The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Yee-ming Chan - One of the best experts on this subject based on the ideXlab platform.
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practice variation in the management of girls and boys with Delayed Puberty
Endocrine Practice, 2020Co-Authors: Jia Zhu, Yee-ming Chan, Henry A. Feldman, Erica A. Eugster, Patricia Y. Fechner, Leena Nahata, Paul S. ThorntonAbstract:Objective: Delayed Puberty is a common condition, and typical management includes "watchful waiting" and/or sex-steroid therapy. We sought to characterize treatment practices and to assess provider comfort with the management of Delayed Puberty in girls and boys. Methods: A national survey of pediatric endocrine providers assessed definitions of Delayed Puberty, practices around sex-steroid therapy, reasons for treatment, and comfort in managing Delayed Puberty in girls and boys. Results: Of 184 respondents (12% participation rate), 64% and 71% used the traditional age cutoffs for defining Delayed Puberty of 13 years for girls and 14 years for boys, respectively. Nearly half (45%) of providers would treat boys relatively earlier than girls, compared to 18% who would treat girls relatively earlier (P<.0001). Providers were more likely to cite bone density as a reason to treat girls and alleviating patient and parental distress, accelerating growth, and "jump starting" Puberty as reasons to treat boys. Greater experience in endocrine practice was associated with greater comfort managing Delayed Puberty in both boys and girls. Approximately 80% of providers agreed that clinical guidelines are needed for the management of Delayed Puberty. Conclusion: There is a high degree of variability in the clinical management of Delayed Puberty, and our results suggest that providers are more hesitant to treat girls compared to boys and have different reasons for treating each. It remains to be determined if these discrepancies in treatment are justified by biologic differences between girls and boys or represent nonevidence-based disparities in care. Abbreviation: U.S. = United States.
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PRACTICE VARIATION IN THE MANAGEMENT OF GIRLS AND BOYS WITH Delayed Puberty.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2019Co-Authors: Jia Zhu, Henry A. Feldman, Erica A. Eugster, Patricia Y. Fechner, Leena Nahata, Paul S. Thornton, Yee-ming ChanAbstract:Objective: Delayed Puberty is a common condition, and typical management includes "watchful waiting" and/or sex-steroid therapy. We sought to characterize treatment practices and to assess provider comfort with the management of Delayed Puberty in girls and boys. Methods: A national survey of pediatric endocrine providers assessed definitions of Delayed Puberty, practices around sex-steroid therapy, reasons for treatment, and comfort in managing Delayed Puberty in girls and boys. Results: Of 184 respondents (12% participation rate), 64% and 71% used the traditional age cutoffs for defining Delayed Puberty of 13 years for girls and 14 years for boys, respectively. Nearly half (45%) of providers would treat boys relatively earlier than girls, compared to 18% who would treat girls relatively earlier (P
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Adult Consequences of Self-Limited Delayed Puberty
Pediatrics, 2017Co-Authors: Jia Zhu, Yee-ming ChanAbstract:Delayed Puberty is a common condition defined as the lack of sexual maturation by an age ≥2 SD above the population mean. In the absence of an identified underlying cause, the condition is usually self-limited. Although self-limited Delayed Puberty is largely believed to be a benign developmental variant with no long-term consequences, several studies have suggested that Delayed Puberty may in fact have both harmful and protective effects on various adult health outcomes. In particular, height and bone mineral density have been shown to be compromised in some studies of adults with a history of Delayed Puberty. Delayed Puberty may also negatively affect adult psychosocial functioning and educational achievement, and individuals with a history of Delayed Puberty carry a higher risk for metabolic and cardiovascular disorders. In contrast, a history of Delayed Puberty appears to be protective for breast and endometrial cancer in women and for testicular cancer in men. Most studies on adult outcomes of self-limited Delayed Puberty have been in small series with significant variability in outcome measures and study criteria. In this article, we review potential medical and psychosocial issues for adults with a history of self-limited Delayed Puberty, discuss potential mechanisms underlying these issues, and identify gaps in knowledge and directions for future research.
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Fertility Issues for Patients with Hypogonadotropic Causes of Delayed Puberty
Endocrinology and metabolism clinics of North America, 2015Co-Authors: Jia Zhu, Yee-ming ChanAbstract:Delayed Puberty presenting with low gonadotropins has multiple causes. Self-limited delay (constitutional delay) is generally considered benign, but adult height and bone mineral density may be compromised, and fertility has not been studied. Functional hypogonadotropic hypogonadism due to a stressor is thought to resolve with removal of the stressor, but reproductive endocrine dysfunction can sometimes persist. Most but not all patients with idiopathic hypogonadotropic hypogonadism, a typically long-lasting condition, can achieve fertility with exogenous hormone therapy. Future studies are needed to determine fertility outcomes in self-limited Delayed Puberty and to more clearly define prognostic factors for fertility in functional and idiopathic hypogonadotropic hypogonadism.
Jia Zhu - One of the best experts on this subject based on the ideXlab platform.
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practice variation in the management of girls and boys with Delayed Puberty
Endocrine Practice, 2020Co-Authors: Jia Zhu, Yee-ming Chan, Henry A. Feldman, Erica A. Eugster, Patricia Y. Fechner, Leena Nahata, Paul S. ThorntonAbstract:Objective: Delayed Puberty is a common condition, and typical management includes "watchful waiting" and/or sex-steroid therapy. We sought to characterize treatment practices and to assess provider comfort with the management of Delayed Puberty in girls and boys. Methods: A national survey of pediatric endocrine providers assessed definitions of Delayed Puberty, practices around sex-steroid therapy, reasons for treatment, and comfort in managing Delayed Puberty in girls and boys. Results: Of 184 respondents (12% participation rate), 64% and 71% used the traditional age cutoffs for defining Delayed Puberty of 13 years for girls and 14 years for boys, respectively. Nearly half (45%) of providers would treat boys relatively earlier than girls, compared to 18% who would treat girls relatively earlier (P<.0001). Providers were more likely to cite bone density as a reason to treat girls and alleviating patient and parental distress, accelerating growth, and "jump starting" Puberty as reasons to treat boys. Greater experience in endocrine practice was associated with greater comfort managing Delayed Puberty in both boys and girls. Approximately 80% of providers agreed that clinical guidelines are needed for the management of Delayed Puberty. Conclusion: There is a high degree of variability in the clinical management of Delayed Puberty, and our results suggest that providers are more hesitant to treat girls compared to boys and have different reasons for treating each. It remains to be determined if these discrepancies in treatment are justified by biologic differences between girls and boys or represent nonevidence-based disparities in care. Abbreviation: U.S. = United States.
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PRACTICE VARIATION IN THE MANAGEMENT OF GIRLS AND BOYS WITH Delayed Puberty.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2019Co-Authors: Jia Zhu, Henry A. Feldman, Erica A. Eugster, Patricia Y. Fechner, Leena Nahata, Paul S. Thornton, Yee-ming ChanAbstract:Objective: Delayed Puberty is a common condition, and typical management includes "watchful waiting" and/or sex-steroid therapy. We sought to characterize treatment practices and to assess provider comfort with the management of Delayed Puberty in girls and boys. Methods: A national survey of pediatric endocrine providers assessed definitions of Delayed Puberty, practices around sex-steroid therapy, reasons for treatment, and comfort in managing Delayed Puberty in girls and boys. Results: Of 184 respondents (12% participation rate), 64% and 71% used the traditional age cutoffs for defining Delayed Puberty of 13 years for girls and 14 years for boys, respectively. Nearly half (45%) of providers would treat boys relatively earlier than girls, compared to 18% who would treat girls relatively earlier (P
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Adult Consequences of Self-Limited Delayed Puberty
Pediatrics, 2017Co-Authors: Jia Zhu, Yee-ming ChanAbstract:Delayed Puberty is a common condition defined as the lack of sexual maturation by an age ≥2 SD above the population mean. In the absence of an identified underlying cause, the condition is usually self-limited. Although self-limited Delayed Puberty is largely believed to be a benign developmental variant with no long-term consequences, several studies have suggested that Delayed Puberty may in fact have both harmful and protective effects on various adult health outcomes. In particular, height and bone mineral density have been shown to be compromised in some studies of adults with a history of Delayed Puberty. Delayed Puberty may also negatively affect adult psychosocial functioning and educational achievement, and individuals with a history of Delayed Puberty carry a higher risk for metabolic and cardiovascular disorders. In contrast, a history of Delayed Puberty appears to be protective for breast and endometrial cancer in women and for testicular cancer in men. Most studies on adult outcomes of self-limited Delayed Puberty have been in small series with significant variability in outcome measures and study criteria. In this article, we review potential medical and psychosocial issues for adults with a history of self-limited Delayed Puberty, discuss potential mechanisms underlying these issues, and identify gaps in knowledge and directions for future research.
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Fertility Issues for Patients with Hypogonadotropic Causes of Delayed Puberty
Endocrinology and metabolism clinics of North America, 2015Co-Authors: Jia Zhu, Yee-ming ChanAbstract:Delayed Puberty presenting with low gonadotropins has multiple causes. Self-limited delay (constitutional delay) is generally considered benign, but adult height and bone mineral density may be compromised, and fertility has not been studied. Functional hypogonadotropic hypogonadism due to a stressor is thought to resolve with removal of the stressor, but reproductive endocrine dysfunction can sometimes persist. Most but not all patients with idiopathic hypogonadotropic hypogonadism, a typically long-lasting condition, can achieve fertility with exogenous hormone therapy. Future studies are needed to determine fertility outcomes in self-limited Delayed Puberty and to more clearly define prognostic factors for fertility in functional and idiopathic hypogonadotropic hypogonadism.
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a shared genetic basis for self limited Delayed Puberty and idiopathic hypogonadotropic hypogonadism
The Journal of Clinical Endocrinology and Metabolism, 2015Co-Authors: Jia Zhu, Ruth Choa, Michael H Guo, Lacey Plummer, Cassandra Buck, Mark R Palmert, Joel N HirschhornAbstract:Background: Delayed Puberty is a common condition and, in the absence of an underlying condition, is self-limited in most cases. Though Delayed Puberty appears to be heritable, no specific genetic cause has yet been reported. In contrast, many genetic causes have been found for idiopathic hypogonadotropic hypogonadism (IHH), a rare disorder in which defects in GnRH secretion or action lead to absent or stalled pubertal development. We hypothesized that there is a shared genetic basis for both self-limited Delayed Puberty and IHH. Methods: We used two approaches to determine if there is genetic overlap between self-limited Delayed Puberty and IHH. First, in pedigrees with a proband with IHH known to carry a variant in an IHH gene, we performed targeted sequencing to determine whether family members with self-limited Delayed Puberty were more likely than family members with normal pubertal timing to share the proband’s variant. Second, in probands with self-limited Delayed Puberty and no family history of IHH, we performed whole-exome sequencing and examined 33,855 ethnically matched controls drawn from the Exome Aggregation Consortium for variants in 21 IHH genes. Variants were characterized as potentially pathogenic based on rarity, severity of mutation, and in silico analyses. Results: In pedigrees with an IHH proband, the proband’s potentially pathogenic variant was shared by 53% (10/19) of Delayed Puberty family members vs. 12% (4/33) of unaffected family members (P = 0.003). In Delayed Puberty subjects with no family history of IHH, 14% (8/56) had potentially pathogenic variants in IHH genes vs. 5.6% (1,907/33,855) of controls (P = 0.01). Such variants were found at a higher frequency in subjects with self-limited Delayed Puberty compared to controls in the specific genes IL17RD, TAC3, and TACR3. Conclusions: For the first time, we report a specific genetic cause for self-limited Delayed Puberty. These findings suggest that variants in IHH genes can contribute to the pathogenesis of self-limited Delayed Puberty. Thus, at least in some cases, self-limited Delayed Puberty shares an underlying pathophysiology with IHH. In addition, our study presents IL17RD, TAC3, and TACR3 as candidate genes for future genetic studies of self-limited Delayed Puberty and highlights both the benefits and limitations of genetic testing.
Sasha Howard - One of the best experts on this subject based on the ideXlab platform.
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Next-generation sequencing approach in the diagnosis of Delayed Puberty
Current Opinion in Endocrine and Metabolic Research, 2020Co-Authors: Tansit Saengkaew, Sasha HowardAbstract:Abstract The inheritance of pubertal timing is strongly influenced by genetic regulators, with conditions of Delayed or absent Puberty segregating within families often with Mendelian inheritance patterns. As such, these conditions are amenable to genetic discovery through next-generation sequencing. This review covers the significant advances in understanding of the biological mechanisms of Delayed Puberty that have occurred in the last 5–10 years with the use of this technology.
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The Genetic Basis of Delayed Puberty.
Frontiers in endocrinology, 2019Co-Authors: Sasha Howard, Leo DunkelAbstract: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 FGFR1 and GNRHR genes. Using next generation sequencing in a large family with isolated self-limited Delayed Puberty, a pathogenic mutation in the CHH gene HS6ST1 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 IGSF10 have been implicated in the pathogenesis of familial late Puberty in a large Finnish cohort. IGSF10 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 FTO 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 EAP1, 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.
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genetics of Delayed Puberty
2019Co-Authors: Sasha Howard, Leo DunkelAbstract:The pathogenesis of Delayed Puberty (DP) encompasses several conditions including functional hypogonadism, most commonly due to self-limited (also known as constitutional) DP, GnRH deficiency leading to hypogonadotropic hypogonadism, and disorders causing primary hypogonadism. Whilst many of the genetic defects responsible for the latter two groups have been identified in the last decade, the genetic basis of self-limited DP remains to a great degree an unsolved mystery. Self-limited 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 GnRH deficiency, most recently via next-generation sequencing and others from large-scale genome-wide association studies in the general population. Results of these studies suggest that a variety of different pathogenic mechanisms affecting the release of the Puberty ‘brake’ can lead to self-limited DP. These include abnormalities of GnRH neuronal development and function, GnRH receptor and LH/FSH abnormalities, metabolic and energy homeostasis derangements and transcriptional regulation of the HPG axis. Thus, genetic causes of DP may have effects as early as in foetal life, throughout early childhood, and on into adolescence.
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Normal and Delayed Puberty
Male Hypogonadism, 2017Co-Authors: Sasha Howard, Leo DunkelAbstract:Puberty is the developmental stage of physical and psychological maturation in which reproductive capacity is attained. The onset of Puberty is driven by the activation of the hypothalamic–pituitary–gonadal axis after the break that restrains this axis during the majority of childhood is released. This review will cover the clinical assessment of Puberty, variation in the timing of Puberty, and the complex factors that regulate the onset and timing of Puberty. In addition, the presentation, diagnosis, and differential diagnosis of male Delayed Puberty will be discussed. Male Delayed Puberty is common, affecting up to three percent of the population. The main differential diagnoses of Delayed Puberty in males include self-limited Delayed Puberty (DP), idiopathic hypogonadotropic hypogonadism (IHH), and hypergonadotropic hypogonadism. Treatment of isolated CDGP involves expectant observation or short courses of low-dose sex steroid supplementation. More complex and involved management is required in males with hypogonadism to achieve both the development of secondary sexual characteristics and to maximize the potential for fertility.
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Role of IGSF10 mutations in self-limited Delayed Puberty
The Lancet, 2016Co-Authors: Sasha Howard, Leo Guasti, Gerard Ruiz-babot, Alessandra Mancini, Alessia David, Helen L Storr, Louise A. Metherell, Michael J.e. Sternberg, Claudia P. Cabrera, Helen R. WarrenAbstract:Abstract Background Abnormal timing of Puberty affects over 4% of adolescents and is associated with adverse health and psychosocial outcomes. Previous studies estimate that 60–80% of variation in the timing of pubertal onset is genetically determined. However, little is known about the genetic control of human Puberty. Self-limited Delayed Puberty segregates in an autosomal dominant pattern; our study aimed to identify novel genetic regulators of disease in these patients. Methods We performed whole-exome sequencing in 18 families with self-limited Delayed Puberty from our cohort, followed by candidate gene sequencing in a further 42 families. The functional consequences of the identified mutations in one candidate gene were interrogated via expression of wild type and mutant proteins in mammalian cells. For this gene we defined tissue expression in human and mouse embryos. The effects of gene knockdown were assessed via in-vitro neuronal migration assays, and in vivo with a transgenic zebrafish model. Findings In ten unrelated families, we identified four rare mutations in IGSF10 in individuals with self-limited Delayed Puberty (adjusted p value after rare variant burden testing=3·4 × 10 –2 ). The identified mutations were in evolutionarily conserved positions, and two mutations resulted in intracellular retention with failure in secretion of the N-terminal fragment of the protein. IGSF10 mRNA was strongly expressed in the nasal mesenchyme in mouse and human embryos during migration of gonadotropin-releasing hormone (GnRH) neurons from their nasal origin towards the hypothalamus. IGSF10 knockdown caused reduced migration of immature GnRH neurons in the in-vitro analysis, and perturbed migration and extension of GnRH neurons in the zebrafish model. Interpretation Our findings strongly support the contention that mutations in IGSF10 cause Delayed Puberty in human beings, through misregulation of GnRH neuronal migration during embryonic development. Funding Wellcome Trust (102745), Rosetrees Trust (M222), and the Barts and the London Charity (417/1551) (SH); Biotechnology and Biological Sciences Research Council (BB/L002671/1) (LG and GB); LD is partly supported by the Academy of Finland (14135); National Institutes for Health Research (NIHR) (MB, HW, and CC); Medical Research Council (MR/K021613/1) (AD); Telethon Foundation (GP13142) (AC); VA is partly supported by a COST STSM (BM1105-16145) and a travel grant sponsored by Development (The Company of Biologists Ltd).
Paul B. Kaplowitz - One of the best experts on this subject based on the ideXlab platform.
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Delayed Puberty in obese boys: Comparison with constitutional Delayed Puberty and response to testosterone therapy
The Journal of pediatrics, 1998Co-Authors: Paul B. KaplowitzAbstract:Abstract Objective: To evaluate the results of a brief course of testosterone therapy in boys with Delayed Puberty and to compare the responses seen in boys with constitutional Delayed Puberty (CDP), boys with obesity, and boys with possible gonadotropin deficiency. Design and setting: A retrospective chart review was done for 36 boys aged 14 years or older, seen between 1983 and 1996 because of Delayed Puberty, who were given 4 monthly injections of testosterone, 100 mg/mo, and had adequate follow-up. Results: There were 23 boys whose findings before and after treatment were consistent with a diagnosis of CDP. Testosterone treatment increased the growth rate from 4.3 cm/y to 11.2 cm/y ( P P P = .00003). Of 5 boys with growth hormone deficiency but unknown gonadotropin status, 2 had lack of progression after testosterone therapy and were believed to have permanent gonadotropin deficiency. Seven of the 36 boys were obese (body mass index, >25), and 6 had a response to testosterone similar to boys with CDP with clear pubertal progression. One obese boy and one nonobese boy were diagnosed as having isolated gonadotropin deficiency. Conclusions: Monitoring the growth and genital responses to a 4-month course of testosterone injections helps to differentiate CDP from gonadotropin deficiency in boys with Delayed Puberty. Obese boys constitute a distinct category of boys with pubertal delay in terms of their growth, but their response to testosterone is similar to that observed in boys with classic CDP. (J Pediatr 1998;133:745-9)
L Tatò - One of the best experts on this subject based on the ideXlab platform.
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Delayed Puberty
La Pediatria medica e chirurgica : Medical and surgical pediatrics, 1996Co-Authors: F Antoniazzi, G Zamboni, L TatòAbstract:Delayed Puberty can be defined as the absence of any signs of Puberty in subjects that have attained an age at the upper limit (+2DS) for the onset of Puberty, that means 13 years in girls and 14 years in boys. The causes of Delayed Puberty can be classified into three groups, functional temporary impairment in gonadotropin and sex steroid secretion (most frequently constitutional delay of Puberty), hypothalamo-pituitary failure with deficiency in gonadotropin secretion, primary gonadal failure with increased gonadotropin levels. The Authors discuss about etiology, diagnostic testing and therapeutic approach in these conditions. The majority of children with Delayed Puberty are males that have only a constitutional delay of growth and Puberty. It is difficult, in teenage years, to distinguish this common and benign condition from true gonadotropin deficiency, in spite of the variety of endocrine tests developed for this purpose. Individuals with constitutional Delayed Puberty with a bone age greater than 11.5 years, show after triptorelin stimulation an increase in LH capable of distinguishing them from patients with gonadotropin deficiency. In our opinion this could be an important screening test to exclude gonadotropin deficiency in boys with Delayed Puberty.
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Use of the gonadotropin-releasing hormone agonist triptorelin in the diagnosis of Delayed Puberty in boys.
The Journal of pediatrics, 1995Co-Authors: G Zamboni, F Antoniazzi, L TatòAbstract:To differentiate gonadotropin deficiency from Delayed Puberty in teenage boys, 0.1 mg/m2 of triptorelin, a gonadotropin-releasing hormone agonist, was administered subcutaneously at 4 AM. Serum gonadotropins and testosterone levels were determined at baseline and 4 hours after the injection. The increase in blood gonadotropin and testosterone levels was significantly greater in patients with Delayed Puberty than in those with gonadotropin deficiency.
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Use of the gonadotropin-releasing hormone agonist triptorelin in the diagnosis of Delayed Puberty in boys
The Journal of Pediatrics, 1995Co-Authors: G Zamboni, F Antoniazzi, L TatòAbstract:Abstract To differentiate gonadotropin deficiency from Delayed Puberty in teenage boys, 0.1 mg/m 2 of triptorelin, a gonadotropin-releasing hormone agonist, was administered subcutaneously at 4 am. Serum gonadotropins and testosterone levels were determined at baseline and 4 hours after the injection. The increase in blood gonadotropin and testosterone levels was significantly greater in patients with Delayed Puberty than in those with gonadotropin deficiency. (J P EDIATR 1995;126:756-8)