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Aim: To evaluate the suitability of serum osteocalcin (OC) as a marker to distinguish between rapidly and non-rapidly progressive central precocious puberty (RP-CPP and NRP-CPP), as well as its potential to assess growth rates following treatment with gonadotropin-releasing hormone agonist (GnRHa)., Methods: Serum levels of OC were measured using enzyme-linked immunosorbent assays in girls diagnosed with either RP-CPP or NRP-CPP as well as in normal control subjects. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value for OC. Multivariate linear regression analysis was used to analyse the main influencing factors associated with OC., Results: Serum OC levels were higher in the CPP girls when compared to normal controls (110.76 ± 43.69 vs 55.97 ± 20.96 ng/mL, P < 0.001). The level in the RP-CPP group was higher than the NRP-CPP group (153.28 ± 33.89 vs 88.33 ± 29.26 ng/mL, P < 0.001). The cut-off value of OC levels for distinguishing between RP-CPP and NRP-CPP was 107.05 ng/mL, the sensitivity was 94.7% and the specificity was 77.8%, which was superior to using the basal luteinising hormone (B-LH) levels, and the area under ROC curve (AUC) were 0.933 versus 0.695, respectively. Following 1-2 years of treatment with GnRHa for girls with CPP, both OC levels and the growth rates decreased to pre-pubertal values. B-LH levels, bone age and body weight were also significant factors, which affected OC levels., Conclusions: Serum OC levels may be a useful marker for distinguishing RP-CPP from NRP-CPP. In addition, it was also found to be a useful predictor for growth rate during GnRHa treatment., (© 2024 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objectives: Gonadotropin-releasing hormone (GnRH) test is the gold standard test to evaluate the hypothalamus-pituitary-gonadal (HPG) axis for the diagnosis of central precocious puberty (CPP). However, the diagnosis of cases with clinical features of CPP whilst have borderline peak luteinizing hormone (LH) remain challenges. We aimed to evaluate diagnostic performance of the average of LH levels measured during GnRH stimulation test., Methods: Cases with diagnosis of CPP and premature thelarche (PT) who had a GnRH stimulation test results were retrospectively reviewed. Anthropometric measurements (weight, height, and body mass index), age and sex-specific standard deviation scores, growth velocity, puberty stages, bone ages, serum FSH, LH, and estradiol levels were measured by electrochemiluminescence immunological method (ECLIA), and the GnRH stimulation test results, which performed by obtaining venous blood samples at basal, 20 th , and 40 th minutes for FSH and LH measurement, were recorded., Results: A total of 76 girls (38 CPP, 38 PT) were included. We detected an average peak LH cut-off value of 4.25 IU/L with 94.7 % sensitivity and 97.4 % specificity, a 97.3 % positive predictive value, and a 94.9 % negative predictive value in GnRH test to differentiate cases with CPP from PT., Conclusions: This is the first study evaluating the diagnostic utility of the average of LH levels measured during GnRH stimulation test. We showed that the average of two LH measurements has a high diagnostic performance. Therefore, it can be used as a valid and reliable diagnostic tool for assessment of HPG axis activation, particularly for cases with a borderline peak LH level., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: To evaluate the role of basal and follicle-stimulating hormone (FSH)-stimulated inhibin B in differentiating premature thelarche from gonadotropin-dependent precocious puberty (GDPP)., Methods: This was a prospective interventional study. Basal and FSH-stimulated inhibin B levels were estimated in girls presenting with thelarche < 8 years age (n = 10), healthy girls with normal pubertal development (pubertal control) (n = 8) and healthy prepubertal girls (prepubertal control) (n = 7). Girls with early puberty were classified as premature thelarche or GDPP based on GnRH agonist stimulation test., Results: Median (IQR) basal inhibin B levels (pg/mL) in premature thelarche was 5.42 (2.91, 30.58) and FSH-stimulated inhibin B was 236.72 (111.53, 4431.73) (P = 0.043). Median (IQR) basal inhibin B in GDPP was 64.11 (24.96, 792.45) pg/mL and FSH-stimulated inhibin B was 833.66 (500.11-1266.18) pg/mL (P = 0.043). Basal inhibin B was discriminatory between GDPP and premature thelarche (P = 0.032). Median (IQR) basal inhibin B in prepubertal and pubertal controls was 20.36 (9.61, 29.12) and 75.48 (58.55, 165.55) pg/mL, respectively., Conclusion: Basal inhibin B is useful in differentiation of premature thelarche from GDPP while the role of FSH-stimulated inhibin B needs to be further explored in large sample size.

Introduction: Central precocious puberty (CPP) is characterized by the early onset of puberty and is associated with the critical processes involved in the pubertal switch. The puberty-related gene pool in the human genome is considerably large though few have been described in CPP. Within those genes, the genomic imprinting features of the MKRN3 and DLK1 genes add additional complexity to the understanding of the pathologic pathways. This study aimed to investigate the molecular etiology in the CPP cohort., Methods: Eighteen familial CPP cases were investigated by Sanger sequencing for five CPP-related genes; DLK1, KISS1, KISS1R, MKRN3, and PROKR2. Segregation analysis was performed in all patients with pathogenic variants. Using an ELISA test, the functional pathogenicity of novel variants was also investigated in conjunction with serum delta-like 1 homolog (DLK1) concentrations., Results: In three probands, a known variant in the MKRN3 gene (c.982C>T/p.(Arg328Cys)) and two novel variants in the DLK1 gene (c.357C>G/p.(Tyr119Ter) and c.67+78C>T) were identified. All three were inherited from the paternal allele. The individuals carrying the DLK1 variants had low detectable DLK1 levels in their serum., Conclusions: The frequencies were 5.5% (1/18) for MKRN3 11% (2/18) for DLK1, and none for either KISS1, KISS1R, and PROKR2. Low serum DLK1 levels in affected individuals supported the relationship between here described novel DLK1 gene variants with CPP. Nonsense nature of c.357C>G/p.(Tyr119Ter) and an alteration in the evolutionarily conserved nucleotide c.67+78C>T suggested the disruptive nature of the variant's compatibility with CPP., (© 2024. The Author(s).)

Purpose: To identify cut-off for basal LH levels and for pelvic ultrasound uterine and ovarian parameters indicating an Hypotalamic-Pituitary-Gonadal (HPG) axis activation as diagnostic of Central Precocious Puberty (CPP)., Methods: 248 girls referred for suspected precocious/early puberty who had undergone a GnRH stimulation test were enrolled and divided into three groups: Premature Idiopathic Thelarche (PIT), CPP, and Early Puberty (EA). For every patient basal serum Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH), basal LH/FSH ratio and pelvic ultrasonographic parameters were also collected. Through the use of Receiver Operating Curves (ROCs) the sensitivity (Se) and specificity (Sp) of basal LH, FSH, LH/FSH ratio and ultrasonographic parameters were evaluated at each level and Area Under the Curve (AUC) was measured., Results: Basal LH model ≥0.14 mIU/mL reached the highest predictability (90.6% and 78.2%, Se and Sp, respectively). Basal LH/FSH ratio ≥0.1 showed a sensitivity of 85.90% and a specificity of 78.14%, while basal FSH cut-off (≥2.36 mIU/mL) had the lowest predictability, with a less favourable sensitivity (71%) and specificity (70.5%). Cut-off point for uterine length as 35 mm, (83.5% and 42.9% of Se and Sp, respectively) was calculated. For ovarian volumes, ROC curves showed very low sensitivity and specificity., Conclusion: A single basal LH measurement under the cut-off limit may be adequate to exclude an HPG axis activation as CPP., (© 2024. The Author(s).)

Purpose: The study aimed to investigate the correlation between the change of sex hormone levels and ocular surface parameters in girls with idiopathic central precocious puberty(ICPP)., Methods: Eighteen girls with ICPP and 18 age-matched normal girls participated in this study, all of the participants had undergone physical measurements, laboratory tests, imaging examination and ocular surface assessments., Results: The Objective Scatter Index (OSI) in the ICPP group was significantly higher than in the control group ( P = 0.031), girls with ICPP showed slightly lower MNITBUT compared to the normal control group, although this difference was not statistically significant. Bivariate analysis revealed a positive association between estradiol and OSI (r=0.383, P =0.021), Additionally, in the study population, both Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) were negatively correlated with Mean noninvasive tear breakup time (MNITBUT) (r=-0.359, P =0.031)(r=-0.357, P =0.032)., Conclusion: In comparison with the normal control group, alterations in the OSI were observed in girls with ICPP. This alteration may be associated with an elevation in estrogen levels. Although there was a slight non-significant decrease in NITBUT in ICPP girls, the negative correlation between LH and FSH with MNITBUT suggests new perspective for further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Yang and Liang.)

Objective: 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)., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Pubertal timing is modulated by complex interactions between the pituitary and gonadal sex steroid hormones. Evidence indicates that sphingolipids are involved in the biosynthesis of steroid hormones at multiple levels., Method: This study recruited adolescent female patients from pubertal and pediatric endocrine clinics in Northern and Southern Taiwan from the Taiwan Puberty Longitudinal Study. A total of 112 plasma samples (22 healthy control, 29 peripheral precocious puberty (PPP), and 61 CPP samples) were collected. We extracted lipids from the plasma samples using the modified Folch method. The un-targeted ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed for the lipid analysis., Results: We identified sphingolipid-linked metabolites, including Cer(18:0/15:0), Cer(18:1/16:0), and Cer(18:1/26:0) as candidate biomarkers for distinguishing girls with CPP from the control group by using an excellent discrimination model (AUC = 0.964). Moreover, Cer(18:0/22:0) and Cer(d18:0/18:1) were identified as potential biomarkers of PPP, with an AUC value of 0.938. Furthermore, CerP(18:1/18:0) was identified as the sole candidate biomarker capable of differentiating CPP from PPP., Conclusions: The biomarkers identified in this study can facilitate the accurate detection of CPP in girls, provide insights into lipid-linked pathophysiology, and present a novel method of monitoring the progression of this disorder., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yang Ching Chen reports financial support was provided by Taipei Medical University. Yang Ching Chen reports a relationship with Taipei Medical University that includes: employment., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Introduction: The peptide hormone Insulin-like Factor 3 (INSL3) is a biomarker of testicular Leydig cells in the male but is also expressed by the theca cells of the ovaries. With the advent of sensitive assays INSL3 can be quantified in female circulation, and we suggest that circulating INSL3 is a novel biomarker for pubertal development in girls. The aim of the study is to quantify INSL3 by LC-MS/MS in sera from normal girls during pubertal transition, and during gonadal suppression by GnRH agonist therapy in girls with central precocious puberty (CPP)., Method: The sensitivity of an established LC-MS/MS-based method for serum INSL3 was improved by switching to a state-of-the-art triple quadruple mass spectrometer (Altis Plus, Thermo)., Results: The limit of detection of the improved LC-MS/MS method for serum INSL3 was 0.01 ug/L (1.5 pM) and the inter-assay CV was < 12%. Serum INSL3 increased during the pubertal transition in healthy girls and changes correlated with the concomitant rise in other measured hormones. In some girls, but not all, INSL3, FSH, inhibin B and estradiol serum concentrations increased prior to first clinical signs of puberty. Serum INSL3 concentrations were increased at baseline in girls with CPP compared to prepubertal controls and decreased during treatment with GnRH agonist followed by a steep rise and normalization after cessation of treatment., Conclusion: The improved method allowed for quantification of INSL3 in longitudinally collected serum samples during pubertal transition in healthy girls as well as in girls with CPP before, during and after treatment with GnRH agonist. Future studies are needed to clarify if INSL3 in combination with other biomarkers enhances the predictive value of differentiating between premature thelarche and CPP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Albrethsen, Hagen and Juul.)

Objectives: To investigate the value of single-phase gonadotropin releasing hormone (GnRH) stimulation test in the diagnosis of central precocious puberty (CPP) in girls with different levels of body mass index (BMI)., Methods: A retrospective analysis was performed for the data of 760 girls with breast development before 7.5 years of age who attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2023. According to the results of GnRH stimulation test and clinical manifestations, they were divided into a CPP group (297 girls) and a non-CPP group (463 girls). According to the values of BMI, the girls were divided into a normal weight group (540 girls), an overweight group (116 girls), and an obese group (104 girls). The receiver operating characteristic (ROC) curve was used to investigate the value of single-phase GnRH stimulation test in the diagnosis of CPP in girls with different levels of BMI., Results: Luteinizing hormone (LH)/follicle-stimulating hormone at 30 minutes after GnRH stimulation had an area under the curve (AUC) of 0.985 in the diagnosis of CPP, which was higher than the AUC at 0, 60, and 90 minutes ( P <0.05). LH at 30 minutes had a similar diagnostic value to LH at 60 minutes ( P >0.05). LH at 30 minutes was negatively correlated with BMI and BMI-Z value ( P <0.05).The AUC for diagnosing CPP in normal weight, overweight, and obese girls at 30 minutes LH was 0.952, 0.965, and 0.954, respectively ( P <0.05)., Conclusions: The 30-minute GnRH stimulation test has a good value in the diagnosis of CPP in girls with different levels of BMI and is expected to replace the traditional GnRH stimulation test, but the influence of BMI on LH level should be taken seriously.

A thorough history and physical examination including Tanner staging and growth assessments can guide differential diagnosis and aid in the evaluation of precocious puberty. Basal luteinizing hormone levels measured using a highly sensitive assay can be helpful in diagnosing central precocious puberty (CPP). Brain MRI is indicated with males diagnosed with CPP and females under the age of 6 with CPP. As more information becomes available regarding the genetic etiologies of CPP, genetic testing may preclude the need for imaging studies and other hormonal testing, especially in familial cases., Competing Interests: Disclosure K. Bangalore Krishna has no relevant disclosures to this article. L.A. Silverman has been a consultant for Tolmar, a Data and Safety Monitoring Board member for Myovant, and with the Speaker’s Bureau for Abbvie., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: MKNR3 is a paternally expressed gene whose mutations are the main cause of central precocious puberty (CPP). Protein circulating levels can be easily measured, as demonstrated in idiopathic CPP and healthy controls. No data are available for patients harboring an MKRN3 mutation. Our aim was to perform MKRN3 mutation screening and to investigate if circulating protein levels could be a screening tool to identify MKRN3 mutation in CPP patients., Methods: We enrolled 140 CPP girls and performed MKRN3 mutation analysis. Patients were stratified into two groups: idiopathic CPP (iCPP) and MKRN3 mutation-related CPP (MKRN3-CPP). Clinical characteristics were collected. Serum MKRN3 values were measured by a commercially available ELISA assay kit in MKRN3-CPP and a subgroup of 15 iCPP patients., Results: We identified 5 patients with MKRN3 mutations: one was a novel mutation (p.Gln352Arg) while the others were previously reported (p.Arg328Cys, p.Arg345Cys, p.Pro160Cysfs*14, p.Cys410Ter). There was a significant difference in circulating MKRN3 values in MKRN3-CPP compared to iCPP (p < 0.001). In MKRN3-CPP, the subject harboring Pro160Cysfs*14 presented undetectable levels. Subjects carrying the missense mutations p.Arg328Cys and p.Gln352Arg showed divergent circulating protein levels, respectively 40.56 pg/mL and undetectable. The patient with the non-sense mutation reported low but measurable MKRN3 levels (12.72 pg/mL)., Conclusions: MKRN3 defect in patients with CPP cannot be predicted by MKRN3 circulating levels, although those patients presented lower protein levels than iCPP. Due to the great inter-individual variability of the assay and the lack of reference values, no precise cut-off can be identified to suspect MKRN3 defect., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Breast development in a girl 3 years of age or younger is a commonly encountered scenario. Nearly all of these cases will either regress or fail to progress during follow-up, confirming a diagnosis of premature thelarche (PT). Studies show that these girls will have onset of true puberty and menses at a normal age. The authors present evidence that laboratory testing, particularly basal and gonadotropin hormone-releasing hormone -stimulated gonadotropin levels, will show overlap between girls with PT and the rare patients with the onset of central precocious puberty before age 3, mainly of whom have hypothalamic hamartomas., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Study Question: Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls?, Summary Answer: 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., What Is Known Already: 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., Study Design, Size, Duration: 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., Participants/materials, Setting, Methods: 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., Main Results and the Role of Chance: 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/24 h; u24LH = 0.035 or 0.08 IU/24 h). The combination of u24FSH > 1.1 IU/24 h and u24LH > 0.08 IU/24 h 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., Limitations, Reasons for Caution: 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., Wider Implications of the Findings: 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., Study Funding/competing Interest(s): No specific funding was used. All authors declared no conflict of interest., Trial Registration Number: In-house #23-5214 registered study., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Purpose: In this prospective study, we aimed to investigate the difference in voice acoustic parameters between girls with idiopathic central precocious puberty (ICPP) and those who developed normally during prepuberty., Materials and Methods: Our study recruited 54 girls diagnosed with ICPP and randomly sampled 51 healthy prepubertal girls as the control. Tanner stages, circulating hormone levels and bone ages of the girls with ICPP and the age and body mass index (BMI) of all participants were recorded. Acoustic analyses were performed using PRAAT computer-based voice analysis software and the mean pitch (F0), jitter, shimmer, noise-to harmonic-ratio (NHR) and harmonic-to-noise ratio (HNR) values were compared in the patient and control groups., Results: The two groups did not significantly differ in age or BMI. In the evaluation of the F0 and jitter values, we were found to be lower in the control group than in the patient group. However, we did not find a statistical significance. The mean shimmer values of the patient group were significantly higher than those of the control group. In addition, a statistically significant difference was noted for the mean HNR and NHR values (P < 0.001). A moderate negative correlation was found between shimmer and hormone levels in the patient group., Conclusions: Voice acoustic parameters one of the defining features of girls with ICPP. Voice changes in acoustic parameters could reflect hormonal changes during puberty. Clinicians should suspect ICPP when there is a change in the voice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To 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., Methods: In 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., Results: Serum 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., Conclusions: Serum irisin level in girls with CPP is significantly increased. An irisin combined index could help the diagnosis of CPP in girls., (© 2024. The Author(s).)

Background: Recent studies suggest a link between the Klotho protein, sex hormones, and insulin-like growth factor-1 (IGF-1), indicating that α-Klotho levels may rise during puberty, including in central precocious puberty (CPP) cases. This study aimed to explore α-Klotho levels in girls with CPP to assess its potential as a diagnostic and monitoring tool for this condition., Methods: In total, 139 girls, comprising 82 patients diagnosed with CPP and 57 healthy prepubertal controls, were enrolled in this study. From March 2020 to May 2023, we assessed both α-Klotho levels and clinical parameters. α-Klotho concentrations were measured using an α-Klotho ELISA kit. For the girls with CPP, we additionally analyzed samples taken 6 months after GnRH agonist treatment., Results: α-Klotho levels were higher in the CPP group compared with the control (CPP group: 2529 ± 999 ng/mL; control group: 1802 ± 675 pg/mL) (P < 0.001), and its level modest decreased after 6 months of GnRH agonist treatment (2147± 789 pg/mL) (P < 0.001). The association between α-Klotho and IGF-1 SDS, follicular stimulating hormone and baseline luteinizing hormone was assessed by partial correlation after adjusting for age, BMI SDS (r= 0.416, p= <0.001; r= 0.261, p= 0.005; r= 0.278, p= 0.002), respectively. Receiver operating characteristic curve analysis identified an α-Klotho cut-off differentiating CPP from controls, with a cut-off of 1914 pg/mL distinguishing girls with CPP from controls with a sensitivity of 69.5% and specificity of 70.2%; the area under the curve was 0.723., Conclusion: The findings of our study are the first step towards deciphering the role of α-Klotho in puberty induction. With additional data and further research, α-Klotho could potentially be utilized as a significant diagnostic and monitoring tool for CPP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Park, Noh and Hwang.)

Introduction: 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., Material and Methods: 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., Results: 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., Conclusions: 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.

Background: A brief gonadotropin-releasing hormone analogues (GnRHa) stimulation test which solely focused on LH 30-minute post-stimulation was considered to identify girls with central precocious puberty (CPP). However, it was tested using traditional statistical methods. With advanced computer science, we aimed to develop a machine learning-based diagnostic model that processed baseline CPP-related variables and a brief GnRHa stimulation test for CPP diagnosis., Methods: We recruited girls suspected of precocious puberty and underwent a GnRHa stimulation test at Children Hospital 2, Vietnam, and Cathay General Hospital, Taiwan. Clinical data, bone age measurement, and 30-min post-stimulation blood test were used to build up the predictive model. The candidate model was developed by different machine learning algorithms that were mainly evaluated by sensitivity, specificity, the area under the receiver operator characteristic curve (AUC), and F1-score in internal and external validation data to classify girls as CPP and non-CPP at different time-points (0-min, 30-min, 60-min, and 120-min post-stimulation)., Results: Among the 614 girls diagnosed with PP, 524 (85.3%) had CPP. The random forest algorithm yielded the highest value of F1-score (0.976), specificity (0.893), positive predicted value (0.987), and relatively high value of AUC (0.972) that contributed to high probability to identify CPP. The performance metrics of the 30-min post-stimulation diagnostic model including sensitivity and specificity surpassed those of the 0-minute model (0-min) and were equivalent to those of the model obtained 60-min and 120-min post-stimulation. Hence, our machine learning-based model helps shorten the stimulation test to 30 minutes after GnRHa injection, in general, it requires 120 minutes for a completed GnRHa stimulation test., Conclusions: We developed a diagnostic model based on clinical features and a single sample 30-minute post-stimulation to identify CPP in girls that can reduce distress for children caused by multiple blood samplings., Competing Interests: The authors have declared that no competing interests exist.

Objective: To compare cardiometabolic factors and adipokines between patients with recently diagnosed CPP and controls without CPP, paired by BMI Z scores (BMIz) and classified into girls with adequate nutritional status and girls who are overweight or obese., Methods: This cross-sectional study was performed from January 2012 to May 2015 at two tertiary care pediatric centers in Mexico City. We included female patients with idiopathic CPP without other chronic pathology and healthy controls. Patients were divided into groups, BMI < 85th and BMI ≥ 85th percentile, according to 2000 CDC Growth Charts. Anthropometric data and fasting plasma concentrations of lipids, glucose, insulin, and leptin were assessed., Results: There were 73 patients with CPP and 82 without CPP. Sixty-six patients were matched between the groups; no significant difference was noted between the groups according to zBMI. However, differences in the bone/chronological age relationship, birth weight and proportions in different Tanner stages were observed. Among girls with normal BMI, the percentage of body fat (24.6% vs 18.9%, p < 0.001), serum triglycerides (102.9 vs 54.3 mg/dl, p < 0.001), leptin (7.46 vs 5.4 ng/ml, p = 0.010) and free leptin (0.44 vs 0.29 ng/ml, p = 0.044) were higher in those with CPP; additionally, girls with CPP presented a higher proportion of hypertriglyceridemia. In the overweight/obese group, adiponectin levels were lower in girls with CPP (6.23 vs 7.28 pg/ml, p = 0.011)., Conclusions: Girls with CPP and normal BMI at diagnosis had a worse cardiometabolic profile, as reflected by higher levels of free leptin, and higher proportion of hypertriglyceridemia than girls without CPP., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: McCune-Albright syndrome is a rare disorder characterized by fibrous dysplasia, café au lait skin spots, and hyperfunctioning endocrinopathies. The coexistence of precocious puberty and growth hormone excess in McCune-Albright syndrome is rare. Both conditions can manifest as accelerated growth, and treatments can be more challenging for such patients. This study aimed to describe the clinical manifestations of combined GH excess and PP in the context of McCune-Albright syndrome and analyze the clinical features and treatments of these patients., Method: Clinical data from 60 McCune-Albright syndrome patients from Peking Union Medical College Hospital were obtained. The demographic characteristics, growth hormone, insulin-like growth factor-1, prolactin, alkaline phosphatase, and sex hormone levels; growth velocity; and bone age data were obtained. The growth velocity Z-score, bone age over chronological age ratio, and predicted adult height Z-score were calculated before and after treatment. Published studies and case reports were systemically searched, and data on demographic, clinical, and biochemical characteristics and treatment outcomes were obtained., Results: We reviewed seven patients among 60 McCune-Albright syndrome patients at Peking Union Medical College Hospital (5 female) and 39 patients (25 female) from the published literature. Six of the seven patients from Peking Union Medical College Hospital and half of the patients from the published studies were pediatric patients. These patients had increased growth velocity Z-scores and bone age over chronological age ratios. After good control of both conditions, the growth velocity Z-score and bone age over chronological age ratio decreased significantly, and the predicted adult height Z-score increased. The final heights and predicted adult height Z-scores were not impaired in patients with gigantism. All the patients had craniofacial fibrous dysplasia associated with optic and otologic complications., Conclusion: McCune-Albright syndrome with growth hormone excess and precocious puberty is more common in girls. Patients have accelerated linear growth and advanced skeletal age, and early and good control of both conditions leads to a reduced growth velocity and stabilized bone age. The predicted adult and final heights are not negatively affected when growth hormone excess is diagnosed in pediatric patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhai, Duan, Yao, Xing, Deng, Wang, Feng, Liang, You, Yang, Lu, Chen, Wang, Pan and Zhu.)

Background: Triptorelin depot is largely used to treat central precocious puberty (CPP) in children, and a 3-month depot has been introduced. However, data about the 3-month gonadotropin-releasing hormone use for treatment of CPP in Korean girls are not available. This study was conducted to compare the efficacy of a triptorelin 11.25 mg 3-month depot with that of a 3.75 mg 1-month depot in suppressing pubertal development for the treatment of CPP., Methods: A retrospective study, including 106 girls with CPP treated with triptorelin, was conducted. Fifty patients were treated with a triptorelin 3-month depot, and 56 were treated with a triptorelin 1-month depot. Serum luteinizing hormone (LH), follicle-stimulating hormone, and estradiol levels were analysed every 6 months after the visit. The height and bone age of each patient was evaluated at the beginning of treatment, after 6 months, and one year after therapy., Results: The baseline characteristics of the girls treated with a 3-month depot were similar to those of the girls treated with a 1-month depot. A suppressed levels of LH to the triptorelin injection (serum LH < 2.5 IU/L) at 6 months was seen in 90.0% and 98.2% of the girls treated with the 3-month and 1-month depots, respectively ( P = 0.160). After 1 year of treatment, a suppressed levels of LH was seen in 93.5% and 100% of the girls treated with the 3-month and 1-month depots, respectively ( P = 0.226). Height velocity showed no significant difference between the two groups. Degree of bone age advancement decreased from 1.22 ± 0.07 and 1.22 ± 0.08 years at baseline ( P = 0.914) to 1.16 ± 0.07 and 1.17 ± 0.08 in the girls treated with the 3-month and 1-month depots after 1 year, respectively ( P = 0.481)., Conclusion: This study showed that the efficacy of long-acting triptorelin 3-month was comparable to 1-month depot regarding hormonal suppression and inhibition of bone maturation. The triptorelin 11.25 mg 3-month depot is an effective treatment for girls with CPP., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Objectives: There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups., Methods: Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group., Results: After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group's basal AMH level; AMH response to GnRH stimulation was not different (p>0.05)., Conclusions: In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: The use of inhibin B (INHB), anti-Müllerian hormone (AMH) and insulin-like growth factor-1 (IGF-1) in differentiating central precocious puberty (CPP) from non-CPP was evaluated., Methods: In total, 115 Chinese girls were recruited (CPP: 44, non-CPP: 71). The diagnostic performance of INHB, AMH and IGF-1 in differentiating CPP from non-CPP was analyzed using receiver operating characteristic (ROC) curves., Results: INHB levels were higher in the CPP group than in the non-CPP group (55.56 ± 22.42 vs. 32.97 ± 15.59 pg/mL; p<0.001). AMH levels were similar in the CPP and non-CPP groups (6.63 ± 3.74 vs. 5.70 ± 3.15 pg/mL; p=0.158), and IGF-1 levels were much higher in the CPP group than in the non-CPP group (290.75 ± 79.78 vs. 200.10 ± 54.01 pg/mL; p<0.001). The area under the ROC curve (AUC) was greatest for INHB (0.819, standard error (SE) 0.041), followed by IGF-1 (0.809, SE 0.047) and AMH (0.567, SE 0.057). Among the ROC curves including combinations of these parameters, the AUC for INHB + IGF-1 was 0.849 and that for INHB + AMH was 0.768., Conclusions: Serum INHB and IGF-1 measurements could predict positive responses to gonadotropin-releasing hormone (GnRH) analog stimulation in girls with precocious puberty., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: A consensus on how to monitor girls with central precocious puberty (CPP) during gonadotropin-releasing hormone agonist (GnRHa) treatment is lacking. Increased, unstimulated basal luteinizing hormone (LH) concentrations have been suggested to indicate lack of suppression. The aim was to evaluate pre-injection basal LH concentrations during GnRHa (leuprorelin 3.75 mg) treatment every four weeks in girls with CPP., Methods: Medical records were reviewed for girls with CPP treated at a single center from 2014-2019. Clinical characteristics and laboratory findings during treatment were systematically recorded., Results: A total of 587 GnRHa pre-injection basal LH concentrations were analyzed in 74 girls. Basal LH was pubertal (≥0.3 IU/L) in 53.5% of blood samples and 87.8% of all girls had a pubertal basal LH concentration at least once. A GnRH test (n=29) was repeated in 23 girls due to suspicion of clinical progression, elevated basal LH or recordable estradiol concentrations. None had a stimulated LH >3.1 IU/L. The predictability of treatment suppression (specificity) of basal LH concentrations was 12.0% when compared to repeated GnRH stimulation tests. Despite shortening the GnRHa injection interval to three weeks, basal LH concentrations remained pubertal in 85.7% girls. A significant reduction in height standard deviation score (p<0.001) and bone age advance (p<0.001) was observed during treatment., Conclusion: Pre-injection basal LH remains at pubertal concentrations during treatment with leuprorelin 3.75 mg in girls with CPP. Clinical monitoring of pubertal progression is preferable to routine basal LH concentrations. Repeat GnRH stimulation testing should be regarded as the gold standard.

Background: The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for confirming the activation of the hypothalamic-pituitary-gonadal axis in central precocious puberty (CPP). However, it is time-consuming and costly. Our aim was to search for a simpler diagnostic modality for CPP by 1) evaluating the performance of basal serum luteinizing hormone (LH), 2) constructing a practical scoring system, and 3) determining the optimal single sampling time for serum LH in the GnRH stimulation test., Methods: Data of girls aged between 3 and 9 years at the time of the GnRH stimulation test, who attended our endocrine clinic at the MacKay Children's Hospital for signs of puberty between July 2014 and June 2019, were analyzed retrospectively. We recorded patients' age, height, weight, breast Tanner stage (BS), bone age, serum LH, and follicle-stimulating hormone (FSH). Receiver operating characteristic (ROC) curves and the Youden index were used to obtain the optimal basal serum LH level. Binary logistic regression was employed to construct a practical scoring system. Cross-sectional, cumulative frequency, and ROC curves were used to simplify the GnRH stimulation test., Results: Overall, 381 sets of GnRH stimulation tests were performed in 313 patients. Basal serum LH ≥ 0.2 IU/L demonstrated 70% sensitivity and 70% specificity for predicting positive GnRH stimulation test results. The practical scoring system (3 × BS + 3 × LH + 4 × FSH) showed 76% sensitivity and 72% specificity. The serum LH level at 30 min after intravenous gonadorelin exhibited 99% sensitivity and 100% specificity., Conclusion: Single sampling of serum LH at 30th minute post-injection of GnRH demonstrated a diagnostic performance equivalent to the traditional GnRH stimulation test in diagnosing CPP. Therefore, this approach could become the simplest diagnostic modality., Competing Interests: Conflict of interest None., (Copyright © 2020. Published by Elsevier B.V.)

Background: Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum luteinizing hormone (LH) ≥0.3 IU/L or LH-releasing hormone (LHRH)-stimulated LH ≥5 IU/L). Stimulation testing is the diagnostic gold standard but is time-consuming and costly. Serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are increased in girls with CPP., Objective: The aim of the study was to assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6-8 years., Methods: The study was a single-center retrospective study. Girls with confirmed CPP (n = 44) and isolated premature precocious adrenarche/ precocious thelarche (PA/PT, n = 16) had baseline biochemical profiling and LHRH stimulation testing. Serum IGF-1 and IGFBP-3 results were converted to standard deviation scores (SDS). Correlations were calculated and receiver operating characteristic curves were plotted., Results: Girls with CPP had higher basal and peak LH, IGF-1 SDS, and growth velocity (p < 0.05). IGF-1 SDS correlated positively with basal and peak LH (p < 0.05). IGF-1 SDS (1.75-2.15) differentiated CPP and PA/PT with 89% sensitivity and 56% specificity (basal LH) and 94% specificity and 55% sensitivity (peak LH). IGFBP-3 SDS did not differ between groups or by CPP parameters., Conclusions: In clinical practice, IGF-1 SDS may be an additional tool for identifying CPP in girls aged 6 to 8 years when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more time-consuming and costly procedures., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Aim: The exact mechanisms that trigger the onset of puberty are not well known. Adipomyokines are postulated to stimulate the central neural network. In the present study, we investigated irisin levels in girls with central precocious puberty (CPP), slowly progressing precocious puberty (SPPP), or premature thelarche (PT); we also studied prepubertal girls and to determine if this adipomyokine could be used as a marker in this context., Methods: A total of 94 girls including 33 with CPP, 31 with precocious puberty (PP) variants (SPPP or PT), and 30 healthy controls were enrolled to the study. The mean irisin levels were compared between groups. The bivariate correlations of irisin levels with clinical and laboratory parameters were assessed. Multivariate linear regression analysis was performed to determine independent predictive factors of irisin levels., Results: Irisin levels were higher in the CPP group compared with the other groups (CPP group: 723.25 ± 62.35 ng/mL; PP variants group: 529.60 ± 39.66 ng/mL; and control group: 325.03 ± 27.53 ng/mL) (P < 0.001). Irisin levels were positively correlated with body mass index standard deviation scores (BMI-SDS), height-SDS, weight-SDS, bone age, uterus long axis, ovary size, baseline FSH and LH, and peak LH levels. Multivariate linear regression analysis revealed that irisin levels had the strongest correlation with peak LH. The other independent predictive factor of irisin levels was BMI-SDS., Conclusions: The mean irisin levels were higher in patients with CPP compared with other groups. The results of this study imply that increased irisin levels may be used as a marker of CPP provided that these findings are confirmed in larger prospective studies., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Gonadotropin-releasing hormone (GnRH) analogs represent the treatment of choice in patients with central precocious puberty (CPP). Recently, GnRH analogs that can be administered every 3 months have been developed and appear to be as safe and effective as one-monthly formulations. However, there are limited data regarding its long term safety and efficacy profile. We aimed to evaluate the long-term safety and efficacy treatment of CPP with GnRH analogs every 3 months., Methods: We prospectively studied all patients who were diagnosed with CPP in our center between January 2015 and December 2019. All patients were treated with intramuscular leuprolide acetate 11.25 mg every 3 months., Results: Twenty-four patients with CPP were included in the study. Mean follow-up was 3.1 years. Height gain ranged between 4 and 6 cm. Bone mineral density (BMD) was not affected. Body mass index (BMI) increased in all subjects but none was obese at the end of follow-up., Conclusions: Treatment of patients with CPP with GnRH analogs every 3 months induces substantial increases in height and does not affect BMI or BMD. Therefore, it represents an attractive option for these young patients.

Context: Girls with premature adrenarche (PA) may have a higher risk of developing polycystic ovary syndrome (PCOS) and metabolic syndrome. The biological purpose of adrenarche is unknown and the role of novel biosynthetic pathways remains unclear., Objective: To compare the urinary steroid metabolome and enzyme activities of girls with PA to age-matched control girls and to published steroid values of girls with normal adrenarche and of women with PCOS and their newborn daughters., Design: Prospective observational study from 2009 to 2014., Setting: Academic pediatric endocrinology referral center., Participants: Twenty-three girls with PA and 22 healthy, age-matched girls., Main Outcome Measures: Steroid metabolites in 24-hour urine samples, including 4 progesterones, 5 corticosterones, aldosterone, 13 androgens, 2 estrogens, 14 glucocorticoids, and enzyme activities represented by metabolite ratios., Results: Girls with PA had a higher body mass index (mean standard deviation scores 0.9 vs -0.3, P = 0.013). Androgen excretion was higher in PA girls than in control girls (median 3257 nmol/24 hours vs 1627 nmol/24 hours, P < 0.001), in particular metabolites from alternate androgen pathways. The amount of progesterone, corticosterone, aldosterone, estrogen, and cortisol metabolites were similar between groups. Activities of 17β-hydroxysteroid-dehydrogenase and of 17,20-lyase were higher in girls with PA. Activities of 3β-hydroxysteroid-dehydrogenase, 21-hydroxylase, and 5α-reductase activity were not different between groups, in contrast to published results on girls with normal adrenarche or PCOS females., Conclusions: Metabolites and enzymes involved in alternate androgen pathways appear to be markers of PA. Prospective studies should assess whether steroid production in PA also differs from adrenarche at normal timing and persists into adulthood., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Premature thelarche (PT) is defined as isolated breast development in girls before eight years of age. Gonadotropin-releasing hormone (GnRH) stimulation test is sometimes used to distinguish between PT and central precocious puberty (CPP), although the interpretation of the test at early ages is challenging. The objective of this study was to determine the follicle stimulating hormone (FSH) and luteinizing hormone (LH) responses to GnRH stimulation in girls with PT below 3 years of age., Methods: A standardized GnRH stimulation test, bone age and pelvic ultrasound were evaluated and those without pubertal progression after a minimum of one-year follow up were included in the study., Results: On GnRH stimulation test, the median (range) baseline LH was 0.29 (0.10-0.74) IU/L, baseline FSH was 4.96 (3.18-7.05) mIU/mL, and the peak median LH was 5.75 (3.31-8.58) IU/L with the peak mean±standard deviation FSH was 40.38±20.37 mIU/mL. Among the patients, 33.3% (n=10) had baseline LH >0.3 IU/L, 67% (n=20) had peak LH >5 IU/l and 16.6% (n=5) >10 IU/L. The mean peak LH/FSH ratio was 0.17±0.09 and was ≤0.43 in all participants., Conclusion: Although consensus statements usually define baseline LH >0.3-0.5 IU/L, peak LH >5 IU/L, and LH/FSH ratios >0.66-1.0 as diagnostic cut-offs for CPP, in children below 3 years of age, the baseline and peak LH values may be similar to pubertal values, possibly due to mini-puberty. A dominant FSH response on GnRH stimulation test is more valuable than the peak LH response in the diagnosis of PT.

Objectives: Treatment of central precocious puberty (CPP) is based on administration of GnRH agonists in order to suppress hypothalamic-pituitary-gonadal axis and thus induce the stabilization or regression of pubertal development. Our aim was to determine whether the single basal serum LH and/or FSH concentration could be an effective tool to assess the efficacy of treatment to suppress activation of hypothalamic-pituitary axis., Patients and Methods: Serum LH and FSH were measured before and after the GnRH injection, as well as E2 basal levels in 60 girls with documented idiopathic CPP at diagnosis and 18 and 30 months after the beginning of therapy., Results: At diagnosis, peaks of >5 IU/L of LH and of FSH were observed in 100 and 91.6% of girls, respectively, with basal LH values of <1 IU/L in 70% and basal FSH levels of <1 IU/L in 10%. E2 were <20 pg/mL in 36.6%. After 18 months, a suppressed peak (i.e. <3 IU/L) was recorded in 85% of girls (p<0.01) for LH and in 98.3% for FSH (p<0.01). Basal LH <1 IU/L was detected in 85% (p<0.01) and basal FSH ≤1 IU/L in 40% (p<0.01). Serum E2 ≤20 pg/mL was recorded in 61.6% (p<0.01). After 30 months, all patients showed LH suppressed peak (p<0.01) and 98.3% suppressed FSH peak (p<0.01). 100% showed basal LH concentrations <1 IU/L (p<0.01) and 38.3% FSH basal values <1 UI/mL (p<0.01). E2 ≤20 pg/mL was observed in 32.72% (p=NS)., Conclusions: Basal LH values are a reliable indicator of the efficacy of GnRHa therapy after 30 months of GnRHa therapy., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Makorin ring finger protein 3 (MKRN3) is associated with the initiation of puberty, and loss of function mutation of MKRN3 is the most common genetic cause of central precocious puberty (CPP). A recent study reported that MKRN3 interacts with and suppresses neural pentraxin-1 precursor (NPTX1) activity via polyubiquitination during early puberty in the mouse hypothalamus. This study investigated the correlation between serum NPTX1 and MKRN3 in CPP girls and predicted the potential role of NPTX1 in pubertal progression., Methods: In this case-control study, we examined 34 girls diagnosed with CPP and 34 healthy prepubertal girls. Anthropometric and hormonal parameters were measured and serum levels of NPTX1 and MKRN3 were evaluated with commercial enzyme-linked immunosorbent assay kits., Results: Serum MKRN3 level decreased significantly in CPP patients compared to controls (344.48 ± 333.77 and 1295.21 ± 780.80 pg/mL, respectively, p<0.001). Serum MKRN3 tended to decrease as Tanner breast stage increased. However, no significant difference was observed in serum NPTX1 levels between patients and controls (20.14 ± 31.75 ng/mL and 12.93 ± 8.28 ng/mL, respectively, p=0.248). The serum level of NPTX1 did not change significantly with the Tanner breast stage. Serum NPTX1 was correlated with the height standard deviation score (r=0.255; p<0.05), but was not correlated with serum MKRN3 level or the others. Conclusion: Although serum NPTX1 level was independent of serum MKRN3 level, the possibility they might be involved in the progression of puberty or CPP remains. Further research is needed to determine their role in the hypothalamus., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Puberty is the transitional period from childhood to adult that leads to growth spurt, sexual maturation and attainment of reproductive capacity. Precocious puberty is defined when secondary sexual characteristics develop before the age of eight for girls and nine for boys. Central precocious puberty (CPP) is diagnosed when the process is driven by premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Many factors promote CPP, and the thyroid function is thought to be one of them. In our previous study, thyroid stimulating hormone (TSH) was higher in the CPP group than that of the participants without CPP. This elevation of TSH in CPP is said to be associated with pubertal luteinizing hormone (LH) elevation. The aim of this study was to evaluate the causal relationship between TSH and LH in CPP patients. A total of 221 girls diagnosed with CPP and treated with GnRH agonists were included. All participants except one showed LH suppression (peak LH < 3 IU/L), and serum levels of follicle stimulating hormone (FSH) were also lower after the treatment. These results indicate that puberty has slowed down and that the patients were successfully treated for CPP. As for thyroid hormones, TSH was significantly lower and free thyroxine (fT4) levels were higher after 12 months of GnRH agonist treatment compared with baseline. With GnRH agonist treatment, the serum levels of LH and TSH were decreased, suggesting that the increase in serum TSH levels is associated with premature LH elevation in girls with CPP.

Background: Central precocious puberty (CPP) has been associated with loss-of-function mutations in 2 paternally expressed genes (MKRN3 and DLK1). Rare defects in the DLk1 were also associated with poor metabolic phenotype at adulthood., Objective: Our aim was to investigate genetic and biochemical aspects of DLK1 in a Spanish cohort of children with CPP without MKRN3 mutations., Patients: A large cohort of children with idiopathic CPP (Spanish PUBERE Registry) was studied. Genomic deoxyribonucleic acid was obtained from 444 individuals (168 index cases) with CPP and their close relatives. Automatic sequencing of MKRN3 and DLK1 genes were performed., Results: Five rare heterozygous mutations of MKRN3 were initially excluded in girls with familial CPP. A rare allelic deletion (c.401&#95;404 + 8del) in the splice site junction of DLK1 was identified in a Spanish girl with sporadic CPP. Pubertal signs started at 5.7 years. Her metabolic profile was normal. Familial segregation analysis showed that the DLK1 deletion was de novo in the affected child. Serum DLK1 levels were undetectable (<0.4 ng/mL), indicating that the deletion led to complete lack of DLK1 production. Three others rare allelic variants of DLK1 were also identified (p.Asn134=; g.-222 C>A and g.-223 G>A) in 2 girls with CPP. However, both had normal DLK1 serum levels., Conclusion: Loss-of-function mutations of DLK1 represent a rare cause of CPP, reinforcing a significant role of this factor in human pubertal timing., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anti-Müllerian hormone (AMH) and inhibin B are considered possible biomarkers of central precocious puberty (CPP). The aim of this study was to evaluate serum levels of AMH and inhibin B, to investigate their regulatory patterns, and to study their clinical significance in girls with CPP. In total, 48 girls with CPP and 35 age-matched prepubertal control girls were enrolled in the study. AMH and inhibin B levels were determined in the CPP and control groups. In the patient group, AMH and inhibin B levels were evaluated during 1 year of gonadotropin releasing hormone analog (GnRHa) treatment. The mean inhibin B level in the CPP group was significantly higher than that in the control. AMH levels were not different between the two groups. After GnRHa treatment. AMH and inhibin B levels decreased significantly. Based on the ROC analysis, the cutoff value for inhibin B to determine CPP was 19.59 pg/mL, with 83.3% sensitivity and 82.9% specificity, and the area under the curve was 0. 852. Inhibin B was useful for determining CPP and the therapeutic effects of GnRHa treatment in girls with CPP. AMH interacted, in part, with the hypothalamo-pituitary gonadal axis, but its clinical implications in CPP should be further investigated.

Objectives Data on the predictive values of parameters included in the diagnostic work-up for precocious puberty (PP) remain limited. We detected the diagnostic value of basal sex hormone levels, pelvic ultrasound parameters and bone age assessment for activation of the hypothalamic-pituitary-gonadal axis in girls with PP, in order to help in the decision to perform GnRH testing. Patients and methods We retrospectively considered 177 girls with PP. According to puberty evolution, the girls were divided into two groups: rapid progressive central precocious puberty (RP-CPP) and non/slowly progressive/transient forms (SP-PP). In all patients we considered Tanner stage, basal luteinizing hormone (LH) and estradiol (E2) values, bone age, and pelvis examination. We assessed the diagnostic value of each variable and identified the number of pathological parameters that best identify patients with RP-CPP. Results Basal LH ≥ 0.2IU/L, E2 level ≥ 50 pmol/L, uterine longitudinal diameter ≥ 3.5 cm, transverse uterine diameter ≥ 1.5 cm, endometrial echo and ovarian volume ≥ 2 cm3 were significantly associated with RP-CPP (p ≤ 0.01). The ability to diagnose RP-CPP was enhanced with increasing number of pathological hormonal and instrumental parameters (p < 0.001). With more than three parameters detected, sensitivity and specificity reached 58% (95%CI 48-67) and 85% (95%CI 74-92), respectively, with a PPV = 86% (95%CI 76-93) and PPN = 54% (95%CI 43-54); the area under the ROC curve was 0.71 (95%CI 0.65-0.78). Conclusion Despite the availability of different tests, diagnosing RP-CPP remains difficult. A diagnosis model including at least three hormonal and/or ultrasound parameters may serve as a useful preliminary step in selecting patients who require GnRH testing for early detection of RC-PP.

The objective of this short communication was the relationship between vitamin D and precocious puberty (PP). In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between vitamin D deficiency and PP. Studies that compared serum vitamin D levels between patients with PP and controls were selected for the systematic meta-analysis. The main outcome was the mean difference in serum vitamin D levels between PP and controls. Vitamin D-deficient subjects were more likely to develop PP. Our findings suggest that PP may be linked to vitamin D deficiency. Thus, providing supplements of vitamin D to PP patients may improve their nutritional status and prevent diseases. But, the amount of vitamin D required is uncertain, so it is important to be careful when taking vitamin D supplements.

Objective: Doses of gonadotropin releasing hormone (GnRH) analogues used to treat idiopathic central precocious puberty (iCPP) vary among clinicians. Study aims were to evaluate the efficacy of a monthly 3.75 mg dose of leuprolide acetate (LA) to suppress the hypothalamo-pituitary-gonadal (HPG) axis in girls with iCPP and to determine factors that may have an impact on the supressing dose., Methods: Study subjects were 220 girls receiving LA for iCPP. LA was started at a dose of 3.75 mg/28 days. Suppression was assessed using the GnRH test at the third month. To assess clinical suppression signs and symptoms of puberty were also evaluated. The dose of LA was increased to 7.5 mg/28 days in those who had a peak luteinising hormone (LH) ≥2 IU/L and in whom adequate clinical suppression of puberty was absent. Receiver operating characteristic curves were used to determine thresholds for clinical and hormonal factors affecting the suppressing dose of LA. Logistic regression analyses were used to investigate thresholds which might differentiate between those requiring high dose for suppression and those in whom lower dose LA was adequate., Results: Peak stimulated LH <2 IU/L was achieved in 88.6% with a dose of LA of 3.75 mg (0.11±0.03 mg/kg). Significant variables for differentiating the two doses were body weight (Wt) of 36.2 kg and/or body mass index (BMI)-standard deviation scores (SDS) of 1.64 (p<0.001). Multiple logistic regressions showed that Wt and BMI-SDS values above thresholds indicated requirement of LA at a dose of 7.5 mg/28 days (p<0.001)., Conclusion: Monthly injections of 3.75 mg LA is an effective treatment in the majority of girls with iCPP. However, a higher initial dose may be preferred in patients with a Wt ≥36 kg or BMI-SDS ≥1.6 for effective suppression of the HPG axis.

If circulating adrenal androgens levels rise before the age of 8 years in girls, this phenomenon is termed premature adrenarche (PA), while the concomitant appearance of pubic hair is called premature pubarche (PP). Girls with PA-PP display an unfavorable hormonal profile compared to their normal peers and have an increased risk of developing polycystic ovary syndrome (PCOS) features peripubertally. However, the sequelae of premature adrenarche remains unclear. We assessed metabolic, hormonal, psychologic profiles, and ovarian morphology in 21 women of mean age (±SD) 21.3±3.3 years, BMI: 23.6±4.4 kg/m 2 with PA-PP, 45 women with PCOS and 26 controls, matched for age and BMI. PA-PP women displayed a favorable lipid profile compared to PCOS and controls. Insulin resistance index (HOMA-IR), however, were similar in PA-PP and PCOS women (2.09±1.42, 2.08±0.83) and higher than controls (1.13±0.49, p <0.05). Circulating androstenedione levels did not differ between PA-PP and PCOS women (0.11±0.05 vs. 0.12±0.03), but was higher than that of controls (0.02±0.0 nmol/l, p <0,05). Ovarian volume was increased in PA-PP and PCOS (11.14±3.3 vs. 10.99±4.61) compared to controls (6.74±1.83 cm 3 ). PA-PP women had a higher score of state/trait anxiety and depressive and eating disorder symptoms than controls, with a pattern that matched that of PCOS women. Only 14% of the PA-PP group fulfilled the Rotterdam PCOS criteria. Some women with a history of PA-PP displayed hormonal and psychologic profile similar to PCOS, and accordingly a regular monitoring of these girls during adulthood is advised., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To evaluate a non-invasive method to assess the progressivity of idiopathic central precocious puberty (CPP) by quantifying perfusion of the pituitary stalk with arterial spin labeling (ASL) and using the gonadotropin-releasing hormone (GnRH) test as a reference test to define progressive CPP., Methods: In a single center retrospective study, 52 consecutive patients, observed between October 2015 and April 2017 and referred with early signs of puberty, were evaluated using the GnRH test and cerebral magnetic resonance imaging (MRI). Patients with peripheral or non-idiopathic puberty were excluded. The distribution of perfusion values between patients with progressive and non-progressive CPP was compared using a nonparametric Mann-Whitney U‑test., Results: In this study 35 patients were included and 29 had progressive CPP. These patients displayed significantly higher cerebral blood flow (CBF) values than the 6 patients with non-progressive CPP (p = 0.006). The median CBF for patients with non-progressive and progressive CPP was 45.25 ml/min/100 g (interquartile range 36.9-54) vs. 65 ml/min/100 g (interquartile range 55.5-74.5), respectively. To determine if the CPP was progressive, the best CBF threshold was 55.5 ml/min/100 g with a sensitivity of 76%, a specificity of 83% and an accuracy of 77%. There were strong significant correlations between CBF and LH peak (r = 0.67, p < 0.001) and between CBF and LH/FSH peaks ratio [r = 0.71, p < 0.001] during the GnRH test., Conclusion: Arterial spin labelling (ASL) offers a novel tool to assess the progressivity of idiopathic CPP.

This study aims to investigate serum makorin ring finger protein 3 (MKRN3) levels in girls with idiopathic central precocious puberty (ICPP) and premature thelarche (PT), in order to determine whether circulating MKRN3 level is associated with ICPP and PT. A total of 90 girls were enrolled in the stud. 30 age-matched girls were allocated for each group (ICPP, PT and healthy controls [HC], respectively). The base LH (B-LH) and E2 levels were higher in ICPP girls than those in HC and PT girls. The peak LH (P-LH) levels and P-LH/P-FSH values were obviously higher in ICPP girls than those in PT girls, while higher peak FSH (P-FSH) levels were detected in PT girls when compared to those in ICPP girls. Kisspeptin levels were lower in HC girls than those in ICPP and PT girls. MKRN3 levels were the highest in HC girls among the three groups. There were relatively strong negative correlations among MKRN3, kisspeptin and P-LH/P-FSH. Circulating MKRN3 can have an important role in the onset of ICPP and PT. However, this should not be used as an independent diagnostic criterion for diagnosing ICPP or differentiating ICPP from PT, but should be used only as an adjunctive diagnostic biomarker.

Background Some studies have examined the effect of gonadal suppression on insulin-like growth factor-1 (IGF-1) levels and the growth velocity (GV) with conflicting results. Methods Forty-four girls treated with gonadotropin-releasing hormone analogue (GnRHa) for central precocious puberty (CPP) were included in the study. IGF-1 levels were examined at the beginning and after 12 months of treatment. Results IGF-1 and IGF-1 standard deviation score (SDS) according to chronological age (CA-IGF-1 SDS) at diagnosis were positively correlated with chronological age (CA), anthropometric measurements, stage of puberty, bone age (BA), BA-CA, follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, uterus length, endometrium thickness and ovarian volume (OV) at diagnosis (p < 0.05). There was no significant difference in IGF-1 levels after treatment. However, there was a negative correlation between ΔIGF-1 SDS and IGF-1 level, CA-IGF-1 SDS and BA-IGF-1 SDS at diagnosis (p < 0.05). There was no correlation between GV and IGF-1, ΔIGF-1. GV was negatively correlated with basal LH level at diagnosis (p = 0.008, r = -0.397). Peak LH levels of the patients who had GV-SDS < 0 were more suppressive than those of the patients who had GV-SDS > 0 after 12 months of treatment. Conclusions It was determined that the IGF-1 level and CA-IGF-1 SDS at baseline were correlated with more advanced pubertal stage prior to treatment. Initiation of treatment with a relatively high level of IGF-1 increased the risk of a decrease in the IGF-1 level. Likewise, the initiation of treatment with a relatively high LH level may increase the risk of low GV, but low GV was not related to the IGF-1 level. Increased sex steroid suppression may increase the risk of low GV.

Introduction: Recent studies have shown 11-oxygenated androgens (11oAs) are the dominant androgens in premature adrenarche (PA). Our objective was to compare 11oAs and conventional androgens in a well-defined cohort of children with PA or premature pubarche (PP) and correlate these androgens with metabolic markers., Methods: A prospective cross-sectional study was conducted at a university hospital. Fasting early morning serum steroids (including 11oAs) and metabolic biomarkers were compared and their correlations determined in children ages 3-8 years (F) or 3-9 years (M) with PA or PP (5 M and 15 F) and healthy controls (3 M and 8 F)., Results: There were no differences between PA, PP, and controls or between PA and PP subgroups for sex, BMI z-score, or criteria for childhood metabolic syndrome. Dehydroepiandrosterone sulfate (DHEAS) was elevated only in the PA subgroup, as defined. 11oAs were elevated versus controls in PA and PP although no differences in 11oAs were noted between PA and PP. Within the case cohort, there was high correlation of T and A4 with 11-ketotestosterone and 11β-hydroxyandrostenedione. While lipids did not differ, median insulin and HOMA-IR were higher but not statistically different in PA and PP., Conclusions: PA and PP differ only by DHEAS and not by 11oAs or insulin sensitivity, consistent with 11oAs - rather than DHEAS - mediating the phenotypic changes of pubarche. Case correlations suggest association of 11oAs with T and A4. These data are the first to report the early morning steroid profiles including 11oAs in a well-defined group of PA, PP, and healthy children., (© 2021 S. Karger AG, Basel.)

Background: A random ultrasensitive luteinizing hormone (LH) (LH-ICMA) ≥0.3 mIU/L is highly accurate in confirming a diagnosis of central precocious puberty (CPP). However, a prepubertal value does not exclude the diagnosis. The clinical differences between patients with CPP who have a pubertal versus prepubertal LH-ICMA have not been clearly defined. Furthermore, there is minimal information regarding the utility of this test in boys with CPP. The objective of this study was to analyze differences between patients diagnosed with CPP who had a pubertal versus prepubertal LH-ICMA, including a cohort of boys., Methods: A retrospective chart review of children diagnosed with CPP within the last 10 years who had a baseline LH-ICMA obtained was performed. Variables analyzed included sex, age, ethnicity, bone age, BMI, etiology, Tanner stage (TS), testicular volume, and menarchal status., Results: Of 27 boys and 126 girls who qualified for the study, the LH-ICMA was pubertal in 87% and prepubertal in 13%. Girls with a pubertal LH-ICMA had higher baseline estradiol concentrations (p < 0.001) and more advanced breast development (p = 0.015) compared to girls with a prepubertal LH-ICMA. Of girls with a prepubertal LH-ICMA, 74% had at least TS 3 breast development and 1 was post-menarchal. The LH-ICMA was pubertal in 96% of the boys with CPP in this study., Conclusions: The LH-ICMA can be prepubertal even in girls with advanced development. To our knowledge, ours is the largest cohort of boys in whom the accuracy of a random LH-ICMA has been reported., (© 2021 S. Karger AG, Basel.)

Objective: To determine basal and gonadotrophin-releasing hormone analogue (GnRHa)-stimulated peak luteinising hormone (LH) cut-offs to diagnose onset of early or normal puberty in girls with each Tanner stage of breast (II and III)., Design, Patients and Measurements: A retrospective study of 601 girls with breast onset before 8 years of age who underwent GnRHa test was conducted. Patients were categorized as CPP and premature thelarche. Each group was divided into two subgroups; Tanner II and III. Cost-effectiveness analysis was performed., Results: In comparison with basal LH cut-off of 0.3 IU/L, basal LH cut-off of 0.2 IU/L had comparable specificity (Tanner II: 98.0% vs 94.8%, Tanner III: 98.8% vs 93.8%), but greater sensitivity (Tanner II: 28.3% vs 41.7%, Tanner III: 45.2% vs 59.3%). Specificity of basal LH cut-off of 0.2 IU/L was not inferior to that of the traditionally used peak LH of 5 IU/L. Using basal LH cut-off of 0.2 IU/L followed by GnRHa test in girls with negative basal LH was more cost-saving when compared with using the cut-off of 0.3 IU/L. Moreover, using basal LH cut-off of 0.2 IU/L followed by GnRHa test provided a cost reduction when compared with performing GnRHa test in all patients., Conclusions: Basal serum LH cut-off of 0.2 IU/L could be a simple and cost-saving tool for initial diagnosis of onset of early or normal puberty in girls with Tanner II and III before proceeding to GnRH testing., (© 2019 John Wiley & Sons Ltd.)

Pubertal hormones play an important role in brain and psychosocial development. However, the role of abnormal HPG axis states in altering brain function and structure remains unclear. The present study is aimed at determining whether there were significant differences in gray matter volume (GMV) and resting state (RS) functional connectivity (FC) patterns in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). We further explored the correlation between these differences and serum pubertal hormone levels. To assess this, we recruited 29 idiopathic CPP girls and 38 age-matched PPP girls. A gonadotropin-releasing hormone (GnRH) stimulation test was performed, and pubertal hormone levels (including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin, and cortisol) were assessed. All subjects underwent multimodal magnetic resonance imaging of brain structure and function. Voxel-based morphometry (VBM) analysis was paired with seed-to-voxel whole-brain RS-FC analysis to calculate the GMV and RS-FC in idiopathic CPP and PPP girls. Correlation analyses were used to assess the effects of pubertal hormones on brain regions with structural and functional differences between the groups. We found that girls with CPP exhibited decreased GMV in the left insula and left fusiform gyrus, while connectivity between the left and right insula and the right middle frontal gyrus (MFG), as well as the left fusiform gyrus and right amygdala, was reduced in girls with CPP. Furthermore, the GMV of the left insula and peak FSH levels were negatively correlated while higher basal and peak E2 levels were associated with increased bilateral insula RS-FC. These findings suggest that premature activation of the HPG axis and pubertal hormone fluctuations alter brain structure and function involved in the cognitive and emotional process in early childhood. These findings provide vital insights into the early pathophysiology of idiopathic CPP., Competing Interests: All authors declare that there are no conflicts of interest in this study., (Copyright © 2019 Tao Chen et al.)

Objective: There are no doubts about the clinical benefits of treatment with GnRH analogs for patients diagnosed with central precocious puberty (CPP). However, laboratory monitoring of CPP is still a matter of considerable controversy in the literature. Therefore, the main objective of this study was to evaluate the cut-off values of stimulated LH that determine gonadotrophic suppression., Methods: Twenty-four girls, on treatment with leuprorelin acetate (LA) at 3.75 mg IM every 28 days, were studied. The clinical parameters used to indicate clinical effectiveness were regression or maintenance of sexual characteristics according to the Tanner stage, growth velocity reduction, reduction or maintenance of the difference between bone age and chronological age and maintenance or improvement of the final height prediction. For the laboratory effectiveness test, basal estradiol, LH, and FSH levels were collected before and 1 and 2 h after the administration of 3.75 mg LA., Results: Eleven girls showed improvement in all clinical parameters, and their effectiveness tests were compared to those of the other patients to calculate the cut-off values, which were ≤3.64 IU/L (p=0.004*) for LH after 1 h and ≤6.10 IU/L (p<0.001*) for LH after 2 h., Conclusion: The LH response after the LA stimulation test, associated with clinical data and within a context of CPP, constitutes a reliable and feasible resource and can assist in monitoring the effectiveness of treatment.

Background: Obesity is associated with many chronic diseases including cortisol rhythm disorder and low testosterone. Furthermore, studies on obese children are quite limited and no concordance results have been obtained, especially for boys in puberty. Moreover, the sample sizes of previous studies were small, and were not representative., Methods: We conducted a cross-sectional survey including 1148 boys aged 6-14 years, they were divided into overweight/obesity (OW/OB) group and normal weight (NW) group. Puberty status was assessed according to Tanner scale and testicular volume. Serum levels of pregnenolone, 17-OH progesterone, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione were detected by LC-MS. Serum free testosterone and sex hormone-binding globulin (SHBG) levels were measured by chemiluminescence immunoassay., Results: The 17-OH progesterone, DHEA, androstenedione and free testosterone levels of OW/OB boys at prepubertal stage or at the age 6 = < 10 years group were higher than those of the NW boys (all the P values were < 0.01). Furthermore, androstenedione and free testosterone levels were lower in OW/OB boys at late puberty, and the trend continued at the post pubertal stage for FT (P < 0.01-0.05). DHEA, androstenedione, and FT levels persisted to be higher at the 10~ < 12 years in OW/OB boys but not for 17-OH progesterone. FT level was lower in the OW/OB group at the 12~ < 15 years group. The SHBG levels in the OW/OB boys were lower than those in the NW ones at the 6~12 years group, and prepubertal to early pubertal stage., Conclusions: Premature adrenarche is more likely in OW/OB boys. More attention should be given to the lower androgen levels of OW/OB boys at late pubertal and post pubertal stages.