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Pediatric Research Dec 2022Attention deficit-hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children; however, studies delineating the association between...
BACKGROUND
Attention deficit-hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children; however, studies delineating the association between ADHD and central precocious puberty are limited. This study aimed to understand whether children with ADHD are at a higher risk of central precocious puberty.
METHODS
This population-based retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan to investigate the association between ADHD and the incidence of central precocious puberty between 2000-2015. We identified ADHD individuals treated with methylphenidate, atomoxetine or not. The control cohort consisted of individuals without ADHD. The outcome measure was central precocious puberty diagnosis.
RESULTS
Among 290,148 children (mean age: 5.83 years), central precocious puberty incidence was 4.24 and 1.95 per 10 person-years in the ADHD and control groups, respectively. Children with ADHD treated with medication had a higher risk than those without ADHD. However, medication use did not affect the incidence of central precocious puberty among children with ADHD.
CONCLUSION
This study showed an association between ADHD and a higher risk of central precocious puberty. Early referral of children with ADHD to a pediatric endocrinologist for evaluation may facilitate correct diagnoses and early interventions.
IMPACT
ADHD is associated with a higher risk of central precocious puberty. This study provides relevant findings, as it is the first nationwide, population-based cohort study to investigate the association between ADHD and the risk of central precocious puberty with a 15-year follow-up. Early referral of children with ADHD to a pediatric endocrinologist for the evaluation of suspected precocious puberty could facilitate correct diagnosis. Early intervention treatment with gonadotropin-releasing hormone agonist might improve final height in children with central precocious puberty.
Topics: Child; Humans; Child, Preschool; Puberty, Precocious; Attention Deficit Disorder with Hyperactivity; Cohort Studies; Gonadotropin-Releasing Hormone; Retrospective Studies
PubMed: 35347278
DOI: 10.1038/s41390-022-02028-5 -
Endocrine Practice : Official Journal... Apr 2024This study aims to explore the significant impact of environmental chemicals on disease development, focusing on their role in developing metabolic and endocrine... (Review)
Review
OBJECTIVE
This study aims to explore the significant impact of environmental chemicals on disease development, focusing on their role in developing metabolic and endocrine diseases. The objective is to understand how these chemicals contribute to the increasing prevalence of precocious puberty, considering various factors, including epigenetic changes, lifestyle, and emotional disturbances.
METHODS
The study employs a comprehensive review of descriptive observational studies in both human and animal models to identify a degree of causality between exposure to environmental chemicals and disease development, specifically focusing on endocrine disruption. Due to ethical constraints, direct causation studies in human subjects are not feasible; therefore, the research relies on accumulated observational data.
RESULTS
Puberty is a crucial life period with marked physiological and psychological changes. The age at which sexual characteristics develop is changing in many regions. The findings indicate a correlation between exposure to endocrine-disrupting chemicals and the early onset of puberty. These chemicals have been shown to interfere with normal hormonal processes, particularly during critical developmental stages such as adolescence. The research also highlights the interaction of these chemical exposures with other factors, including nutritional history, social and lifestyle changes, and emotional stress, which together contribute to the prevalence of precocious puberty.
CONCLUSION
Environmental chemicals significantly contribute to the development of certain metabolic and endocrine diseases, particularly in the rising incidence of precocious puberty. Although the evidence is mainly observational, it adequately justifies regulatory actions to reduce exposure risks. Furthermore, these findings highlight the urgent need for more research on the epigenetic effects of these chemicals and their wider impact on human health, especially during vital developmental periods.
Topics: Adolescent; Animals; Humans; Endocrine Disruptors; Endocrine System; Endocrine System Diseases; Puberty; Puberty, Precocious; Observational Studies as Topic
PubMed: 38185329
DOI: 10.1016/j.eprac.2024.01.006 -
The Journal of Clinical Endocrinology... Jan 2021The 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...
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.
Topics: Age Determination by Skeleton; Biomarkers; Body Mass Index; Case-Control Studies; Child; Female; Fibronectins; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Puberty, Precocious; Turkey
PubMed: 33034623
DOI: 10.1210/clinem/dgaa720 -
Frontiers in Endocrinology 2023Some studies have investigated the association between vitamin D levels and precocious puberty (PP) but with limited sample sizes and inconsistent conclusions across... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Some studies have investigated the association between vitamin D levels and precocious puberty (PP) but with limited sample sizes and inconsistent conclusions across studies.
METHODS
Until July 2022, a comprehensive electronic search of works of literature was conducted in MEDLINE, Web of Science, and CNKI (Chinese National Knowledge Infrastructure). A systematic review and meta-analysis of 15 case-control studies with 2145 cases and 2063 controls was conducted to explore the relationship between vitamin D and PP. Stratified analyses by year of publication, country, diagnosis category of PP, child's sex, and methods of 25(OH)D test were conducted.
RESULTS
There was a negative correlation between 25(OH)D concentrations and PP in all study populations (SMD = -1.046, 95%CI = -1.366, -0.726). The pooled SMD remained significant in Chinese studies (SMD = -1.113, 95%CI = -0.486, -0.741), studies published before or after 2018 (SMD = -0.9832 and -1.185, 95%CI = -2.044, -1.133 and -1.755, -0.726), studies with female children (SMD = -1.114, 95%CI = -1.446, -0.781), and studies using electrochemiluminescence to detect 25(OH)D (SMD = -0.999, 95%CI = -1.467, -0.531). Vitamin D deficiency also increased the risk of PP (OR = 1.531, 95%CI = 1.098, 2.134). Unfortunately, heterogeneity was high in all analyses, and there was some publication bias.
CONCLUSION
This systematic review and meta-analysis demonstrated an association between vitamin D and precocious puberty. We recommend more high-quality studies, especially prospective cohort studies with big sample sizes or some randomized controlled intervention trials, to validate the reliability of the results.
Topics: Child; Humans; Female; Vitamin D; Puberty, Precocious; Prospective Studies; Reproducibility of Results; Vitamins
PubMed: 38116317
DOI: 10.3389/fendo.2023.1298374 -
Acta Bio-medica : Atenei Parmensis Dec 2023The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to...
BACKGROUND
The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors.
METHODS
We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk.
RESULTS
Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders.
CONCLUSION
Monitoring and early diagnosis of these conditions are of paramount importance for successful management.
Topics: Female; Humans; Male; Child; Diabetes Mellitus, Type 2; Gonadotropin-Releasing Hormone; Puberty, Precocious; Obesity; Puberty
PubMed: 38054666
DOI: 10.23750/abm.v94i6.15316 -
Italian Journal of Pediatrics Mar 2020Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms...
BACKGROUND
Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms underlying the increase in pulsatile GnRH secretion at puberty have yet to be fully elucidated. The aim of our research was to verify the role of KISSR1 (previously named GPR54) and MKRN3 genes on pubertal timing.
METHODS
We analyzed the DNA sequence of these genes in 13 girls affected by central precocious puberty (CPP) who showed onset of puberty before 8 years of age, and in 6 girls affected by early puberty (EP) between 8 and 10 years of age.
RESULTS
Direct sequencing of the KISS1R (GPR54) gene revealed two SNPs. One SNP is a missense variant (rs 350,132) that has been previously reported in connection to CPP in Korean girls. The other variant that we found in the GPR54 gene (rs764046557) was a missense SNP located in exon 5 at position 209 of the aminoacid. We identified this variant in only one CPP patient. Automatic sequencing of MKRN3 in all patients revealed three variants in eight subjects. In 6 out of 19 (31.5%) patients (3/13 CPP patients and 3/6 EP patients) we found the synonymous variant c.663C > T (rs2239669). Another synonymous variant (rs140467331) was found in one of our CPP patients, as well as one missense variant (rs760981395) in another CPP patient.
CONCLUSION
In conclusion, we identified sequence variations of the KISS1R and MKRN3 genes, two of the most frequent genetic causes of ICPP. Our results suggest that these variants might be inducible factors in the pathogenesis of CPP.
Topics: Age Factors; Child; Female; Humans; Italy; Mutation, Missense; Polymorphism, Single Nucleotide; Puberty, Precocious; Receptors, Kisspeptin-1; Sexual Development; Ubiquitin-Protein Ligases
PubMed: 32228714
DOI: 10.1186/s13052-020-0808-6 -
Problemy Endokrinologii May 2023In 90% cases of girls and 25-60% cases of boys the cause of gonadotropin-dependent precocious puberty (PP) is unclear. Up to 25-27.5% of gonadotropin-dependent PP cases...
BACKGROUND
In 90% cases of girls and 25-60% cases of boys the cause of gonadotropin-dependent precocious puberty (PP) is unclear. Up to 25-27.5% of gonadotropin-dependent PP cases are monogenic and suggest autosomal-dominant inheritance with incomplete sex-dependent penetrance. To date, mutations in genes KISS1, KISS1R, MKRN3, DLK1 have been described as causal variants leading to precocious hypothalamic-pituitary axis activation in childhood. Genetic testing in patients with hereditary forms of PP can expand our knowledge of underlying molecular mechanisms of the disease and it is also necessary for genetic counselling.
AIM
To study clinical features and genetic characteristics of patients with idiopathic gonadotropin-dependent precocious puberty.
MATERIALS AND METHODS
A group of patients with idiopathic gonadotropin-dependent precocious puberty and positive family history (early or precocious puberty) was examined. Laboratory and instrumental diagnostic tests, full-exome sequencing (NGS, next-generation sequencing) were provided for all patients.
RESULTS
The study included 30 patients (29 girls, 1 boy) with idiopathic gonadotropin-dependent precocious puberty. The median of patients age at the time of the examination was 7,2 years [6,5; 7,7]. Positive family history presented in all cases: in 40% of patients on father's side, in 37% - on mother's side, in 23% of patients PP was diagnosed in siblings. The fullexome sequencing was conducted to 21 patients: in 61,9% of cases (95% CI [40;79]) nucleotide variants were identified in genes, associated with gonadotropin-dependent precocious puberty. MKRN3 gene defect was detected in most cases (77% cases (95% CI [49; 92]), which consistent with international data on its highest prevalence in the monogenic forms of PP. In 23% of cases (95% CI [7; 50]) nucleotide variants were identified in other candidate genes associated with neuroontogenesis and neuroendocrine regulation mechanisms of hypothalamic-pituitary axis.
CONCLUSION
Our study confirms that detailed family history data in children with PP provides a rational approach to molecular-genetic testing. Data of inheritance pattern and clinical manifestations will simplify the diagnosis of hereditary forms of disease and enhance genetic counselling of families, followed by timely examination and administration of pathogenetic therapy.
Topics: Male; Child; Female; Humans; Puberty, Precocious; Mutation; Genes, Tumor Suppressor; Genetic Testing; Gonadotropins; Ubiquitin-Protein Ligases
PubMed: 37448272
DOI: 10.14341/probl13215 -
Frontiers in Endocrinology 2023Since the outbreak of COVID-19 pandemic, several centers of pediatric endocrinology worldwide have observed a significant increase in the number of girls presenting with...
OBJECTIVE
Since the outbreak of COVID-19 pandemic, several centers of pediatric endocrinology worldwide have observed a significant increase in the number of girls presenting with precocious or early puberty. We aimed to compare the incidence rates of female precocious puberty before and during the different phases of COVID-19 pandemic.
METHODS
We have retrospectively analyzed all the consultations recorded in the outpatient clinic database of the Endocrinology Unit of Bambino Gesù Children's Hospital, Rome, Italy, from the lockdown start in March 2020 up to September 2020, in comparison with the consultations recorded in the same months of 2019, 2021 and 2022. Age, height, weight, body mass index, Tanner's pubertal stage and bone age at presentation, birth weight, ethnicity, family history of central precocious puberty (CPP), maternal age at menarche, history of adoption were retrieved from clinical records. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) both at baseline and after gonadotropin-releasing hormone (GnRH) stimulation, and basal estradiol levels were collected.
RESULTS
In 2019, 78 girls with suspected precocious puberty were referred for endocrinological consultation, compared to 202 girls in 2020, 158 girls in 2021 and 112 girls in 2022. A significant increase in the proportion of girls diagnosed with rapidly progressive CPP was observed in 2020, compared to 2019 (86/202 18/78, p<0.01). In the following periods of 2021 and 2022, a gradual decrease in the number of cases of progressive CPP was evident, so much that the number of cases was not significantly different from that observed in 2019 (56/158 in 2021 and 35/112 in 2022, p=0.054 and p=0.216 respectively, compared to 2019).
CONCLUSIONS
Our research suggests that drastic lifestyle changes, such as those imposed by COVID-19 lockdown, and the consequent stress may affect the regulation of pubertal timing. The remarkable increase in CPP cases observed during the 2020 first pandemic wave seems to be reduced in 2021 and 2022, concurrently with the progressive resumption of daily activities. These data seem to support the hypothesis of a direct relationship between profound life-style changes related to the pandemic and the rise in precocious puberty cases.
Topics: Child; Female; Humans; Puberty, Precocious; Pandemics; Retrospective Studies; COVID-19; Communicable Disease Control; Italy
PubMed: 36926039
DOI: 10.3389/fendo.2023.1132769 -
Endocrinology and Metabolism Clinics of... Jun 2024
Topics: Humans; Puberty, Precocious; Puberty; Female; Puberty, Delayed
PubMed: 38677874
DOI: 10.1016/j.ecl.2024.03.002 -
Sleep Medicine Reviews Oct 2022Narcolepsy type 1 (NT1) is a rare neurological sleep disorder triggered by postnatal loss of the orexin/hypocretin neuropeptides. Overweight/obesity and precocious... (Review)
Review
Narcolepsy type 1 (NT1) is a rare neurological sleep disorder triggered by postnatal loss of the orexin/hypocretin neuropeptides. Overweight/obesity and precocious puberty are highly prevalent comorbidities of NT1, with a close temporal correlation with disease onset, suggesting a common origin. However, the underlying mechanisms remain unknown and merit further investigation. The main question we address in this review is whether the occurrence of precocious puberty in NT1 is due to the lack of orexin/hypocretin or rather to a wider hypothalamic dysfunction in the context of neuroinflammation, which is likely to accompany the disease given its autoimmune origins. Our analysis suggests that the suspected generalized neuroinflammation of the hypothalamus in NT1 would tend to delay puberty rather than hastening it. In contrast, that the brutal loss of orexin/hypocretin would favor an early reactivation of gonadotropin-releasing hormone (GnRH) secretion during the prepubertal period in vulnerable children, leading to early puberty onset. Orexin/hypocretin replacement could thus be envisaged as a potential treatment for precocious puberty in NT1. Additionally, we put forward an alternative hypothesis regarding the concomitant occurrence of sleepiness, weight gain and early puberty in NT1.
Topics: Child; Gonadotropin-Releasing Hormone; Humans; Narcolepsy; Neuroinflammatory Diseases; Neuropeptides; Orexins; Puberty, Precocious
PubMed: 36096986
DOI: 10.1016/j.smrv.2022.101683