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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 -
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 -
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 -
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 -
Best Practice & Research. Clinical... Aug 2018Central precocious puberty (CPP) results from early activation of the hypothalamic - pituitary -gonadal (HPG) axis and follows the same sequence as normal puberty. While... (Review)
Review
Central precocious puberty (CPP) results from early activation of the hypothalamic - pituitary -gonadal (HPG) axis and follows the same sequence as normal puberty. While many factors involved in pubertal initiation remain poorly understood, the kisspeptin system is known to play a key role. Currently, mutations in the kisspeptin system, MKRN3, and DLK1 have been identified in sporadic and familial cases of CPP. The diagnosis is based on physical exam findings indicating advancing puberty and on laboratory tests confirming central HPG axis activation. GnRH analogs are the mainstay of treatment and are used with the goal of height preservation. Newer extended release formulations continue to be developed. Currently there is no evidence of long-term complications associated with treatment. However, many areas remain to be explored such as targeted therapies and aspects of clinical management. Further investigation into psychological effects and additional data regarding long-term outcomes, particularly in males, is needed.
Topics: Calcium-Binding Proteins; Child; Female; Gonadotropin-Releasing Hormone; Humans; Intercellular Signaling Peptides and Proteins; Kisspeptins; Male; Membrane Proteins; Mutation; Puberty, Precocious; Ribonucleoproteins; Ubiquitin-Protein Ligases
PubMed: 30086862
DOI: 10.1016/j.beem.2018.05.008 -
Hormone Research in Paediatrics 2019This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses... (Review)
Review
This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses topics related to changes in GnRHa usage in children and adolescents over the last decade. Topics related to the use of GnRHa in precocious puberty include diagnostic criteria, globally available formulations, considerations of benefit of treatment, monitoring of therapy, adverse events, and long-term outcome data. Additional sections review use in transgender individuals and other pediatric endocrine related conditions. Although there have been many significant changes in GnRHa usage, there is a definite paucity of evidence-based publications to support them. Therefore, this paper is explicitly not intended to evaluate what is recommended in terms of the best use of GnRHa, based on evidence and expert opinion, but rather to describe how these drugs are used, irrespective of any qualitative evaluation. Thus, this paper should be considered a narrative review on GnRHa utilization in precocious puberty and other clinical situations. These changes are reviewed not only to point out deficiencies in the literature but also to stimulate future studies and publications in this area.
Topics: Adolescent; Child; Female; Gonadotropin-Releasing Hormone; Humans; Male; Puberty, Precocious
PubMed: 31319416
DOI: 10.1159/000501336 -
Best Practice & Research. Clinical... Sep 2021Sexual maturation in humans is characterized by a unique individual variability. Pubertal onset is a highly heritable polygenic trait but it is also affected by... (Review)
Review
Sexual maturation in humans is characterized by a unique individual variability. Pubertal onset is a highly heritable polygenic trait but it is also affected by environmental factors such as obesity or endocrine disrupting chemicals. The last 30 years have been marked by a constant secular trend toward earlier age at onset of puberty in girls and boys around the world. More recent data, although more disputed, suggest an increased incidence in idiopathic central precocious puberty. Such trends point to a role for environmental factors in pubertal changes. Animal data suggest that the GnRH-neuronal network is highly sensitive to endocrine disruption during development. This review focuses on the most recent data regarding secular trend in pubertal timing as well as potential new epigenetic mechanisms explaining the developmental and transgenerational effects of endocrine disrupting chemicals on pubertal timing.
Topics: Animals; Endocrine Disruptors; Female; Humans; Male; Obesity; Puberty; Puberty, Precocious; Sexual Maturation
PubMed: 34563408
DOI: 10.1016/j.beem.2021.101579 -
American Family Physician Nov 2017Disorders of puberty can profoundly impact physical and psychosocial well-being. Precocious puberty is pubertal onset before eight years of age in girls and before nine... (Review)
Review
Disorders of puberty can profoundly impact physical and psychosocial well-being. Precocious puberty is pubertal onset before eight years of age in girls and before nine years of age in boys. Patients with early isolated pubertal changes, prepubertal linear growth, and no worrisome neurologic symptoms typically have a benign pattern of development and should be monitored in the appropriate clinical context. Among patients with true precocious puberty, or full activation of the hypothalamic-pituitary-gonadal axis, most girls have an idiopathic etiology, whereas it is commonly due to identifiable pathology on imaging in boys. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); thyroid function testing; and bone age radiography. Brain magnetic resonance imaging should be performed in girls younger than six years, all boys with precocious puberty, and children with neurologic symptoms. Delayed puberty is the absence of breast development in girls by 13 years of age and absence of testicular growth to at least 4 mL in volume or 2.5 cm in length in boys by 14 years of age. Constitutional delay of growth and puberty is a common cause of delayed puberty; however, functional or persistent hypogonadism should be excluded. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); and bone age radiography. Abnormal growth velocity necessitates assessment of serum thyroid function, prolactin, and insulinlike growth factor I. Boys 14 years and older and girls 13 years and older may benefit from sex steroid treatment to jump-start puberty. Referral to a pediatric endocrinologist may be warranted after the initial evaluation.
Topics: Adolescent; Age of Onset; Body Height; Child; Estradiol; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Male; Menarche; Puberty, Precocious; Sexual Maturation
PubMed: 29094880
DOI: No ID Found -
Clinical Endocrinology Oct 2021Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. The current state of knowledge of the complex neural... (Review)
Review
Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. The current state of knowledge of the complex neural network acting at the level of the hypothalamus and the GnRH neuron to control puberty onset has expanded, particularly in the context of molecular interactions. Along with these advances, the knowledge of pubertal physiology and pathophysiology has also increased. This review focuses on regulatory abnormalities occurring at the hypothalamic level of the HPG axis to cause CPP. The clinical approach to diagnosis of puberty and pubertal disorders is also reviewed, with a particular focus on aetiologies of CPP. The recent identification of mutations in MKRN3 and DLK1 in familial as well sporadic forms of CPP has changed the state of the art of the approach to patients with CPP. Genetic advances have also had important repercussions beyond consideration of puberty alone. Syndromic disorders and central nervous system lesions associated with CPP are also discussed. If untreated, these conditions may lead to adverse physical, psychosocial and medical outcomes.
Topics: Gonadotropin-Releasing Hormone; Humans; Mutation; Puberty; Puberty, Precocious; Ubiquitin-Protein Ligases
PubMed: 33797780
DOI: 10.1111/cen.14475 -
Journal of Clinical Research in... 2009This review describes several aspects of the management of precocious puberty (PP) and variants in girls and boys. PP is characterized by early pubertal changes,... (Review)
Review
This review describes several aspects of the management of precocious puberty (PP) and variants in girls and boys. PP is characterized by early pubertal changes, acceleration of growth velocity and rapid bone maturation that often result in reduced adult height. Onset of pubertal signs before the age of 8 years in girls and 9 years in boys should always be evaluated carefully. The main principles of therapy are to stop the progression of secondary sex characteristics and menses (in girls), to increase final adult height, to promote psychosocial well-being, and to treat the underlying cause if known.
Topics: Breast; Child; Female; Gonadotropins; Humans; Hypothyroidism; Male; Puberty; Puberty, Precocious; Reference Values
PubMed: 21274291
DOI: 10.4274/jcrpe.v1i4.3