PURPOSE: Andrological pathologies in adulthood often originate from conditions arising during childhood, adolescence, or even as early as the gestational and neonatal periods. Despite their clinical relevance, pediatric...PURPOSE: Andrological pathologies in adulthood often originate from conditions arising during childhood, adolescence, or even as early as the gestational and neonatal periods. Despite their clinical relevance, pediatric andrological disorders remain underrepresented in the literature and no shared position statements or comprehensive guidelines are currently available. The present paper complements a previous publication by the same societies, entitled “Management of andrological disorders from infancy to adolescence and transitional age: Part-1 – The SIAMS–SIEDP position statement”, by further expanding on these topics. METHODS: SIAMS, in collaboration with SIEDP, convened a multidisciplinary expert task force to develop updated guidelines on the diagnosis and management of andrological disorders from childhood through adolescence and into the transitional age. The resulting recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: In this Part-2 of the guidelines, a comprehensive literature review was conducted, focusing on English-language articles related to “cryptorchidism,” “micropenis,” “hypospadias,” “testicular tumors,” “epididymitis,” “orchitis,” “differences/disorders of sexual development,” and “testicular torsion”. For each condition, three key aspects were analyzed: diagnosis, clinical management, and treatment. Based on this analysis, specific recommendations and suggestions were developed for each disorder. CONCLUSIONS: The multidisciplinary guidelines presented in this paper complement those published in the previous Part-1 document. Developed through collaboration among leading medical societies in the field, this joint effort led to a consensus on a set of practical recommendations and suggestions aimed at supporting healthcare professionals in optimizing both andrological and overall health during the transitional age.
PURPOSE: In this study, we aimed to identify subclinical retinal and choroidal changes in patients with type 2 diabetes mellitus without diabetic retinopathy (NDR) over two years and evaluate the risk factors associated...PURPOSE: In this study, we aimed to identify subclinical retinal and choroidal changes in patients with type 2 diabetes mellitus without diabetic retinopathy (NDR) over two years and evaluate the risk factors associated with diabetic retinal neurodegeneration (DRN). METHODS: In this prospective cohort study, retinal and choroidal thicknesses were measured using optical coherence tomography (OCT), and OCT angiography was used to analyze vessel density. RESULTS: Among 8020 eyes, 6644 were control eyes, and 1376 were NDR eyes, with 808 eyes completing the 2-year follow-up assessment. The NDR group exhibited significantly thinner overall retinal thickness (RT), ganglion cell-inner plexiform layer, and choroidal thickness compared to the control group (P = 0.043, P = 0.013, and P = 0.031, respectively). Additionally, the NDR group showed significant annual thinning in 3-mm overall RT, retinal nerve fiber layer, and ganglion cell complex thickness, with losses of − 1.14 μm/y, − 0.27 μm/y, and − 0.62 μm/y, respectively. Factors such as age, female sex, cardiovascular events, and axial length were negatively associated with DRN. CONCLUSION: Our patient cohort demonstrated that DRN precedes the microvascular changes characteristic of DR and progresses over time. Choroidal morphological features were altered and may correspond to DRN.
PURPOSE: Anorexia nervosa (AN) is a severe eating disorder with high morbidity that typically arises during adolescence. While genetic predisposition contributes to its development, emerging evidence highlights the role...PURPOSE: Anorexia nervosa (AN) is a severe eating disorder with high morbidity that typically arises during adolescence. While genetic predisposition contributes to its development, emerging evidence highlights the role of environmental stressors and epigenetic mechanisms—particularly DNA methylation—in mediating these effects. This study aimed to investigate genome-wide DNA methylation alterations in young female adolescents with AN and functional hypogonadotropic hypogonadism, compared to healthy pubertal controls, to explore in particular potential epigenetic biomarkers of metabolic dysfunction and pubertal delay. METHODS: Peripheral blood DNA was extracted from 10 young adolescent girls with AN and 11 age-matched healthy controls. Genome-wide DNA methylation analysis was performed using the Infinium MethylationEPIC BeadChip (850 K) array, which interrogates over 850,000 CpG sites. Differentially methylated regions (DMRs) and CpG sites were identified, followed by functional annotation. Ingenuity Pathway Analysis (IPA) was conducted to investigate the biological significance of the methylation changes. RESULTS: A total of 87 DMRs were identified, with 69% showing hypomethylation in the AN group. These included genes such as CLU and MKRN3, involved in hypothalamic regulation and pubertal timing. Additionally, 2072 differentially methylated CpG sites were found, affecting genes linked to metabolism (e.g., LEPR, NR1H3) and puberty (e.g., GHR, DLK1). Ninety-two genes encoding zinc-finger proteins, including MKRN3, showed altered methylation. IPA revealed enrichment in pathways related to leptin, sirtuin, estrogen, and GnRH signaling. CONCLUSION: Young female adolescents with AN exhibited distinct methylation profiles, primarily hypomethylation, affecting genes involved in energy homeostasis and pubertal development. These epigenetic alterations may represent biomarkers of metabolic dysfunction and pubertal delay in AN.
OBJECTIVE: Graves’ disease (GD) patients with an advanced radioiodine uptake (RAIU) peak (4 h/24 h ratio > 1.0) exhibit rapid iodine turnover, which compromises radiation dose delivery and increases 131I therapy failure....OBJECTIVE: Graves’ disease (GD) patients with an advanced radioiodine uptake (RAIU) peak (4 h/24 h ratio > 1.0) exhibit rapid iodine turnover, which compromises radiation dose delivery and increases 131I therapy failure. This study aimed to evaluate whether short-term lithium carbonate pretreatment could correct this aberrant kinetic profile and improve the biochemical milieu in this high-risk subgroup. DESIGN & METHODS: This single-center retrospective cohort included 162 GD patients with an advanced peak, allocated to lithium carbonate (250 mg tid for 7 days before and 2 days after the RAIU test, n = 81) or a control group receiving standard care (n = 81). Primary outcomes were post-intervention 24-h RAIU and 4 h/24 h RAIU ratio; secondary outcomes included changes in serum free T3 (FT3) and free T4 (FT4) levels. RESULTS: Compared to controls, the lithium group achieved a significantly higher 24-h RAIU (85.5% ± 11.5% vs. 65.7% ± 22.1%, P < 0.001). Crucially, the 4 h/24 h ratio was normalized to 0.92 ± 0.20 in the lithium group versus 1.27 ± 0.40 in controls (P < 0.001). Lithium pretreatment also significantly reduced FT3 (− 7.4 ± 10.1 vs. + 3.2 ± 14.7 pmol/L) and FT4 levels (− 16.2 ± 15.3 vs. + 4.1 ± 18.5 pmol/L) (both P < 0.001). Adverse events were mild (6.2%, 5 patients), transient, and did not affect treatment. CONCLUSIONS: Short-term lithium carbonate pretreatment effectively reverses rapid iodine turnover, enhances radioiodine retention, and attenuates rebound hyperthyroidism in GD patients with an advanced RAIU peak. This practical adjunctive strategy therefore holds promise for improving the efficacy of subsequent radioiodine therapy and warrants prospective validation.
PURPOSE: Cushing’s syndrome (CS) affects children in 10% of cases and is occasionally associated with the abuse of health-related products causing exogenous glucocorticoid (GC) excess. A 15-year-old girl presented with s...PURPOSE: Cushing’s syndrome (CS) affects children in 10% of cases and is occasionally associated with the abuse of health-related products causing exogenous glucocorticoid (GC) excess. A 15-year-old girl presented with suspected CS: endogenous hypercortisolism and exposure to GC containing drugs were ruled out. She reported using an anti-lice foam for one year. After discontinuation, her clinical condition gradually and completely reversed. This study aims to investigate whether compounds, such as pyrethrins and piperonyl butoxide (PBO), contained in the anti-lice product have GC-like activity. METHODS: Serum levels of pyrethrins and PBO in the patient and controls were measured by LC-MS/MS. To test whether PBO has GC-like effects, the GloResponse 9XGAL4UAS-luc2P HEK293 (GloHEK) cell line was incubated with PBO and luminescence (LUM) was measured. RESULTS: During anti-lice product exposure patient’s PBO serum levels were ~ 25-fold higher than control samples. Six months after product discontinuation, PBO levels in patient’s serum decreased to levels comparable to controls. PBO did not affect the viability of GloHEK cells at the concentration employed in the luciferase assay (10 µM). Baseline GloHEK cell LUM was significantly increased by PBO (> 7-fold; p < 0.01), an effect reversed by a GC antagonist. CONCLUSION: PBO contained in the anti-lice product has a GC-like transcriptional activity. These results support the hypothesis that CS signs and symptoms were related to anti-lice product exposure, causing a foam-induced Cushing. The use of pharmaceutical and non-pharmaceutical products should always be investigated in patients with CS.
Apaydin T, Kani HT, Keklikkiran C
… +2 more, Yilmaz Y, Yavuz DG
J Endocrinol Invest
· 2026 May · PMID 41719003
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PURPOSE: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and acromegaly is unclear due to the complex metabolic effects of growth hormone (GH). GH stimulates gluconeogenesis, gly...PURPOSE: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and acromegaly is unclear due to the complex metabolic effects of growth hormone (GH). GH stimulates gluconeogenesis, glycogenolysis, and lipolysis, increasing free fatty acids, a risk factor for MASLD, but may also protect against hepatic fat accumulation. In this study, we aimed to evaluate the impact of acromegaly and GH levels on liver steatosis and fibrosis using non-invasive FibroScan imaging. METHODS: This cross-sectional study included 58 patients with acromegaly, 61 age- and sex-matched metabolically comparable controls, and 82 healthy controls. Hepatic steatosis and fibrosis were assessed via controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by vibration-controlled transient elastography. Moderate to severe steatosis was defined as CAP > 260 dB/m, and significant fibrosis as LSM ≥ 8.0 kPa. RESULTS: Both acromegaly patients and metabolically healthy individuals exhibited lower CAP (241.8 ± 50.0 and 231.7 ± 51.9 dB/m) and LSM (4.7 ± 1.4 and 4.8 ± 1.8 kPa) scores than metabolically matched controls (CAP 281.7 ± 61.2 dB/m; LSM 5.5 ± 1.8 kPa; CAP p < 0.001; LSM p = 0.012). Moderate-to-severe steatosis was observed in 36.2% of acromegaly patients, 27.7% of healthy individuals, and 68.8% of metabolically matched controls (p < 0.001), while significant liver fibrosis occurred in 5.2%, 7.3%, and 14.7%, respectively (p = 0.154). GH levels were lower in acromegaly patients with MASLD (p < 0.001) compared to those without. CAP correlated negatively with GH and positively with BMI, waist circumference, and triglycerides, whereas LSM correlated positively with age, BMI, and triglycerides. CONCLUSIONS: Hepatic steatosis was less frequent in acromegaly than in metabolically comparable individuals, and GH was inversely associated with hepatic steatosis scores, possibly suggesting a protective role of GH independent of metabolic comorbidities.
PURPOSE: CYP27B1 is the rate-limiting enzyme in the activation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D3. This study aimed to characterize the spatial expression of CYP27B1 in...PURPOSE: CYP27B1 is the rate-limiting enzyme in the activation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D3. This study aimed to characterize the spatial expression of CYP27B1 in mouse and human kidneys and to investigate the contribution of renal CYP27B1 to systemic vitamin D metabolism using inducible conditional knockout models. METHODS: Immunofluorescent co-staining with segment-specific markers was used to localize CYP27B1 in kidney tissue. Mice with selective Cyp27b1 knockdown in renal tubular cells were generated by crossing Cyp27b1lox/lox mice, in which exon 8 was flanked with loxP sites, with inducible Pax8-Cre or Cdh16-Cre lines. RESULTS: In mice, CYP27B1 immunoreactivity was detected in proximal and distal tubules under basal conditions but increased specifically in proximal tubules under elevated enzyme activity. In healthy human kidneys, CYP27B1 staining was confined to proximal convoluted tubules. Cyp27b1lox/lox mice showed no overt phenotype, however, loxP insertion significantly reduced full-length Cyp27b1 mRNA expression in the kidney and various other tissues, which in some cases was accompanied by a PTH-independent increase in incomplete Cyp27b1 transcripts, as detected by exon 2–3 spanning primers. In Pax8-Cre+;Cyp27b1lox/lox mice, doxycycline-induced Cre expression further reduced full-length Cyp27b1 transcripts selectively in the kidney. In contrast, tamoxifen-induced deletion in Cdh16-Cre+;Cyp27b1lox/lox mice was less effective and showed more off-target effects. Circulating 1,25(OH)₂D₃ levels remained stable, and calcium and bone homeostasis were preserved or minimally affected. CONCLUSION: Kidney-selective Cyp27b1 knockdown by inducible Cre-mediated recombination is insufficient to silence 1,25(OH)2D3 synthesis, suggesting potent compensatory mechanisms that buffer loss of renal Cyp27b1 transcription.
PURPOSE: We aimed to elucidate the expression of VDR (vitamin D receptor) in human adrenal medulla and pheochromocytoma cells and to investigate the potential associations between VDR and the clinicopathological characte...PURPOSE: We aimed to elucidate the expression of VDR (vitamin D receptor) in human adrenal medulla and pheochromocytoma cells and to investigate the potential associations between VDR and the clinicopathological characteristics of pheochromocytoma. METHODS: The expression of VDR at the mRNA level in FFPE (Formalin-Fixed Paraffin Embedded) tissues from 31 pheochromocytomas, 4 adrenal cortex and 4 adrenal medulla was assessed via highly sensitive digital PCR. For pheochromocytoma patients, the clinical and histopathological features were retrospectively assessed. RESULTS: VDR mRNA expression in adrenal medulla and pheochromocytoma cells was compared to the expression in the adrenal cortex, which was set at 1.0. The median VDR mRNA expression in pheochromocytoma samples was lower than that in both unaltered medulla and cortex. No statistically significant correlations were detected between VDR mRNA expression in pheochromocytomas and most of the clinical parameters. The VDR expression level did not significantly correlate with the vitamin D concentration in the patients’ serum. However, VDR expression in tumors was negatively associated with somatostatin receptor 2 (SSTR2) levels, with the confounding influence of sex and the interaction with elevated 3-methoxytyramine concentrations. CONCLUSION: Our study is the first to characterize the expression of the vitamin D receptor (VDR) in both the intact adrenal medulla and pheochromocytoma cells. The highest median VDR expression was observed in the adrenal cortex, followed by intermediate levels in the adrenal medulla, and the lowest expression in pheochromocytoma cells. However, further studies are needed to clarify the relationship between vitamin D and catecholaminergic cells.
BACKGROUND: Estrogens are fundamental to bone health, exerting life-long effects onbone metabolism. They regulate skeletal growth and maturation during adolescence andmaintain bone remodeling in adulthood. The decline in...BACKGROUND: Estrogens are fundamental to bone health, exerting life-long effects onbone metabolism. They regulate skeletal growth and maturation during adolescence andmaintain bone remodeling in adulthood. The decline in estrogen levels during perimenopauseand postmenopause leads to bone mass loss. Emerging evidence also supports a role forprogestins in bone metabolism. Several estrogen-progestins formulations are available andwidely used for contraception in fertile women and as hormone replacement therapy (HRT) incases of primary or secondary ovarian insufficiency as well as in physiologic menopause.Advances in both synthetic and natural preparations allowed for more personalized treatmentapproaches. When selecting estrogen-progestin therapies, it is essential to consider their impacton bone health and remodelling. OBJECTIVE: This narrative review examines the effects of variousestrogen-progestin regimens on bone metabolism across the female lifespan, focusing on mechanisms of action, safety profiles, and clinical applications. Here we show that combined oralcontraceptives (COCs) are generally safe for bone mineral density (BMD) in adult women;however, caution is advised in adolescence, especially with very low-dose estrogen formulations.In hypogonadal women, postmenopausal hormone replacement therapy (HRT) is key forosteoporosis prevention. Physiological regimens, preferably transdermal estrogen at doseshigher than those used in typical postmenopausal therapy, may offer better bone protection.Additionally, oral gonadotropin-releasing hormone receptor (GnRH-R) antagonists combinedwith add-back therapy represent a novel long-term option for managing uterine fibroids andendometriosis without compromising BMD. In postmenopausal women, both HRT and selectiveestrogen receptor modulators (SERMs) effectively reduce fracture risk and support bone health. MAIN RESULTS & IMPLICATIONS: Optimizing therapeutic strategies to balance efficacy and safety, iscritical to ensuring personalized care that preserves bone health and enhances quality of lifeacross a woman's lifespan.
Grugni G, Rocchetti A, Bucolo C
… +32 more, Buganza R, Buoncuore G, Colao A, Corica D, Crinò A, Dassie F, de Sanctis L, Delvecchio M, Di Candia F, Faienza MF, Fintini D, Greco D, Guazzarotti L, Lo Preiato V, Maffei P, Mariani M, Mozzillo E, Pagotto U, Pajno R, Patti G, Rutigliano I, Salvatore M, Sartorio A, Scarano E, Siena S, Tamaro G, Tornese G, Vitale R, Wasniewska M, Zampino G, Torreri P, Maghnie M
PURPOSE: This study is a cross-sectional analysis of data from the Italian registry for patients with PWS, aimed at assessing the prevalence of endocrine and metabolic abnormalities in 539 patients with Prader-Willi synd...PURPOSE: This study is a cross-sectional analysis of data from the Italian registry for patients with PWS, aimed at assessing the prevalence of endocrine and metabolic abnormalities in 539 patients with Prader-Willi syndrome (PWS), aged 0.0 to 61.6 years. Demographic and genetic data were also analyzed. METHODS: Patients were recruited from 18 PWS referral centers participating in the Italian PWS registry. Each subject underwent comprehensive health screening as part of routine clinical care. RESULTS: The analysis of database revealed: (1) a reduction of obesity prevalence compared to previous data in the Italian population of PWS (51.0% versus 62.6%); (2) a high frequency of endocrine disorders (hypogonadism 53.5%, hypothyroidism 16.1%, central adrenal insufficiency 5.9%, precocious puberty 5.6%); (3) 337 individuals were undergoing GH therapy (62.5%), including 286 < 18 years (91.4%) and 51 > 18 years (22.6%); (4) a high prevalence of altered glucose metabolism (27.4%), dyslipidemia (29.7%), hyperuricemia (10.4%), hypovitaminosis D (50.2%), osteoporosis (6.9%), metabolic dysfunction-associated steatotic liver disease (33.3%) and cholelithiasis (13.3%); (5) endocrine and metabolic abnormalities were more frequent among patients > 18 years; (6) patients > 18 years had a higher rate of paternal 15q11.2-q13 deletions and a lower rate of maternal uniparental disomy for chromosome 15 than younger individuals (61.1% versus 40.9% and 31.0% versus 46.0%, respectively; p < 0.001); (7) the median age at genetic diagnosis was lower in the younger group compared to those > 18 years (0.1 years versus 3.7 years; p < 0.001). CONCLUSION: Our findings confirm the high prevalence of endocrine and metabolic comorbidities in Italian subjects with PWS.
Emerging evidence indicates excessive fluoride exposure damage thyroid/parathyroid, with oxidative stress and mitochondrial dysfunction as crucial mechanisms. However, epidemiological research on their involvement in flu...Emerging evidence indicates excessive fluoride exposure damage thyroid/parathyroid, with oxidative stress and mitochondrial dysfunction as crucial mechanisms. However, epidemiological research on their involvement in fluoride-induced thyroid/parathyroid dysfunction and modification of oxidative stress-related SNPs are insufficient. Therefore, we conducted a cross-sectional study (n = 401) among children aged 7-13 in areas with drinking water fluoride exposure in Tongxu County, Henan Province, China. This study examined the associations between urinary fluoride (UF) levels and thyroid/parathyroid function in children, as well as mediation effect of DNA copy number (mtDNA-CN) and interactions between UF and superoxide dismutase (SOD) SNPs. The population was divided into two groups based on children safety guidance of UF (WS/T 256-2005), with respective UF levels of 0.73 mg/L and 2.21 mg/L. Results revealed that for each 1 mg/L increase in children UF, thyroid volume (Tvol) increased by 0.34 cm (95%CI: 0.21, 0.46), parathyroid hormone (PTH) levels decreased by 1.40 ng/L (95%CI: -0.21, 0.17), mtDNA-CN reduced by 0.13 unit (95%CI: -0.22, - 0.04). Notably, in girls, the UF-Tvol association was partially mediated by relative mtDNA-CN (mediation proportion = 33.08%). Additionally, the GG genotype carriers of SOD2 rs4880 exhibited a larger Tvol (P = 0.017). The TT carriers of SOD3 rs13306703 exhibited higher PTH levels (P < 0.001). GMDR analysis identified an interaction between SOD2 rs4880, SOD3 rs10370 polymorphisms, and UF on Tvol. These findings linked fluoride exposure to thyroid function change in children. mtDNA-CN partially mediating the UF-Tvol association in girls. Genetic variants in SOD2 and SOD3 may modify the effect of fluoride exposure on thyroid.
le Roux CW, Done N, Brnabic AJM
… +8 more, Zion A, Lipkovich I, Kadziola Z, Dunn JP, Desai U, Kirson N, Dimitriadis GK, Kan H
J Endocrinol Invest
· 2026 Feb · PMID 41661445
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PURPOSE: The SURMOUNT-5 trial demonstrated greater weight reduction with tirzepatide vs. semaglutide in adults with obesity without diabetes. This study compared real-world weight reduction and cardiometabolic parameters...PURPOSE: The SURMOUNT-5 trial demonstrated greater weight reduction with tirzepatide vs. semaglutide in adults with obesity without diabetes. This study compared real-world weight reduction and cardiometabolic parameters associated with tirzepatide and semaglutide for obesity management. METHODS: A retrospective cohort study was conducted using Truveta de-identified US electronic health record data. Adults with obesity or overweight and ≥ 1 obesity-related complication, without diabetes, who initiated tirzepatide or semaglutide December 2023–June 2024 and adhered to treatment, were followed for 6 months. Primary outcome was percentage weight change from baseline. Secondary outcomes included weight-reduction targets and changes in body mass index (BMI) and cardiometabolic parameters. Primary analysis employed propensity-score weighted regression. Sensitivity analyses included modified intention-to-treat. RESULTS: Among 2,396 on-treatment patients (1,003 tirzepatide; 1,393 semaglutide), greater 6-month mean percentage weight reduction was observed with tirzepatide (–11.15% vs. −8.83%; adjusted difference −2.32%-points [95% CI: −3.17, −1.48]). Higher proportions of tirzepatide-treated patients achieved 5%, 10%, 15%, and 20% weight-reduction targets. Greater reductions in BMI, blood pressure, and haemoglobin A1c were observed with tirzepatide. More patients received higher doses of semaglutide (≥ 1.7 mg; 67.7%) vs. tirzepatide (≥ 10 mg; 42.4%). Sensitivity analysis findings were consistent. CONCLUSIONS: Consistent with clinical trials, real-world tirzepatide treatment was associated with greater 6-month weight reduction and more frequent achievement of weight-reduction targets and improvements in select cardiometabolic parameters than semaglutide among adults with obesity without diabetes. This early emergence of tirzepatide’s comparative advantage over semaglutide was observed despite more semaglutide-treated patients receiving higher doses than tirzepatide-treated patients.
BACKGROUND AND PURPOSE: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of developing cognitive impairment and mood disorders. At present, the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RA...BACKGROUND AND PURPOSE: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of developing cognitive impairment and mood disorders. At present, the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RA) on cognitive function in these patients has gained attention. This study explores changes in cognitive and emotional functions and the influencing factors in patients with T2DM, following polyethylene glycol loxenatide (PEG-Loxe) treatment. METHODS: This study was conducted from April 2022 to January 2024 in the endocrinology departments of 16 hospitals. Patients with T2DM who had inadequate glycemic control despite at least 8 weeks of stable dietary modifications, exercise, and hypoglycemic drug therapy were enrolled. These patients received PEG-Loxe (0.2 mg/week for 12 weeks) along with their current treatment. Cognitive and emotional performances were assessed alongside blood tests for clinical indicators like glucose and lipid levels. RESULTS: A total of 269 patients were enrolled in this study. Treatment with PEG-Loxe showed statistically significant differences in Montreal Cognitive Assessment (MoCA), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS) scores before and after treatment. Correlation analysis revealed that changes in both fasting blood glucose (∆FBG) and 30-minute postprandial blood glucose (∆30-min PBG) were significantly negatively correlated with ∆MoCA (r = − 0.269, P < 0.001; r = − 0.196, P = 0.007). A generalized linear model (GLM) showed that FBG significantly impacted cognitive improvement (P < 0.001), with a coefficient of − 0.1455, indicating that each unit increase in FBG reduced MoCA score by 0.1455 points. The intercept of the model was 0.6740 and was significant (P < 0.001). CONCLUSION: After 12 weeks of PEG-Loxe treatment, cognitive function and anxiety and depression symptoms in patients with T2DM were significantly improved. The glycemic control status was also significantly correlated with cognitive performance. This study confirmed that PEG-Loxe offers added benefits for cognitive improvement in T2DM management.
PURPOSE: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasingly prevalent in pediatric populations, especially among children with obesity. Genetic risk variants for MASLD- particularly the 148M...PURPOSE: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasingly prevalent in pediatric populations, especially among children with obesity. Genetic risk variants for MASLD- particularly the 148M allele of the patatin-like phospholipase domain-containing 3 (PNPLA3) gene - have been linked to various clinical outcomes and have recently led to the identification of a “liver-specific” MASLD subtype, distinct from the classical cardiometabolic MASLD phenotype. While adult evidence shows divergent effects of this gene especially on extrahepatic outcomes, similar pediatric data in the context of MASLD remain limited. METHODS: A total of 629 children with obesity and ultrasound-detected MASLD were evaluated. Patients were classified according to the presence/absence of the 148M allele of PNPLA3 gene. Kidney damage (KD) was defined as reduced estimated glomerular filtration rate (eGFR < 90mL/min/1.73m2), while subclinical hypothyroidism (SH) was defined by thyroid stimulating hormone (TSH) > 4.5µUI/ml with normal free triiodothyronine and free thyroxine levels. Hepatic fibrosis was estimated through an indirect measure such as Pediatric NAFLD Fibrosis Index (PNFI). Prediabetes was defined according to diagnostic criteria. RESULTS: The 148M allele of PNPLA3 was associated with lower eGFR and higher TSH, glycaemia, and PNFI values (all p < 0.05). Carriers showed an adjusted odds ratio of 1.67 for fibrosis, 2.24 for SH, 3.74 for KD, and 1.09 for prediabetes, respectively (all p < 0.05). CONCLUSION: The 148M allele of PNPLA3 influences hepatic and extrahepatic outcomes in children with MASLD. Although preliminary, these data suggest that genetic stratification could enhance risk prediction and guide personalized monitoring and treatment strategies in pediatric MASLD.
Pettersen T, Fuskevåg OM, Figenschau YA
… +4 more, Evensen EK, Furberg AS, Winther A, Grimnes G
J Endocrinol Invest
· 2026 May · PMID 41649750
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PURPOSE: Increasing evidence suggests a role of 11-oxygenated adrenal androgens (11-OxyA) (11-ketotestosterone, 11KT; 11β-hydroxytestosterone, 11OHT; 11-ketoandrostenedione, 11KA4; 11β-hydroxyandrostenedione, 11OHA4) in...PURPOSE: Increasing evidence suggests a role of 11-oxygenated adrenal androgens (11-OxyA) (11-ketotestosterone, 11KT; 11β-hydroxytestosterone, 11OHT; 11-ketoandrostenedione, 11KA4; 11β-hydroxyandrostenedione, 11OHA4) in several hyperandrogenic disorders. This study aimed to describe distributions of 11-OxyA in a healthy young adult population and explore the relation between hormonal contraceptives and 11-OxyA. METHODS: This study utilized cross-sectional data from the third Fit Futures Study conducted in Norway. 11-OxyA in fasting blood samples were analyzed by liquid chromatography tandem mass spectrometry technique (LC-MS/MS). Contraceptive use was registered and categorized as combined hormonal contraceptives (CHC) or gestagen-only contraceptives. Descriptive statistics were used to report 11-OxyA distributions. Independent t-tests and ANOVA were used to compare biomarker concentrations between groups. RESULTS: The study included 289 males and 337 females with median age of 27 years. Males had 9-30% higher 11-OxyA concentrations than females (all p's < 0.01). Among the females, 25.5% used CHC, 36.7% used gestagen-only contraceptives, and 37.8% used non-hormonal contraceptives or no contraceptives. As concentrations of 11-OxyA in gestagen-only contraceptives users were similar to non-users, these groups were combined. CHC users had 25-29% lower concentrations of 11KT, 11OHT, and 11KA4 than non-CHC users (all p's < 0.001). After exclusion of CHC users, sex differences attenuated and was no longer significant for 11KT. CONCLUSION: Females had lower concentrations of 11-OxyA than males, partly explained by use of CHC, as users had significantly lower concentrations of 11-OxyA than non-CHC users, except 11OHA4. These findings suggest an additional mechanism for CHC in treatment of hyperandrogenic conditions, in which 11-OxyA are elevated.