Search Results (121)

Background/Objectives: Non-classical congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency represents the mildest form of congenital adrenal hyperplasia and is frequently diagnosed only after the onset of clinical signs in childhood. Newborn screening programs for CAH are primarily designed to detect classical forms and show limited sensitivity for NCCAH. The clinical significance of neonatal 17-hydroxyprogesterone (17-OHP) values below recall thresholds remains incompletely defined. Methods: We retrospectively analyzed clinical, auxological, hormonal, and genetic data from pediatric patients diagnosed with NCCAH between 2018 and 2023 at a tertiary referral center. Neonatal screening 17-OHP concentrations, basal and ACTH-stimulated 17-OHP levels at diagnosis, bone age advancement, pubertal status, and hydrocortisone treatment were evaluated. Correlations between hormonal parameters, age at onset, and treatment dose were assessed. Results: Thirty-five patients (30 females) were included, with a mean age at clinical onset of 7.52 ± 0.36 years for females and 6.25 ± 0.29 years for males. Premature pubarche was the most frequent presenting sign (94.3%), and central precocious puberty was diagnosed in 31.4% of cases. The mean neonatal screening 17-OHP level was 4.53 ± 0.7 ng/mL; only two patients exceeded the screening recall cut-off. At diagnosis, mean basal and ACTH-stimulated 17-OHP levels were 15.1 ± 3.35 and 55.2 ± 11.3 ng/mL, respectively. Age at clinical onset was inversely correlated with both basal and stimulated 17-OHP levels, while hydrocortisone dose correlated positively with biochemical severity. Bone age advancement was observed in all patients. Conclusions: Most children with NCCAH display mildly elevated neonatal 17-OHP values that do not trigger screening recall. Higher biochemical severity is associated with earlier clinical presentation and higher glucocorticoid requirements. Neonatal 17-OHP concentrations, even when below cut-off values, may represent an early indicator of disease severity and warrant further investigation. Full article

Background/Objectives: Precocious puberty in girls currently appears to be one of the main problems in pediatric endocrine gynecology. Early onset of menstruation (EOM) means that the age at which the first menstruation occurs is lower than the average/median for the population, which ranges from 12 to 13 years and depends primarily on ethnic origin. Depending on age and severity of symptoms, these disorders negatively affect girls’ quality of life in many areas, including school life, family relationships, and everyday life. Methods: This article provides a scoping review summarizing scientific evidence from human studies on the association between substances derived from green tea (flavanols) and soy (isoflavones) and precocious puberty in girls. Results: Despite the relatively small number of girls enrolled in the studies, available scientific evidence from randomized controlled trials (RCTs) suggests that polyphenols from decaffeinated green tea (DGTP) may contribute to lowering the age of first menstruation in girls living with obesity. The effect of soy isoflavones or soy in the context of premature menstruation in girls is unclear. Most studies report that it may have no effect on the age of first menstruation, while individual studies suggest that very early exposure to soy (< 4 months of age) may result in earlier puberty, and others suggest that higher consumption of soy isoflavones delays this process. Conclusions: Further well-designed intervention studies in humans are needed to better understand the endocrine and metabolic relationships regarding the role and importance of specific polyphenols in the pathogenic mechanisms of the development and treatment of precocious puberty in girls. Full article

Background/Objectives: Precocious puberty (PP), defined as the onset of secondary sexual characteristics before 8 years in girls and 9 years in boys, is associated with psychosocial distress, compromised adult height, and long-term metabolic risk. Early identification remains challenging, as current diagnostic approaches are largely reactive and rely on invasive or resource-intensive testing. This narrative review examines how artificial intelligence (AI) can support earlier risk prediction and detection of PP through integration of clinical, hormonal, imaging, lifestyle, and environmental data. Methods: A narrative literature review was conducted using PubMed, Scopus, Embase, Web of Science, and Google Scholar to identify relevant studies published between 2005 and 2025. Eligible studies included original research and high-quality reviews that examined AI-based approaches, such as machine learning and deep learning, in pediatric endocrinology, particularly for the prediction or diagnosis of central or peripheral precocious puberty. Studies incorporating clinical, hormonal, radiological, lifestyle, environmental, or multi-omics data relevant to AI modeling were included. Results: AI models, including XGBoost, random forest, convolutional neural networks, and regression-based approaches, have demonstrated potential utility in predicting central precocious puberty using hormonal, imaging, and growth data. Reported applications include automated bone age assessment, lifestyle and dietary risk stratification, and exploratory use of wearable-derived behavioral data. However, progress is limited by small pediatric datasets, population bias, limited interpretability, and unresolved ethical challenges related to privacy, consent, and equity. Conclusions: Artificial intelligence represents a promising decision-support approach for earlier, non-invasive, and individualized risk assessment in precocious puberty. Future progress will depend on the integration of longitudinal, multimodal data, the development of ethical models, and interdisciplinary collaboration among pediatric endocrinologists, data scientists, and public health stakeholders. Full article

Idiopathic central precocious puberty (CPP) is increasingly observed in girls. Premature thelarche (PT) and exaggerated thelarche (ET) are early pubertal variants that can be challenging to distinguish from CPP in clinical practice. Exosomal microRNAs are stable biomarkers capable of crossing the blood–brain barrier. Although miR-30b-5p has been reported to increase in pubertal boys and girls, human studies investigating microRNAs in CPP and puberty remain limited. To investigate exosomal microRNA expression profiles and associated pathways in early pubertal development, we conducted a cross-sectional study of 28 girls aged 6–8 years. Serum exosomal microRNA expression was analyzed using next-generation sequencing. Differentially expressed microRNAs (DEmiRNAs) between groups were identified, followed by pathway enrichment analysis. Distinct exosomal miRNA expression patterns were observed among the CPP, ET, and control groups, with 307 DEmiRNAs identified. The CPP, PT, and ET groups exhibited distinct miRNA expression profiles compared with the control group. miR-30b-5p was upregulated in the CPP, ET, and PT groups compared with the control group. Pathway enrichment analysis revealed the involvement of various signaling pathways including AGE–RAGE, MAPK, and mTOR signaling pathways. Serum exosomal microRNAs may serve as biomarkers for early puberty and provide insight into metabolic influences on pubertal development. Full article

This study aimed to determine the sexual maturation pattern of Shenxian pigs by combining observation, teaser boar testing, and back-pressure methods, and to apply this pattern for early breeding to shorten the generation interval and increase production efficiency. Subsequently, high-throughput transcriptome technology was used to compare gene expression levels in testicular tissues of Shenxian pigs before and after sexual maturity, as well as between sexually mature Shenxian pigs and Shenxian × Large White crossbred pigs. Functional analysis of differentially expressed genes (DEGs) was conducted to screen candidate genes related to sexual maturation and precocity in Shenxian pigs. The results showed that boars reached sexual maturity at an average age of 116 days in winter and 129 days in summer. For sows, the first estrus occurred at 114 days, the second at 134 days, and the third at 154 days in winter; corresponding ages in summer were 125, 144, and 164 days, respectively. The duration of estrus was around 3 days, and the estrus interval was approximately 20 days for both seasons. Comparative trials revealed no significant change in production performance when selection and first mating were conducted at 5 months of age compared to previous practices. Transcriptome sequencing of testicular tissues before and after sexual maturity in Shenxian pigs identified 6016 upregulated genes, primarily associated with reproduction and sperm function, influencing sexual maturation. The comparison between sexually mature Shenxian pigs and crossbred pigs identified 582 upregulated genes, mainly involved in hormone synthesis, affecting the onset of puberty in Shenxian pigs. After intersecting and functionally analyzing the upregulated genes from both sets, SRD5A1 and CYP11B2 were selected as the most likely candidate genes to affect precocious puberty in Shenxian pigs. Full article

Human sexual development begins in the prenatal period and continues throughout life, shaped by both biological and psychosocial factors. Somatic development leads to reproductive maturity through several stages regulated by the hypothalamic–pituitary–gonadal axis. Psychosexual development, described in classical theories such as Freud’s and in contemporary models, emphasizes the development of gender identity and sexual behaviors from infancy through early and middle childhood into adolescence, a period characterized by the integration of sexual and emotional components. This developmental trajectory evolves from a biologically driven process into a conscious, socially shaped phenomenon through concretization, mentalization, and socialization. To synthesize current knowledge, this paper is based on a literature review conducted across multiple databases, with studies selected and evaluated for relevance to both somatic and psychosexual development. Understanding the dynamics of these processes is essential for clinical practice, sexual education, and health prevention. It emphasizes integrated clinical practices that employ a multidisciplinary approach, incorporating both medical treatment and psychological support, particularly in the care of children and adolescents with disorders of sexual development. This article presents a comprehensive overview of human sexual development from the prenatal period through adolescence, considering its somatic and psychosexual aspects. Full article

Central precocious puberty (CPP) may be influenced by gut microbiota through changes in short-chain fatty acids (SCFAs), β-glucuronidase activity, and enterohepatic estrogen recycling. This narrative review integrates current evidence from human and animal studies exploring microbial contributions to pubertal timing. Across multiple cohorts, CPP is associated with loss of SCFA-producing commensals, such as Bacteroides, and increased abundance of taxa like Alistipes, Ruminococcus, and Lachnoclostridium. These microbial shifts are linked to altered SCFA profiles, diminished anti-inflammatory and neuroendocrine modulation, and enhanced reabsorption of estrogens via microbial β-glucuronidase activity. Experimental models support a causal connection: gut dysbiosis accelerates pubertal onset, whereas microbiota-targeted interventions can restore hormonal balance and delay activation of the HPG axis. While some overlap with obesity-associated microbiota exists, the endocrine-specific microbial changes observed in CPP suggest partially distinct mechanisms. Overall, the gut microbiota emerges as both a modulator and potential biomarker of early pubertal onset. Its integration into pediatric endocrine frameworks could improve early risk assessment and guide future interventions, though further validation through standardized, longitudinal, and diverse population studies is still required. Full article

The onset of puberty is a critical developmental milestone regulated by complex neuroendocrine networks that integrate genetic, metabolic, and environmental cues. Among the molecular systems coordinating this transition, neurotrophins—including brain-derived neurotrophic factor (BDNF), nerve growth factor, neurotrophin-3, and neurotrophin-4/5—have emerged as important modulators of hypothalamic maturation and the activation of gonadotropin-releasing hormone (GnRH) neurons. Beyond their established roles in neuronal survival and differentiation, neurotrophins contribute to hypothalamic circuit plasticity, influence GnRH neuronal activity, and participate in the integration of metabolic and environmental signals relevant to reproductive maturation. Experimental studies, primarily based on animal and cellular models, demonstrate that BDNF and its receptor play a role in normal pubertal onset, whereas disruptions in neurotrophin signaling have been implicated in central precocious puberty, delayed puberty, and hypogonadotropic hypogonadism. In humans, available evidence is more limited and derives mainly from genetic studies, circulating neurotrophin measurements, and clinical observations. This review provides an integrative synthesis of current experimental and clinical data on neurotrophin-mediated regulation of pubertal timing, highlighting both physiological mechanisms and pathological conditions. While neurotrophins represent promising modulators at the intersection of neurodevelopment, metabolism, and reproduction, further longitudinal and translational human studies are required to define their diagnostic and therapeutic potential in pediatric endocrinology. Full article

Obesity in the pediatric population has become a public health problem with an increasing prevalence in recent years. The gut microbiota and its metabolites, especially short-chain fatty acids (SCFAs), play vital roles in the development of pediatric obesity. This manuscript aims to highlight the link between the gut microbiota and obesity by examining microbial imbalances, such as altered Firmicutes/Bacteroidetes ratios and altered SCFA production, especially butyrate, propionate, and acetate. Advances in genomic technologies, such as 16S rRNA sequencing, have enabled personalized treatments and detailed profiling of microbial diversity. This review includes not only preclinical studies but also clinical trials of interventions, such as probiotics, synbiotics, prebiotics, and butyrate supplements. These may modify the microbiota and SCFA levels to reduce obesity and related conditions, such as metabolic syndrome and precocious puberty. Future research should focus on using advanced genomic sequencing techniques to develop new therapeutic strategies, as well as on creating a complex predictive algorithm for assessing metabolic risk in pediatric patients with obesity, an innovation that can be extended to other metabolic conditions. Full article

Precocious puberty, characterized by the abnormally early onset of secondary sexual development, has been increasing in prevalence worldwide. Current pharmacological treatments, including GnRH agonists, are effective but associated with adverse effects, highlighting the need for safer alternatives. In this study, we investigated the preventive effects of an herbal extract complex composed of Eclipta prostrata and Hordeum vulgare (EHEC) on precocious puberty induced by danazol administration and a high-fat diet (HFD) in rat models. EHEC delayed vaginal opening (VO) and reduced ovarian maturation in both models. Furthermore, EHEC attenuated the elevation in hypothalamic GnRH mRNA expression observed in both models, without affecting body weight. These findings suggest that EHEC modulates the hypothalamic–pituitary–gonadal axis and may serve as a potential natural therapeutic agent for the prevention of precocious puberty. Full article

Background: Central precocious puberty (CPP) is diagnosed through a combination of clinical, auxological, and biochemical parameters, with pharmacological stimulation tests considered the diagnostic gold standard. In recent years, triptorelin, a long-acting Gonadotropin-Releasing Hormone (GnRH) analog, has been increasingly adopted in clinical practice due to limited availability of native GnRH. Objective: To compare the clinical, auxological, and hormonal profiles of girls diagnosed with idiopathic CPP using either the classical GnRH stimulation test or the triptorelin test. Methods: This retrospective study included 136 female patients diagnosed with CPP and followed for at least two years at a single pediatric endocrinology unit. Of these, 101 underwent a GnRH stimulation test, and 35 were assessed using the triptorelin test. Baseline and stimulated hormonal parameters, growth data, and IGF-1 levels were collected. A multivariate linear regression model was used to explore the influence of age, test type, and other covariates on the LH peak response. Results: Anthropometric and baseline hormonal parameters were comparable between the two groups. The LH peak was significantly higher in the GnRH group (9.8 ± 3.1 IU/L at 60 min) than in the triptorelin group (6.8 ± 2.4 IU/L at 4 h). FSH levels were also significantly lower following triptorelin stimulation (p = 0.004), while the LH/FSH ratio did not differ significantly. Multivariate analysis confirmed that triptorelin was associated with a lower LH peak (β = −2.2, p = 0.008), particularly in younger patients, with a significant interaction between age and test type (β = 0.6, p = 0.022). Conclusions: Both GnRH and triptorelin stimulation tests are valid tools for CPP diagnosis. However, the GnRH test appears to elicit a more robust LH response, especially in younger patients, whereas the triptorelin test is associated with delayed and lower LH peaks. Full article

McCune–Albright Syndrome (MAS) is a rare mosaic disorder caused by somatic activating mutations of the GNAS gene, resulting in constitutive Gsα signaling and a broad spectrum of clinical phenotypes. The syndrome typically presents with fibrous dysplasia (FD) of bone, café-au-lait macules, and endocrinopathies such as gonadotropin-independent precocious puberty, hyperthyroidism, and/or growth hormone excess. FD, which characterizes the skeletal phenotype, results in the replacement of normal bone with disorganized fibro-osseous tissue, often leading to pain, deformities, and increased risk of fractures. This review discusses the following: 1. The molecular biology of the GNAS locus and its relation to the pathophysiology of FD/MAS; 2. The skeletal manifestations of FD/MAS; 3. Bone biomechanics and organizational skeletal aberrations observed in FD/MAS; and 4. Current and future therapeutic strategies for patients with FD/MAS. While there is much current literature available regarding FD/MAS, this review specifically aims to outline core understandings and summarize some of the latest investigations into the genotypic and phenotypic foundations of the disorders, while shedding new light on the biomechanical aberrations observed in skeletal structure within them and comparing them to those observed in related disease processes such as osteoporosis and Paget’s disease. Full article

Prepubescent children and young adolescents (ages 7–14) are in a critical developmental stage for establishing the foundations of healthy sexual behavior. Increasing rates of precocious puberty, combined with limited access to accurate and age-appropriate sexual health education, heighten the vulnerability of this age group to sexual health risks. These risks include early and often coerced sexual initiation, exposure to sexual abuse, and consequent outcomes such as sexually transmitted infections and early pregnancies. However, comprehensive cross-regional analyses and evidence-based interventions addressing the sexual health needs of this age group remain limited. Addressing this gap promotes mutual learning, context-specific adaptation, and global alignment of sexual health support efforts, crucial for achieving the Sustainable Development Goal target of universal access to sexual and reproductive health care. This scoping review aims to map the available evidence on the scope and characteristics of sexual health interventions for prepubescents and young adolescents in the United States and Sub-Saharan Africa. The proposed scoping review will be conducted in accordance with the Arksey and O’Malley framework and Joanna Briggs Institute (JBI) methodology for scoping review. A systematic search of English-language articles published from 2010–2025 will be conducted across PubMed, CINAHL, PsycINFO, Scopus, Web of Science, ERIC, and African Index Medicus. Five reviewers will screen the articles in Covidence and independently assess full-text articles using a standardized data extraction form. Discrepancies will be resolved through discussion and with a sixth reviewer. The review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Data will be summarized and synthesized to identify patterns in interventions, delivery methods, outcomes, and implications for practice, research, and policy. Comparative and gap analyses will highlight similarities, differences, and priorities for future research and interventions. An adolescent sexual health expert will help validate and contextualize findings. Results can guide strategies to address shared challenges and advance universal access to sexual health support for prepubescents and young adolescents. 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

Background/Objectives: Central precocious puberty (CPP) is diagnosed via gonadotropin-releasing hormone (GnRH) stimulation testing, which can be burdensome in pediatric settings. This study evaluated the utility of baseline hormonal markers—particularly insulin-like growth fac-tor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3)—as auxiliary tools for CPP diagnosis in Korean children. Methods: We retrospectively analyzed patients who underwent GnRH stimulation testing. Baseline LH, FSH, IGF-1, and IGFBP-3 levels were assessed, along with standard deviation scores (SDS) calculated using two different reference intervals. Multivariable logistic regression was performed to improve diagnostic accuracy. Performance was evaluated using area under the curve (AUC) values from receiver operating characteristic (ROC) analyses, stratified by sex. Results: Among 2464 Korean children (2025 girls and 439 boys), CPP diagnosis rates were 54.2% in girls and 65.6% in boys. Among baseline markers, FSH showed the highest AUCs using raw values with sex-specific cutoffs (AUC = 0.767 in girls and 0.895 in boys). Although IGF-1 SDS and IGFBP-3 SDS showed AUCs < 0.7 when used alone, predictive models incorporating these SDS values yielded higher performance (AUC = 0.800 in girls and 0.920 in boys. Conclusions: SDS-based IGF-1 and IGFBP-3 enhance CPP diagnosis when used in predictive models, emphasizing the need for sex-specific interpretation and standardized reference intervals in real-world clinical practice. Full article