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Frontiers in Endocrinology 2022Childhood obesity is a major public health problem worldwide, and the relationship between obesity and central precocious puberty has long been confirmed, however, the... (Review)
Review
Childhood obesity is a major public health problem worldwide, and the relationship between obesity and central precocious puberty has long been confirmed, however, the mechanisms underlying this association remain elusive. This review provides an overview of the recent progress regarding how childhood obesity impacts on hypothalamic-pituitary-gonadal axis and pubertal onset, focusing on adipokines (leptin and ghrelin), hormone (insulin), and lipid (ceramide), as well as critical signaling pathways (AMPK/SIRT, mTOR) that integrate the peripheral metabolism and central circuits. Notably, prevention of obesity and CPP is beneficial for the adult life of the children, thus we further summarize the potential strategies in treating and preventing childhood obesity and CPP. The updated understanding of metabolic stress and pediatric endocrine disease will arise the attention of society, and also contribute to preventing more serious comorbidities in the later period of life in children.
Topics: Adult; Child; Humans; Puberty, Precocious; Pediatric Obesity; Adipokines; Insulin; Ceramides
PubMed: 36465655
DOI: 10.3389/fendo.2022.1056871 -
The Lancet. Diabetes & Endocrinology Mar 2016Central precocious puberty results from the premature activation of the hypothalamic-pituitary-gonadal axis. It mimics physiological pubertal development, although at an... (Review)
Review
Central precocious puberty results from the premature activation of the hypothalamic-pituitary-gonadal axis. It mimics physiological pubertal development, although at an inappropriate chronological age (before 8 years in girls and 9 years in boys). It can be attributable to cerebral congenital malformations or acquired insults, but the cause in most cases in girls remains unknown. MKRN3 gene defects have been identified in familial disease, with important basic and clinical results. Indeed, genetic analysis of this gene should be included in the routine clinical investigation of familial and idiopathic cases of central precocious puberty. Gonadotropin-releasing hormone agonists are the gold-standard treatment. The assessment and management of this disease remain challenging for paediatric endocrinologists. In this Series paper, we describe current challenges involving the precise diagnosis and adequate treatment of this disorder.
Topics: Child; Female; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Puberty, Precocious; Ribonucleoproteins; Ubiquitin-Protein Ligases
PubMed: 26852255
DOI: 10.1016/S2213-8587(15)00380-0 -
Hormone Research in Paediatrics 2022Spanning from bench to bedside, the history of normal and precocious puberty is characterized by a series of remarkable advances that have illuminated reproductive... (Review)
Review
Spanning from bench to bedside, the history of normal and precocious puberty is characterized by a series of remarkable advances that have illuminated reproductive physiology and profoundly impacted clinical care. Early recognition of the hypothalamic and pituitary control of ovarian and testicular function led to the identification of GnRH as the key driver of pubertal onset. Decades later, discovery of the kisspeptin system further refined our understanding of human reproductive neuroendocrinology. Development of long-acting analogs of GnRH revolutionized the treatment of precocious puberty worldwide and ushered in the current era of an ever-expanding therapeutic armamentarium. Identification of monogenic etiologies of precocious puberty has further illustrated the exquisite complexity that comprises neurosecretory modulation of the hypothalamic GnRH neuron and may well lead to exciting novel targeted therapies.
Topics: Humans; Gonadotropin-Releasing Hormone; Neuroendocrinology; Neurons; Puberty; Puberty, Precocious
PubMed: 36446322
DOI: 10.1159/000526464 -
Minerva Pediatrica Dec 2020Precocious puberty (PP) is a common reason for referral to pediatric endocrinology clinics, with a strong female predominance. PP is a broad term encompassing benign... (Review)
Review
Precocious puberty (PP) is a common reason for referral to pediatric endocrinology clinics, with a strong female predominance. PP is a broad term encompassing benign variants of normal development, gonadotropin-dependent precious puberty (GDPP), and gonadotropin-independent precocious puberty (GIPP). This article reviews the definitions, physiology, clinical presentation, evaluation and treatment of these conditions.
Topics: Child; Female; Gonads; Humans; Hypothalamo-Hypophyseal System; Male; Puberty; Puberty, Precocious; Sex Factors
PubMed: 32748611
DOI: 10.23736/S0026-4946.20.05970-8 -
Indian Journal of Pediatrics Jun 2023Precocious puberty is a common presentation to pediatricians with a significant overlap between physiology and pathology. While most girls with precocious puberty have... (Review)
Review
Precocious puberty is a common presentation to pediatricians with a significant overlap between physiology and pathology. While most girls with precocious puberty have no identifiable cause, boys are more likely to have a pathological cause. The trend of earlier onset of thelarche with slow pubertal tempo has led to a significant increase in the number of girls presenting with precocious puberty. Advanced growth, bone age, uterine maturation, and elevated LH suggest rapidly progressive puberty. The critical issues in evaluating a child presenting with precocious puberty include its confirmation, exclusion of physiological variants, identification of the cause, and determining the need for treatment. Step-wise evaluation with emphasis on clinical parameters provides cost-effective assessment. Gonadotropin-releasing hormone (GnRH) analogs remain the mainstay of treatment for central precocious puberty but should be restricted to individuals with rapidly progressive puberty and compromised final height. The management of rarer forms of peripheral precocious puberty (McCune Albright syndrome, congenital adrenal hyperplasia, and testotoxicosis) involves using experimental drugs under the guidance of specialists.
Topics: Child; Male; Female; Humans; Puberty, Precocious; Gonadotropin-Releasing Hormone; Adrenal Hyperplasia, Congenital
PubMed: 37074536
DOI: 10.1007/s12098-023-04554-4 -
Best Practice & Research. Clinical... Apr 2018Over the past 20 years, a clear secular trend toward the earlier onset of puberty has been described. A better knowledge should help clinicians attempting to define both... (Review)
Review
Over the past 20 years, a clear secular trend toward the earlier onset of puberty has been described. A better knowledge should help clinicians attempting to define both precocious and delayed puberty (PP and DP, respectively). The definition of PP for girls is the appearance of secondary sex characteristics development before the age of 8 years, while DP is based on the absence of thelarche at the age of 13 years. Regarding PP, one should clinically distinguish between true precocious puberty, i.e., complete or central PP, and incomplete PP, which refers to premature thelarche, premature pubarche, and isolated menarche. Evaluation of girls of PP requires careful examination of the clinical expression, a GnRH test, and imaging of the central neurosystem. GnRH analog is considered the gold standard treatment of central precocious puberty. Peripheral PP should be managed according to the underlying causes. DP is suspected in girls with no breast development by the age of 13 years, or absence of menarche at 15 years with secondary sex characteristics. The clinical examination along with endocrine, radiological, and genetic investigation should be able to identify girls with permanent hypogonadism as opposed to those with transitory hypogonadism, who undergo spontaneous but DP. Estrogen therapy should be discussed according to the causes of DP. In all cases, emotional and psychosocial disorders should be considered for these girls with disorders of puberty.
Topics: Adolescent; Child; Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Menarche; Puberty, Delayed; Puberty, Precocious
PubMed: 29422239
DOI: 10.1016/j.bpobgyn.2017.11.004 -
The Lancet. Child & Adolescent Health Dec 2023Central precocious puberty (CPP) refers to early activation of the hypothalamic-pituitary-gonadal (HPG) axis and is manifested by breast development in girls or... (Review)
Review
Central precocious puberty (CPP) refers to early activation of the hypothalamic-pituitary-gonadal (HPG) axis and is manifested by breast development in girls or testicular enlargement in boys before the normal physiological age ranges. CPP can be precipitated by intracranial pathology, exposure to high levels of sex steroids, or environmental risk factors, but most cases are idiopathic. Monogenic causes have also been identified. In this Review, we summarise pathophysiology, risk factors, diagnosis, and management of CPP. Concern for CPP should prompt referral to paediatric endocrinology where diagnosis is confirmed by clinical, biochemical, radiological, and genetic testing. CPP is treated with a gonadotropin-releasing hormone analogue, the primary aims of which are to increase adult height and postpone development of secondary sexual characteristics to an age that is more commensurate with peers. Although long-term outcomes of treatment with gonadotropin-releasing hormone analogues are reassuring, additional research on the psychological effect of CPP is needed.
Topics: Adult; Child; Female; Humans; Male; Gonadotropin-Releasing Hormone; Puberty, Precocious
PubMed: 37973253
DOI: 10.1016/S2352-4642(23)00237-7 -
BMJ (Clinical Research Ed.) Jan 2020
Review
Topics: Anthropometry; Counseling; Gonadotropins; Humans; Medical History Taking; Primary Health Care; Puberty, Precocious; Referral and Consultation
PubMed: 31932347
DOI: 10.1136/bmj.l6597 -
Frontiers in Endocrinology 2022During the year 2020, the COVID-19 pandemic rapidly became a severe health emergency worldwide. In order to contrast the spread of the novel SARS-CoV-2, many countries... (Review)
Review
During the year 2020, the COVID-19 pandemic rapidly became a severe health emergency worldwide. In order to contrast the spread of the novel SARS-CoV-2, many countries implemented extraordinary restrictive measures, such as a strict lockdown and school closures. The pandemic had a great impact on children and adolescents' daily life, leading to a much more sedentary lifestyle, to larger use of electronic devices and to an increase in stress-related symptoms. These conspicuous changes acted as disruptors of children's normal development. Since the beginning of the pandemic, many studies reported an increase in the number of precocious puberty cases as well as a faster progression rate of puberty itself, if compared to the pre-pandemic years. In this review, our aim was to evaluate the incidence of new cases of early and precocious puberty during the COVID-19 pandemic, analyzing variations in the timing of puberty and in pubertal progression rate, and to investigate the role of environmental and lifestyle factors during the pandemic in modulating the physiopathology of pubertal development. While a direct effect of SARS-CoV-2 infection remains, at the moment, a remote hypothesis, both physical and psychological factors related to the pandemic seem to have a role in triggering GnRH pulsatile secretion leading to earlier pubertal onset. It is indeed important to stress the need to clarify the exact role of COVID-19 in early pubertal onset comparing data from all over the world; long-term comprehensive studies are also pivotal to explain whether this phenomenon will continue while we resume pre-pandemic habits.
Topics: Child; Adolescent; Humans; Puberty, Precocious; COVID-19; Pandemics; SARS-CoV-2; Communicable Disease Control
PubMed: 36699035
DOI: 10.3389/fendo.2022.1107911 -
European Journal of Pediatrics Oct 2021The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in... (Review)
Review
The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. It is classified as central precocious puberty when premature maturation of the hypothalamic-pituitary-gonadal axis occurs, and as peripheral precocious puberty when there is excessive secretion of sex hormones, independent of gonadotropin secretion. Precocious sexual maturation is more common in girls, generally central precocious puberty of idiopathic origin. In boys, it tends to be linked to central nervous system abnormalities. Clinical evaluation should include a detailed history and physical examination, including anthropometric measurements, calculation of growth velocity, and evaluation of secondary sexual characteristics. The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. Hormonal assessment and imaging are required for diagnosis and identification of the etiology. Genetic testing should be considered if there is a family history of precocious puberty or other clinical features suggestive of a genetic syndrome. Long-acting gonadotropin-releasing hormone analogs are the standard of care for central precocious puberty management, while peripheral precocious puberty management depends on the etiology.Conclusion: The aim of this review is to address the epidemiology, etiology, clinical assessment, and management of precocious sexual maturation. What is Known: • The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. • Long-acting gonadotropin-releasing hormone agonist (GnRHa) is the standard of care for CPP management, and adequate hormone suppression results in the stabilization of pubertal progression, a decline in growth velocity, and a decrease in bone age advancement. What is New: • Most cases of precocious sexual maturation are gonadotropin-dependent and currently assumed to be idiopathic, but mutations in genes involved in pubertal development have been identified, such as MKRN3 and DLK1. • A different preparation of long-acting GnRHa is now available: 6-month subcutaneous injection.
Topics: Child; Female; Gonadotropin-Releasing Hormone; Humans; Male; Puberty; Puberty, Precocious; Sexual Maturation; Ubiquitin-Protein Ligases
PubMed: 33745030
DOI: 10.1007/s00431-021-04022-1