Increased frequency of idiopathic central precocious puberty in girls during the COVID-19 pandemic: preliminary results of a tertiary center study

Objectives Recent studies have demonstrated an increase in the frequency of idiopathic central precocious puberty (CPP) during the severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic. We compared the demographic, anthropometric, and clinical characteristics of idiopathic CPP patients diagnosed during a one-year period of the COVID-19 pandemic with the characteristics of patients diagnosed during the same period in the previous three-years. Methods Demographic, clinical, anthropometric, and laboratory data of all patients diagnosed in our Pediatric Endocrinology clinic with idiopathic CPP during a one-year period of the COVID-19 pandemic (April 2020–March 2021) and a three-year period before the pandemic (April 2017–March 2020) were evaluated retrospectively. Results A total of 124 patients (124 girls, zero boys) diagnosed with idiopathic CPP were included in this study. Sixty-six patients in the three-year period before the COVID-19 pandemic (April 2017–March 2020) and 58 patients (46.8%) in the one-year period during the COVID-19 pandemic period (April 2020–March 2021) were diagnosed with idiopathic CPP. Conclusions This study’s findings suggest that the number of girls diagnosed with idiopathic CPP during the one-year study period during the pandemic was more than double that of any of the previous three-years.

The Study of the Pathogenesis of Idiopathic Central Precocious Puberty Based on Gut Microbiota

Object To analyze the correlation between gut microbiota (GM) and hyperandrogenemia, insulin resistance, carbohydrate metabolism, and explore whether the pathogenesis of idiopathic central precocious puberty (ICPP) and polycystic ovary syndrome (PCOS) is consistent based on GM. Methods In this study, we have recruited 27 ICPP (ICPP group) and 23 healthy children (healthy group), and collected the blood and fecal samples from the participants. Blood samples were tested for hormones, including the follicle-stimulating hormone, luteinizing hormone, estradiol, prolactin, and testosterone. DNA was extracted from fecal samples, and amplified and sequenced with 16S rDNA V3-V4 region. Finally, we annotated the sequencing results, counted the differences in hormone indicators and GM composition between the two groups, and analyzed the correlation with clinical indicators. At the same time, we reviewed the literature on GM and PCOS.Results Compared with the healthy group, the ICPP group exhibited significantly higher levels of the hormone and other indicators (P < 0.05). At the phylum level, the ICPP group showed significantly enriched Proteobacteria than the healthy group (4.85% vs 2.92%). At the genus level, the abundances of Roseburia and Prevotella were significantly higher in the ICPP group than those in the healthy group (7.55% vs 2.01%, 3.95% vs 0.19%), but Bacteroides were obviously decreased in the ICPP group (29.96% vs 44.91%). In addition, the potential associations underlying the sex hormonal secretion and the carbohydrate metabolism pathways of GM increased significantly in the ICPP group. Conclusion The alternations of GM in ICPP patients are closely related to carbohydrate metabolism, hyperandrogenism, and insulin resistance, indicating similar pathogenesis with polycystic ovary syndrome.

The Assessment of Brain Volume Differences in Idiopathic Central Precocious Puberty Girls; Comparison of Age-Matched Girls and Normal Puberty Girls

Objective: Although there have been several studies on the neuroanatomical changes in idiopathic central precocious puberty (ICPP), the association between each brain region and ICPP has not yet been clearly elucidated. This study aimed to evaluate the difference in brain structure in ICPP compared with age-matched healthy controls and normal puberty controls, and additionally the correlation between brain volume difference and the luteinizing hormone (LH). Materials and Methods: The study enrolled fifteen girls with ICPP, as well as 15 age-matched healthy girls and 15 normal puberty girls as controls. The subjects underwent a 1.5 Tesla Avanto MR Scanner. Anatomical T1-weighted images were acquired with a T1 spin-echo sequence. The volumes of total and regional brain were compared with each of the two control groups and analyzed through the paired T-test, and the brain region related to the peak LH level was also analyzed through a simple correlation test. Results: The mean age of the ICPP group, age-matched group, and puberty group were 8.0 ± 0.9 years, 7.8 ± 0.9 years, and 11.9 ± 0.9 years, respectively. In our findings, the regional cerebral volumes in ICPP were different from age-matched controls. Compared with controls, ICPP showed a significant increase in gray matter (GM) volumes (the medial prefrontal cortex, superior parietal gyrus, supramarginal gyrus, angular gyrus, postcentral gyrus, superior occipital gyrus, cuneus, hippocampus, parahippocampal gyrus, posterior cingulate gyrus (PCgG), cerebellar cortex (Cb)) and in white matter (WM) volumes (the insular, caudate, splenium of corpus callosum (p < 0.001)). Especially, the GM volumes of the PCgG (r = 0.57, p = 0.03) and Cb (r = 0.53, p = 0.04) were correlated positively with LH concentrations stimulated by the gonadotropin-releasing hormone agonist. Compared to the normal puberty control, no significant difference in GM volume was found. Conclusions: This study showed the overall brain volumetric differences between ICPP girls and age-matched controls using voxel-based morphometric analysis, and further showed the correlation between brain volume and the sex hormone in ICPP. Through a comparison between the two groups, the cerebral development pattern of ICPP is similar to that of normal puberty, and these local differences in cerebral volume may affect social and congenital changes. These findings will be useful for understanding the neuroanatomical mechanisms on the specific morphological variations associated with ICPP.

The study of the pathogenesis of idiopathic central precocious puberty based on gut microbiota

Object To analyze the correlation between gut microbiota (GM) and hyperandrogenemia, insulin resistance, carbohydrate metabolism, and explore whether the pathogenesis of idiopathic central precocious puberty (ICPP) and polycystic ovary syndrome (PCOS) is consistent based on GM. Methods In this study, we have recruited 27 ICPP (ICPP group) and 23 healthy children (healthy group), and collected the blood and fecal samples from the participants. Blood samples were tested for hormones, including the follicle-stimulating hormone, luteinizing hormone, estradiol, prolactin, and testosterone. DNA was extracted from fecal samples, and amplified and sequenced with 16S rDNA V3-V4 region. Finally, we annotated the sequencing results, counted the differences in hormone indicators and GM composition between the two groups, and analyzed the correlation with clinical indicators. At the same time, we reviewed the literature on GM and PCOS. Results Compared with the healthy group, the ICPP group exhibited significantly higher levels of the hormone and other indicators (P < 0.05). At the phylum level, the ICPP group showed significantly enriched Proteobacteria than the healthy group (4.85% vs 2.92%). At the genus level, the abundances of Roseburia and Prevotella were significantly higher in the ICPP group than those in the healthy group (7.55% vs 2.01%, 3.95% vs 0.19%), but Bacteroides were obviously decreased in the ICPP group (29.96% vs 44.91%). In addition, the potential associations underlying the sex hormonal secretion and the carbohydrate metabolism pathways of GM increased significantly in the ICPP group. Conclusion The alternations of GM in ICPP patients are closely related to carbohydrate metabolism, hyperandrogenism, and insulin resistance, indicating similar pathogenesis with polycystic ovary syndrome.

The Diagnostic Utility of the Basal Luteinizing Hormone Level and Single 60-Minute Post GnRH Agonist Stimulation Test for Idiopathic Central Precocious Puberty in Girls

ObjectiveThe present study aimed to assess the diagnostic utility of the Luteinizing hormone (LH) levels and single 60-minute post gonadotropin-releasing hormone (GnRH) agonist stimulation test for idiopathic central precocious puberty (CPP) in girls.MethodsData from 1,492 girls diagnosed with precocious puberty who underwent GnRH agonist stimulation testing between January 1, 2016, and October 8, 2020, were retrospectively reviewed. LH levels and LH/follicle-stimulating hormone (FSH) ratios were measured by immuno-chemiluminescence assay before and at several timepoints after GnRH analogue stimulation testing. Mann–Whitney U test, Spearman’s correlation, χ2 test, and receiver operating characteristic (ROC) analyses were performed to determine the diagnostic utility of these hormone levels.ResultsThe 1,492 subjects were split into two groups: an idiopathic CPP group (n = 518) and a non-CPP group (n = 974). Basal LH levels and LH/FSH ratios were significantly different between the two groups at 30, 60, 90, and 120 minutes after GnRH analogue stimulation testing. Spearman’s correlation analysis showed the strongest correlation between peak LH and LH levels at 60 minutes after GnRH agonist stimulation (r = 0.986, P &lt; 0.001). ROC curve analysis revealed that the 60-minute LH/FSH ratio yielded the highest consistency, with an area under the ROC curve (AUC) of 0.988 (95% confidence interval [CI], 0.982–0.993) and a cut-off point of 0.603 mIU/L (sensitivity 97.3%, specificity 93.0%). The cut-off points of basal LH and LH/FSH were 0.255 mIU/L (sensitivity 68.9%, specificity 86.0%) and 0.07 (sensitivity 73.2%, specificity 89.5%), respectively, with AUCs of 0.823 (95% CI, 0.799–0.847) and 0.843 (95% CI, 0.819–0.867), respectively.ConclusionsA basal LH value greater than 0.535 mIU/L can be used to diagnose CPP without a GnRH agonist stimulation test. A single 60-minute post-stimulus gonadotropin result of LH and LH/FSH can be used instead of a GnRH agonist stimulation test, or samples can be taken only at 0, 30, and 60 minutes after a GnRH agonist stimulation test. This reduces the number of blood draws required compared with the traditional stimulation test, while still achieving a high level of diagnostic accuracy.

The study of the pathogenesis of idiopathic central precocious puberty based on gut microbiota

Object To analyze the correlation between gut microbiota (GM) and hyperandrogenemia, insulin resistance, carbohydrate metabolism, and explore whether the pathogenesis of idiopathic central precocious puberty (ICPP) and polycystic ovary syndrome (PCOS) is consistent based on GM. Methods In this study, we have recruited 27 ICPP (ICPP group) and 23 healthy children (healthy group), and collected the blood and fecal samples from the participants. Blood samples were tested for hormones, including the follicle-stimulating hormone, luteinizing hormone, estradiol, prolactin, and testosterone. DNA was extracted from fecal samples, and amplified and sequenced with 16S rDNA V3-V4 region. Finally, we annotated the sequencing results, counted the differences in hormone indicators and GM composition between the two groups, and analyzed the correlation with clinical indicators. At the same time, we reviewed the literature on GM and PCOS. Results Compared with the healthy group, the ICPP group exhibited significantly higher levels of the hormone and other indicators (P < 0.05). At the phylum level, the ICPP group showed significantly enriched Proteobacteria than the healthy group (4.85% vs 2.92%). At the genus level, the abundances of Roseburia and Prevotella were significantly higher in the ICPP group than those in the healthy group (7.55% vs 2.01%, 3.95% vs 0.19%), but Bacteroides were obviously decreased in the ICPP group (29.96% vs 44.91%). In addition, the potential associations underlying the sex hormonal secretion and the carbohydrate metabolism pathways of GM increased significantly in the ICPP group. Conclusion The alternations of GM in ICPP patients are closely related to carbohydrate metabolism, hyperandrogenism, and insulin resistance, indicating similar pathogenesis with polycystic ovary syndrome.

Genetic factors of idiopathic central precocious puberty and their polygenic risk in early puberty

Objective: To investigate the genetic characteristics of idiopathic central precocious puberty (ICPP) and validate its polygenic risk for early puberty. Design and methods: A bootstrap subsampling and genome-wide association study was performed on Taiwanese Han Chinese girls comprising 321 ICPP patients and 148 controls. Using previous GWAS data on pubertal timing, a replication study was performed. A validation group was also investigated for the weighted polygenic risk score (wPRS) of the risk of early puberty. Results: A total of 105 SNPs for the risk of ICPP were identified, of which 22 yielded an area under the receiver operating characteristic curve of 0.713 for the risk of early puberty in the validation group. A replication study showed that 33 SNPs from previous GWAS data of pubertal timing were associated with the risk of ICPP (training group: P-value < 0.05). In the validation group, a cumulative effect was observed between the wPRS and the risk of early puberty in a dose-dependent manner [validation group: Cochran-Armitage trend test: P-value < 1.00E-04; wPRS quartile 2 (Q2) (odds ratio [OR] = 5.00, 95% confidence interval [CI]: 1.5516.16), and wPRS Q3 (OR = 11.67, 95% CI: 2.4455.83)]. Conclusions: This study reveals the ICPP genetic characteristics with 22 independent and 33 reported SNPs in the Han Chinese population from Taiwan. This study may contribute to understand the genetic features and underlying biological pathways that control pubertal timing and pathogenesis of ICPP and also to the identify of individuals with a potential genetic risk of early puberty.

The association between family impact and health-related quality of life of children with idiopathic central precocious puberty in Chongqing, China

Background Idiopathic central precocious puberty (ICPP) reduces patient health-related quality of life (HRQoL). The impacts of disease and treatment on families are also an important concern. This study aimed to assess the association between family impact and HRQoL of children with ICPP. Methods We conducted a case–control study in Chongqing, China. A case group of 134 children with ICPP aged 5–12 years and their caregivers was recruited from a children’s hospital in Chongqing. A total of 210 gender- and age-matched subjects from two primary schools were selected as controls. PedsQLTM4.0 Generic Core Scales (GCS) and PedsQL™ Family Impact Module (FIM) were used in this study. Results Children with ICPP scored lower than controls in all HRQoL domains except physical functioning. In particular, the two groups were significantly different in emotional functioning scores (d = 0.414, P < 0.001). Compared with controls, ICPP families had lower scores in all dimensions of the FIM scale (d = 0.288–1.030, all P < 0.05). Factors associated with HRQoL of ICPP patients included: age of patients, type of medical treatment, employment status of caregivers, educational level of caregivers, parent HRQoL and family functioning (all P < 0.05). Conclusions Children with ICPP demonstrated lower quality of life and greater family impact compared to healthy controls. In addition, less impact of disease on parent HRQoL and family functioning was associated with better HRQoL of ICPP patients, patients aged older, treated with drug combination, cared by employed or well-educated caregivers reported better HRQoL. Health care professionals should pay more attention to younger patients treated with GnRHa alone, and provide targeted interventions for caregivers depending on their demographic background to reduce family impact and thereby improve patient HRQoL.