Central Precocious Puberty In Girls Research Articles

Diagnostic Value of Stimulated Urine Luteinizing Hormone After Triptorelin Stimulation Test in Girls with Central Precocious Puberty.

To investigate the diagnostic value of urine luteinizing hormone (ULH) after the triptorelin stimulation test detected by immunochemiluminometric assay (ICMA) in girls with central precocious puberty (CPP). The girls with precocious puberty were included. The triptorelin stimulation test at 8:30 a.m. was performed. Two consecutive 12-hour urine samples were collected after the test, defined as the first 12-hour and second 12-hour urine, respectively. ICMA measured ULH. Urine creatinine (Cr) concentration was measured. CPP and peripheral precocious puberty (PPP) were diagnosed by the same pediatric endocrinologist based on clinical symptoms, signs, and progression of clinical development. A total of 97 cases (CPP n=69; PPP n=28) were included, with 12 cases not meeting the receiver operating characteristic analysis criteria. The first and second 12-hour ULH/Cr in the CPP group were higher than those in the PPP group. When the first 12-hour ULH/Cr was≥287.252 IU/mol, the sensitivity and specificity for diagnosing CPP were 87.3% and 90.9%, respectively. When the second 12-hour ULH/Cr was≥152.769 IU/mol, the sensitivity and specificity for diagnosing CPP were 92.1% and 90.9%, respectively. The area under the curve of the first and second 12-hour ULH/Cr were 0.933 and 0.954, respectively. The ULH detection method after the triptorelin stimulation test has clinical significance for diagnosing CPP in girls. When blood sampling compliance in girls with precocious puberty is poor, the first 12-hour ULH/Cr≥288 IU/mol (or second 12-hour≥153 IU/mol) after the triptorelin stimulation test can serve as a laboratory indicator for diagnosis of CPP.

Effectiveness of the triptorelin stimulation test compared with the classic gonadotropin-releasing hormone stimulation test in diagnosing central precocious puberty in girls.

The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). Gonadorelin (Relefact) is used for the test but is not always readily available; triptorelin is used as an alternative. The purpose of this study was to evaluate the diagnostic validity of the triptorelin test compared with the GnRH test in the diagnosis of CPP in girls. This retrospective study included 100 girls with premature thelarche (PT) who underwent a hypothalamic-pituitary-gonadal axis evaluation. In the overall group, 50 girls were tested with intravenous gonadorelin (Relefact) and 50 girls were tested with subcutaneous triptorelin acetate (Decapeptyl). Luteinizing hormone (LH) and follicle-stimulating hormone levels were measured at baseline and 30, 45, 60, and 90 minutes after gonadorelin injection or 30, 60, 90, and 120 minutes after triptorelin injection. Clinical characteristics of age, height, weight, body mass index, and bone age were similar between the 2 groups. The highest LH level was reached 60 minutes after stimulation in both groups. Approximately 20% of the gonadorelin group and 24% of the triptorelin group were diagnosed with CPP (P=0.52). Among those diagnosed with CPP, the mean peak LH concentrations were 8.15 mIU/mL and 9.73 mIU/mL in the gonadorelin and triptorelin groups, respectively. The triptorelin test showed similar trends of LH elevation and diagnostic rate compared with the traditional GnRH test for diagnosing CPP. This suggests that the triptorelin test may be a valid alternative to the GnRH test for differentiating CPP from self-limiting PT. Our study also demonstrated that a triptorelin stimulation test for up to 120 minutes was sufficient to diagnose CPP.

Irisin combined index to diagnose central precocious puberty in girls: a cross-sectional study

BackgroundTo investigate serum irisin levels in girls at different developmental status and explore the significance of irisin for the diagnosis of central precocious puberty (CPP) in girls.MethodsIn this cross-sectional study 111 girls were enrolled, including 43 cases of CPP, 44 cases of peripheral precocious puberty (PPP) and 24 cases of girls with normal sexual development as controls. The data on age, weight and height, measured blood levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and irisin were collected. Pelvic Doppler ultrasound was performed to evaluate uterine length, transverse diameter, anteroposterior diameter. The girls were divided into non-CPP group and CPP group according to gonadotropin-releasing hormone (GnRH) stimulation test.ResultsSerum irisin levels were significantly higher in CPP group than in PPP group and normal control group. Serum irisin level was positively correlated with basal LH level, basal FSH level, peak LH level, peak LH /FSH ratio, uterine volume, bone age, and bone age index. The area under the curve, cut-off value, sensitivity and specificity of serum irisin were 0.958, 219.255 pg/ml, 100% and 80.6%. The combined diagnosis of CPP in girls by serum irisin and serum basal LH combined with uterine volume had an AUC, sensitivity, and specificity of 0.994, 97.6%, and 100%, superior to that of the single index.ConclusionsSerum irisin level in girls with CPP is significantly increased. An irisin combined index could help the diagnosis of CPP in girls.

Elevated serum irisin levels in boys with central precocious puberty independent of BMI.

Central precocious puberty (CPP) is a prevalent endocrine disorder. Research has indicated that pubertal development is linked to nutritional metabolism. Irisin, a novel myokine/adipokine, has been identified as a potential predictor of CPP in girls. This study aims to examine the relationship between serum irisin levels and CPP in boys. An enzyme-linked immunosorbent assay (ELISA) was used to measure serum irisin levels in 32 boys diagnosed with CPP and 33 prepubertal age-matched boys as normal controls (NC). To assess the impact of body mass index (BMI) on irisin levels, both the CPP and NC groups were divided into overweight/obese and normal-weight subgroups. Spearman correlation analysis was employed to assess the connection between irisin and clinical and biochemical parameters. Additionally, a receiver operating characteristic curve was utilised to determine the optimal threshold value for irisin. In the normal-weight subgroups, boys with CPP exhibited elevated irisin levels compared to controls, but not in the overweight/obese subgroups. The optimal cut-off value for irisin levels to predict CPP in the normal-weight groups was 93.09 ng/mL, yielding a sensitivity of 47.6% and a specificity of 100%. Furthermore, a positive correlation was noted between irisin levels and bone age (BA), bone age advancement (BA-CA), and BMI. Serum irisin levels correlate with BMI and pubertal development. Given its limited sensitivity, irisin level can only be utilised as a supplementary rather than a standalone diagnostic indicator for CPP.

Pineal cysts may promote pubertal development in girls with central precocious puberty: a single-center study from China.

Pineal cysts have long been considered a benign intracranial variation. However, in our clinical practice, it has been observed that some children with central precocious puberty (CPP) who have pineal cysts experience rapid progression in adolescent development. In recent years, there has been a significant increase in the prevalence of CPP in girls, leading to more diagnoses of CPP among children with pineal cysts. Despite this, there is no consensus regarding whether pineal cysts contribute to CPP as one of its organic factors. This study aimed to analyze the clinical characteristics of pineal cysts in children with CPP and explore the potential effects of pineal cysts on puberty development. This single-center study retrospectively analyzed clinical data from girls aged 3 to 10 years who underwent head/pituitary magnetic resonance imaging at the Children's Hospital Affiliated to Zhengzhou University between 2019 and 2022. The study categorized the detection rates of pineal cysts based on systematic disease classification and compared the rates of cyst detection between girls diagnosed with CPP and those without CPP. Subsequently, CPP-diagnosed girls with pineal cysts were examined. Among CPP-diagnosed girls meeting the study's criteria, those with pineal cysts formed the 'cyst group,' while those without cysts were matched in a 1:1 ratio based on age and body mass index to form the 'non-cyst group.' Comparative analyses were conducted to assess the clinical characteristics between these two groups. CPP-diagnosed girls with cysts were further subdivided into three groups according to cyst size (≤5 mm, 5.1-9.9 mm, and ≥10 mm) to investigate potential differences in clinical characteristics among these subgroups. The study involved an analysis of clinical data from girls diagnosed with CPP and included imaging follow-ups to explore the progression of pineal cysts over time. Among the 23,245 girls who underwent head/pituitary magnetic resonance imaging scans, the detection rate of pineal cysts was 3.6% (837/23,245), with most cases being associated with endocrine diseases. The detection rate of pineal cysts in CPP patients was 6.4% (262/4099), which was significantly higher than the 3.0% (575/19,146) in patients without CPP. In comparison to the non-cyst group, the cyst group exhibited statistically significant increases in estradiol levels, peak luteinizing hormone (LH) levels, peak LH/follicle-stimulating hormone (FSH) ratios, uterine body length, and cervix length (P < 0.001). As cyst size increased, there were significant rises in LH peak, peak LH/FSH ratio, uterine body length, and cervical length (P < 0.01). Estradiol levels and left ovarian volume also showed an increasing trend (P < 0.05). Among girls who underwent follow-up imaging, 26.3% (5/19) exhibited an increase in cyst size. Pineal cysts are relatively common in children with CPP. They may affect the pubertal development process, with larger cysts correlating to faster pubertal development. Therefore, the authors hypothesize that pineal cysts may trigger CPP in some cases, especially when the cysts are larger than 5mm in size, as indicated by our data.

Peak serum luteinising hormone cut-off during gonadotropin-releasing hormone analogue test for diagnosing central precocious puberty was lower in girls with obesity as compared with girls with normal weight.

Serum luteinising hormone (LH) concentration has been reported to be lower in girls with overweight and obesity (OW/OB) as compared with girls with normal weight (NW). This study aimed to evaluate peak serum LH concentration during gonadotropin-releasing hormone analogue (GnRHa) test in girls with OW/OB and NW who had central precocious puberty (CPP) and to determine peak serum LH cut-off for diagnosing CPP in girls with OW/OB. Medical records of 971 girls with premature breast development who underwent subcutaneous GnRHa (100 µgof triptorelin acetate) test were reviewed. All girls were classified as either CPP or premature thelarche. All of them were further classified into two groups according to their body mass index as NW and OW/OB groups for each Tanner stage. There were 634 and 337 girls in NW and OW/OB groups, respectively. CPP was diagnosed in 600 girls (249 had Tanner stage II and 351 had Tanner stage III). There were no differences in peak serum LH concentrations between CPP girls with NW and OW/OB. Peak serum LH cut-off of 5 IU/L (the current widely used cut-off) had a sensitivity and a specificity of 75% and 90%, respectively in NW group. Peak serum LH cut-off for CPP diagnosis was lower at 4 IU/L in the OW/OB group with greater sensitivity and specificity of 86% and 93%, respectively. The results were reproducible for each Tanner stage of breasts. Lower peak serum LH cut-off to 4 IU/L for diagnosing CPP in girls with OW/OB should be considered to avoid underdiagnosis of the condition.

Diagnostic model based on multiple factors for girls with central precocious puberty.

The GnRH stimulation test has been used as the gold standard for the diagnosis of central precocious puberty (CPP), but it has some practical barriers. This study intends to build a diagnostic model of CPP in girls based on the population in northern China. A total of 163 girls with precocious puberty (PP) were included from December 2018 to December 2019. Multifactor logistic regression analysis was conducted. Based on the results of multivariate logistic regression analysis, a nomogram was established for clinical application. A multi logistic regression model showed that LH (OR=1.238, 95 % CI: 1.067-1.436, p=0.005), inhibin B (OR=1.066, 95 % CI: 1.032-1.100, p<0.001), bone age (OR=1.563, 95 % CI: 1.037-2.358, p=0.033), and uterine length (OR=1.180, 95 % CI: 1.034-1.348, p=0.014) were diagnostic factors for CPP. The prediction model AUC was 0.906 (95 % CI: 0.852-0.959, p<0.001). We successfully developed a nomogram model for CPP patients based on clinical data. The diagnostic prediction model included four indicators: basal LH, inhibin B, bone age, and uterine body length.

Rare presentation of pituitary stalk lipoma as central precocious puberty in a girl

Central precocious puberty (CPP) in girls is most commonly idiopathic. Here, we present a case of a 5-year 3-month-old child who presented with CPP with a stalk lipoma on magnetic resonance imaging. On examination, the sexual maturity rating was A1P1B (Rt B1, Lt B2), respectively. The hormonal evaluation revealed pubertal gonadotropin and E2 levels, respectively, with pubertal ultrasound (USG) parameters. She was started on gonadotropin-releasing hormone agonist therapy and is on regular follow-up. This case highlights stalk lipoma as a cause of CPP.

Analysis of serum insulin-like growth factor-1, fibroblast growth factor 23, and Klotho levels in girls with rapidly progressive central precocious puberty

To study the levels of serum insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF23), and Klotho, and to study their relationship with girls with rapidly progressive central precocious puberty (RP-CPP). This is a cross-sectional study on the progression rate of central precocious puberty in girls, who complained of breast development before the age of 8 years and were followed between June 2021 and June 2022. At the same time, 28 healthy girls less than 8 years old who had not started puberty were recruited as the control group. The physical examination and laboratory evaluation of each group was completed. Only patients with CPP received pelvic ultrasound examination and bone age test. Bone age index (BAI), basal LH levels (BLH), basal LH levels/basal FSH levels (BFSH), peak LH (PLH)/peak FSH (PFSH), IGF-1, Klotho, FGF23, and ovarian volume in the RP-CPP group were higher than those in slowly progressive CPP (SP-CPP) group. In the RP-CPP group, IGF-1 was correlated with Klotho, FGF23, and BLH; Klotho was correlated with FGF23 and BLH; FGF23 was correlated with BLH.Conclusion: The BLH, FGF23, Klotho, and IGF-1 have a certain correlation with RP-CPP, which may play an important role in the speed of girls’ sexual development.What is Known:• The association between IGF-1 and RP-CPP.What is New:• We found the association between FGF23, Klotho and RP-CPP.

Rapid weight gain in early life is associated with central precocious puberty in girls, not in boys - a nationwide population-based study in Korea.

This study aimed to investigate the effect of rapid weight gain (RWG) on the incidence of central precocious puberty (CPP) using nationwide population-based data. A total of 253,967 children (101,841 boys and 152,126 girls) who underwent regular health consultations under the National Health Insurance Service from 2007 to 2010 were followed up until the age of 10 years for boys and 9 years for girls. We calculated differences in the weight Z-scores from 4-6 months to 9-12 months (infancy) and from 9-12 months to 18-24 months or 30-36 months (toddlerhood) using the lambda-mu-sigma method. The population was subdivided into four groups: RWGinf/tod (infancy > + 0.67 standard deviation score [SDS], toddlerhood > 0 SDS), RWGinf (infancy > + 0.67 SDS, toddlerhood < 0 SDS), RWGtod (toddlerhood > + 0.67 SDS), and control (no RWG). The diagnosis of CPP was based on the diagnostic codes of the International Classification of Diseases 10th revision and the prescription of gonadotropin-releasing hormone agonists. The cumulative risk of CPP based on age was analyzed using Kaplan-Meier survival curves, and the association between the RWG groups and CPP was assessed using multivariate logistic regression analysis. CPP was diagnosed in 268 boys and 9,225 girls. For the girls, the CPP-free probability was the highest in the control group, followed by the RWGtod, RWGinf, and RWGinf/tod groups (log-rank p < 0.001). However, the incidence of CPP did not vary significantly for the boys. Compared to the control group, the other groups had a higher risk of CPP in girls (RWGinf/tod: adjusted odds ratio [aOR] 1.35, 95%, confidence interval [95% CI] 1.13-1.62; RWGinf: aOR 1.25, 95% CI 1.13-1.38; and RWGtod: aOR 1.18, 95% CI 1.09-1.28). This nationwide population-based study demonstrated that any RWG from birth to 3 years of age contributed to an increased risk of CPP in girls but not in boys. Girls who experienced RWG during both infancy and toddlerhood had the highest risk of developing CPP. These findings suggest that early detection and appropriate management of excessive weight gain in early life may be important for preventing CPP in girls.

Value of pelvic ultrasound combined with pituitary MRI in diagnosis of central precocious puberty in girls.

This study aimed to investigate the value of pelvic ultrasound combined with pituitary magnetic resonance imaging (MRI) based on an artificial intelligence algorithm in the diagnosis of girls with central precocious puberty (CPP), providing reference for the prevention and control of CPP in girls. 75 girls with CPP and 75 normal girls in Nantong First People's Hospital were studied. Pelvic ultrasound parameters were compared between the two groups based on an artificial intelligence algorithm. Pituitary MRI parameters were analyzed, and pituitary function parameters were explored. The results showed that the diagnostic sensitivity, specificity, and accuracy of the convolutional neural network (CNN) algorithm were 72.3%, 74.6%, and 78.3%, respectively. The sensitivity, specificity, and accuracy of CNN algorithm were significantly higher (p<0.05). The long diameter, anteroposterior diameter, and transverse diameter of the uterus in the precocious puberty (PP) group were significantly larger than those in the normal group (NG). The ovarian long diameter, ovarian anteroposterior diameter, and ovarian transverse diameter in PP group were significantly larger than those in NG. Uterine volume and ovarian volume in PP group were clearly higher than those in NG. The largest follicle diameter was clearly larger in PP patients than in NG patients. The coronal height, coronal width, sagittal height, and sagittal anteroposterior diameter of PP group were clearly higher than those of NG (p<0.05). The sagittal cross-sectional area of pituitary MRI morphology in PP group was significantly greater than that in NG. The pituitary MRI morphology pituitary volume was 272.68 mm in PP group and 191.37 mm in NG, and the pituitary volume was clearly larger in PP group than in NG. The pituitary function parameters estradiol (E2), luteinizing hormone (LH) peak, follicle-stimulating hormone (FSH) peak, and LH peak/FSH peak were greater in PP group than in NG. In summary, the uterine size and ovarian size of girls and the pituitary function index in PP group were larger. Pelvic ultrasound and pituitary MRI indexes can better diagnose CPP and can be widely used in clinical practice with positive diagnostic value.

The utilization of basal luteinizing hormone in combination with the basal luteinizing hormone and follicle-stimulating hormone ratio as a diagnostic tool for central precocious puberty in girls.

Intravenous gonadotropin-releasing hormone (IV GnRH) testing is the gold standard for confirming a central precocious puberty (CPP) diagnosis. However, this test is not widely available commercially. Therefore, our study aim was to establish cutoff values for basal gonadotropin level and gonadotrophin responses to a 100-μg subcutaneous IV GnRH test that can distinguish between CPP and premature thelarche (PT) to discover a simple method to detect CPP. Girls between the ages of 6 and 8 years who attended the pediatric endocrinology outpatient clinic at our tertiary hospital between 2019 and 2022 were included in this study. They were evaluated for breast development, and a subcutaneous 100-μg GnRH test was administered by measuring the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in blood samples at baseline and then 30, 60, 90, and 120 minutes after injection. CPP is characterized by increased height velocity, advanced bone age, and progression of breast development. The cutoff value for diagnosis of CPP was determined using a receiver operating characteristic (ROC) analysis. In 86 Thai girls (56 with CPP and 30 with PT), the ROC analysis showed 71.4% and 100% sensitivity and specificity, respectively, for basal LH (cutoff ≥ 0.2 IU/L) plus the basal LH/FSH ratio (cutoff ≥ 0.1). The optimal cutoff values for peak LH (cutoff ≥ 7 IU/L) demonstrated a sensitivity of 94.6% and a specificity of 100%, whereas the LH value at 30 and 60 minutes after injection (cutoff ≥ 6 IU/L) demonstrated sensitivities of 92.9% and 94.6% and a specificity of 100%, respectively. Combining the basal LH (cutoff: 0.2 IU/L) and the basal LH/FSH ratio (cutoff: 0.1) can easily and cost-effectively diagnose CPP in a girl in breast Tanner stage II.

Comprehensive analysis of untargeted metabolomics and lipidomics in girls with central precocious puberty.

Central precocious puberty (CPP) is a rare condition that causes early sexual development in children. Although the cure is effective, the etiology of central precocious puberty is unclear. In total, 10 girls with central precocious puberty and same number of age-matched female controls were enrolled. Plasma samples were collected from each participant and subjected to untargeted metabolomics and lipidomics. Student's t-tests were employed to compare the mean of each metabolite and lipid. Furthermore, orthogonal partial least-squares discriminant analysis was conducted and the variable importance in the projection was calculated to identify differentially expressed metabolites or lipids. Subsequent bioinformatics was conducted to investigate the potential function of differentially expressed metabolites and lipids. Fifty-nine differentially expressed metabolites were identified based on the criteria used (variable importance in the projection >1 and a P value < 0.05). Kyoto Encyclopedia Genes and Genome (KEGG) enrichment analysis showed that differentially expressed metabolites were enriched in four pathways: beta-alanine metabolism, histidine metabolism, bile secretion, and steroid hormone biosynthesis. As for the lipidomics, 41 differentially expressed lipids were observed and chain length analysis and lipid saturation analysis yielded similar results. Significant differences between the two groups were only observed in (O-acyl) ω-hydroxy fatty acids (OAHFA). The present study showed that antibiotic overuse, increased meat consumption, and obesity may have potential roles in the development of central precocious puberty in girls. Several metabolites have diagnostic value but further research is required.

Development and Validation of a Combined MRI Radiomics, Imaging and Clinical Parameter-Based Machine Learning Model for Identifying Idiopathic Central Precocious Puberty in Girls.

Idiopathic central precocious puberty (ICPP) impairs child development, without early intervention. The current reference standard, the gonadotropin-releasing hormone stimulation test, is invasive which may hinder diagnosis and intervention. To develop a model for accurate diagnosis of ICPP, by integrating pituitary MRI, carpal bone age, gonadal ultrasound, and basic clinical data. Retrospective. A total of 492 girls with PP (185 with ICPP and 307 peripheral precocious puberty [PPP]) were randomly divided by reference standard into training (75%) and internal validation (25%) data. Fifty-one subjects (16 with ICPP, 35 with PPP) provided by another hospital as external validation. T1-weighted (spin echo [SE], fast SE, cube) and T2-weighted (fast SE-fat suppression) imaging at 3.0 T or 1.5 T. Radiomics features were extracted from pituitary MRI after manual segmentation. Carpal bone age, ovarian, follicle and uterine volumes and endometrium presence were assessed from radiographs and gonadal ultrasound. Four machine learning methods were developed: a pituitary MRI radiomics model, an integrated image model (with pituitary MRI, gonadal ultrasound and bone age), a basic clinical model (with age and sex hormone data), and an integrated multimodal model combining all features. Intraclass correlation coefficients were used to assess consistency of segmentation. Receiver operating characteristic (ROC) curves and the Delong tests were used to assess and compare the diagnostic performance of models. P < 0.05 was considered statistically significant. The area under of the ROC curve (AUC) of the pituitary MRI radiomics model, integrated image model, basic clinical model, and integrated multimodal model in the training data was 0.668, 0.809, 0.792, and 0.860. The integrated multimodal model had higher diagnostic efficacy (AUC of 0.862 and 0.866 for internal and external validation). The integrated multimodal model may have potential as an alternative clinical approach to diagnose ICPP. 3. Stage 2.

Approach to the Patient: Central Precocious Puberty.

Central precocious puberty (CPP) classically refers to premature activation of the hypothalamic-pituitary-gonadal axis with onset of sexual development before the age of 8 years in girls and 9 years in boys. A decrease in the age of thelarche has been reported over the past several decades; however, the tempo of pubertal progression can be slower and adult height may not be adversely affected in many of the girls who experience thelarche at 6-8 years. Outside of this secular trend in the development itself, the past several decades have also brought about advances in diagnosis and management. This includes the widespread use of an ultrasensitive luteinizing hormone assay, decreasing the need for stimulation testing and a better understanding of the genetics that govern the onset of puberty. Additionally, management of CPP using gonadotropin-releasing hormone analogs (GnRHas) has changed with the advent of new longer-acting formulations. Emerging long-term outcomes of GnRHa administration with regards to obesity, cardiovascular risk factors and fertility are reassuring. Despite these advancements, clinical care in CPP is hampered by the lack of well-designed controlled studies, and management decisions are frequently not supported by clear practice guidelines. Data in boys with CPP are limited and this article focuses on the diagnosis and management of CPP in girls, particularly, in those who present with thelarche at the age of 6-8 years.

The Role of SNPs in the Pathogenesis of Idiopathic Central Precocious Puberty in Girls

The initiation of puberty is a crucial timepoint of development, with its disruptions being associated with multiple physical and psychological complications. Idiopathic Central Precocious Puberty (iCPP) has been correlated with Single-Nucleotide Polymorphisms (SNPs) of certain genes that are implicated in various steps of the process of pubertal onset. The aim of this review was to gather current knowledge on SNPs of genes associated with iCPP. We searched articles published on the PubMed, EMBASE and Google Scholar platforms and gathered current literature. KISS1, KISS1R, PLCB1, PRKCA, ITPR1, MKRN3, HPG axis genes, NPVF/NPFFR1, DLK1, KCNK9Q, LIN28B, PROK2R, IGF-1, IGF2, IGF-1R, IGF-2R, IGFBP-3, insulin, IRS-1, LEP/LEPR, PPARγ2, TAC3, TACR3, Estrogen receptors, CYP3A4 and CYP19A1 were studied for implication in the development of precocious puberty. SNPs discovered in genes KISS1, KISS1R, PLCB1, MKRN3, NPVF, LIN28B, PROK2R, IRS-1 TAC3, and CYP3A4 were significantly correlated with CPP, triggering or protecting from CPP. Haplotype (TTTA)13 in CYP19A1 was a significant contributor to CPP. Further investigation of the mechanisms implicated in the pathogenesis of CPP is required to broaden the understanding of these genes' roles in CPP and possibly initiate targeted therapies.

Value of basal luteinizing hormone level combined with uterine volume measurement in the early diagnosis of central precocious puberty in girls with different Tanner stages

To study the value of basal luteinizing hormone (LH) level combined with uterine volume measurement in the early diagnosis of central precocious puberty (CPP) in girls with different Tanner stages. A retrospective analysis was performed on the girls who presented with breast development before the age of 8 years and attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to September 2022. According to the results of gonadotropin-releasing hormone (GnRH) agonist test, the girls with peak LH ≥5.0 IU/L and peak LH/follicle stimulating hormone ≥0.6 were enrolled as the positive group, and the other girls were enrolled as the negative group. The two groups were compared in terms of the basal LH level and uterine volume. The receiver operating characteristic (ROC) curve was used to analyze their value in the early diagnosis of CPP. For the girls with Tanner B2 and B3 stages, the positive group had significantly higher basal LH level and uterine volume than the negative group (P<0.05). The basal LH level had an optimal cut-off value of 0.325 IU/L and 0.505 IU/L respectively in the diagnosis of Tanner stage B2/B3 CPP, while uterine volume had an optimal cut-off value of 1.639 mL and 2.158 mL respectively. Basal LH level combined with uterine volume measurement had a significantly larger area under the ROC curve than uterine volume measurement alone (P<0.001), but with no significant difference compared with that of basal LH level measurement alone (P>0.05). Basal LH level combined with uterine volume measurement is valuable in the early diagnosis of CPP in girls with different Tanner stages, which provides a basis and guiding significance for clinical diagnosis of CPP.

Serum 25-hydroxyvitamin D levels and the risk of idiopathic central precocious puberty in girls

IntroductionPrior studies have found inconsistent results regarding the relationship between vitamin D status and Idiopathic Central Precocious Puberty (ICPP). ObjectiveTo assess the role of serum 25-hydroxyvitamin D (25 [OH]D) levels in ICPP development. MethodThe authors retrospectively collected data from 221 girls with ICPP and 144 healthy girls between January 2017 and December 2019. The participants’ serum 25(OH)D levels were measured using an automatic chemiluminescence method, and the association between serum 25(OH)D levels and the risk of ICPP was assessed using multivariate logistic regression analysis. Odds Ratios (OR) with 95% Confidence Intervals (95% CI) were calculated as effect estimates. ResultsSerum 25(OH)D levels in the ICPP group were significantly lower than those in healthy controls (p < 0.001). Multivariate analysis indicated that girls with insufficient vitamin D levels (OR = 0.201; 95% CI 0.094–0.428; p < 0.001) and sufficient vitamin D levels (OR = 0.141; 95% CI 0.053–0.375; p < 0.001) both had a lower risk of ICPP than girls with vitamin D deficiency. Moreover, the authors found that the height (p = 0.014), weight (p = 0.014), breast stage (p = 0.010), mother's height (p < 0.001), and luteinizing hormone/follicle-stimulating hormone ratio (p = 0.010) in girls with ICPP could be associated with levels of vitamin D. ConclusionThis study found that a low serum 25(OH)D level is an independent risk factor for ICPP, and several characteristics of girls with ICPP could be affected by their vitamin D status.

A new DLK1 defect in a family with idiopathic central precocious puberty: elucidation of the male phenotype.

We aimed to investigate a cohort of female and male patients with idiopathic central precocious puberty (CPP), negative for Makorin Ring Finger Protein 3 (MKRN3) defect, by molecular screening for Delta-like 1 homolog (DLK1) defects. DLK1 is an imprinted gene, whose mutations have been described as a rare cause of CPP in girls and adult women with precocious menarche, obesity and metabolic derangement. We enrolled 14 girls with familial CPP and 13 boys with familial or sporadic CPP from multiple academic hospital centers. Gene sequencing of DLK1 gene was performed. Circulating levels of DLK1 were measured and clinical and biochemical characteristics were described in those with DLK1 defects. A novel heterozygous mutation in DLK1, c.288_289insC (p.Cys97Leufs*16), was identified in a male proband, his sister and their father. Age at onset of puberty was in line with previous reports in the girl and 8years in the boy. The father with untreated CPP showed short stature. No metabolic derangement was present in the father except hypercholesterolemia. Undetectable Dlk1 serum levels indicated the complete lack of protein production in the three affected patients. A DLK1 defect has been identified for the first time in a boy, underscoring the importance of genetic testing in males with idiopathic or sporadic CPP. The short stature reported by his untreated father suggests the need for timely diagnosis and treatment of subjects with DLK1 defects.

Gonadotropin-releasing hormone analogue and recombinant human growth hormone treatment for idiopathic central precocious puberty in girls.

To investigate the effectiveness and safety of gonadotropin-releasing hormone analogue (GnRHa) in combination with recombinant human growth hormone (rhGH) in girls with central precocious puberty (CPP). Clinical data of 80 girls diagnosed with idiopathic central precocious puberty (ICPP) between January 2017 and June 2021 were retrospectively analyzed. Treatment strategy involved GnRHa alone (group A: n=34) and GnRHa+rhGH (group B: n=46). Children's heights (Ht), weights (Wt) and sex hormone levels were measured every 3 months after treatment and bone age (BA) every six months. Heights, growth velocity (GV), predicted adult height (PAH), weights, body mass index (BMI), sex hormone levels and bone age were compared between the two groups. Children in group B showed greater height gain at the 12th, 24th and 30th months after treatment (p<0.05) than those in group A, had faster growth rates in the first and second year following treatment (p<0.05) and better PAH (p<0.05). No statistical differences in weight or BMI were found between the two groups before treatment or at any time after treatment (p>0.05). Levels of LH and FSH were lower in both groups after treatment with no statistical differences between groups (p>0.05). The gap between bone age and chronological age gradually decreased in both groups and no abnormal progression of bone age or other adverse side effects occurred. The combination of GnRHa with rhGH produced better height gains than GnRHa alone for patients with CPP. The gonadal axis was suppressed and progression of bone age delayed with good safety and efficacy.