Association of screen exposure/sedentary behavior and precocious puberty/early puberty.

Background: In recent years, with the development of society, children's daily exposure to screen time has gradually increased. Screen exposure and sedentary behavior have brought a host of harms to children's lives. The aim of this study was to explore the effects of screen exposure and sedentary behavior on precocious puberty and early development. Methods: This is a cross-sectional study in the school-based population. A total of 3,560 children were recruited from Qufu City, Shandong province using multistage stratified cluster random sampling. All study subjects had a physical examination by professional pediatricians in October 2019, and were investigated with health questionnaires. Precocious puberty is defined as development of secondary sexual signs in boys before 9 years or in girls before 8 years. Screen time was calculated as the average of screen time on weekdays and weekend days, and sedentary time was calculated as the average of sedentary time on weekdays and weekend days. After adjusting for potential confounders, logistic regression was used to examine the association between screen exposure and sedentary behavior and early puberty and precocious puberty. Results: Sedentary time was a risk factor for precocious puberty and early development (OR = 1.428, 95% CI = 1.087-1.876) in girls without adjustment. No significant association was found between screen exposure and early puberty and early development both in girls and boys. Conclusions: Excessive sedentary behavior was associated with an increased risk of early puberty, especially in girls, while there was no significant association between screen exposure and early puberty and early development. In addition, further longitudinal investigations are needed to determine the causal relationship between screen exposure, sedentary behavior and precocious puberty.

Revising LH cut-off for the diagnosis of central precocious puberty via triptorelin stimulation assay.

INTRODUCTION: Precocious puberty (PP) in girls is defined by thelarche before age 8. The diagnostic gold standard is an increased LH level following gonadotropin-releasing hormone (GnRH) stimulation. Alternatively, GnRH analogues like triptorelin can be used, though their interpretation varies. Since 2000, we have used a triptorelin-induced LH cut-off of 15 IU/L, 4 h post-stimulus. However, many girls showed LH values below this threshold despite evident pubertal progression. PURPOSE: To establish a new LH threshold post-triptorelin stimulation for earlier diagnosis of central precocious puberty (CPP) in girls showing pubertal progression and to evaluate additional parameters for diagnostic accuracy. METHODS: We enrolled 186 girls with thelarche onset between ages 1-8 and a GnRH analogue assay performed between 2015-2019 without signs of axis activation. Within this cohort, 62 patients repeated the triptorelin test due to rapid pubertal progression. The assay involved administering 100 mcg/m² of triptorelin and measuring LH, FSH, and estradiol levels before and four hours post-injection. RESULTS: Patients with axis activation at the second test had significantly higher post-stimulus LH levels at the first test compared to those below 15 IU/L. They also had higher basal LH levels, elevated LH/FSH ratio, and increased growth velocity. Statistical analysis identified a new post-stimulus LH threshold of 5 IU/L. CONCLUSION: We propose a LH value of 5 IU/L after triptorelin administration as a new threshold for early CPP diagnosis. While the LH/FSH ratio and growth velocity are associated with axis activation, they did not significantly enhance diagnostic accuracy when combined with the LH value.

A Phase 3, Open-Label, Single-Arm Trial of the Efficacy and Safety of Triptorelin 6-Month Formulation in Chinese Children with Central Precocious Puberty.

INTRODUCTION: This phase 3 study assessed the efficacy, safety, and pharmacokinetics of the 6-month prolonged release (PR) formulation in Chinese children with central precocious puberty (CPP). METHODS: In this open-label study (NCT05029622), Chinese children (girls < 9 years, boys < 10 years) received two doses of triptorelin pamoate 22.5 mg (day 1 and month 6). Primary endpoint was the proportion at month 6 with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 5 IU/L after gonadotropin-releasing hormone stimulation). Secondary endpoints included safety assessments, hormone level changes, and clinical parameters from baseline. RESULTS: Overall, 66 children completed the study (93.9% girls; median age 8.0 [range 5-9] years). At month 6, all patients had LH suppression; this was maintained at month 12 in 98.5% of patients. Mean basal and peak LH and follicle-stimulating hormone levels were suppressed throughout follow-up. All patients at months 3 to 12 had sex hormone suppression to prepubertal levels. Stable or reduced breast development was seen for 98.4% and 93.5% of girls at month 6 and 12, respectively; all boys had regression or stable genital development until month 12. Compared with baseline (9.82 cm/year), mean growth velocity was 5.88 cm/year at month 6 and 5.17 cm/year at month 12. Mean bone age/chronological age ratio decreased from 1.27 at baseline to 1.23 and 1.21 at month 6 and 12, respectively. In girls, 64.5% showed decreased uterine length at month 6 and 12 versus baseline, while 75.0% of boys showed stable testicular volume versus baseline. Thirteen patients (19.7%) had 22 drug-related treatment emergent adverse events (TEAEs); no grade ≥ 3 TEAEs were reported. CONCLUSION: The efficacy and safety profile of triptorelin 6-month PR in Chinese children with CPP was consistent with data previously reported in non-Chinese children with CPP, supporting this as a viable treatment option for Chinese children with CPP. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov identifier, NCT05029622.

WHAT IS CENTRAL PRECOCIOUS PUBERTY (CPP)?: CPP is a condition where reproductive organs and sexual characteristics develop too early, before the age of 8 years in girls or 9 years in boys. CPP can negatively affect the mental health of patients and their caregivers. It can also lead to long-term problems like obesity and diabetes. CPP is caused by high levels of a hormone called luteinizing hormone. HOW IS CPP TREATED?: Triptorelin is an injectable treatment that can lower luteinizing hormone levels. Triptorelin injections are available for use once every month, once every 3 months, or once every 6 months. The injection for use once every 6 months (the 6-monthly injection) is not currently approved for CPP treatment in China. WHAT DID THIS STUDY LOOK AT?: This study assessed how well the 6-monthly triptorelin injections worked in 66 Chinese children with CPP. One injection was given at the start of the study and one after 6 months. WHAT WERE THE RESULTS?: Six months after their first injection, all children had luteinizing hormone levels that were below those seen with CPP. The development of sexual characteristics had slowed, such as pubic hair growth, breast and uterine length for girls, and testicular volume for boys. In addition, the rate at which children were increasing in height had also slowed down. These treatment effects were also seen at 12 months (6 months after the second injection). No children stopped treatment because of side effects. The researchers concluded that 6-monthly triptorelin may be a good treatment option for Chinese children with CPP.

Osteocalcin: may be a useful biomarker for early identification of rapidly progressive central precocious puberty in girls.

OBJECTIVE: To assess serum osteocalcin (OC) as a potential biomarker for the early detection of rapidly progressive central precocious puberty (RP-CPP) in girls. METHODS: Serum OC levels were quantified using enzyme-linked immunosorbent assays (ELISAs). In the retrospective analysis, receiver operating characteristic (ROC) curve analysis was employed to evaluate the ability of OC to identify RP-CPP. A prospective study and screening tests were utilized to assess the potential of OC for use in the early prediction of RP-CPP. Variable selection in the multivariate analysis was conducted using the Bayesian Information Criterion (BIC) and binary logistic regression was employed to construct the diagnostic prediction model. RESULTS: Girls with RP-CPP had significantly higher serum OC levels compared to girls with non-rapidly progressive central precocious puberty (NRP-CPP) (149.04±40.50 vs. 89.10±31.83 ng/mL, P < 0.001). The optimal OC cut-off point for differentiating RP-CPP from NRP-CPP was 107.05 ng/mL, the area under the ROC curve (AUC) was 0.90 (95%CI: 0.851-0.949; P < 0.001), with a sensitivity of 91.1% and specificity of 70.7%. The results of the prospective study indicated that changes in OC precede alterations in estradiol (E2) and bone age (BA). A diagnostic prediction model that includes duration of breast development, BA, OC, high-density lipoprotein cholesterol (HDL-C), and uterine length achieved an AUC of 0.961, with a sensitivity of 94.1% and specificity of 91.5% for the detection of RP-CPP. If OC is excluded from the model, the AUC decreases to 0.894, with sensitivity and specificity declining to 80.5% and 83.1%, respectively. CONCLUSIONS: Serum OC levels may serve as a promising biomarker for the early differentiation between RP-CPP and NRP-CPP in girls. The diagnostic prediction model that incorporates duration of breast development, BA, OC, HDL-C, and uterine length effectively identifies girls with RP-CPP.

ADHD and Risk of Precocious Puberty: Considering the Impact of MPH.

BACKGROUND/OBJECTIVES: The complex association between attention-deficit/hyperactivity disorder (ADHD) and methylphenidate (MPH) with precocious puberty (PP) is still unclear. This study aims to investigate the association between ADHD, MPH, and PP. METHODS: This is a nationwide cohort study including a total of 3,342,077 individuals, 186,681 with ADHD and 3,155,396 without. First, we compared the risk of PP between ADHD cases and non-ADHD cases. Second, we compared the risk of PP between MPH users and non-MPH users in patients with ADHD. RESULTS: Patients with ADHD were at a greater risk of PP (adjusted hazard ratio [aHR], 2.01 [95% CI, 1.91-2.11]). In our moderation analyses, the female gender was a positive additive effect modifier of the association between ADHD and PP, whereas tics and intellectual disability were negative effect modifiers. In patients with ADHD, MPH users had a significantly lower risk of PP (aHR, 0.63 [95% CI 0.57-0.70]), and females had a negative effect modification on the association between MPH and PP. CONCLUSIONS: Our study found that children with ADHD were at a greater risk of PP. Girls with ADHD were a group particularly vulnerable to PP. Comorbid tics or intellectual disability was associated with a lower risk of PP. Among patients with ADHD, MPH was protective against PP, especially in girls. However, these preliminary results need further validation due to the nature of them being from an electronic database study. Unmeasured confounding factors might affect the association between MPH and PP.

Community Awareness and Knowledge About Precocious Puberty in Riyadh City, Saudi Arabia.

Background Puberty is the process of physical maturation where an adolescent reaches sexual maturity and becomes capable of reproduction. On average, puberty typically begins between 8 and 13 years old in females and 9 and 14 years old in males. The traditional definition of precocious puberty is the development of secondary sexual characteristics before eight years of age in girls and nine years in boys. In this study, we aimed to assess the knowledge and awareness of Riyadh residents in Saudi Arabia about precocious puberty and its complications. Methodology A cross-sectional study was conducted to estimate the awareness and knowledge among Riyadh residents about precocious puberty and its complications; 426 participants were included in this study. Participants completed a pretested self-administered questionnaire that included sociodemographic data, knowledge about precocious puberty definition, risk factors, complications, and treatment. Results This study enrolled 426 participants. Overall, 10.1% were correct about the precocious puberty age for girls, and 8.5% knew about the precocious puberty age for boys. The overall mean knowledge score among the study sample was 5.56 (SD = 2.79), with poor knowledge being prominent and constituting 68.8%, while fair and good knowledge were 30% and 1.2%, respectively. Working in a non-medical field was the sole independent significant predictor of incorrect answers of knowledge about precocious puberty. Conclusions Awareness strategies are needed to increase awareness among the community to encourage prevention and treatment for precocious puberty as the awareness and knowledge of Riyadh residents in Saudi Arabia about precocious puberty and its complications are low.

Potential Role of Sleep Disturbance in the Development of Early Puberty: Past Clinical Evidence for Future Management.

The incidence of early puberty in children has been increasing. It has been suspected that both genetic and various environmental factors such as nutrition and hormonal exposure could influence the mechanisms underlying the earlier onset of puberty. Interestingly, several previous studies have reported a strong connection between sleep and puberty. Specifically, it was discovered that luteinizing hormone (LH), a potential marker for the onset of puberty, was increased during the deep sleep period. Furthermore, a high prevalence of early puberty was observed in patients with sleep disorders, especially in those experiencing narcolepsy. In this review article, findings related to the association between sleep disturbance and early puberty have been comprehensively summarized. Any contrary findings are also included and discussed. Advances in the knowledge surrounding sleep disturbance have led to a greater understanding of a correlation between early puberty and sleep disorder and provide alternative therapeutic options for the treatment of central precocious puberty in the future.

Diversity of Molecular Functions of RNA-Binding Ubiquitin Ligases from the MKRN Protein Family.

Makorin RING finger protein family includes four members (MKRN1, MKRN2, MKRN3, and MKRN4) that belong to E3 ubiquitin ligases and play a key role in various biological processes, such as cell survival, cell differentiation, and innate and adaptive immunity. MKRN1 contributes to the tumor growth suppression, energy metabolism, anti-pathogen defense, and apoptosis and has a broad variety of targets, including hTERT, APC, FADD, p21, and various viral proteins. MKRN2 regulates cell proliferation, inflammatory response; its targets are p65, PKM2, STAT1, and other proteins. MKRN3 is a master regulator of puberty timing; it controls the levels of gonadotropin-releasing hormone in the arcuate nucleus neurons. MKRN4 is the least studied member of the MKRN protein family, however, it is known to contribute to the T cell activation by ubiquitination of serine/threonine kinase MAP4K3. Proteins of the MKRN family are associated with the development of numerous diseases, for example, systemic lupus erythematosus, central precocious puberty, Prader-Willi syndrome, degenerative lumbar spinal stenosis, inflammation, and cancer. In this review, we discuss the functional roles of all members of the MKRN protein family and their involvement in the development of diseases.

The Role of DLK1 Deficiency in Central Precocious Puberty and Association with Metabolic Dysregulation.

INTRODUCTION: Precocious puberty is defined as the appearance of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Central precocious puberty (CPP) is a rare condition that is diagnosed when premature activation of the hypothalamic-pituitary-gonadal axis is detected, in association with precocious breast development or testicular growth. Idiopathic CPP is historically considered to be the most common form, but in recent years defects in a small but growing number of genes regulating the timing of puberty have been identified in an increasing proportion of cases of CPP. Delta-like non-canonical Notch ligand 1 (DLK1) is understood to be one of the key genes involved in the etiology of CPP, although its mechanistic role is not yet fully understood. CASE PRESENTATION: We identified a novel de novo variant of DLK1 (c.835C>T; p.Gln279*) in an 8-year-old girl of Bangladeshi origin. She presented with an advanced Tanner staging of B4P4A2, significantly advanced bone age (BA, 13 years), a near-adult proportioned uterus, with a history of menarche at the age of 7.4 years. Diagnosis was confirmed by raised basal luteinizing hormone concentration. She was found to have truncal obesity associated with abnormal fasting insulin levels and mildly elevated cholesterol levels. These findings are consistent with previous literature describing an association between patients with DLK1 deficiency and an impaired metabolic profile. The patient was treated for 2 years with GnRH agonists with ongoing biochemical follow-up into adolescence. CONCLUSION: This case illustrates the susceptibility to metabolic derangement for patients with mutations in DLK1 and the need for ongoing monitoring after puberty. Our summary of previously identified DLK1 variants and their metabolic consequences demonstrates the frequency of obesity, lipid abnormalities, and insulin dysregulation in this patient cohort in childhood and beyond. This knowledge can guide future clinical practice for patients with CPP patients due to DLK1 deficiency.

Predictive value of transabdominal pelvic ultrasonography for the diagnosis of central precocious puberty: A single-center observational retrospective study.

This single-center, observational, retrospective study aimed to evaluate the diagnostic accuracy of pelvic ultrasonographic parameters for detecting central precocious puberty (CPP) in a cohort of female pediatric patients undergoing gonadotropin stimulation tests. The study population consisted of 47 female patients with a suspicion of CPP. Thirty four out of 47 patients (72.34%) were subsequently diagnosed with CPP based on the current laboratory diagnostic criteria (LH peak > 5 IU/L). The ultrasonography results of 39 out of 47 patients (82.97%) were categorized as pubertal, while 31 out of 34 participants (91.17%) in the CPP group exhibited pubertal ultrasonography features. In 13 out of 47 girls (27.65%), a CPP diagnosis was ruled out; however, among these 13 patients, eight exhibited pubertal ultrasonography features suspicious of CPP. We observed a robust concordance between the GnRH test results indicative of pubertal activation and the presence of pubertal pelvic ultrasonographic features in 31 out of 34 children (91.17%). A significant correlation was found between ovarian volume and basal LH and LH/ FSH ratio, and also for basal LH, LH peak, LH/FSH ratio and peak LH/FSH ratio (p = 0.026, p = 0.011, p = 0.031, p = 0.004, respectively). Pelvic ultrasonography had a sensitivity of 91.17% and a specificity of 38.46% in differentiating CPP from premature thelarche.

EVALUATION OF OXIDATIVE STRESS MARKERS IN GIRLS WITH PREMATURE THELARCHE AND PRECOCIOUS PUBERTY.

Context: Oxidative products take part in various physiological processes and overproduction of oxidative products is involved in the etiology of many diseases. Objectives: We aimed to evaluate thiol-disulfide homeostasis (TDH); one of the oxidative stress parameters, in girls with premature thelarche (PT) and precocious puberty (PP). Design: This case-control study was conducted between January 2022 and July 2022. Subjects and Methods: TDH parameters, involving native thiol (NT), disulfide, and total thiol (TT), were evaluated in 39 girls with PT, 41 girls with PP and 46 healthy prepubertal girls. The correlations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) levels with the TDH parameters were determined and ROC curve analysis was performed. Results: NT, TT and NT/TT ratio were higher in the PT and PP groups compared to the control group (p<0.01). Disulfide/NT ratio and disulfide/TT ratio were lower in the PT and PP groups compared to the control group (p<0.05). All the TDH values did not statistically differ between the PP and PT group (p>0.05). There was a positive correlation between LH level, FSH level, and NT level, TT level, NT/TT ratio. The best parameter to discriminate PT or PT and control groups were NT and TT (p<0.01). Conclusion: TDH is altered in girls with PT and PP. NT and TT levels can be useful to discriminate prepubertal girls with lipomastia and girls with PP and PT in clinical practice. Further studies on larger cohorts of patients are required to clarify our results.

Comparison of central precocious puberty frequency before and during COVID-19: a systematic review and meta-analysis.

OBJECTIVE: The current systematic review and meta-analysis assessed the prevalence of central precocious puberty (CPP) throughout the novel coronavirus disease 2019 (COVID-19) pandemic. DESIGN: A systematic review and meta-analysis were carried out following the principles outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, 2020). DATA SOURCES: PubMed, Embase, Web of Science, and WANFANG databases were searched from January 1, 2019, to March 30, 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: (1) children and adolescents ≤ 15 years; (2) studies with the outcome of frequency of central precocious puberty, measured prior to and throughout the COVID-19 pandemic; (3) a novel CPP diagnosis was created depending on all of the following criteria: girls with a chronological age < 8 years and boys with a chronological age < 9 years at the onset of symptoms, basal luteinizing hormone (LH) levels > 0.3 UI/L, and/or GnRH-stimulated peak LH levels > 5 IU/L. DATA EXTRACTION AND SYNTHESIS: The process of extracting data and evaluating the likelihood of bias was carried out by two independent reviewers. The data were pooled employing the generic inverse-variance method and presented as mean differences (MDs) with 95% CIs. The evaluation of heterogeneity was conducted employing the Cochran Q statistic, and the degree of heterogeneity was measured employing the I2 statistic. RESULTS: This meta-analysis included 17 studies. In contrast to the same period prior to the COVID-19 pandemic, the occurrence of CPP elevated (OR = 2.57; 95% CI, 1.85-3.56). Moreover, body mass index standard deviation score (BMI SDS) differences between CPP patients prior to COVID-19 and throughout the pandemic follow-up was 0.12 (95% CI - 0.01 to 0.25 P = 0.06). CONCLUSION: Overall, CPP frequency significantly elevated throughout the COVID-19 pandemic. Given the restricted number of cohort investigations in this meta-analysis, additional research may be conducted on larger groups of children in order to establish a correlation between the observed rise in precocious puberty and specific pathogenic factors.

Three Therapy Regimens and Their Cost-effectiveness for Girls With Central Precocious Puberty: A Real-World Clinical Study.

The objective of this study was to evaluate the effectiveness and cost-effectiveness of different therapy regimens for girls with central precocious puberty (CPP). This study retrospectively analyzed CPP girls from 2013 to 2021 and grouped them into GnRHa, Mixed, and GnRHa+GH based on therapy regimen. While comparing the differences among these groups, initial age and bone age of GnRHa group girls were significantly lower than Mixed and GnRHa+GH groups, but their growth level was significantly higher (P < .05). In the Mixed group, starting with GnRHa alone, the predicted adult height improvement (ΔPAH) decreased to -1.0 cm in the second year, prompting addition of growth hormone (GH) therapy in the third year, resulting in a ΔPAH increase to 3.0 cm. At therapy completion, final predicted adult heights (PAHs) were similar among the groups at 155.6 to 156.7 cm, with ΔPAH between 5.8 and 6.5 cm and no significant intergroup differences (P > .05). Younger CPP girls with greater height can begin therapy with GnRHa alone. Consideration of combining GH therapy depends on growth velocity and PAH during treatment.

Serum phoenixin levels in girls with central precocious puberty and premature thelarche.

BACKGROUND AND AIM: Phoenixin (PNX), a newly discovered neuropeptide associated with reproduction, has been speculated to be involved in precocious puberty. Therefore, we assessed serum PNX levels in girls with precocious puberty. METHODS: Serum phoenixin-14 (PNX-14) and phoenixin-20 (PNX-20) levels were determined in girls with central precocious puberty (CPP) and premature thelarche (PT) and in healthy controls (n = 58 per group). Spearman's correlation was used to analyze the correlations between variables. Receiver operating characteristic curves were used to evaluate the performance of PNX for the diagnosis of CPP. Significant predictors of serum PNX levels were determined using least absolute shrinkage and selection operator regression and multiple linear regression analyses. RESULTS: Serum PNX-14 and PNX-20 levels were significantly higher in girls with CPP than in the controls; however, no significant differences in serum PNX-14 and PNX-20 levels were observed between girls with PT and the controls. PNX-20 levels were positively correlated with basal luteinizing hormone (LH) levels, peak LH levels, the peak LH to follicle-stimulating hormone (FSH) ratio, and estradiol levels. No significant correlation was observed between PNX-14 levels and any of these parameters. Multivariate linear regression analysis revealed that PNX-20 levels exhibited the strongest correlation with peak LH/FSH values. The areas under the curve (AUCs) of PNX-14 and PNX-20 for predicting CPP were 0.628 (cut-off value, 100.12 pg/mL; sensitivity, 44.6%; specificity, 77.6%) and 0.775 (cut-off value, 360.03 pg/mL; sensitivity, 66.5%; specificity, 79.3%), respectively. When these two indicators were combined, the AUC was 0.785. CONCLUSIONS: Serum PNX levels may be associated with precocious puberty in girls and can be used as an auxiliary CPP indicator. However, given the low sensitivity and specificity of PNX, it should not be used as a single diagnostic indicator of CPP.

Disorders of puberty and neurodevelopment: A shared etiology?

The neuroendocrine control of puberty and reproduction is fascinatingly complex, with up- and down-regulation of key reproductive hormones during fetal, infantile, and later childhood periods that determine the correct function of the hypothalamic-pituitary-gonadal axis and the timing of puberty. Neuronal development is a vital element of these processes, and multiple conditions of disordered puberty and reproduction have their etiology in abnormal neuronal migration or function. Although there are numerous documented cases across multiple conditions wherein patients have both neurodevelopmental disorders and pubertal abnormalities, this has mostly been described ad hoc and the associations are not clearly documented. In this review, we aim to describe the overlap between these two groups of conditions and to increase awareness to ensure that puberty and reproductive function are carefully monitored in patients with neurodevelopmental conditions, and vice versa. Moreover, this commonality can be explored for clues about the disease mechanisms in these patient groups and provide new avenues for therapeutic interventions for affected individuals.

Comprehensive study on central precocious puberty: molecular and clinical analyses in 90 patients.

CONTEXT: Defects in MKRN3, DLK1, KISS1, and KISS1R and some disorders, such as Temple syndrome (TS14), cause central precocious puberty (CPP). Recently, pathogenic variants (PVs) in MECP2 have been reported to be associated with CPP. OBJECTIVE: We aimed to clarify the contribution of (epi)genetic abnormalities to CPP and clinical and hormonal features in each etiology. SUBJECTS AND METHODS: We conducted targeted sequencing for MKRN3, DLK1, MECP2, KISS1, and KISS1R and methylation analysis for screening of imprinting disorders such as TS14 associated with CPP in 90 patients with CPP (no history of brain injuries and negative brain MRI) and collected their clinical and laboratory data. We measured serum DLK1 levels in three patients with TS14 and serum MKRN3 levels in two patients with MKRN3 genetic defects, together with some etiology-unknown patients with CPP and controls. RESULTS: We detected eight patients with TS14 (six, epimutation; one, mosaic maternal uniparental disomy chromosome 14; one, microdeletion) and three patients with MKRN3 genetic defects (one, PV; one, 13-bp deletion in the 5'-untranslated region (5'-UTR); one, microdeletion) with family histories of paternal early puberty. There were no patients with PVs identified in MECP2, KISS1, or KISS1R. We confirmed low serum MKRN3 level in the patient with a deletion in 5'-UTR. The median height at initial evaluation of TS14 patients was lower than that of all patients. Six patients with TS14 were born small for gestational age (SGA). CONCLUSION: (Epi)genetic causes were identified in 12.2% of patients with CPP at our center. For patients with CPP born SGA or together with family histories of paternal early puberty, (epi)genetic testing for TS14 and MKRN3 genetic defects should be considered. (271/250).

Development and application of a nomogram model for predicting the risk of central precocious puberty in obese girls.

Objective: The purpose of this study is to develop and assess a nomogram risk prediction model for central precocious puberty (CPP) in obese girls. Methods: We selected 154 cases of obese girls and 765 cases of non-obese girls with precocious puberty (PP) who underwent the gonadotropin-releasing hormone stimulation test at the Jiangxi Provincial Children's Hospital. Univariate analysis and multivariate analysis were conducted to identify predictors of progression to CPP in girls with PP. A predictive model was developed and its predictive ability was preliminarily evaluated. The nomogram was used to represent the risk prediction model for CPP in girls with obesity. The model was validated internally using the Bootstrap method, and its efficacy was assessed using calibration curves and clinical decision analysis curves. Results: In obese girls with PP, basal luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels, as well as uterine volume, were identified as independent risk factors for progression to CPP. In non-obese girls, the basal LH level, bone age, and uterine volume were identified as independent risk factors for progression to CPP. With an AUC of 0.896, the risk prediction model for obese girls, was found to be superior to that for non-obese girls, which had an AUC of 0.810. The model displayed strong predictive accuracy. Additionally, a nomogram was used to illustrate the CPP risk prediction model for obese girls. This model performs well in internal validation and is well calibrated, providing a substantial net benefit for clinical use. Conclusion: A medical nomogram model of CPP risk in obese girls comprised of basal LH value, basal FSH value, and uterine volume, which can be used to identify those at high risk for progression of CPP in obese girls and develop individualized prevention programs.

Behavioral Changes in a Pediatric Patient With Sotos Syndrome: A Case Emphasizing the Importance of Coordinated Care.

Sotos syndrome is a rare overgrowth condition characterized by tall stature, distinctive facial features, and learning disabilities. It is primarily caused by a microdeletion of the nuclear receptor-binding set domain protein 1 (NSD1) gene on chromosome 5q35. Patients often present with various clinical manifestations, including tall stature, precocious puberty, cardiac anomalies, and mild intellectual disability. Management of Sotos syndrome involves a multidisciplinary approach due to its complex nature and potential comorbidities. This case discusses the management of a 10-year-old female with a known gene mutation consistent with Sotos syndrome that presented to the clinic with behavioral changes, and highlights the importance of integrated care models when addressing complex clinical scenarios.

The role of MicroRNAs as fine-tuners in the onset of puberty: a comprehensive review.

MicroRNA (miRNA) are small, noncoding RNA molecules that play pivotal roles in gene expression, various biological processes, and development of disease. MiRNAs exhibit distinct expression patterns depending on time points and tissues, indicating their relevance to the development, differentiation, and somatic growth of organisms. MiRNAs are also involved in puberty onset and fertility. Although puberty is a universal stage in the life cycles of most organisms, the precise mechanisms initiating this process remain elusive. Genetic, hormonal, nutritional, environmental, and epigenetic factors are presumed contributors. The intricate regulation of puberty during growth also suggests that miRNAs are involved. This study aims to provide insight into the understanding of miRNAs roles in the initiation of puberty by reviewing the existing research.