Diagnosis Of Central Precocious Puberty Research Articles

Diagnostic Value of Single LH and LH/FSH Ratio at 60-minute after GnRHa Stimulation Test for Central Precocious Puberty.

To evaluate the diagnostic value of luteinizing hormone (LH) and LH/follicle stimulating hormone (FSH) ratio at 60 min after gonadotropin-releasing hormone analogs (GnRHa) stimulation test for central precocious puberty (CPP) in girls. Two hundred and fifty-seven girls, aged 3 to 7.5 y, suspected of precocious puberty at authors' hospital from April 2020 through November 2023 were enrolled in the study. The blood was taken at 0, 30, 60 min after GnRHa stimulation test, and LH and LH/FSH were detected by chemiluminescence assay. The diagnostic efficacy was analysed by Mann-Whitney U test, spearman's correlation analysis and receiver operating characteristic (ROC) analysis. The proportion of obesity was analysed by Chi-square test. LH and LH/FSH at different times were statistically significantly different (P <0.05) between the CPP and non-CPP groups. Spearman's correlation analysis showed that the level of LH and LH/FSH at 60 min had the strongest consistency with the peak of LH (r = 0.9988, P <0.001) and LH/FSH (r = 0.9981, P <0.001). ROC curve analysis showed that the area under the ROC curves at 60 min of LH and LH/FSH were 0.975 and 0.997 with a cut-off value of 5.70 IU/L and 0.609, respectively. The peak of LH and LH/FSH in the diagnosis of CPP can be determined by LH and LH/FSH at 60 min after the triptorelin acetate is injected. This will reduce the number of blood draws required compared with the traditional stimulation test, which is more effective and acceptable for children.

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.

Diagnostic value of stimulated urine luteinizing hormone after triptorelin stimulation test in girls with CPP.

To investigate the diagnostic value of urine luteinizing hormone (ULH) after triptorelin stimulation test detected by immunochemiluminometric assay (ICMA) in girls with central precocious puberty (CPP). The girls with precocious puberty were involved. The triptorelin stimulation test at 8:30 a.m.were performed. Two consecutive 12-hour urine samples were collected after the test, defined as 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 CPP group were higher than those in PPP group. When 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 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 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 the compliance of blood sampling in girls with precocious puberty is poor, 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.

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.

Urinary gonadotropin assay on 24-h collections as a tool to detect early central puberty onset in girls: determination of predictive thresholds.

Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24h; u24LH = 0.035 or 0.08 IU/24h). The combination of u24FSH > 1.1 IU/24h and u24LH > 0.08 IU/24h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. No specific funding was used. All authors declared no conflict of interest. In-house #23-5214 registered study.

Central Precocious Puberty in Italian Boys: Data From a Large Nationwide Cohort.

There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000. We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones. We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities. The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis < 7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started. In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature.

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.

Organic metal chalcogenide-assisted metabolic molecular diagnosis of central precocious puberty.

Metabolic analysis in biofluids based on laser desorption/ionization mass spectrometry (LDI-MS), featuring rapidity, simplicity, small sample volume and high throughput, is expected to be a powerful diagnostic tool. Nevertheless, the signals of most metabolic biomarkers obtained by matrix-assisted LDI-MS are too limited to achieve a highly accurate diagnosis due to serious background interference. To address this issue, nanomaterials have been frequently adopted in LDI-MS as substrates. However, the "trial and error" approach still dominates the development of new substrates. Therefore, rational design of novel LDI-MS substrates showing high desorption/ionization efficiency and no background interference is extremely desired. Herein, four few-layered organic metal chalcogenides (OMCs) were precisely designed and for the first time investigated as substrates in LDI-MS, which allowed a favorable internal energy and charge transfer by changing the functional groups of organic ligands and metal nodes. As a result, the optimized OMC-assisted platform satisfyingly enhanced the mass signal by ≈10 000 fold in detecting typical metabolites and successfully detected different saccharides. In addition, a high accuracy diagnosis of central precocious puberty (CPP) with potential biomarkers of 12 metabolites was realized. This work is not only expected to provide a universal detection tool for large-scale clinical diagnosis, but also provides an idea for the design and selection of LDI-MS substrates.

A Short-Duration Gonadotropin-Releasing Hormone Stimulation Test for the Diagnosis of Central Precocious Puberty.

Background and Objectives: The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard method for diagnosing central precocious puberty (CPP), although it requires multiple blood samplings over 120 min. This study aimed to evaluate if a shorter test may have an equivalent diagnostic accuracy. Materials and Methods: We retrospectively reviewed the GnRH tests of 188 consecutive pediatric patients (169 females) referred for signs of early pubertal development. The diagnostic accuracy of the hormonal levels was evaluated at different time points (15, 0, 60, 90, and 120 min after the GnRH stimulus). Results: A diagnosis of CPP was made in 130 cases (69%), with 111 (85%) being female. Sensitivity and specificity ratings higher than 99% for the diagnosis of CPP were achieved for LH levels ≥4.7 mU/mL at 30 and 60 min after the stimulus (area under the ROC curve (AUC) = 1), with no further increase in the diagnostic accuracy in the remaining time points. No sex differences in diagnostic accuracy were found. The LH/FSH ratio at 30 min showed a sensitivity of 94.9%, with an AUC of 0.997 and a value ≥0.76. Conclusions: A short-duration GnRH test of 60 min provided optimal results for the diagnosis of CPP. Extending the test for an extra hour is therefore unnecessary and inadvisable.

Factors associated with the dietary patterns of children with precocious puberty

Objectives To investigate the nutritional status and factors associated with dietary patterns, sociodemographic variables and physical activity practice in children diagnosed with central precocious puberty (CPP). Methods Cross-sectional study with 85 female children aged 10 years with a diagnosis of CPP. Nutritional assessment was performed through body mass index (BMI), waist circumference (WC) and body composition by measurements of skinfolds (SF) and bioelectrical impedance (BIA). The Principal Component Analysis (PCA) was used, followed by varimax orthogonal rotation to identify dietary patterns, and Poisson regression to verify associations between variables, using a significance level of 5%. Results The group had a mean age of 8.4 years (1.30) and lived mostly in urban areas (52 – 61.2%). Excess weight was observed in 64.7% according to the BMI, 32.9% according to the WC and 63.5% according to body fat%. Two main dietary patterns were identified: the “western” and the “healthy” patterns. The identified dietary patterns were not associated with nutritional status, assessed according to all considered indicators. WC and body fat% were inversely associated with physical activity practice (PR=1.96, CI=1.12-3.43) and directly associated with the individuals’ urban area of residence (PR=0.63, CI= 0. 42-0.94), respectively. Conclusion: The results showed a high prevalence of excess weight, which was inversely associated with physical activity practice and directly with urban area of residence, although nutritional status is not associated with the identified dietary patterns. These results highlight the need for educational and informative measures to fight obesity.

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.

Basal gonadotropin levels combine with pelvic ultrasound and pituitary volume: a machine learning diagnostic model of idiopathic central precocious puberty

ObjectiveThe current diagnosis of central precocious puberty (CPP) relies on the gonadotropin-releasing hormone analogue (GnRHa) stimulation test, which requires multiple invasive blood sampling procedures. The aim of this study was to construct machine learning models incorporating basal pubertal hormone levels, pituitary magnetic resonance imaging (MRI), and pelvic ultrasound parameters to predict the response of precocious girls to GnRHa stimulation test.MethodsThis retrospective study included 455 girls diagnosed with precocious puberty who underwent transabdominal pelvic ultrasound, brain MRI examinations and GnRHa stimulation testing were retrospectively reviewed. They were randomly assigned to the training or internal validation set in an 8:2 ratio. Four machine learning classifiers were developed to identify girls with CPP, including logistic regression, random forest, light gradient boosting (LightGBM), and eXtreme gradient boosting (XGBoost). The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, area under receiver operating characteristic (AUC) and F1 score of the models were measured.ResultsThe participates were divided into an idiopathic CPP group (n = 263) and a non-CPP group (n = 192). All machine learning classifiers used achieved good performance in distinguishing CPP group and non-CPP group, with the area under the curve (AUC) ranging from 0.72 to 0.81 in validation set. XGBoost had the highest diagnostic efficacy, with sensitivity of 0.81, specificity of 0.72, and F1 score of 0.80. Basal pubertal hormone levels (including luteinizing hormone, follicle-stimulating hormone, and estradiol), averaged ovarian volume, and several uterine parameters were predictors in the model.ConclusionThe machine learning prediction model we developed has good efficacy for predicting response to GnRHa stimulation tests which could help in the diagnosis of CPP.

Use of the Subcutaneous Triptorelin Stimulation Test for Diagnosis of Central Precocious Puberty.

The gold standard gonadotropin-releasing hormone (GnRH) stimulation test uses the response to intravenously injected gonadorelin to diagnose central precocious puberty (CPP). However, gonadorelin is not always readily available. This study investigated the diagnostic efficacy of the subcutaneous triptorelin test and the optimal blood sampling time for diagnosis of CPP. This study retrospectively examined the medical records of 220 girls who had undergone either the triptorelin or gonadorelin test and compared their clinical characteristics. We retrospectively compared clinical parameters between girls diagnosed with CPP (n = 111) and idiopathic premature thelarche (IPT) (n = 109) using three different diagnostic methods: the gonadorelin, triptorelin 120 min, and triptorelin 180 min tests. The diagnostic ability of the stimulated luteinizing hormone (LH) concentration in the triptorelin test for CPP was evaluated using receiver operating characteristic (ROC) analysis. The CPP group exhibited higher basal and peak gonadotropin levels, more advanced bone age, and a lower body mass index standard deviation score than the IPT group. In the gonadorelin test group, all girls with CPP exhibited a peak LH response 30-60 min after intravenous gonadorelin injection. In the triptorelin test group, most girls with CPP exhibited a peak LH response 60-180 min after subcutaneous triptorelin injection (n = 68). On the ROC curve, a peak LH concentration of ≥ 4.52 IU/L at 120 min had the highest CPP diagnostic accuracy, with sensitivity and specificity of 100% and 95.83%, respectively.

THU193 Clinical Usefulness Of Repetitive GnRH Stimulation Test For The Diagnosis Of Central Precocious Puberty

Abstract Disclosure: S. Heo: None. Y. Shim: None. H. Lee: None. J. Hwang: None. J. Lim: None. Objective In girls, breast development under 8 years of age and peak serum luteinizing hormone (LH) is 5 IU/L or higher in gonadotropin releasing hormone (GnRH) stimulation tests is a standard method for diagnosing central precocious puberty (CPP). Although breast development and bone age progress rapidly compared to chronological age, repeated GnRH stimulation tests do not exceed 5 IU/L in some cases. We aimed to analyze the clinical characteristics of girls who repeatedly examined the GnRH stimulation test. Methods We retrospectively reviewed the medical records of 988 girls under 9 years of age who visited our hospital due to breast development more than Tanner stage II and whose bone age was more than a year advanced than the chronological age and examined GnRH stimulation test twice or more. According to peak luteinizing hormone (LH) at first GnRH stimulation test, patients were divided into 5 groups that &amp;lt; 1.0 IU/L (group 1, n=34), ≥1.0 to &amp;lt; 2.0 IU/L (group 2, n=219), ≥2.0 to &amp;lt; 3.0 IU/L (group 3, n=297), ≥3.0 to &amp;lt; 4.0 (group 4, n=252) and ≥4.0 to &amp;lt; 5.0 (group 5, n=186). We analyzed the incidence of CPP through the repetitive GnRH stimulation test and factors associated with the outcomes using a Cox proportional hazard model. Results Mean age of total of 988 girls was 7.68 ± 0.67 years and the period between the first and last GnRH stimulation test was 216.40 ± 145.14 days. CPP was diagnosed in 138 patients. Incidence of CPP were differed by groups that 0%, 1.4%, 6.1%, 20.6%, 34.9% each groups. When group 1 and each groups were compared using the Cox proportional hazard regression model, difference between bone age and chronological age (95% CI, 1.27-2.35, p&amp;lt;0.001) (BA-CA) and basal follicle-stimulating hormone (95% CI, 1.01-1.48, p=0.039) showed a statistically significant positive correlation when stratifying the peak LH at GnRH stimulation test. Conclusion In the diagnosis of CPP, the GnRH stimulation test is gold standard. But the lower the peak LH in GnRH stimulation test, the more other factors such as difference between bone age and chronological age, basal FSH should be considered in the possibility of CPP. Presentation: Thursday, June 15, 2023

Metabolic characteristics and pathogenesis of precocious puberty in girls: the role of perfluorinated compounds

BackgroundPrecocious puberty (PP) in girls is traditionally defined as the onset of breast development before the age of 8 years. The specific biomarkers of premature thelarche (PT) and central precocious puberty (CPP) girls are uncertain, and little is known about their metabolic characteristics driven by perfluorinated compounds (PFCs) and clinical phenotype. This study aimed to screen specific biomarkers of PT and CPP and elucidate their underlying pathogenesis. The relationships of clinical phenotype-serum PFCs-metabolic characteristics were also explored to reveal the relationship between PFCs and the occurrence and development of PT and CPP.MethodsNuclear magnetic resonance (NMR)-based cross-metabolomics strategy was performed on serum from 146 PP (including 30 CPP, 40 PT, and 76 unspecified PP) girls and 64 healthy girls (including 36 prepubertal and 28 adolescent). Specific biomarkers were screened by the uni- and multivariate statistical analyses. The relationships between serum PFCs and clinical phenotype were performed by correlation analysis and weighted gene co-expression network analysis to explore the link of clinical phenotype-PFCs-metabolic characteristics in PT and CPP.ResultsThe disordered trend of pyruvate and butyrate metabolisms (metabolites mapped as formate, ethanol, and 3-hydroxybutyrate) were shared and kept almost consistent in PT and CPP. Eight and eleven specific biomarkers were screened for PT and CPP, respectively. The area under curve of specific biomarker combination was 0.721 in CPP vs. prepubertal, 0.972 in PT vs. prepubertal, 0.646 in CPP vs. prepubertal integrated adolescent, and 0.822 in PT vs. prepubertal integrated adolescent, respectively. Perfluoro-n-heptanoic acid and perfluoro-n-hexanoic acid were statistically different between PT and CPP. Estradiol and prolactin were significantly correlated with PFCs in CPP and PT. Clinical phenotypes and PFCs drive the metabolic characteristics and cause metabolic disturbances in CPP and PT.ConclusionsThe elevation of formate, ethanol, and 3-hydroxybutyrate may serve as the early diagnostic indicator for PP in girls. But the stratification of PP still needs to be further determined based on the specific biomarkers. Specific biomarkers of CPP and PT exhibited good sensitivity and can facilitate the classification diagnosis of CPP and PT. PFC exposure is associated with endocrine homeostasis imbalance. PFC exposure and/or endocrine disturbance directly or indirectly drive metabolic changes and form overall metabolic network perturbations in CPP and PT.

Role of luteinizing hormone urinary levels in the diagnostic and therapeutic management of female central precocious puberty

BackgroundDiagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is represented by GnRH (gonadotropin-releasing hormone) stimulation test. Some undoubted limitations of this procedure led the international scientific community to look for cheaper and less invasive alternative diagnostic methods, such as luteinizing hormone urinary levels (uLH) measurement. This study aims to define the reliability of urinary LH levels as a biomarker of pubertal development, both concerning the initial diagnostic management and the monitoring of patients with central precocious puberty undergoing therapy with GnRH analogues. Furthermore, the study plans to detect the potential association between LH peak serum (pLH) and urinary LH in patients undergoing diagnostic tests with GnRH and to identify a possible cut-off of uLH that may be suggestive of ensued successful hormonal stimulation.MethodsThe study includes 130 female patients with suspected precocious puberty or in follow-up during suppressive therapy. After the collection of the informed consent, the patients underwent clinical evaluation, auxological assessment, and hormone assays (basal levels of LH, FSH, and oestradiol; GnRH stimulating test in patients with suspected precocious puberty; urinary LH assay on the first-morning urine sample, collected after waking up).ResultsTwo uLH cut-off values have been identified: the first of 0.25 UI/L [C.I. 95% 0.23–0.27], able to distinguish between pubertal and pre-pubertal patients, the second of 0.45 UI/L [C.I. 95% 0,20 − 0,70] suggestive of occurred hormonal stimulation in patients with diagnosis of CPP at GnRH test. All 30 patients with CPP in follow-up during suppressive therapy presented uLH values ≤ 0.45 IU/L (pU < 0.05), and uLH collected in prepubertal group control.ConclusionsuLH assays on the first morning urine specimen could be considered a low-cost and minimally invasive tool for precocious puberty diagnosing and monitoring, making possible to be easily performed even by a general pediatrician. Thus, this could help referring only selected patients to pediatric endocrinologists. After an appropriate validation, this approach could reasonably reduce hospital attendance and costs of performing more invasive procedures, with a more significant emotional impact on the pediatric patient.

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.

Clinical significance of serum MBD3 detection in girls with central precocious puberty.

Diagnosis of central precocious puberty (CPP) in girls remains a huge challenge. The current study was to measure the serum expression of methyl-DNA bind protein 3 (MBD3) in CPP girls and assess its diagnostic efficacy. To begin with, we enrolled 109 CPP girls and 74 healthy pre-puberty girls. Then, MBD3 expression in their serum samples was measured via reverse transcription-quantitative polymerase chain reaction, and its diagnostic efficacy on CPP was assessed via the receiver operating characteristic (ROC) curve, followed by correlation analysis between serum MBD3 and patient age, gender, bone age, weight, height, body mass index, basal luteinizing hormone (LH), peak LH, basal follicle-stimulating hormone (FSH), peak FSH, and ovarian size using bivariate correlations method. Finally, independent predictors of MBD3 expression were confirmed using multivariate linear regression analysis. MBD3 was highly expressed in sera of CPP patients. The area under the ROC curve of MBD3 diagnosing CCP was 0.9309, with 1.475 cut-off value (92.66% sensitivity and 86.49% specificity). MBD3 expression positively correlated with basal LH, peak LH, basal FSH, and ovarian size, among which basal LH was considered the strongest independent predictor of MBD3, followed by basal FSH and peak LH. In summary, serum MBD3 could act as a biomarker in aiding CPP diagnosis.

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.