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Expert Review of Endocrinology &... Mar 2019Precocious puberty (PP) is one of the most common reasons for referral to pediatric endocrinologists. Gonadotropin-releasing hormone analogs (GnRHas) are the gold... (Review)
Review
INTRODUCTION
Precocious puberty (PP) is one of the most common reasons for referral to pediatric endocrinologists. Gonadotropin-releasing hormone analogs (GnRHas) are the gold standard for the treatment of central precocious puberty (CPP) and have an impressive record of safety and efficacy. However, ongoing refinements in diagnosis and management continue to lead to important advancements in clinical care.
AREAS COVERED
The aim of this review is to cover current considerations and controversies regarding the diagnosis of CPP, as well as new findings in regards to etiology and treatment modalities.
EXPERT COMMENTARY
There is emerging evidence of monogenic etiologies of CPP and significant progress in the expansion of newer formulations of GnRHas. Despite these exciting developments, areas of uncertainty in the diagnosis and treatment of CPP remain. While long-term outcomes of patients treated for CPP are encouraging, only short-term follow-up is available with respect to the newer extended release GnRHa preparations, and how they compare with historically used formulations is unknown. A particular shortage of information exists pertaining to CPP in boys and regarding the psychological implications of PP in girls, and more research is needed. Continued investigation will yield new insights into the underlying genetics and optimal treatment strategies for CPP.
Topics: Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious; Risk Factors; Treatment Outcome
PubMed: 30763521
DOI: 10.1080/17446651.2019.1575726 -
Pediatric Annals Jan 2023
Topics: Rats; Humans; Animals; Puberty, Precocious; Endocrinologists; Screen Time; Gonadotropin-Releasing Hormone
PubMed: 36625799
DOI: 10.3928/19382359-20221206-01 -
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 -
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 2022To compared the incidence rates and clinical features of precocious girls before and during the COVID-19 pandemic among Shanghai school-aged girls, and explored the...
OBJECTIVE
To compared the incidence rates and clinical features of precocious girls before and during the COVID-19 pandemic among Shanghai school-aged girls, and explored the potential mechanisms.
METHODS
This cross-sectional study collected medical data about precocious girls between 2016 and 2020 from Shanghai Children's Medical Center. Data of inpatient precocious girls from March to August in 2016-2019 (n=246) and 2020 (n=237) were collected. Subjects with abnormal brain and pituitary gland MRI reports, other endocrine diseases or chronic diseases were excluded. Finally, 209 precocious girls were included in the 2016-2019 group and 191 precocious girls were include in the 2020 group. Monthly incidence rates and clinical features were compared between before and during the COVID-19 pandemic. Linear regression models were used to examine the associations between biomarkers to explore the potential mechanisms.
RESULTS
Monthly incidence rates of precocious puberty in outpatient girls from March to December 2020 (0.44-1.36%) and in inpatient girls from March to August 2020 (27.04-47.83%) were higher than those in 2016-2019 (0.30-0.52% and 10.53-18.42%, respectively). Serum concentrations of GnRH were higher in the 2020 group than in the 2016-2019 group (2.81 vs 1.99 mg/L). Serum concentrations of MKRN3 (1.02 vs 1.93 ng/ml) and ghrelin (0.38 vs 0.88 ng/ml) were lower in the 2020 group than in the 2016-2019 group. Moreover, the serum concentration of ghrelin was positively associated with the serum concentration of MKRN3 [0.891 (, 0.612, 1.171); 0.001].
CONCLUSIONS
These findings suggest an increased incidence of precocious puberty during the COVID-19 pandemic among Shanghai school-aged girls, which may be associated with decreased serum concentrations of MKRN3 and ghrelin, and indicated ghrelin as a potential regulatory mechanism of puberty.
Topics: COVID-19; Child; China; Cross-Sectional Studies; Female; Ghrelin; Humans; Pandemics; Puberty, Precocious; Ubiquitin-Protein Ligases
PubMed: 35392135
DOI: 10.3389/fendo.2022.839895 -
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 -
BMC Pediatrics Sep 2023The purpose of this study is to explore the related factors of precocious puberty in children.
BACKGROUND
The purpose of this study is to explore the related factors of precocious puberty in children.
METHODS
1239 children who underwent physical examination in our hospital from January 2020 to December 2022 were analyzed, including 198 precocious children and 1041 normal children. According to the age of 198 precocious children and 1041 normal children, 205 normal children were selected, and the remaining 836 normal children were excluded. They were divided into precocious group and normal group. The general data of the two groups were recorded. Logistic regression was used to analyze the influencing factors of precocious puberty in children.
RESULTS
There were statistically significant differences (P < 0.05) between the two groups in sex, bone age, daily exercise time, E2, FSH, LH, leptin, mother's menarche time, living environment, consumption of nutritional supplements, consumption of foods containing pigments and preservatives, consumption of high-protein foods, and sleeping time. The multifactor logistic regression analysis shows that the risk factors of children's precocious puberty included gender (female), bone age (> 10 years old), and daily exercise time (< 0.9 h), E2 (≥ 66.00pmol/L), FSH (≥ 6.00U/L), LH (≥ 3.50U/L), leptin (≥ 8.00 µ G/L), mother's menarche time (< 12 years old), living environment (chemical industry zone), consumption of nutritional supplements (often), consumption of high-protein food (often), and sleep time (< 10 h).
CONCLUSION
In conclusion, children's gender, bone age, exercise habits, E2, FSH, LH, leptin, mother's menarche time, living environment, eating habits, sleep time and other factors are closely related to precocious puberty in children. Reminding parents to actively prevent related factors in clinical work is helpful to prevent the occurrence of precocious puberty in children.
Topics: Humans; Child; Female; Leptin; Puberty, Precocious; Risk Factors; Dietary Supplements; Follicle Stimulating Hormone
PubMed: 37697362
DOI: 10.1186/s12887-023-04265-x -
British Medical Journal (Clinical... Feb 1983
Topics: Adolescent; Child; Cyproterone; Female; Humans; Male; Medroxyprogesterone; Pituitary Hormone-Releasing Hormones; Puberty, Precocious
PubMed: 6402194
DOI: 10.1136/bmj.286.6366.664 -
Journal of Clinical Research in... Aug 2022Early puberty is development of secondary sex characteristics earlier than the expected normal age range. We subjectively observed an increased frequency of early...
OBJECTIVE
Early puberty is development of secondary sex characteristics earlier than the expected normal age range. We subjectively observed an increased frequency of early puberty during the Coronavirus disease-2019 (COVID-19) lockdown and aimed to show the clinical, demographic characteristics of the cases and the change in its incidence.
METHODS
Female patients with central precocious puberty (CPP, n=28) and rapidly progressive early puberty (RPEP, n=61), presenting to our clinic before (January 2019-March 2020) and during the COVID-19 pandemic (April 2020-June 2021) were included.
RESULTS
Among 28 CPP cases, six (21%) presented before the pandemic lockdown, whereas 22 (79%) were diagnosed during the COVID-19 pandemic lockdown. While RPEP was seen in 16 (26%) patients before the pandemic, 45 (74%) patients were diagnosed during the lockdown period. Presentation with menarche was seen in 15 RPEP patients; two (13%) were in the prepandemic period and 13 (87%) were in the lockdown period. Chronological age, bone age, bone age to chronological age ratio, height, weight, and body mass index standard deviation scores of patients with RPEP and CPP were similar between the prepandemic and pandemic period.
CONCLUSION
In this cohort, the frequency of CPP and RPP cases were significantly (p<0.001) increased during the COVID-19 pandemic, possibly due to environmental changes.
Topics: COVID-19; Communicable Disease Control; Female; Gonadotropin-Releasing Hormone; Humans; Menarche; Pandemics; Puberty, Precocious
PubMed: 35633642
DOI: 10.4274/jcrpe.galenos.2022.2022-12-11