Search Results (178)

Background: Cystic fibrosis-related diabetes (CFRD) is a frequent comorbidity in individuals with cystic fibrosis (CF). While insulin secretion defects are the primary mechanism in CFRD pathophysiology, insulin resistance may contribute as an additional risk factor. Early detection of insulin resistance may help identify patients at higher risk for earlier CFRD development. Objective: The aim of this study was to evaluate the ability of the Matsuda Index to identify insulin resistance in pediatric CF patients and to compare it with HOMA-IR as complementary indicators of glucose metabolism. Methods: In this cross-sectional study, fifty children with CF aged 6–16 years were included. The study involved measuring anthropometric data, fasting insulin, fasting glucose levels, glycated hemoglobin (HbA1c), and C-peptide. An assessment of glucose and insulin levels was performed on the patients through an oral glucose tolerance test (OGTT) at 0, 60, and 120 min. The Matsuda Index was computed, wherein a threshold of ≤4.5 signifies the presence of insulin resistance. Statistical analyses were conducted to compare insulin resistance and sensitivity across groups, using t-tests, correlation, and ANOVA. Results: Among the 50 observed patients, the average Matsuda index score was 17.08 with a standard deviation of 11.16. Eleven individuals (22%) exhibited insulin resistance with a Matsuda Index ≤ 4.5. These patients showed significantly higher insulin levels at 60 and 120 min during the OGTT, with statistically significant p-values of 0.008 and 0.002, respectively. Conclusions: The Matsuda Index may serve as a useful adjunctive tool to help identify insulin resistance in pediatric CF patients, particularly during puberty. Early detection of insulin resistance through the Matsuda Index may facilitate risk stratification and enable timely interventions that could potentially delay the onset or progression of CFRD. However, it should be noted that the ≤4.5 cut-off value was derived from adult studies, and its validity in pediatric CF populations has not been established, which represents a limitation of our finding. Full article

Background/Objectives: Copper is an essential trace element for physiological processes related to reproduction, but its impact on the hypothalamic–pituitary–ovarian (HPOA) axis and its specific mechanism remain unclear. Methods: In vivo study: 21-day-old female Sprague Dawley (SD) rats were randomly assigned to five groups (n = 10 per group), with all groups fed a basal diet and supplemented with CuSO₄·5H₂O to achieve copper ion concentrations of 0, 15, 30, 45, or 60 mg/kg in the diet. During the second phase of proestrus, blood samples, hypothalamic tissues, pituitary tissues, and ovarian tissues were collected. In vitro study: Primary mixed hypothalamic neurons were isolated and cultured from fetal SD rats on embryonic day 17. After identification by NSE immunofluorescence staining, six copper ion concentration groups (0, 15.6, 31.2, 46.8, 62.4, and 78 μmol/L) were established. The optimal copper concentration for cell viability and GnRH secretion was screened using CCK-8 assay (Sangon, Shanghai, China) and ELISA (Mlbio, Shanghai, China). On this basis, the cells were treated with different concentrations of PKC agonist (PMA) and PKC inhibitor (chelerythrine). Cell viability was evaluated by CCK-8 assay, the expression level of PKC was detected by Western blot, and the optimal concentration with no obvious toxicity was selected for subsequent mechanism research. Results: Dietary copper dose-dependently regulated rat puberty onset; the 45 mg/kg copper group had the earliest onset, and showed significantly increased levels of reproduction-related hormones (GnRH, FSH, LH, E₂) in serum and HPOA axis. Hypothalamic transcriptomics revealed significantly enriched GnRH signaling pathways and GABAergic synaptic pathways. Mechanistically, this copper dose upregulated hypothalamic KISS-1, GPR54, and PKC (mRNA/protein), and downregulated GABA/GABA-R. Adding 46.8 μmol/L copper (as Cu²⁺, equivalent to optimal in vivo level) could activate the KISS-1/GPR54-GnRH system in hypothalamic neurons; regulating PKC activity could synchronously affect the expression of KISS-1, GPR54, GnRH, and GABA/GABA-R, with additional copper enhancing this effect in vitro experiments. Conclusions: This study demonstrates for the first time that dietary copper at 45 mg/kg promotes puberty onset in SD rats. The mechanism involves activation of the hypothalamic PKC pathway, which inhibits GABAergic neurotransmission while activating the KISS-1/GPR54-GnRH system, thereby enhancing HPOA axis activity and gonadotropin secretion. Full article

Traumatic brain injury (TBI) in childhood is a major global health concern and a leading cause of morbidity and mortality in the pediatric population. Its incidence is rising worldwide, with early childhood and adolescence representing the most vulnerable age groups. Beyond acute neurological injury, post-traumatic endocrine dysfunction has emerged as an underrecognized but clinically significant sequela, with potential long-term consequences for growth, puberty, metabolism, and overall quality of life. The hypothalamic–pituitary axis (HPA) is uniquely vulnerable due to its anatomical and vascular characteristics, making pituitary cells—particularly somatotrophs and gonadotrophs—susceptible to ischemic, traumatic, and inflammatory damage. Reported prevalence of post-TBI pituitary dysfunction in children ranges from 5 to 57%, reflecting a deep heterogeneity in injury severity, diagnostic methods, and timing of evaluations. Growth hormone deficiency (GHD) is the most frequently reported abnormality, with presentations varying from transient to persistent forms. Gonadal axis disturbances, including hypogonadotropic hypogonadism and, less commonly, central precocious puberty, highlight the impact of TBI on pubertal development. Adrenal dysfunctions, though less frequent, may be life-threatening if unrecognized, while posterior pituitary disorders, such as diabetes insipidus, usually revealed acutely, are often transient. Importantly, many endocrine sequelae manifest months to years after the initial trauma, complicating a timely diagnosis. Current evidence underscores the need for structured, longitudinal endocrine surveillance after pediatric TBI, with baseline and follow-up assessments at defined intervals. Early recognition and intervention, including hormone replacement when appropriate, may improve neurocognitive recovery and overall rehabilitation outcomes. Future multicenter studies and standardized screening protocols should be considered essential to clarify incidence, natural history, and optimal management strategies for post-traumatic endocrine dysfunction in children. Full article

Benzene, toluene, ethylbenzene, and xylene (BTEX) are a common class of volatile organic compounds linked to adverse health outcomes. Although BTEX have been shown to have endocrine disrupting properties, their potential impacts on pubertal development in children remain unclear. In this study, for the first time, we investigated the possible association of BTEX exposure with precocious puberty (PP) and early puberty (EP) in children. We conducted a case–control study that included 246 children diagnosed with PP or EP and a controls category matched for sex and age. Urinary concentrations of seven BTEX metabolites and the oxidative DNA damage biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured by high-performance liquid chromatography-tandem mass spectrometry. Compared with the control groups, urinary catechol (1,2-DB) levels were significantly higher in both PP (median: 85.3 vs. 42.4 μg/g creatinine) and EP children (median: 62.0 vs. 48.1 μg/g creatinine). Binary logistic regression models showed that 1,2-DB was positively associated with EP (OR = 1.36, 95% CI: 1.10, 1.69), while trans,trans-muconic acid (MU) was negatively correlated with PP (OR = 0.47, 95% CI: 0.24, 0.92), and PGA was negatively correlated with EP (OR = 0.73, 95% CI: 0.56, 0.93) adjusted for confounders. Stratified analyses showed that the relationship between BTEX metabolites and EP varied by parental education level. Our findings revealed that exposure to BTEX, especially benzene, may influence pubertal timing in children, but there was no relationship between oxidative DNA damage and PP or EP. The biological mechanism of BTEX exposure affecting pubertal development requires further investigation. Full article

Notably, the widespread ubiquity of arsenic and graphene oxide in the environment validates the occurrence of their co-exposure, posing significant threats to target organisms, including humans. Herein, prepuberty, puberty, and maturity were investigated using anogenital distance, vaginal opening, first estrus, reproductive hormone profiles, cyclicity, sexual behaviour and pregnancy outcomes to assess the impact of exposure to arsenic and/or graphene oxide on the puberty of offspring female rats after maternal exposure during gestation and lactation periods. Zero-day pregnant Sprague Dawley females were randomly divided into four groups, each receiving a different treatment via drinking water from gestation day 0 to postnatal day 21: control group (CON, drinking water); arsenic group (ARS, 10 mg/L sodium arsenite); graphene oxide group (GOX, 0.5 mg/mL); and co-exposure group (ARS + GOX; 10 mg/L of arsenic combined with 0.5 mg/mL of graphene oxide). Individually or combined, arsenic and graphene oxide exposure increase the sexual retardation and female masculinization, as evidenced by a significant increase in anogenital distance, delay in the first estrus cycle, and prolongation in the timing of the vaginal opening. At maturity, the offspring exhibited a significant elevation of testosterone and a significant decrease in estradiol. Offspring females showed inhibited receptivity to their male mates, indicated by lower lordosis quotient and intensity. Additionally, there was an increase in the number of estrous cycles but a decrease in their duration. Moreover, an increase in implantation loss and the number of resorbed embryos, along with a reduction in viable fetuses. In conclusion, reproductive deterioration was more significant in the offspring exposed to combined arsenic and graphene oxide compared to those exposed to ARS or GOX alone, indicating that arsenic exposure is exacerbated when combined with graphene oxide during the experimental episode. Full article

Background: Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs) are prevalent, complex conditions marked by chronic pain, joint instability, and multisystem involvement. Despite affecting an estimated 1 in 500 individuals, these conditions remain poorly understood and inconsistently diagnosed. This study aimed to define their clinical burden through a large-scale, international survey. Methods: A cross-sectional, anonymous survey was distributed globally from September 2023 to March 2024. Of 9258 responses, 3906 met inclusion criteria (hEDS: n = 3360; HSD: n = 546). The 418-item questionnaire assessed symptoms, comorbidities, healthcare utilization, and quality of life. The 95% confidence intervals (CIs) were calculated for comparison. Results: Participants with hEDS reported a mean of 24 comorbid conditions and an average diagnostic delay of 22.1 years. Common diagnoses included gastrointestinal disorders (84.3% [95% CI: 98.3–99.2%]), dysautonomia (71.4% [95% CI: 69.9–72.9%]), and chronic pain (98.9% [95% CI: 98.3–99.2%]). In contrast, HSD respondents reported a mean of 17 comorbidities, a 17.5-year time to diagnosis, and lower rates of key complications. Triggering events, such as puberty and infections were commonly reported preceding hEDS or HSD symptom onset. Comparison to the All of Us dataset revealed significantly elevated prevalence ratios of neurological, immune, and autonomic diagnoses. Conclusions: This global survey highlights the extensive multisystemic burden and diagnostic delays faced by individuals with hEDS and HSDs. The high prevalence of immune, neurological, gastrointestinal, and autonomic dysfunctions challenges the notion of these conditions as isolated connective tissue disorders. These findings highlight the need for updated diagnostic frameworks and mechanistic studies that explore multifactorial etiologies beyond the connective tissue paradigm. Full article

We aim to provide a translational model to investigate the reproductive consequences of pubertal delay using the GnRH agonist triptorelin in transgender girls, tested in particular on testicular maturation in peripubertal rats. A total of 30 Sprague Dawley rats were utilized, with 10 subjects assigned to each of three groups from day P30 postpartum (prepubertal) until day P95 (postpubertal), mimicking treatment timing in patients. Rats received triptorelin at three time points (P30, P50, and P71), or only at P30 and P50. Control rats were injected with vehicle. Plasma testosterone levels were determined using MRM analysis. Testes and epididymides were examined histologically. There were significantly lower testosterone levels at postnatal day 48 in treated rats, indicating delayed puberty, with further reductions by day 69. By day 93, testosterone levels had recovered in rats given vehicle at P71 but remained low in the triptorelin-continuous group, suggesting the reversibility of the treatment. Treated rats had smaller testes; however, the majority of the testicular parenchyma was unaffected, with most seminiferous tubules displaying complete spermatogenesis. However, focal atrophic changes were observed in 1–30% of the parenchyma. One-third of the short-term group and half of the long-term group were classified as atrophic. Despite these changes, all treated rats had mature sperm in the epididymis, ensuring their fertility. In conclusion, triptorelin treatment promotes a decline in testosterone levels accompanied by discrete atrophy of the seminiferous tubules, which is partially reversible and compatible with sperm production and fertility preservation. Triptorelin could be an appropriate treatment prior to estrogen therapy for patients seeking gender transition. Full article

Background: Childhood obesity is a growing global health concern, with an increasing prevalence of severe obesity among young children. This study aimed to determine the average age of severe obesity onset in Polish children and evaluate the time gap between diagnosis and referral for specialized care. Methods: This data analysis was conducted across four Polish pediatric endocrinology centers specializing in childhood obesity management (Szczecin, Cracow, Zabrze, Rzeszów) between July 2022 and November 2023. The study included 367 children and adolescents (186 boys, 181 girls) aged 0–18 years, diagnosed with severe obesity based on age-specific BMI criteria. Anthropometric measurements were performed during the patient’s inclusion into the study and based on past medical records. BMI and BMI Z-scores were calculated for all current and past measurements. Results: The median age of the study population at the moment of inclusion into the study was 13.7 ± 2.9 years (range: 2.2–18 years). The median BMI was 40.9 ± 5.1 kg/m² (range: 30.1–65.8 kg/m²), and the median BMI Z-score was 2.7 ± 0.4 (range: 2.3–6.2). Out of the 367 children included, 327 (89%) had entered puberty. An analysis of past measurements revealed that 83% of children had severe obesity at their earliest recorded BMI measurement, with n median onset age of 3.2 years. The median age of referral to specialized care was 10 ± 5.0 years, reflecting a delay of almost 7 years from diagnosis to targeted medical care. Conclusions: This study highlights a substantial delay between the onset of severe obesity and referral for specialized care, underscoring the need for earlier intervention strategies tailored to age, sex, and developmental stage. Full article

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being. Full article

Background: As the first approved GnRH agonist, leuprorelin is distinguished by its broad application in managing central precocious puberty (CPP). Despite the extensive use of leuprorelin in CPP management, uncertainties still persist regarding its long-term efficacy and safety. We conducted a systematic review and meta-analysis to assess the long-term efficacy and safety of leuprorelin treatment in children with CPP. Methods: We conducted electronic searches in PubMed, Embase, and the Cochrane Library up until 15 November 2023. All relevant studies concerning leuprorelin treatment in children with CPP were included. Results: The final adult height of children with CPP eventually reached the target height, with a significant difference of MD: 1.75 cm (95% CI: 0.46–3.03). The MD in BMI standard deviation score between baseline and post-leuprorelin treatment was −0.03 (95% CI: −0.28–0.22). For the onset of menstrual puberty, the MD between children with CPP who received leuprorelin treatment and those who did not was 0.73 years latency (95% CI: −0.74–2.20) without significant difference. The timing of menstrual puberty of the leuprorelin-treated group was 15.83 months (95% CI: 11.62–20.03) after the discontinuation of leuprorelin treatment. The proportion of menstrual regularity was 85% (95% CI: 75–91%), and the average incidence rate of polycystic ovary syndrome (PCOS) was 8% (95% CI: 3–22%) for children with CPP that treated with leuprorelin. Conclusions: Leuprorelin treatment does not affect BMI or the onset of menstrual puberty in the long term, but has positive effects on adult height for children with CPP. Moreover, no severe adverse events related to leuprorelin treatment were observed. Full article

This longitudinal study investigated the incidence and characteristics of injuries among U9, U11, and U13 male football players in an academy setting over a six-season period, from 2016/17 to 2021/22. A total of 374 injuries were analyzed, with a particular focus on muscle injuries, including Delayed Onset Muscle Soreness (DOMS), muscle ruptures, and contusions. The study revealed that the highest injury incidence occurred in the U13 group, with quadriceps injuries being most prevalent in both the U13 and U11 groups. The study found that muscle injuries accounted for a significant proportion of all injuries, particularly in the U13 group, where muscle injuries increased over time. Intrinsic factors such as physical development during puberty and extrinsic factors like training intensity and psychological pressures may contribute to the higher injury rates in older age groups. Additionally, seasonal fluctuations in injury rates were observed, with a notable decline during the COVID-19 lockdowns in 2019/20 and 2020/21, followed by an increase post-lockdown due to deconditioning. The study highlights the vulnerability of young athletes to muscle injuries, particularly during growth spurts, and calls for further research into training methods and injury prevention strategies to mitigate these risks. Full article

This overview explores the complex relationship between environmental factors, particularly obesity, and the timing of puberty, with a focus on how hormonal and genetic interactions are influenced by external conditions. Puberty (gonadarche) is characterised by the activation of the hypothalamic–pituitary–gonadal (HPG) axis. The onset and progression of puberty vary significantly among individuals, primarily due to genetic factors, with key genes like kisspeptin 1 (KISS1) and makorin ring finger protein 3 (MKRN3) playing a crucial role. Cohesively, this paper emphasises that environmental factors, particularly obesity and exposure to endocrine-disrupting chemicals (EDCs), have become significant influences on the timing of puberty. Childhood obesity has risen significantly in recent decades and the age of pubertal onset has declined over the same period. Obesity greatly disrupts hormone regulation in pre-pubertal children. Leptin accelerates the onset of puberty in girls but not in boys. The underlying mechanism is proposed to be the increase in Kiss1/GnRH signalling. On the contrary, excess leptin in boys suppresses testosterone production by increasing oestrogen conversion. Low adiponectin in obese girls may contribute to earlier puberty due to a reduced inhibition of Kiss1/GnRH signalling. Low adiponectin in boys is linked to delayed puberty due to its role in maintaining insulin sensitivity and testosterone production. Hyperinsulinemia influences pubertal timing through central and peripheral mechanisms. Insulin acting synergistically with leptin promotes the earlier onset of puberty in girls but not in boys. The effects of exposure to certain EDCs—mostly obesogenic chemicals that mimic the action of natural hormones—on the timing of puberty remain unclear; hence, further research on this topic is needed. Addressing and preventing obesity in children could potentially mitigate these alterations in pubertal timing. Full article

Understanding the structure of play in competitive contexts is essential for an accurate performance analysis. This study examined the effects of sex and age category on the temporal and formal structure of play in youth tennis. Methods: Twenty-four semi-final and final matches were selected from under-12 (Open Super 12-Auray) and under-14 (Les Petits As) tournaments. Temporal structure was assessed through total match time, mean set and game duration, rally duration, and percentage of active time. Formal structure variables comprised the number of sets per match, games per set, points per game, strokes per rally, and stroke frequency. A structured, external, non-participant observational methodology was employed. No sex-based differences were detected. When grouped by age category, U-12 players recorded longer rally durations—9.48 s in boys and 8.76 s in girls (p < 0.001)—and a higher number of strokes per rally—6.75 strokes in boys and 6.14 strokes in girls (p < 0.001). In contrast, U-14 players exhibited a greater stroke frequency (46.44 strokes/min) (p < 0.008). The changes in game intensity aligned with expectations based on previous tactical investigations and the maturation processes characteristic of puberty. Full article

Introduction: Handgrip strength, measured by dynamometry (HGD), is a key measure in assessing physical condition and nutritional status. Its correlation with anthropometric measures and body composition makes it an accessible method for the evaluation of cardiovascular health. This study aimed to develop a new reference for right-hand dynamometry in the Spanish population and compare it with previous references. Material and Methods: A total of 3281 subjects aged 3 to 16 years (1608 females) from the PESCA, PASOS, and ASOMAD projects were included. Handgrip strength was measured using the same methodology in all cases. Data on age, weight, height, and BMI were collected, and the handgrip strength per kilogram of body weight was calculated. Sexual dimorphism in the temporal development of strength was analyzed, and multiple correlations were established between dynamometry and anthropometric variables. Results: Percentile curves and tables for dynamometry are presented for each sex, including data from as early as 3 years old, for the first time. Conclusions: Sexual dimorphism in strength development is confirmed, becoming more pronounced with puberty. In absolute terms, our study shows a decrease in handgrip strength among adolescents, occurring earlier and more markedly in females. When compared to the previous literature, the 16-year-old male adolescents in our study exhibited lower strength than those from 40 and 16 years ago. Full article

Precocious puberty (PP) is characterized by the early onset of secondary sexual characteristics and accelerated growth, which often result in compromised adult height (AH). Central precocious puberty (CPP), a subset of PP, is treated with gonadotropin-releasing hormone analogs (GnRHa) to suppress premature hormonal activation and delay epiphyseal closure, thereby preserving height potential. The present review examined the effects of GnRHa on AH outcomes in girls with idiopathic CPP. Although AH is greater with GnRHa therapy than without it, the treatment does not consistently restore the patient’s genetic potential. The benefits of the treatment are most evident in girls in whom idiopathic CPP is diagnosed before 6 years of age and they achieve a height gain of 4.5–14.1 cm, which is unattainable without treatment. However, the treatment of older children (ages 6–8) shows conflicting results, with the AH outcome varying among previous reports. In particular, slowly progressive CPP is known to have a favorable height prognosis even without treatment. Another factor influencing the AH prognosis is the timing of GnRHa discontinuation; the best time to discontinue GnRHa therapy for the best AH outcome is reportedly the bone age of approximately 12 years. In conclusion, although GnRHa therapy significantly improves the AH, especially in early-onset CPP, its effectiveness is uncertain in borderline or late-onset cases. Further research is required to formulate more precise criteria for patient selection and treatment discontinuation to optimize height outcome in girls with idiopathic CPP. Full article