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Pediatric Research Apr 2024Obesity is an important cause for the precocious or early puberty. However, the association between obesity-related loci and the risk of precocious puberty as well as...
BACKGROUND
Obesity is an important cause for the precocious or early puberty. However, the association between obesity-related loci and the risk of precocious puberty as well as the effect of gene-environment interaction are unclear, especially in the Chinese children population.
METHODS
This was a case-control study using baseline data from two cohorts and hospital cases in China. 15 SNPs loci and several environmental factors were included in the analysis of 1201 participants. Chi-square test and logistic regression were used to analyze the association between SNPs and precocious puberty. Additionally, exploratory factor analysis was conducted on 13 environmental variables, and then to explore their interaction with genes on precocious puberty.
RESULTS
The effect allele C of rs571312, and G of rs12970134 MC4R were associated with precocious puberty in girls with obesity. Regarding the gene-environment interaction, we found that when girls were in the high socioeconomic status, the rs571312 (OR: 3.996; 95% CI: 1.694-9.423) and rs12970134 (OR: 3.529; 95% CI: 1.452-8.573) risk genotypes had a greater effect on precocious puberty.
CONCLUSIONS
The obesity risk gene polymorphisms MC4R rs571312 and rs12970134 were associated with precocious puberty in Chinese girls with obesity, and girls with risk genotypes and high socioeconomic status should be given extra attention.
IMPACT
This is the first study that identified the association between rs571312 and rs12970134 of MC4R gene and precocious puberty in Chinese children. We found that when girls were in the high socioeconomic status, the risk genotypes of rs571312 and rs12970134 had a greater effect on precocious puberty. The results of this study have great public health implications. It is recommended that girls who are in high socioeconomic status and have a high genetic risk for early sexual maturity should closely monitor their pubertal development and consider early intervention strategies.
PubMed: 38649724
DOI: 10.1038/s41390-024-03168-6 -
Endokrynologia Polska 2024Central precocious puberty (CPP) is a prevalent endocrine disorder. Research has indicated that pubertal development is linked to nutritional metabolism. Irisin, a novel...
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.
Topics: Child; Humans; Male; Body Mass Index; Case-Control Studies; Fibronectins; Puberty, Precocious
PubMed: 38646987
DOI: 10.5603/ep.98509 -
Neurological Sciences : Official... Apr 2024We present the case of a 6-year-old girl who initially presented with acute pelvic pain, ultimately diagnosed with imperforate hymen leading to hematocolpos....
We present the case of a 6-year-old girl who initially presented with acute pelvic pain, ultimately diagnosed with imperforate hymen leading to hematocolpos. Further investigation revealed additional clinical features including academic struggles, mood swings, and cutaneous findings, prompting consideration of a neurocutaneous syndrome. Magnetic Resonance Imaging (MRI) revealed features consistent with tuberous sclerosis complex (TSC), including radial migration lines in the subcortical white matter and an incidental arachnoid cyst. Notably, this case exhibited a unique presentation with absence of typical TSC findings such as subependymal nodules or cortical tubers. Additionally, precocious puberty, rarely associated with TSC, was observed, suggesting a potential link between hypothalamic lesions and hormonal imbalance. This case underscores the importance of comprehensive evaluation in pediatric patients presenting with seemingly unrelated symptoms, as it may unveil underlying conditions necessitating tailored management strategies.
PubMed: 38637341
DOI: 10.1007/s10072-024-07523-7 -
Child's Nervous System : ChNS :... Jul 2024Craniopharyngioma is a common intracranial tumour in children. Clinical manifestations are related to hypothalamic/pituitary deficiencies, visual impairment, and... (Review)
Review
BACKGROUND
Craniopharyngioma is a common intracranial tumour in children. Clinical manifestations are related to hypothalamic/pituitary deficiencies, visual impairment, and increased intracranial pressure. Defects in pituitary function cause shortages of growth hormone, gonadotropin, corticotropin, thyrotropin, and vasopressin, resulting in short stature, delayed puberty, feebleness, lethargy, polyuria, etc. However, manifestations involving precocious puberty (PP) are rare.
CASE REPORT
In both patients, surgical resection was performed after the diagnosis of craniopharyngioma, and breast development occurred postoperatively at one month in one patient and at one year and three months in the other patient. Central precocious puberty (CPP) was diagnosed via relevant examinations. Leuprorelin was injected subcutaneously every 28 days, and changes in height, weight, bone age, gonadal ultrasound and sex hormones were recorded. During the follow-up of the two children, the sex hormone levels were significantly reduced, and significant acceleration in bone age was not observed.
CONCLUSIONS
CPP was induced by craniopharyngioma surgery, and treatment with gonadotropin-releasing hormone analogues (GnRHa) inhibited sexual development and bone age progression. More attention should be given to monitoring for CPP during long-term follow-up of craniopharyngiomas in the clinic.
Topics: Humans; Craniopharyngioma; Leuprolide; Pituitary Neoplasms; Postoperative Complications; Puberty, Precocious
PubMed: 38635073
DOI: 10.1007/s00381-024-06406-8 -
Frontiers in Endocrinology 2024The first phase of the GAIL study ("Girls treated with an Aromatase Inhibitor and Leuprorelin," ISRCTN11469487) has shown that the combination of anastrozole and...
Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study.
BACKGROUND
The first phase of the GAIL study ("Girls treated with an Aromatase Inhibitor and Leuprorelin," ISRCTN11469487) has shown that the combination of anastrozole and leuprorelin for 24 months is safe and effective in improving the predicted adult height (PAH) in girls with early puberty and compromised growth prediction by +1.21 standard deviation score (SDS; +7.51 cm) compared to inhibition of puberty alone, +0.31 SDS (+1.92 cm).
OBJECTIVES AND HYPOTHESES
In the second phase of the GAIL study, we assessed the adult height (AH)/near-adult height (NAH) at the end of the first phase and, in addition, the efficacy of anastrozole monotherapy thereafter in further improving NAH.
METHODS
We measured the AH (age 16.5 years)/NAH [bone age (BA), 15 years] of the 40 girls included, divided into two matched groups: group A (20 girls on anastrozole + leuprorelin) and group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups: A1 and A2. Group A1 ( = 10), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until BA 14 years, with a 6-month follow-up. Group A2 ( = 10) and group B ( = 20), who received only the combined treatment and leuprorelin alone, respectively, were recalled for evaluation of AH/NAH.
RESULTS
AH or NAH exceeded the PAH at the completion of the 2-year initial phase of the GAIL study in all groups, but the results were statistically significant only in group A1: NAH-PAH group A1, +3.85 cm (+0.62 SDS, = 0.01); group A2, +1.6 cm (+0.26 SDS, = 0.26); and group B, +1.7 cm (+0.3 SDS, = 0.08). The gain in group A1 was significantly greater than that in group A2 ( = 0.04) and in group B ( = 0.03). Anastrozole was determined to be safe even as monotherapy in Group A1.
CONCLUSIONS
In early-maturing girls with compromised growth potential, the combined treatment with leuprorelin and anastrozole for 2 years or until the age of 11 years resulted in a total gain in height of +9.7 cm when continuing anastrozole monotherapy until the attainment of NAH, as opposed to +7.4 cm if they do not continue with the anastrozole monotherapy and +3.6 cm when treated with leuprorelin alone. Thus, the combined intervention ends at the shortest distance from the target height if continued with anastrozole monotherapy until BA 14 years.
Topics: Female; Adult; Humans; Adolescent; Child; Anastrozole; Leuprolide; Aromatase Inhibitors; Puberty, Precocious; Puberty; Body Height
PubMed: 38628587
DOI: 10.3389/fendo.2024.1366970 -
Hormone Research in Paediatrics Apr 2024Ovarian Sertoli cell tumors represent a subset of sex cord stromal tumors and are exceedingly rare in prepubertal children. Here, we report a girl with vaginal bleeding...
INTRODUCTION
Ovarian Sertoli cell tumors represent a subset of sex cord stromal tumors and are exceedingly rare in prepubertal children. Here, we report a girl with vaginal bleeding due to a Sertoli cell tumor who was originally thought to have McCune-Albright syndrome (MAS).
CASE PRESENTATION
A previously healthy girl presented at age 2 years 6 months with breast development and vaginal bleeding. On exam, she had Tanner 4 breasts, Tanner 1 pubic hair, estrogenized vaginal mucosa, and a café-au-lait macule. Laboratory studies revealed an elevated estradiol with suppressed gonadotropins and negative tumor markers. Her bone age was advanced by more than 3 years. Pelvic ultrasound (US) revealed an enlarged uterus and a slightly larger left compared to right ovary. She was started on tamoxifen for presumed MAS. A repeat pelvic US 1 month later showed a heterogenous mass in the left ovary which was subsequently resected. Pathology revealed a Sertoli cell tumor, lipid-rich variant. Germline sequencing revealed a pathogenic STK11 variant, diagnostic for Peutz-Jeghers syndrome (PJS).
CONCLUSION
The findings in our patient were strikingly similar to those encountered in MAS. To our knowledge, our patient is the youngest ever reported to present with precocious puberty due to a Sertoli cell tumor in the setting of PJS.
PubMed: 38626741
DOI: 10.1159/000538945 -
Journal of Pediatric Endocrinology &... May 2024To understand possible predictors of the onset of menses after gonadotropin-releasing hormone agonist treatment cessation in girls with central precocious puberty (CPP). (Clinical Trial)
Clinical Trial
OBJECTIVES
To understand possible predictors of the onset of menses after gonadotropin-releasing hormone agonist treatment cessation in girls with central precocious puberty (CPP).
METHODS
This exploratory post hoc analysis of a phase 3 and 4 trial of girls with CPP treated with once-monthly intramuscular leuprolide acetate examined onset of menses after treatment completion using a time-to-event analysis. Pretreatment and end-of-treatment chronologic age (CA), bone age (BA)/CA ratio, and Tanner breast stage; pretreatment menses status; and end-of-treatment BA and body mass index (BMI) were studied as potential factors influencing the onset of menses.
RESULTS
Median time to first menses after stopping treatment was 18.3 months among 35 girls (mean age at onset of treatment, 6.8 years) examined. Of 26 girls experiencing menses, 11 (42 %) menstruated at 16-21 months after stopping treatment. Most girls with pretreatment BA/CA≥1.4 started menstruating very close to 18 months after stopping treatment; those with less advanced BA/CA experienced menses at 9-18 months. End-of-treatment BA/CA≥1.2 was associated with a quicker onset of menses (14.5 vs. 18.5 months for BA/CA<1.2, p=0.006). End-of-treatment BA≥12 years predicted longer time to menses. No relationship with time to menses was observed for pretreatment menarche status, pretreatment or end-of-treatment Tanner breast stage (<3/≥3) or CA (<6/≥6 or ≤11/>11), or end-of-treatment BMI percentiles (<85.6/≥85.6 and <92.6/≥92.6).
CONCLUSIONS
Pretreatment menarche status or CA do not appear to predict onset of menses, but pre- and end-of-treatment BA/CA may be helpful in anticipating time to first menses after stopping treatment.
Topics: Child; Female; Humans; Age Determination by Skeleton; Body Mass Index; Follow-Up Studies; Gonadotropin-Releasing Hormone; Leuprolide; Menarche; Menstruation; Prognosis; Puberty, Precocious; Time Factors
PubMed: 38618862
DOI: 10.1515/jpem-2023-0543 -
Environmental Research Jul 2024The increasing prevalence of precocious puberty (PP) has emerged as a significant medical and social problem worldwide. However, research on the relationship between...
BACKGROUND AND AIM
The increasing prevalence of precocious puberty (PP) has emerged as a significant medical and social problem worldwide. However, research on the relationship between long-term air pollution exposure and PP has been relatively limited. We thus investigated the association between long-term air pollution exposure and the onset of PP in South Korea.
METHODS
We investigated a retrospective cohort using the Korea National Health Insurance Database. Six-year-old children born from 2007 to 2009 were examined (2013-2015). We included boys ≤10 years and girls aged ≤9 years who visited hospitals for early pubertal development, were diagnosed with PP per the ICD-10 (E228, E301, and E309), and received gonadotropin-releasing hormone agonist treatment. We analyzed data for boys up until 10 years old (60-month follow-up) and for girls up to 9 years old (48-month follow-up). We assessed the association between long-term air pollution exposure and the onset of PP using a Cox proportional hazard model. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) per 1 μg/m increase in fine particulate matter (PM) and particulate matter (PM) and per 1 ppb increase in sulfur dioxide (SO), nitrogen dioxide (NO), and ozone (O).
RESULTS
This study included 1,205,784 children aged six years old between 2013 and 2015. A positive association was found between the 48-month moving average PM (HR: 1.019; 95% CI: 1.012, 1.027), PM (HR: 1.009; 95% CI: 1.006, 1.013), SO (HR: 1.037; 95% CI: 1.018, 1.055), and O (HR: 1.006; 95% CI: 1.001, 1.010) exposure and PP in girls but not boys.
CONCLUSIONS
This study provides valuable insights into the harmful effects of air pollution during childhood and adolescence, emphasizing that air pollution is a risk factor that should be managed and reduced.
Topics: Humans; Republic of Korea; Puberty, Precocious; Child; Female; Male; Air Pollution; Retrospective Studies; Air Pollutants; Particulate Matter; Environmental Exposure; Child, Preschool; Ozone
PubMed: 38614201
DOI: 10.1016/j.envres.2024.118916 -
Orphanet Journal of Rare Diseases Apr 2024Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or...
BACKGROUND
Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported.
RESULTS
Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR.
CONCLUSIONS
Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.
Topics: Male; Female; Humans; Child; Citrullinemia; Amino Acid Metabolism, Inborn Errors; Abnormalities, Multiple; Angelman Syndrome; Mitochondrial Membrane Transport Proteins
PubMed: 38610036
DOI: 10.1186/s13023-024-03148-3 -
Heliyon Apr 2024X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder caused by pathogenic variants in the gene. The symptoms include primary adrenal insufficiency (PAI),...
X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder caused by pathogenic variants in the gene. The symptoms include primary adrenal insufficiency (PAI), progressive spinal cord disease, inflammatory demyelinating cerebral disease, and primary hypogonadism. It is exceptionally rare that pediatric PAI is accompanied by central precocious puberty (CPP). The purpose of this study was to better understand the diversity of clinical manifestations of X-ALD and to identify the gene mutation in a case of a boy with X-ALD accompanied by CPP. We collected clinical, laboratory and imaging data, and used whole-exome sequencing (WES) analysis to evaluate the pathogenicity of the variant. We also predicted the potential deleterious effects of the novel mutation using Mutation Taster and generated three-dimensional protein structures using Swiss-Model and PyMOL Viewer software. The patient presented with PAI accompanied by CPP. Adrenal gland CT revealed adrenal hypoplasia. Gonadotropin-releasing hormone stimulation tests revealed CPP. WES revealed a novel variant (c.1376dup) in the gene, which resulted in a reading frameshift and a premature termination codon (p.Leu461ProfsTer95). Sanger sequencing confirmed that the variant was inherited from his heterozygous mother. Mutation Taster predicted that the variant could be harmful. The overall three-dimensional structures of the mutant wild-type proteins were visually distinct. Our results shed light on additional aspects of X-ALD. The premature activation of the hypothalamic-pituitary-gonadal axis may possibly be related to the pathogenic gene mutation.
PubMed: 38596053
DOI: 10.1016/j.heliyon.2024.e28987