Central Precocious Puberty Group 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.

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.

α-Klotho levels in girls with central precocious puberty: potential as a diagnostic and monitoring marker.

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. 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. 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. 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.

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

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

Evaluation of quality of life in children with precocious puberty.

This study aimed to investigate the quality of life of patients with central precocious puberty (CPP) who required treatment and premature thelarche (PT) followed up without treatment and to compare the groups with and without treatment among themselves and with healthy children. This study is designed as a case-control study. A total of 193 children including 59 children with CPP, 53 children with PT, 81 healthy children and their parents were included in the study. A questionnaire was applied to evaluate the sociodemographic characteristics that would affect the quality of life. The 'Pediatric Quality of Life Inventory (PedsQL)' was used to assess the quality of life. The PedsQL total scale score was 78.10 ± 17.13, 79.35 ± 11.54 and 79.52 ± 14.65, the psychosocial health summary score was 78.86 ± 16.83, 79.40 ± 12.54 and 79.94 ± 14.94 and physical health summary score was 75.81 ± 20.69, 79.41 ± 15.04 and 78.25 ± 17.52 in CPP, PT and control groups, respectively; however, there was no statistical difference (p > .05). In the scale administered to the parents, scores were similar in the three groups. No difference was found between CPP, PT and control groups in terms of sociodemographic data in the study (p > .05). Unlike previous studies, in this study the effects of sociodemographic characteristics and whether treatment was initiated or not on quality of life were investigated. Although the scale scores of the CPP group were lower than the PT and control group, there was no statistically significant difference, indicating that quality of life was not negatively affected in the CPP group receiving treatment.

Network pharmacology combined with lipidomics to reveal the regulatory effects and mechanisms of Kangzao granules in the hypothalamus of rats with central precocious puberty

Central precocious puberty (CPP) is a prevalent endocrine disorder that primarily affects children, specifically females, and is associated with various physical and psychological complications. Although Kangzao granules (KZG) are efficacious in managing CPP, the underlying mechanisms remain unclear. Therefore, this study aimed to elucidate the therapeutic mechanisms of KZG using network pharmacology, molecular docking, pharmacodynamics, and pathway validation. A putative compound–target–pathway network was constructed using Cytoscape, before KEGG and Gene Ontology enrichment analyses were conducted. Moreover, molecular docking was performed using AutoDockTools. Quality control of the 10 key components of KZG was carried out using UHPLC-ESI/LTQ-Orbitrap-MS/MS, and hypothalamic lipids were analyzed using UHPLC-Q-Exactive Orbitrap MS/MS. In total, 87 bioactive compounds that targeting 110 core proteins to alleviate CPP were identified in KZG. Lipidomic analysis revealed 18 differential lipids among the CPP, KZG, and control groups, wherein fatty acids were significantly reduced in the model group; however, these changes were effectively counteracted by KZG treatment. Molecular docking analysis revealed a strong binding affinity between flavonoids and RAC-alpha serine/threonine-protein kinase (AKT) when docked into the crystal structure. Moreover, a substantial disruption in lipid metabolism was observed in the model group; however, treatment with KZG efficiently reversed these alterations. Furthermore, the phosphoinositide 3-kinase/AKT signaling pathway was identified as a pivotal regulator of hypothalamic lipid metabolism regulator. Overall, this study highlights the effectiveness of a multidisciplinary approach that combines network pharmacology, lipidomics, molecular docking, and experimental validation in the elucidation of the therapeutic mechanisms of KZG in CPP treatment.

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.

THU196 Insulin-like Growth Factor-1 As A Screening Tool For Central Precocious Puberty

Abstract Disclosure: L. Chung: None. M. Im: None. Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard test for diagnosing central precocious puberty (CPP), which needs time and effort to perform. Recently, many studies confirmed that Insulin-like growth factor-1 (IGF-1) is involved in the initiation and progression of puberty. With this inspection, we assumed that the IGF-1 level might be correlated with the pubertal stage in central precocious puberty. This study aimed to investigate the value of IGF-1 levels in screening central precocious puberty. The medical records of 359 patients with a chief complaint of premature breast development and visited the pediatric endocrinology clinic in Myongji Hospital from January 2017 to October 2022 were reviewed. Two hundred thirty-three girls with central precocious puberty (CPP) and 126 girls with premature thelarche (PT) diagnosed were enrolled. Each subject had IGF-1 and GnRH stimulation test results. The anthropometric data between CPP and PT showed no statistical differences except for weight and the existence of lipomastia. The hormonal indicators including peak luteinizing hormone (peak LH), peak follicular stimulating hormone (peak FSH), and estradiol were statistically different between the two groups (P &amp;lt; 0.001). IGF-1 levels were significantly higher in CPP group than in PT group. The IGF-1 levels were positively correlated with peak LH, the diagnostic indicator of CPP. The area under the curve (AUC) of IGF-1 was 0.709. IGF-1 levels were correlated with the diagnostic indicator of CPP. IGF-1 would be a useful tool for screening CPP. Keywords: girls; IGF-1; GnRH stimulation test; precocious puberty. Presentation: Thursday, June 15, 2023

Apparent diffusion coefficient (ADC) measurements and morphometric evaluation of the cranium in age-matched children with central precocious puberty.

Central precocious puberty (CPP) is one of the common reasons for referral to pediatric endocrinology. Magnetic resonance imaging (MRI) is used to rule out intracranial pathologies. However, there is insufficient information in the literature about bone marrow abnormalities on MRI in CPP cases. The aim of this study was to evaluate the apparent diffusion coefficient (ADC) values obtained from bone marrow diffusion weight images (DWI) of cranial bone structures and the status of sphenooccipital synchondrosis (SOS) in CPP. MRI data from 6-to 9-year-old girls with CPP and a healthy control group were evaluated. Anthropometric data, FSH, LH, and oestradiol tests were recorded, and the relationship between SOS status, DWI-ADC values of the clivus, parietal bone, and occipital protuberance were compared. The study included 146 girls, 79 CPP, and 67 healthy aged 6-9 years (median: 8 (2)). The diagnosis age was 8.30 ± 0.8 years. The ADC values were significantly lower on CPP than normal controls (p=<0.05). In the CPP group, pattern 1 was found at 2 % (n=2), pattern 2 at 3.5 % (n=3), and pattern 3 at 3.5 % (n=3) in clivus sphenooccipital synchondrosis. There was no correlation between the mean parietal, occipital, and clivus ADC values and any variable (p>0.05). DWI-MRI ADC analysis can be used as a quantitative radiological marker for early detection of CPP, even before changes in sphenooccipital synchondrosis.

Comparison of Makorin Ring Finger Protein 3 Levels Between Obese and Normal Weight Patients with Central Precocious Puberty.

Genetic studies of familial central precocious puberty (CPP) have suggested that makorin ring finger protein 3 (MKRN3) is the primary inhibitor of gonadotropin-releasing hormone (GnRH) secretion. Obesity in girls can cause early puberty by affecting the hypothalamic-pituitary-gonadal (HPG) axis. This study evaluated the serum MKRN3 level of patients with CPP and its relationship with body mass index (BMI). The study included 92 CPP and 86 prepubertal healthy controls (HC) aged 6-10 years. The CPP and HC groups were divided into obese and non-obese subgroups to evaluate whether BMI affects MKRN3. Patients' presenting complaints, chronological age, height age, bone age, Tanner stage, standard deviation scores for weight, height, and BMI, levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and MKRN3, and pelvic ultrasonography findings were recorded. The serum MKRN3 levels were lower in the CPP group and lowest in the CPP-obese subgroup. There were significant differences in MKRN3 levels between the CPP-obese and CPP-normal weight (p=0.02), CPP-obese and HC-obese (p<0.001), and CPP-obese and HC-normal weight (p=0.03) groups. MKRN3 and BMI were negatively correlated in all cases (r=-0.326, p<0.001). The negative correlation between BMI and MKRN3, and lower MKRN3 levels in CPP-obese patients, suggests that adipose tissue has a role in the onset of puberty. More comprehensive studies are needed to determine the relationship between MKRN3 and adipose tissue.

Differential diagnosis of precocious puberty in girls during the COVID-19 pandemic: a pilot study

BackgroundTo investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19 pandemic. We explored predicted adult height (PAH) discrepancy to guide appropriate diagnosis and treatment.MethodsFrom January 2020 to December 2021, Chinese girls aged 6 to 8 years with precocious puberty were recruited. They were divided into IPT and CPP groups. Clinical characteristics, including height, weight, body mass index (BMI), basal luteinizing hormone (LH), oestradiol, uterine length and volume, follicle numbers (d > 4 mm) and bone age (BA) were recorded. We analysed differential diagnosis and PAH discrepancy in both groups. Binary logistic regression analysis was used to explore risk factors for CPP, and receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of related indexes.ResultsSixty patients, including 40 girls with IPT and 20 girls with CPP, were recruited. The prevalence of overweight and obesity in the entire cohort was 25% (15/60) and was significantly higher in IPT than CPP, 32.5% (13/40) vs. 10% (2/20), respectively (P=0.045). There were significant differences in LH, uterine volume, follicle numbers and BA (P<0.05). The impaired PAH of IPT and CPP was 0.01 ± 1.19 SD and 0.62 ± 0.94 SD with significant differences (P=0.047). Logistic regression analysis showed that LH and follicle numbers were independent risk factors for CPP. The ROC curve showed that the area under the curve (AUC) of LH and follicle numbers were 0.823 and 0.697. The sensitivity and specificity of LH with a cut off of 0.285 IU/L were 78.9% and 77.8%. The sensitivity and specificity of follicle numbers with a cut off of 3.5 were 89.5% and 52.8%.ConclusionThe prevalence of overweight and obesity in 6- to 8-year-old girls with precocious puberty was high. Auxological data should not be used in the differential diagnosis of IPT and CPP. Basal LH above 0.285 IU/L and follicle numbers greater than 4 were important features suggestive of CPP. PAH was impaired in individuals with CPP, but it was not impaired in individuals with IPT.

Effect of gonadotropin-releasing hormone agonist treatment on near final height in girls with central precocious puberty and early puberty.

The aim of this study was to examine whether gonadotropin-releasing hormone (GnRH) agonist treatment is effective in preserving final height in patients with central precocious puberty (CPP) or early puberty (EP). The medical records of 40 patients with CPP and 206 patients with EP who completed GnRH agonist treatment following diagnosis were analyzed retrospectively. Height and height standard deviation (height SDS) scores based on bone age (BA) were measured and calculated at baseline, after treatment completion, and at final follow-up to compare changes within and between groups. Predicted adult height (PAH) was estimated by the height corresponding to height SDS for BA in girls at 18 years 11 months of age based on the growth chart. PAH at baseline did not differ significantly between the CPP group (153.67±4.95) and the EP group (154.77±3.72). In the CPP group, PAH significantly increased at treatment completion (156.01±4.61) and at final follow-up (158.52±6.04) compared to baseline. In the EP group, PAH significantly increased at treatment completion (157.7±3.60) and at final follow-up (159.31±4.26) compared to baseline. The increase in PAH at all timepoints compared to baseline did not significantly differ between the CPP and EP groups. Both CPP and EP groups had significantly greater PAH after treatment, with no difference in the amount of increase between groups. These results show that GnRH agonist treatment can help increase final height even in patients diagnosed with EP after the age of 8 years.

Serum kisspeptin, neurokinin Band inhibin B levels can be used as alternative parameters to distinguish idiopathic CPP from premature thelarche in the early stages of puberty.

There is controversial results about serum kisspeptin, neurokinin-B (NKB), anti-Müllerian hormone (AMH)and inhibin B (INHB) levels in girls with central precocious puberty (CPP). Aim of this study is to evaluate serum levels of these four peptides in patients presented with early pubertal signs, and to evaluate their diagnostic validity in the diagnosis of CPP. Cross-sectional study. Study included 99 girls (51 CPP, 48 premature thelarche [PT]) whose breast development started before 8 years and 42 age-matched healthy prepubertal girls. Clinical findings, antropometric measurements, laboratory and radiological findings were recorded. Gonadotropin-releasing hormone (GnRH) stimulation test was performed in all cases with early breast development. Kisspeptin, NKB, INHBand AMH levels were measured in fasting serum samples using enzyme-linked immunosorbent assay method. There was no statistically significant difference between mean ages of girls with CPP (7.1 ± 1.2 years), PT (7.2 ± 1.3 years)and prepubertal controls (7.0 ± 1.0 years). Serum kisspeptin, NKBand INHB levels were higher in CPP group compared to PT and control groups, while serum AMH level was lower in CPP group. Serum kisspeptin, NKB, and INHB were all positively correlated with bone age (BA) advancement, and peak luteinizing hormonein GnRH test. Multiple stepwise regression analysis revealed that the most important factors used to differentiate CPP from PT were advanced BA, serum kisspeptin, NKB and INHB levels (AUC: 0.819, p < .001). We, firstshowed in the same patients' group that serum kisspeptin, NKB and INHB were higher in patients with CPP and can be used as alternative parameters to distinguish CPP from PT.

Effect of Exercise and Detraining on Signs of Puberty and Selected Inflammatory Markers in Girls with Precocious Puberty.

We examined the effects of aerobic exercise and detraining on adiponectin, resistin, tumor necrosis factor alpha (TNF-α), white blood cell, and pubertal signs (uterine length, ovarian volume, luteinizing hormone [LH], and follicle-stimulating hormone [FSH]) in girls with central precocious puberty (CPP). Thirty girls with CPP (7-9 yr old) were randomly divided into CPP and CPP + Exercise (EX) groups. Fifteen healthy age-matched girls without precocious puberty participated for comparison with CPP. Subjects in the CPP + EX group attended 12 wk of aerobic exercise protocol three sessions a week. In the baseline, after completing the exercise protocol and after 4 wk of detraining, all the parameters were measured. In the CPP and healthy groups, all the parameters were measured in all three stages. To measure adiponectin, resistin, and TNF-α, the ELISA method was used. LH and FSH were measured by electrochemiluminescence immunoassay. White blood cell counts were analyzed by an automated blood cell counter. Repeated-measures ANOVA was used to analyze the results. CPP girls have lower adiponectin ( P = 0.01) and higher TNF-α levels ( P = 0.001) than healthy girls. In the CPP + EX group, after 12 wk, body weight and fat mass decreased, and adiponectin increased significantly ( P = 0.02). Resistin ( P = 0.02), TNF-α ( P = 0.02), neutrophils ( P = 0.01), and signs of puberty significantly ( P < 0.05) decreased. After detraining, no significant change was observed except TNF-α, which increased significantly ( P = 0.03). In the CPP group, no significant change was observed in any of the parameters; only LH ( P = 0.0001) and uterine length and ovarian volume ( P = 0.003, P = 0.001) decreased after 12 and 16 wk, respectively. Aerobic exercise can have a positive effect on the state of inflammation and pubertal signs. Positive effects remain after 4 wk of detraining.

Effectiveness of Pelvic Ultrasonography in the Diagnosis of Central Precocious Puberty and Its Differentiation from Similar Conditions

Background: Differentiation of patients with central precocious puberty (CPP) from healthy individuals and patients with CPP-like conditions [isolated premature thelarche (IPT) and isolated premature adrenarche (IPA)] is important for selecting an appropriate treatment. The gonadotropin-releasing hormone stimulation test is used as the gold standard for differentiating CPP from other conditions. Despite its high specificity, this test has disadvantages, such as low sensitivity, time-consuming sampling, and need for multiple blood samples. Objectives: This study aimed to investigate the use of pelvic ultrasonography (US) and its parameters in distinguishing CPP patients from those with similar conditions and healthy individuals. Patients and Methods: In this case-control study, a total of 183 patients, who were referred to the endocrinology department of Ali Asghar Hospital in Tehran, Iran for the evaluation of CPP, were recruited cconsecutively from 2015 to 2019. All the participants were Iranians and classified based on the clinical and laboratory findings. Pelvic US parameters were evaluated in all groups. One-way analysis of variance (ANOVA) was used to compare the mean values of continuous variables between the groups. Moreover, a post-hoc test was performed for pairwise comparisons between the groups if the result of ANOVA test was statistically significant. Finally, the receiver-operating characteristic (ROC) curve analysis was performed to determine the best cutoff points for US parameters. Results: Of 183 children, 62 were allocated to the control group (33.87%), 93 to the CPP group (50.81%), 16 to the IPT group (8.74%), and 12 to the IPA group (6.55%). The results showed no significant difference between the groups regarding chronological age and body mass index, while the bone age (107.76 ± 19.81 months) (P &lt; 0.001) and height (129.53 ± 8.97 cm) were significantly higher in the CPP group compared to the other groups (P = 0.003). All US parameters were significantly different between the CPP and control groups. There were also significant differences between CPP patients and those with IPT and IPA in terms of all parameters, except for the cervical anteroposterior diameter and ovarian volume. The best parameters for differentiating CPP from other conditions were the uterine volume (cutoff value, 1.40; 75.27% sensitivity; 75.56% specificity), uterine transverse diameter (cutoff value, 13.5 mm; 72.04% sensitivity; 71.11% specificity), and fundus/cervix (F/C) ratio (cutoff value, 0.98; 78.49% sensitivity; 70% specificity). Conclusion: The pelvic US parameters can improve the diagnosis of CPP and play an auxiliary role in distinguishing the treatment needed. Based on the findings, the best diagnostic parameter and its cutoff value can vary depending on ethnicity and type of study.

Türkiye’nin Trakya bölgesinde erken prepubertal gelişim ile takip edilen 367 çocuğun biyokimyasal klinik ve etiyolojik özellikleri

Background: Appearance of menarche before nine years of age, secondary sex characteristics before 8 in girls and 9 in boys is defined as Precocious Puberty (PP).&#x0D; Objective: The aim of this study was to describe etiologies, clinical findings, and compare anthropometric properties and biochemical characteristics of children with PP.&#x0D; Methods: In this single-centre study, 367 patients of whom medical records were reviewed diagnosed as premature thelarche (PT), premature adrenarche (PA), Central PP (CPP), and peripheral PP (PPP). The diagnosis was based on clinical, laboratory, and radiologic investigations and their follow-up.&#x0D; Results: During six years, 349 girls (%95,1) and 18 boys (%4,9) diagnosed as PP. The most common etiologies were CPP;127 (%34,6), PT;117 (%31,9), PA;112(%30,5) and PPP 11(%3), respectively. CPP group had significantly higher levels of height, weight, body mass index (BMI) and obesity/overweight incidence, estradiol (E2), basal luteinizing hormone (LH), peak LH, and peak LH/ follicle-stimulating hormone (FSH) ratio and higher uterine dimensions compared to the PT group while the PT group had significantly higher levels of peak FSH compared to the CPP group (p

Relationship between prolactin level and puberty in girls with early breast development.

Prolactin (PRL) stimulates the mammary glands development; however, it also inhibits gonadotropin-releasing hormone (GnRH) secretion. We evaluated the relationship between PRL levels and puberty in girls with precocious breast development. This study included 244 girls with breast development < 8 years of age. Patients were categorized as central precocious puberty (CPP) [peak luteinizing hormone (LH) levels≥ 5 IU/L after GnRH stimulation] versus non-CPP (NPP) group. High PRL was defined as serum PRL > 17.9ng/mL. High PRL was more common in NPP than in CPP group (17.6 vs. 8.1%, p=0.025), although mean PRL levels did not differ. In NPP group, the high PRL group had lower peak LH/follicle-stimulating hormone (FSH) ratio, and later LH peak time after GnRH stimulation than normal PRL group (all p<0.05). PRL levels of the subgroups according to the peak LH time (15, 30, 45, 60, and 90min after GnRH stimulation) were different in NPP group, but not in CPP group. PRL levels tended to be higher as the peak LH time was delayed. High PRL was associated with decreased odds for CPP (OR=0.42, p=0.043). Girls with NPP showed higher proportion of high PRL than CPP group. High PRL group showed more features of prepubertal response in NPP group, and associated with decreased odds for CPP, suggesting the possibility of PRL role on breast development while suppressing hypothalamic-pituitary-gonadal axis activation in NPP girls.

Central precocious puberty during COVID-19 pandemic and sleep disturbance: an exploratory study

BackgroundIncreased incidence of central precocious puberty (CPP) after coronavirus infectious disease-19 lockdown has been reported. Our study aims in investigating changes in CPP rates and in sleep patterns in CPP and healthy controls.MethodsCPP were retrospectively evaluated from April 2020 to April 2021. Parents of girls diagnosed with CPP during lockdown and of matched healthy controls filled out a questionnaire about sleep disturbances (SDSC questionnaire) and sleep schedules.ResultsThirty-five CPP and 37 controls completed the survey. Incidence of new CPP cases significantly increased in 2020–2021 compared to 2017–2020 (5:100 vs 2:100, p = 0.02). Sleep disturbance rates did not differ between CPP and healthy controls before lockdown. During lockdown, CPP reported higher rates of sleep disturbs for total score (p = 0.005), excessive somnolence (p = 0.049), sleep breathing disorders (p = 0.049), and sleep–wake transition disorders (p = 0.005). Moreover, CPP group more frequently shifted toward later bedtime (p = 0.03) during lockdown compared to controls. Hours of sleep and smartphone exposure around bedtime did not differ between groups.ConclusionsOur study confirms the observation of increased incidence of CPP after lockdown measures. Additionally, CPP showed higher rates of sleep disturbances and later bedtime compared to controls. The causality link between sleep disturbances and CPP should be further investigated to gain knowledge in this association.