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Endocrinology and Metabolism Clinics of... Jun 2024Premature pubarche (PP) is a common and usually benign variant of normal puberty most often seen in 5-year-old to 9-year-old children. Some providers routinely order... (Review)
Review
Premature pubarche (PP) is a common and usually benign variant of normal puberty most often seen in 5-year-old to 9-year-old children. Some providers routinely order laboratory testing and a bone age to try to rule out other diagnoses including nonclassic congenital adrenal hyperplasia and gonadal or adrenal tumors. I review the natural history of PP and studies which suggest that without clinical features such as rapid growth and progression or genital enlargement, it is unlikely that a treatable condition will be found. Therefore it is recommended that patients with PP not undergo testing unless there are red flags at the time of the initial visit.
Topics: Humans; Puberty, Precocious; Child; Female; Child, Preschool
PubMed: 38677863
DOI: 10.1016/j.ecl.2024.02.001 -
Italian Journal of Pediatrics Apr 2022Increased incidence of central precocious puberty (CPP) after coronavirus infectious disease-19 lockdown has been reported. Our study aims in investigating changes in...
BACKGROUND
Increased 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.
METHODS
CPP 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.
RESULTS
Thirty-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.
CONCLUSIONS
Our 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.
Topics: COVID-19; Communicable Disease Control; Female; Humans; Pandemics; Puberty, Precocious; Retrospective Studies; Sleep; Sleep Wake Disorders
PubMed: 35461296
DOI: 10.1186/s13052-022-01256-z -
Frontiers in Endocrinology 2023Prader-Willi syndrome (PWS, OMIM176270) is a rare genetic disorder with recognizable dysmorphic features and multisystemic consequences such as endocrine, neurocognitive... (Review)
Review
Prader-Willi syndrome (PWS, OMIM176270) is a rare genetic disorder with recognizable dysmorphic features and multisystemic consequences such as endocrine, neurocognitive and metabolic ones. Although most patients with Prader-Willi syndrome exhibit hypogonadotropic hypogonadism, there is variability regarding sexual maturation, with precocious puberty occurring in rare cases. Our aim is to elaborate a thorough review of Prader-Willi patients with central precocious puberty, in order to raise awareness of such cases and to enhance our knowledge regarding the diagnosis and prompt treatment of this particular PWS patients.
Topics: Humans; Prader-Willi Syndrome; Puberty, Precocious; Sexual Maturation; Hypogonadism; Knowledge
PubMed: 37251677
DOI: 10.3389/fendo.2023.1150323 -
Archives of Endocrinology and Metabolism Aug 2019Pubertal timing in humans is determined by complex interactions including hormonal, metabolic, environmental, ethnic, and genetic factors. Central precocious puberty... (Review)
Review
Pubertal timing in humans is determined by complex interactions including hormonal, metabolic, environmental, ethnic, and genetic factors. Central precocious puberty (CPP) is defined as the premature reactivation of the hypothalamic-pituitary-gonadal axis, starting before the ages of 8 and 9 years in girls and boys, respectively; familial CPP is defined by the occurrence of CPP in two or more family members. Pioneering studies have evidenced the participation of genetic factors in pubertal timing, mainly identifying genetic causes of CPP in sporadic and familial cases. In this context, rare activating mutations were identified in genes of the kisspeptin excitatory pathway (KISS1R and KISS1 mutations). More recently, loss-of-function mutations in two imprinted genes (MKRN3 and DLK1) have been identified as important causes of familial CPP, describing novel players in the modulation of the hypothalamic-pituitary-gonadal axis in physiological and pathological conditions. MKRN3 mutations are the most common cause of familial CPP, and patients with MKRN3 mutations present clinical features indistinguishable from idiopathic CPP. Meanwhile, adult patients with DLK1 mutations present high frequency of metabolic alterations (overweight/obesity, early onset type 2 diabetes and hyperlipidemia), indicating that DLK1 may be a novel link between reproduction and metabolism. Arch Endocrinol Metab. 2019;63(4):438-44.
Topics: Calcium-Binding Proteins; Gene Silencing; Humans; Intercellular Signaling Peptides and Proteins; Kisspeptins; Membrane Proteins; Methylation; Mutation; Phenotype; Puberty, Precocious; Receptors, Kisspeptin-1; Ribonucleoproteins; Ubiquitin-Protein Ligases
PubMed: 31460623
DOI: 10.20945/2359-3997000000164 -
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 -
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 -
The Journal of International Medical... May 2021To explore self-consciousness and depression in children with precocious puberty (PP) and analyse its effect on children of both sexes.
OBJECTIVE
To explore self-consciousness and depression in children with precocious puberty (PP) and analyse its effect on children of both sexes.
METHODS
Sixty children with PP and 60 non-PP children matched for sex and age participated in the study. Children were assessed using the Birleson Depression Self-Rating Scale for Children and the Piers-Harris Children's Self-Concept Scale.
RESULTS
There were significant differences in physical appearance and attributes, anxiety, happiness and satisfaction between PP children and non-PP children. PP children had significantly higher depression than non-PP children. In the PP group, girls were significantly more prone to anxiety and unhappiness than boys. Conclusion: There were sex differences in the effect of PP on children's self-consciousness, and girls were more prone to anxiety and unhappiness. More attention should be paid to improving the physical and mental health of children with PP.
Topics: Anxiety; Child; Consciousness; Depression; Female; Humans; Male; Puberty, Precocious; Self Concept
PubMed: 34057841
DOI: 10.1177/03000605211020227 -
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 -
International Journal of Environmental... Apr 2022In the COVID-19 pandemic, there was an increase in consultations for precocious puberty. We aim to analyze differences in female puberty before and during the COVID-19...
In the COVID-19 pandemic, there was an increase in consultations for precocious puberty. We aim to analyze differences in female puberty before and during the COVID-19 pandemic. A cross-sectional analytical study was designed at the Pediatric Endocrinology Clinic of the University Hospital of the Federal University of Maranhão in São Luis, Brazil. We included 55 girls with precocious puberty, 22 who started puberty during the pandemic and 33 who started puberty before the pandemic. Clinical, anthropometric, laboratory and imaging variables were compared between groups. Statistics were performed to determine if there was a statistical difference between the groups. Girls with puberty during the pandemic had higher Z-scores for weight (1.08 ± 1.29 versus 0.69 ± 0.83; = 0.04), lower ovarian volume (1.88 ± 0.95 versus 3.15 ± 2.31; = 0.01), and smaller differences between thelarche noticed by the parents and the diagnosis (6.63 ± 5.21 versus 12.15 ± 9.96; = 0.02). The association between precocious puberty during the pandemic with higher Z-scores for weight, lower ovarian volume, and a reduction in the time between the perception of pubertal findings by parents and the diagnosis suggests the influence of the pandemic on the normal time of puberty.
Topics: COVID-19; Child; Cross-Sectional Studies; Female; Humans; Male; Pandemics; Puberty; Puberty, Precocious
PubMed: 35457600
DOI: 10.3390/ijerph19084733 -
Biomedicine & Pharmacotherapy =... Dec 2022Precocious puberty in children is one of the common endocrine diseases in paediatrics. Epidemiological surveys have shown that the number of children with precocious... (Review)
Review
Precocious puberty in children is one of the common endocrine diseases in paediatrics. Epidemiological surveys have shown that the number of children with precocious puberty has significantly increased globally. Precocious puberty negatively affects the physical and mental health of children and may increase the risk of hypertension, diabetes, obesity and infertility in adulthood. Therefore, the initiating factors of adolescence have become core issues in the study of sexual development in children. Owing to developments in molecular genetics, many studies have been able to show that precocious puberty is mostly resulted in autosomal inheritance. For instance, makorin ring finger protein 3 gene (MKRN3) may be implicated in familial CPP. Gonadotropin-releasing hormone agonist (GnRHa) is the gold standard for treatment, but its safety still requires long-term evaluation and management. Traditional medicinal plants have been used in clinical treatments and in exploring novel treatment methods. From the collected datas, in Asia, traditional Chinese medicine treatment is based on the principles of nourishing Yin, lowering fire and draining fire from the liver to help precocious children and alleviate or delay the onset of precocious puberty by medicinal plants such as Anemarrhena asphodeloides Bge., Phellodendron amurense Rupr., Rehmannia glutinosa and Poria cocos Wolf. They play an important role in exploring the pharmacological mechanisms of precocious puberty treatment effects and drug development. Therefore, by elucidating the occurrence and development of precocious puberty, this review provides novel and valuable insights of paediatric endocrine therapy accessing the published researches on the effectiveness of traditional herbal medicine in the treatment of precocious puberty and its therapeutic mechanisms.
Topics: Child; Humans; Puberty, Precocious; Plants, Medicinal; Gonadotropin-Releasing Hormone; Medicine, Traditional; Ubiquitin-Protein Ligases
PubMed: 36411607
DOI: 10.1016/j.biopha.2022.113907