body composition, QoL, health-related quality of life (HRQoL), and depressive symptoms. Participants without PCOS were divided into two groups according to BMI: < 25 kg/m2 [median age 30 years (27-33)] and ≥ 25 kg/m2 [median age 32 years (29-35)]. The study included 47 women with polycystic ovary syndrome (PCOS) phenotypes A and B. The median age was 29 years (25-35), and the median body mass index (BMI) was 32.08 kg/m2 (28.48-36.40). Women with PCOS showed a higher risk of depression (24% with moderate to severe risk) compared with women without PCOS, both with and without overweight or obesity (5% and 3%, respectively). Additionally, women with PCOS consistently reported lower QoL and HRQoL scores, particularly in the physical, environmental, and overall QoL domains, as well as in functional capacity, pain, general health status, vitality, emotional well-being, and mental health domains of HRQoL. Based on these findings, we concluded that body composition does not appear to be a determining factor for increased risk of depressive symptoms or poorer perceptions of QoL and HRQoL in women with PCOS.
To evaluate the impact of a structured tele-education program on hospital hyperglycemia and diabetes, focusing on residents' medical knowledge and inpatient care. This open-label, multicenter, randomized clinical trial enrolled internal medicine residents from four university hospitals in southern Brazil. Teams were block-randomized to an intervention group that received an online lecture plus 30 days of tele-education via WhatsApp, or to a control group with no intervention. The primary outcome was medical knowledge, assessed with a validated 10-item questionnaire. Secondary outcomes included quality of insulin prescriptions, hypoglycemia and hyperglycemia rates, and hospital length of stay (LOS). Analyses were performed using SPSS v29 (5% significance). Fifty residents completed the study. The intervention group achieved higher post-intervention knowledge scores than the control group (median 8 vs. 6 correct answers; p = 0.005) and showed significant improvement from preto post-test (6 to 8; p < 0.001), with consistent gains across centers. Clinical data from 149 hospitalized patients were analyzed (mean age 67.8 years; 55% female); 56% had diabetes, and 44% had hospital-related hyperglycemia. There was a nonsignificant trend toward more appropriate NPH (p = 0.107) and regular insulin (p = 0.203) prescriptions in the intervention group. Median LOS was longer in the intervention group (19 vs. 13 days; p = 0.009). The tele-education program improved residents' knowledge of inpatient hyperglycemia. Larger studies are needed to confirm clinical effects and long-term outcomes of tele-education in hospital glycemic management.
Previous studies suggest a bidirectional relationship between thyroid dysfunction and sleep disorders. However, prospective evidence regarding the impact of sleep characteristics on subclinical hypothyroidism remains limited. This study aimed to evaluate the association between insomnia symptoms, sleep duration, and sleep debt and the incidence of subclinical hypothyroidism. We conducted a prospective cohort analysis of 7,983 euthyroid participants from the second wave (2012-2014) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who were not taking thyroid-related or psychiatric medications. Insomnia symptoms (initial, middle, and terminal), sleep duration, sleep debt, sociodemographic characteristics, and health behaviors were assessed via questionnaires. Subclinical hypothyroidism was defined as thyrotropin >4.0 μIU/mL and normal free thyroxine in the third wave (2016-2018). Crude and adjusted log-binomial regression models estimated relative risks (RR) and 95% confidence intervals (95% CI). The incidence of subclinical hypothyroidism was 6.6% for both sexes. In women, middle insomnia was associated with a 35% reduced risk of subclinical hypothyroidism (RR: 0.65; 95% CI: 0.44-0.92). Among men, sleep debt was linked to a 30% increased incidence (RR: 1.30; 95% CI: 1.01-1.66), and in the continuous model, each additional hour of sleep debt raised the risk by 9% (RR: 1.09; 95% CI: 1.02-1.14). Of the sleep characteristics assessed, middle insomnia due to nocturnal awakenings appeared to be protective against subclinical hypothyroidism among women, while sleep debt increased the risk among men.
To investigate the impact of smoking on serum selenium levels, autoimmune activity, and macular microvascular density in patients with clinically inactive thyroid-associated orbitopathy (TAO), using optical coherence tomography angiography (OCTA). This retrospective cross-sectional study included 44 patients with inactive TAO (24 smokers, 20 non-smokers) and 32 ageand sex-matched healthy controls. All participants underwent ophthalmologic evaluation and laboratory testing for thyroid hormones, selenium, and thyroid-stimulating immunoglobulin (TSI). Macular vessel density was measured using spectral-domain OCTA at the superficial capillary plexus, deep capillary plexus, outer retinal layer, and choriocapillaris. Clinical activity score (CAS) was used to assess disease activity. The collected data were analyzed statistically. Smokers with TAO exhibited significantly higher CAS (p = 0.016) and TSI levels (p = 0.027), and lower serum selenium concentrations (p = 0.042) compared to non-smokers. Central superficial and deep capillary plexus densities were significantly reduced in smokers versus healthy controls (p = 0.029 and p = 0.017, respectively). No significant differences were observed between smokers and non-smokers within the TAO group, or in the outer retinal layer and choriocapillaris layers among all groups. Smoking status was associated with lower selenium levels, higher TSI levels, and increased CAS. Furthermore, retinal microvascular attenuation detected by OCTA, even in the absence of clinical activity in TAO, may serve as a significant indicator of persistent vascular deterioration.
Epidemiological studies have revealed that glucose variability (GV) is a predictor of stroke, cognitive impairment, and dementia in patients with type 2 diabetes mellitus (T2DM). However, evidence on the associations of GV with white matter hyperintensity (WMH) and cerebrovascular abnormalities remains scarce. This study aimed to explore the relationships of GV with WMH and cerebrovascular abnormalities using epidemiological and Mendelian randomization (MR) approaches. The MR approach was used to assess the effects of genetic proxies for GV on MRI outcomes. This cross-sectional study was conducted at a medical center where patients with T2DM were recruited. The measures for fasting plasma glucose (FPG) and HbA1c variability included the standard deviation, coefficient of variation, average real variability (ARV), and variability independent of the mean (VIM). Brain magnetic resonance images were analyzed to assess WMHs and cerebrovascular abnormalities. For MR, instrumental variables were used to assess the causal relationships between glycemic variability and outcome based on two-stage regression analysis. This study included 2,247 subjects, of whom 1,122 had WMH and 957 had cerebrovascular abnormalities. We found 80 independent single-nucleotide polymorphisms associated with GV but not with WMH or cerebrovascular abnormalities, which were subsequently used as genetic instruments. Genetically increased, unweighted FPG-VIM was linked with WMH (odds ratio 1.17 [95% CI 1.08, 1.27] per standard deviation). All genetically increased, unweighted and weighted GV measures were associated with cerebrovascular abnormalities, except FPG-ARV. Our study provided evidence that genetically predicted GV was associated with WMH and cerebrovascular abnormalities, supporting a potential causal link under MR assumptions.
To examine the associations of handgrip strength and CT-derived muscle and visceral fat indices with insulin resistance in middle-aged women with prediabetes and newly diagnosed type 2 diabetes. This cross-sectional study included 44 women aged 40-60 years attending a tertiary endocrinology clinic. Participants were classified according to the American Diabetes Association (ADA, 2022) criteria as having prediabetes (n = 29) or newly diagnosed type 2 diabetes (n = 15). All participants underwent anthropometric assessment, biochemical testing, L3-level CT imaging for visceral adipose tissue (VAT) and psoas muscle measurements, and handgrip strength evaluation using a digital dynamometer. Insulin resistance was assessed using the homeostatic model assessment for insulin resistance (HOMA-IR). Multivariable linear regression analysis was performed to identify independent factors associated with HOMA-IR. Dominant-hand grip strength demonstrated an inverse association with HOMA-IR (β = -0.297, p = 0.033). VAT volume and BMI were not significantly associated with HOMA-IR after adjustment (p > 0.75). The overall model explained 28% of the variance in HOMA-IR (R2 = 0.28; adjusted R2 = 0.14). Psoas muscle thickness showed a borderline inverse relationship with HOMA-IR (p = 0.079). In this cohort of women with early glucose dysregulation, handgrip strength was independently associated with insulin resistance, whereas visceral adiposity was not. These findings suggest that muscle performance may represent a clinically relevant correlation of early metabolic impairment. Longitudinal studies are needed to clarify the temporal relationships.
Postoperative weight regain remains a challenge after bariatric surgery and affects long-term outcomes. This study aimed to develop a clinical model to predict weight regain within 12 months, prior to surgery by using preoperative inflammatory, metabolic, and ferritin as biomarkers. This retrospective observational study included 394 patients with obesity who underwent bariatric surgery (2020-2023), including laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). Patients were divided into a training set (70%, n = 276) and a validation set (30%, n = 118) using a random number table. Weight regain was defined as a ≥ 10% increase from the postoperative nadir (median time to regain: 8.2 months). Key variables included peripheral blood inflammatory markers [systemic immune-inflammation index (SII, calculated as platelet count × neutrophil count/lymphocyte count), neutrophil-to-lymphocyte ratio (NLR)], glycolipid metabolism indicators [low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)], and ferritin levels. Multivariate logistic regression was used to identify independent predictive variables, and the nomogram model was validated via calibration, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA). The weight regain rate was 19.9% (55/276) in the training set. Independent predictive variables included elevated SII (OR=1.004; 95% CI = 1.000-1.007), LDL-C (OR = 1.873; 95% CI = 1.054-3.329), ferritin (OR = 1.005; 95% CI = 1.003-1.008), and reduced HDL-C (OR = 0.103; 95% CI = 0.013-0.844) (all P < 0.05). The model showed strong discrimination (training AUC = 0.852, 95% CI = 0.795-0.910; validation AUC = 0.812, 95% CI = 0.709-0.915) and good calibration (Hosmer-Lemeshow P > 0.05). DCA confirmed the model's clinical utility across threshold probabilities. Preoperative SII, LDL-C, ferritin, and HDL-C levels effectively predict postoperative weight regain. Early monitoring of these biomarkers may guide personalized interventions to improve long-term outcomes.
Cushing'sdisease (CD), caused by an adrenocorticotropin-secreting pituitary adenoma, is a rare but severe endocrine disorder associated with high cardiometabolic morbidity and mortality. Diagnosis is challenging as many symptoms are nonspecific, and biochemical or imaging results may be inconclusive, contributing to substantial diagnostic delay. Although the core features of CD are consistent across the lifespan, certain clinical manifestations of chronic hypercortisolism vary from childhood through older age, reflecting differences in growth, puberty, metabolism, and comorbidity burden. In children, impaired growth coupled with weight gain is most prominent, whereas adolescents often present with pubertal disturbances and psychological or academic difficulties. Adults typically exhibit the classic Cushingoid features such as round face, plethora, and central obesity, along with metabolic and reproductive complications. Older individuals typically present with frailty, sarcopenia, fractures, and cognitive decline. Age also influences the interpretation of endocrine tests, the accuracy of pituitary magnetic resonance imaging, the role of inferior petrosal sinus sampling, perioperative risks, and the long-term impact of remission or persistent disease. Given this context, this narrative review used five representative clinical vignettes (pediatric, adolescent, adult female, adult male, and elderly) to illustrate how the presentation, diagnostic evaluation, and management of CD vary across the lifespan. Each case was paired with a structured synthesis of current evidence, highlighting both shared principles and age-specific nuances essential for timely diagnosis, appropriate treatment selection, and effective long-term multidisciplinary care. Understanding age-related differences is crucial to improving outcomes and reducing the substantial morbidity and mortality associated with CD throughout the lifespan.
To investigate the involvement of regulators of pluripotency and self-renewal of embryonic stem cells in adrenocortical tumors (ACT). Clinicopathological data and tissues from 114 ACT patients (96 pediatric-pACT; 18 adults) were analyzed. Normal fetal (n = 33) and postnatal adrenals (n = 26) were used as controls. STAT3, NANOG, SOX2, and OCT4 expression was evaluated by qPCR and IHC. We evaluated intracellular NANOG localization by immunofluorescence and its interaction with beta-catenin after inhibiting the Wnt pathway in a beta-catenin-mutated ACT cell line (NCI-H295). IHC showed NANOG, OCT4, SOX2, and STAT3 expression in fetal adrenals until mid-pregnancy, disappearing thereafter. Positive OCT4 nuclear staining was found in 32% of pACT samples and was associated with metastasis (OR = 2.28; 95% CI:1.13-4.59; P < 0.05). ACTs presented lower SOX2 mRNA expression (P < 0.01). STAT3 mRNA levels were higher in cortisol-secreting ACT (P = 0.01) and in adult adenomas (P < 0.01). NANOG mRNA was higher in p.S45P CTNNB1 mutated ACT (P < 0.01). NCI-H295 cells exhibit nuclear NANOG expression, which was decreased by inhibiting the Wnt/beta-catenin pathway (P < 0.01). Markers of pluripotency and self-renewal of embryonic stem cells are expressed until mid-pregnancy, contributing to the adult adrenal stem cell niche. They are absent postnatally but are expressed in a subset of ACT. Specifically, pS45P beta-catenin-mutated ACTs express more NANOG. Increased OCT4 expression in pACT is associated with worse prognosis, and inhibiting the Wnt/beta-catenin pathway in these cells impairs NANOG expression.