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Endocrine Reviews Oct 2019This review presents a comprehensive discussion of the clinical condition of delayed puberty, a common presentation to the pediatric endocrinologist, which may present... (Review)
Review
This review presents a comprehensive discussion of the clinical condition of delayed puberty, a common presentation to the pediatric endocrinologist, which may present both diagnostic and prognostic challenges. Our understanding of the genetic control of pubertal timing has advanced thanks to active investigation in this field over the last two decades, but it remains in large part a fascinating and mysterious conundrum. The phenotype of delayed puberty is associated with adult health risks and common etiologies, and there is evidence for polygenic control of pubertal timing in the general population, sex-specificity, and epigenetic modulation. Moreover, much has been learned from comprehension of monogenic and digenic etiologies of pubertal delay and associated disorders and, in recent years, knowledge of oligogenic inheritance in conditions of GnRH deficiency. Recently there have been several novel discoveries in the field of self-limited delayed puberty, encompassing exciting developments linking this condition to both GnRH neuronal biology and metabolism and body mass. These data together highlight the fascinating heterogeneity of disorders underlying this phenotype and point to areas of future research where impactful developments can be made.
Topics: Animals; Epigenesis, Genetic; Female; Gonadotropin-Releasing Hormone; Humans; Male; Phenotype; Puberty, Delayed; Sex Characteristics
PubMed: 31220230
DOI: 10.1210/er.2018-00248 -
BMJ (Clinical Research Ed.) Oct 1992
Topics: Child; Child Development; Female; Growth Disorders; Humans; Male; Puberty, Delayed
PubMed: 1422357
DOI: 10.1136/bmj.305.6857.790 -
Frontiers in Endocrinology 2022Distinguishing between self limited delayed puberty (SLDP) and congenital hypogonadotropic hypogonadism (CHH) may be tricky as they share clinical and biochemical... (Review)
Review
Distinguishing between self limited delayed puberty (SLDP) and congenital hypogonadotropic hypogonadism (CHH) may be tricky as they share clinical and biochemical characteristics. and appear to lie within the same clinical spectrum. However, one is classically transient (SDLP) while the second is typically a lifetime condition (CHH). The natural history and long-term outcomes of these two conditions differ significantly and thus command distinctive approaches and management. Because the first presentation of SDLP and CHH is very similar (delayed puberty with low LH and FSH and low sex hormones), the scientific community is scrambling to identify diagnostic tests that can allow a correct differential diagnosis among these two conditions, without having to rely on the presence or absence of phenotypic red flags for CHH that clinicians anyway seem to find hard to process. Despite the heterogeneity of genetic defects so far reported in DP, genetic analysis through next-generation sequencing technology (NGS) had the potential to contribute to the differential diagnostic process between SLDP and CHH. In this review we will provide an up-to-date overview of the genetic architecture of these two conditions and debate the benefits and the bias of performing genetic analysis seeking to effectively differentiate between these two conditions.
Topics: Humans; Puberty, Delayed; Hypogonadism; Diagnosis, Differential
PubMed: 36726466
DOI: 10.3389/fendo.2022.1069741 -
Journal of the Endocrine Society Sep 2022A girl presenting with delayed puberty and elevated gonadotropins may have a range of conditions such as Turner syndrome (TS), primary ovarian insufficiency (POI), and...
A girl presenting with delayed puberty and elevated gonadotropins may have a range of conditions such as Turner syndrome (TS), primary ovarian insufficiency (POI), and 46,XY disorders of sexual development (DSD). An organized and measured approach to investigation can help reach a timely diagnosis. Management of young people often requires specialist multidisciplinary input to address the endocrine and nonendocrine features of these complex conditions, as well as the psychological challenges posed by their diagnosis. Next-generation sequencing within the research setting has revealed several genetic causes of POI and 46,XY DSD, which may further facilitate an individualized approach to care of these young people in the future. Pubertal induction is required in many and the timing of this may need to be balanced with other issues specific to the condition (eg, allowing time for information-sharing in 46,XY DSD, optimizing growth in TS). Shared decision-making and sign-posting to relevant support groups from the outset can help empower young people and their families to manage these conditions. We describe 3 clinical vignettes of girls presenting with delayed puberty and hypergonadotropic amenorrhea and discuss their clinical management in the context of current literature and guidelines.
PubMed: 35935072
DOI: 10.1210/jendso/bvac108 -
Journal of Pediatric Endocrinology &... Nov 2016
Topics: Adolescent; Animals; Child; Chronic Disease; Disease Progression; Endocrine Disruptors; Environmental Pollutants; Family Health; Female; Genetic Variation; Humans; Male; Precision Medicine; Puberty, Delayed; Puberty, Precocious
PubMed: 27771625
DOI: 10.1515/jpem-2016-0394 -
European Journal of Dentistry Jul 2021Precocious puberty indicates quick growth inception and delayed puberty indicates retardation in growth. This study aimed to investigate whether dental development is...
OBJECTIVES
Precocious puberty indicates quick growth inception and delayed puberty indicates retardation in growth. This study aimed to investigate whether dental development is synchronous with somatic development.
MATERIALS AND METHODS
In this study, 62 girls and 34 boys with precocious puberty aged 5 to 9, 29 girls with delayed puberty aged 13 to 16, and 43 boys with delayed puberty aged 14 to 17; 169 children (91 girls and 78 boys) with normal development were compared about their dental ages through their panoramic radiographs by using the Demirjian method and skeletal ages from hand-wrist radiographs by using Greulich-Pyle atlas.
RESULTS
The findings showed that, in all cases, the dental age values were higher than chronologic and skeletal age values to a statistically significant degree. In the precocious puberty group, the dental age values were higher than chronologic age values to a statistically significant degree. In the delayed puberty group, the difference determined between the chronological age and the dental age was not found to be statistically significant.
CONCLUSION
Given that the Demirjian method is inclined to make calculations that are higher than the chronological age, our findings suggest that the dental development was faster in the precocious puberty group and retarded in the delayed puberty group.
PubMed: 34041730
DOI: 10.1055/s-0041-1726156 -
Cureus Apr 2022Puberty is a developmental stage characterized by the appearance of secondary sexual characteristics which leads to complete physical, psychosocial, and sexual... (Review)
Review
Puberty is a developmental stage characterized by the appearance of secondary sexual characteristics which leads to complete physical, psychosocial, and sexual maturation. The current practice of hormonal therapy to induce puberty in adolescent males is based on published consensus and expert opinion. Evidence-based guidelines on optimal timing and regimen in puberty induction in males are lacking, and this reflects some discrepancies in practice among endocrinologists. It is worth mentioning that the availability of various hormonal products in markets, their different routes of administration, and patients/parents' preference also have an impact on clinical decisions. This review outlines the current clinical approach to delayed puberty in boys with an emphasis on puberty induction.
PubMed: 35530907
DOI: 10.7759/cureus.23864 -
Frontiers in Endocrinology 2019Delayed pubertal onset has many etiologies, but on average two-thirds of patients presenting with late puberty have self-limited (or constitutional) delayed puberty.... (Review)
Review
Delayed pubertal onset has many etiologies, but on average two-thirds of patients presenting with late puberty have self-limited (or constitutional) delayed puberty. Self-limited delayed puberty often has a strong familial basis. Segregation analyses from previous studies show complex models of inheritance, most commonly autosomal dominant, but also including autosomal recessive, bilineal, and X-linked. Sporadic cases are also observed. Despite this, the neuroendocrine mechanisms and genetic regulation remain unclear in the majority of patients with self-limited delayed puberty. Only rarely have mutations in genes known to cause aberrations of the hypothalamic-pituitary-gonadal axis been identified in cases of delayed puberty, and the majority of these are in relatives of patients with congenital hypogonadotropic hypogonadism (CHH), for example in the and genes. Using next generation sequencing in a large family with isolated self-limited delayed puberty, a pathogenic mutation in the CHH gene was found as the likely cause for this phenotype. Additionally, a study comparing the frequency of mutations in genes that cause GnRH deficiency between probands with CHH and probands with isolated self-limited delayed puberty identified that a significantly higher proportion of mutations with a greater degree of oligogenicity were seen in the CHH group. Mutations in the gene have been implicated in the pathogenesis of familial late puberty in a large Finnish cohort. disruption represents a fetal origin of delayed puberty, with dysregulation of GnRH neuronal migration during embryonic development presenting for the first time in adolescence as late puberty. Some patients with self-limited delayed puberty have distinct constitutional features of growth and puberty. Deleterious variants in have been found in families with delayed puberty with extremely low BMI and maturational delay in growth in early childhood. Recent exciting evidence highlights the importance of epigenetic up-regulation of GnRH transcription by a network of miRNAs and transcription factors, including , during puberty. Whilst a fascinating heterogeneity of genetic defects have been shown to result in delayed and disordered puberty, and many are yet to be discovered, genetic testing may become a realistic diagnostic tool for the differentiation of conditions of delayed puberty.
PubMed: 31293522
DOI: 10.3389/fendo.2019.00423 -
British Medical Journal (Clinical... Jun 1985
Topics: Female; Fetal Diseases; Humans; Male; Pregnancy; Pregnancy Complications; Puberty, Delayed
PubMed: 3924237
DOI: 10.1136/bmj.290.6483.1745-b -
Neuroendocrinology 2018The genetic control of puberty remains an important but mostly unanswered question. Late pubertal timing affects over 2% of adolescents and is associated with adverse... (Review)
Review
The genetic control of puberty remains an important but mostly unanswered question. Late pubertal timing affects over 2% of adolescents and is associated with adverse health outcomes including short stature, reduced bone mineral density, and compromised psychosocial health. Self-limited delayed puberty (DP) is a highly heritable trait, which often segregates in an autosomal dominant pattern; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. Some insights into the genetic mutations that lead to familial DP have come from sequencing genes known to cause gonadotropin-releasing hormone (GnRH) deficiency, most recently via next-generation sequencing, and others from large-scale genome-wide association studies in the general population. Investigation of the genetic control of DP is complicated by the fact that this trait is not rare and that the phenotype is likely to represent a final common pathway, with a variety of different pathogenic mechanisms affecting the release of the puberty "brake." These include abnormalities of GnRH neuronal development and function, GnRH receptor and luteinizing hormone/follicle-stimulating hormone abnormalities, metabolic and energy homeostatic derangements, and transcriptional regulation of the hypothalamic-pituitary-gonadal axis. Thus, genetic control of pubertal timing can range from early fetal life via development of the GnRH network to those factors directly influencing the puberty brake during mid-childhood.
Topics: Animals; Genetic Predisposition to Disease; Humans; Puberty, Delayed
PubMed: 28926843
DOI: 10.1159/000481569