|
1
|
Liu X, Li P, Yang X, Xie T, Xu H. Exploration of the molecular mechanism of modified Danggui Liuhuang Decoction in treating central precocious puberty and its effects on hypothalamic-pituitary-gonadal axis hormones. Hereditas 2025; 162:56. [PMID: 40200320 PMCID: PMC11980125 DOI: 10.1186/s41065-025-00420-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 03/19/2025] [Indexed: 04/10/2025] Open
Abstract
AIM To evaluate the molecular mechanism of modified Danggui Liuhuang Decoction (MDGLHD) in treating central precocious puberty (CPP). METHODS CPP-related genes were obtained from GEO dataset, MalaCard, DisGeNET and GeneCards databases. MDGLHT ingredients and targets were obtained in TCMSP, HERB, and SwissTargetPrediction databases. Protein-protein interaction (PPI) network was constructed and analyzed using STRING database and Cytoscape 3.9.1. Genetic ontological (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed with DAVID and Metascape databases. Molecular docking was performed with PyMoL and AutoDock-Vina software. The GnRH secretion model was established by E2 induction of GT1-7 cells. CCK-8, ELISA and qRT-PCR were used to detect the effects of MDGLHD on gonadotropin-releasing hormone (GnRH) secretion and endocrine signaling receptor gene expression. RESULTS 318 potential targets of MDGLHD in CPP treatment were screened out. Quercetin, kaempferol, and (S)-Canadine were considered to be the most important active ingredients in MDGLHD. Bioinformatics analysis showed that these targets were associated with response to hormone, JAK-STAT signaling pathway and HIF-1 signaling pathway. Quercetin, kaempferol, and (s)-Canadine had good binding affinity with tumor protein p53 (TP53), estrogen receptor 1(ESR1), Jun proto-oncogene (JUN), MYC proto-oncogene (MYC) and AKT serine/threonine kinase 1 (AKT1). In vitro experiments showed that MDGLHD extract can inhibit GnRH secretion and the expression of neuroendocrine signaling receptor protein gene. CONCLUSION MDGLHD treatment of CPP is achieved through multi-components, multi-targets and multi-pathways, and inhibition of GnRH secretion and neuroendocrine signaling.
Collapse
Affiliation(s)
- Xiaqing Liu
- Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, P. R. China
| | - Pinggan Li
- Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, P. R. China
| | - Xiangna Yang
- Department of Traditional Chinese Medicine, Guangzhou Women and Children's Medical Center, Guangzhou, 510620, Guangdong, P. R. China
| | - Ting Xie
- Department of Children's Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, 510620, Guangdong, P. R. China
| | - Hua Xu
- Pediatrics of Traditional Chinese Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 16, Airport Road, Guangzhou, 510405, Guangdong, P. R. China.
| |
Collapse
|
|
2
|
Olivas-Martínez A, Ventura-Wischner PS, Fernandez MF, Freire C. Influence of exposure to endocrine disruptors and other environmental chemicals on breast development in girls: A systematic review of human studies. Int J Hyg Environ Health 2025; 263:114487. [PMID: 39566420 DOI: 10.1016/j.ijheh.2024.114487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 10/18/2024] [Accepted: 11/13/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND Age at thelarche has decreased over recent decades. This change in female puberty timing may be influenced by exposure to endocrine disrupting chemicals (EDCs) during critical periods of development. OBJECTIVE To review the scientific literature for evidence on the association of exposure to EDCs and other environmental chemicals with the timing of thelarche in girls. METHODS A systematic search for original peer-reviewed articles published up to July 2023 was conducted in three databases (Medline/PubMed, Scopus, and Web of Science), following the PECO strategy and PRISMA guidelines. The quality of evidence and reporting and the risk of bias were evaluated using GRADE, STROBE, and ROBINS-E tools. RESULTS Out of 3094 articles retrieved in the search, 67 met the review inclusion criteria. Data from 10 out of the 14 studies offering high-quality suggest that in utero and/or childhood exposure to certain synthetic and natural chemicals is associated with earlier breast development in girls; 8 of these 10 studies described a relationship with exposure to organohalogenated compounds in utero and to phthalates in childhood. CONCLUSIONS This systematic review provides the first overview of available human data on the association of EDCs/environmental chemicals with the timing of thelarche. Further high-quality research is urgently needed to fully elucidate the influence of this exposure on breast development timing in girls.
Collapse
Affiliation(s)
- Alicia Olivas-Martínez
- Instituto de Investigación Biosanitaria (ibs.GRANADA), 18012, Granada, Spain; Centre for Biomedical Research (CIBM), University of Granada, 18016, Granada, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain
| | - Paula Sol Ventura-Wischner
- Institut D'Investigació en Ciències de La Salut Germans Trias I Pujol, 08916, Badalona, Barcelona, Spain; Servicio de Pediatria, Hospital Universitari Arnau de Vilanova, 25198, Lleida, Spain
| | - Mariana F Fernandez
- Instituto de Investigación Biosanitaria (ibs.GRANADA), 18012, Granada, Spain; Centre for Biomedical Research (CIBM), University of Granada, 18016, Granada, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain
| | - Carmen Freire
- Instituto de Investigación Biosanitaria (ibs.GRANADA), 18012, Granada, Spain; Centre for Biomedical Research (CIBM), University of Granada, 18016, Granada, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain; Department of Legal Medicine, Toxicology, and Physical Anthropology, School of Medicine, University of Granada, 18016, Granada, Spain.
| |
Collapse
|
|
3
|
Alonso GF. Precocious puberty, pandemic and beyond. Pituitary 2024; 27:916-924. [PMID: 39060817 DOI: 10.1007/s11102-024-01434-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/17/2024] [Indexed: 07/28/2024]
Abstract
WHO declared SARS-COVID19 a pandemic in March 2020. Most governments declared health emergency states and implemented various measures. Since then, changes in the reasons for medical consultations were observed in healthcare institutions. Pediatric endocrinologists perceived an increase in the number of consultations related to early or accelerated CPP during the months following the lockdown that different governments had established. Several papers reported the increment in incidence in Central Precocious Puberty, especially in girls. Reports from different parts of the world highlighted a two to threefold rise in the number of cases of precocious puberty treated in Pediatric Endocrinology Centers. This trend of CPP incidence strongly suggests that changes in habits and the environment in which boys and girls were immersed during the lockdown, have played a significant role in triggering the early onset of the gonadotrophic axis.
Collapse
Affiliation(s)
- Guillermo F Alonso
- Pediatric Endocrinology Section, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
| |
Collapse
|
|
4
|
Cassio A, Marescotti G, Aversa T, Salerno M, Tornese G, Stancampiano M, Tuli G, Faienza MF, Cavarzere P, Fava D, Parpagnoli M, Bruzzi P, Ibba A, Calcaterra V, Mameli C, Grandone A, Cherubini V, Assirelli V, Franchina F, Capalbo D, Di Mase R, Tamaro G, Cavasin J, Munarin J, Russo G, Wasniewska M. Central Precocious Puberty in Italian Boys: Data From a Large Nationwide Cohort. J Clin Endocrinol Metab 2024; 109:2061-2070. [PMID: 38308814 PMCID: PMC11244209 DOI: 10.1210/clinem/dgae035] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Indexed: 02/05/2024]
Abstract
CONTEXT There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000. OBJECTIVE We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones. METHODS We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities. RESULTS The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis < 7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started. CONCLUSION In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature.
Collapse
Affiliation(s)
- Alessandra Cassio
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgery Sciences, University of Bologna, 40138 Bologna, Italy
| | - Gloria Marescotti
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Tommaso Aversa
- Department of Human Pathology of Adulthood and Childhood, University of Messina, 98125 Messina, Italy
- Pediatric Unit, University Hospital, 98122 Messina, Italy
| | - Mariacarolina Salerno
- Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University Federico II, 80131 Naples, Italy
| | - Gianluca Tornese
- Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, 34137 Trieste, Italy
- Department of Medicine, Surgery and Health Sciences, University of Trieste, 34129 Trieste, Italy
| | - Marianna Stancampiano
- Department of Pediatrics, Endocrine Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Gerdi Tuli
- Department of Pediatric Endocrinology, Regina Margherita Children's Hospital, Department of Pediatric Sciences, University of Turin, 10126 Torino, Italy
| | - Maria Felicia Faienza
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “A. Moro”, 70124 Bari, Italy
| | - Paolo Cavarzere
- Pediatric Division, Department of Pediatrics, University Hospital of Verona, 37126 Verona, Italy
| | - Daniela Fava
- Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genoa 16147, Italy
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa 16142, Italy
| | - Maria Parpagnoli
- Department of Diabetology and Endocrinology, Meyer Children Hospital IRCCS, 50139 Florence, Italy
| | - Patrizia Bruzzi
- Pediatric Unit Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Anastasia Ibba
- Pediatric Endocrinology Unit and Newborn Screening Center, Pediatric Microcitemic Hospital, ASL Cagliari, 09121 Cagliari, Italy
| | - Valeria Calcaterra
- Child and Adolescent Unit, Department of internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Chiara Mameli
- Department of Biomedical and Clinical Sciences, University of Milan, 20157 Milan, Italy
| | - Anna Grandone
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, 80138, Napoli, Italy
| | - Valentino Cherubini
- Department of Women's and Children's Health, Salesi Hospital, 60126 Ancona, Italy
| | - Valentina Assirelli
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgery Sciences, University of Bologna, 40138 Bologna, Italy
| | - Francesca Franchina
- Department of Human Pathology of Adulthood and Childhood, University of Messina, 98125 Messina, Italy
- Pediatric Unit, University Hospital, 98122 Messina, Italy
| | - Donatella Capalbo
- Pediatric Endocrinology Unit, Department of Mother and Child University Hospital Federico II Naples, 80131 Naples, Italy
| | - Raffaella Di Mase
- Pediatric Endocrinology Unit, Department of Mother and Child University Hospital Federico II Naples, 80131 Naples, Italy
| | - Gianluca Tamaro
- Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, 34137 Trieste, Italy
| | - Julia Cavasin
- Department of Medicine, Surgery and Health Sciences, University of Trieste, 34129 Trieste, Italy
| | - Jessica Munarin
- Department of Pediatric Endocrinology, Regina Margherita Children's Hospital, Department of Pediatric Sciences, University of Turin, 10126 Torino, Italy
| | - Gianni Russo
- Department of Pediatrics, Endocrine Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Malgorzata Wasniewska
- Department of Human Pathology of Adulthood and Childhood, University of Messina, 98125 Messina, Italy
- Pediatric Unit, University Hospital, 98122 Messina, Italy
| |
Collapse
|
|
5
|
Wang Y, Jin C, Li H, Liang X, Zhao C, Wu N, Yue M, Zhao L, Yu H, Wang Q, Ge Y, Huo M, Lv X, Zhang L, Zhao G, Gai Z. Gut microbiota-metabolite interactions meditate the effect of dietary patterns on precocious puberty. iScience 2024; 27:109887. [PMID: 38784002 PMCID: PMC11112371 DOI: 10.1016/j.isci.2024.109887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/21/2024] [Accepted: 04/30/2024] [Indexed: 05/25/2024] Open
Abstract
Precocious puberty, a pediatric endocrine disorder classified as central precocious puberty (CPP) or peripheral precocious puberty (PPP), is influenced by diet, gut microbiota, and metabolites, but the specific mechanisms remain unclear. Our study found that increased alpha-diversity and abundance of short-chain fatty acid-producing bacteria led to elevated levels of luteinizing hormone and follicle-stimulating hormone, contributing to precocious puberty. The integration of specific microbiota and metabolites has potential diagnostic value for precocious puberty. The Prevotella genus-controlled interaction factor, influenced by complex carbohydrate consumption, mediated a reduction in estradiol levels. Interactions between obesity-related bacteria and metabolites mediated the beneficial effect of seafood in reducing luteinizing hormone levels, reducing the risk of obesity-induced precocious puberty, and preventing progression from PPP to CPP. This study provides valuable insights into the complex interplay between diet, gut microbiota and metabolites in the onset, development and clinical classification of precocious puberty and warrants further investigation.
Collapse
Affiliation(s)
- Ying Wang
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| | - Chuandi Jin
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Hongying Li
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| | - Xiangrong Liang
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| | - Changying Zhao
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Nan Wu
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Min Yue
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Lu Zhao
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- Central Laboratory, Weifang People’s Hospital/The First Affiliated Hospital of Shandong Second Medical university, Weifang 261000, China
- Shandong Laibo Biotechnology Co., Ltd., Jinan 250101, China
| | - Han Yu
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| | - Qian Wang
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| | - Yongsheng Ge
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| | - Meiling Huo
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| | - Xin Lv
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| | - Lehai Zhang
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| | - Guoping Zhao
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- Microbiome-X, National Institute of Health Data Science of China, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- CAS Key Laboratory of Computational Biology, Bio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
- Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China
| | - Zhongtao Gai
- Children’s Hospital Affiliated to Shandong University, Shandong University, Jinan 250022, China
- Jinan Children’s Hospital, Jinan 250022, China
| |
Collapse
|
|
6
|
Dong L, Zhou W, Lin Z, Tang L, Deng X, Chen B, Huang W, Xiong Q. Polymorphism rs5780218, rs12998 and rs10158616 in KISS1 gene among the Hubei province Chinese girls with the central precocious puberty. Endocrine 2024; 84:1229-1237. [PMID: 38358556 DOI: 10.1007/s12020-024-03716-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 01/23/2024] [Indexed: 02/16/2024]
Abstract
PURPOSE Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. To elucidate the molecular genetic basis of CPP, we here investigated the effects of polymorphism rs5780218, rs12998 and rs10158616 in KISS1 gene on CPP susceptibility. METHODS The three KISS1 gene polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing in 422 healthy Hubei Chinese girls and 384 Hubei Chinese girls with CPP. RESULTS Single-locus analysis demonstrated that rs5780218 and rs12998 were significantly associated with CPP susceptibility in Hubei Chinese girls. Haplotype analysis exhibited that the AGG carrying the risk allele A of rs5780218 and the -GG carrying the protective allele - of rs5780218 were associated with increased and decreased CPP susceptibility in Hubei Chinese girls, respectively. The following meta-analysis confirmed the contribution of rs5780218 and rs12998 on CPP susceptibility in Chinese girls. CONCLUSIONS rs5780218 and rs12998 in the KISS1 gene may participate in genetic susceptibility to CPP in Chinese girls, and the KISS1 gene rs5780218 may serve as a genetic biomarker of CPP. However, the present findings should be validated in future studies with larger sample sizes in other ethnic populations.
Collapse
Affiliation(s)
- Lijuan Dong
- Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China
| | - Weiguang Zhou
- Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China
| | - Zhongchao Lin
- Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China
| | - Lingyu Tang
- Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China
| | - Xinyi Deng
- Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China
| | - Bifeng Chen
- Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China.
| | - Wei Huang
- Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China.
| | - Qiantao Xiong
- Department of Laboratory, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, China.
| |
Collapse
|
|
7
|
Huttunen H, Kärkinen J, Varimo T, Miettinen PJ, Raivio T, Hero M. Central precocious puberty in boys: secular trend and clinical features. Eur J Endocrinol 2024; 190:211-219. [PMID: 38523472 DOI: 10.1093/ejendo/lvae021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 01/29/2024] [Accepted: 02/07/2024] [Indexed: 03/26/2024]
Abstract
OBJECTIVE Recent studies suggest that boys enter puberty at a younger age, and the incidence of male central precocious puberty (CPP) is increasing. In this study, we explore the incidence of male CPP and identify key clinical and auxological indicators for organic CPP (OCPP). DESIGN A retrospective registry-based study. METHODS The medical records of 43 boys treated with CPP at the Helsinki University Hospital between 1985 and 2014 were reviewed. Clinical, auxological, and endocrine data of the CPP patients were included in the analyses. RESULTS Based on brain MRI, 26% of patients had OCPP. Between 2010 and 2014, the CPP incidence in boys was 0.34 per 10 000 (95% CI 0.20-0.60). Between 1990 and 2014, the male CPP incidence increased (incidence rate ratio [IRR] 1.10, P = .001). This increase was driven by rising idiopathic CPP (ICPP) incidence (IRR 1.11, 95% CI 1.05-1.19, P < .001), while OCPP incidence remained stable (P = .41). Compared with the patients with ICPP, the patients with OCPP were younger (P = .006), were shorter (P = .003), and had higher basal serum testosterone levels (P = .038). Combining 2 to 4 of these readily available clinical cues resulted in good to excellent (all, area under the curve 0.84-0.97, P < .001) overall performance, differentiating organic etiology from idiopathic. CONCLUSIONS The estimated incidence of CPP in boys was 0.34 per 10 000, with 26% of cases associated with intracranial pathology. The increase in CPP incidence was driven by rising ICPP rates. Patients with OCPP were characterized by shorter stature, younger age, and higher basal testosterone levels, providing valuable cues for differentiation in addition to brain MRI. Utilizing multiple cues could guide diagnostic decision-making.
Collapse
Affiliation(s)
- Heta Huttunen
- New Children's Hospital, Pediatric Research Center, Helsinki University Hospital, Helsinki 00014, Finland
| | - Juho Kärkinen
- New Children's Hospital, Pediatric Research Center, Helsinki University Hospital, Helsinki 00014, Finland
| | - Tero Varimo
- New Children's Hospital, Pediatric Research Center, Helsinki University Hospital, Helsinki 00014, Finland
| | - Päivi J Miettinen
- New Children's Hospital, Pediatric Research Center, Helsinki University Hospital, Helsinki 00014, Finland
| | - Taneli Raivio
- New Children's Hospital, Pediatric Research Center, Helsinki University Hospital, Helsinki 00014, Finland
- Stem Cells and Metabolism Research Program, Research Program Unit, University of Helsinki, Helsinki 00014, Finland
| | - Matti Hero
- New Children's Hospital, Pediatric Research Center, Helsinki University Hospital, Helsinki 00014, Finland
| |
Collapse
|
|
8
|
Hoskyns RB, Howard SR. Effects of the COVID-19 pandemic on the incidence of central precocious puberty; a narrative review. J Pediatr Endocrinol Metab 2024; 37:102-109. [PMID: 38097507 DOI: 10.1515/jpem-2023-0507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 11/20/2023] [Indexed: 02/09/2024]
Abstract
Central precocious puberty (CPP) is the premature activation of the hypothalamus-pituitary-gonadal axis, resulting in the early development of secondary sexual characteristics. CPP classically occurs before the age of 8 years in girls and 9 years in boys. The aetiology of this precocious onset of puberty is governed by complex mechanistic interactions between genetic and environmental factors. The rates of CPP have been documented to have been rising before the COVID-19 pandemic; despite this, the incidence of CPP has increased exponentially since the start of the pandemic. There are multiple theories potentially explaining this change in incidence of CPP over COVID-19. These include the direct effect of SARS-coV-2 infection, increasing body mass index of adolescents over sequential lockdowns, changes in sleep patterns, increased use of electronic devices and levels of stress, and additionally potential earlier detection of signs of CPP by parents and carers. Whilst there is evidence from observational cohorts, case studies and animal models for each of these factors, it is difficult to definitively prove which has had the greatest impact due to the mainly retrospective nature of the human research that has been conducted. Moreover, studies set in diverse settings with varying population make comparison complex. Additionally, each country responded differently to the COVID-19 pandemic and the lockdowns varied between locations, hence the effect of lockdown was not equal or universal. Despite this, similar trends have been identified, with various lifestyle changes that occurred over the pandemic being potentially influential factors on the development of CPP.
Collapse
Affiliation(s)
- Rebecca B Hoskyns
- Barts and the London School of Medicine and Dentistry, QMUL, London, UK
| | - Sasha R Howard
- Centre for Endocrinology, William Harvey Research Institute, QMUL, London, UK
- Department of Paediatric Endocrinology, Royal London Children's Hospital, Barts Health NHS Trust, London, UK
| |
Collapse
|
|
9
|
Cleemann Wang A, Hagen CP, Johannsen TH, Madsen AG, Cleemann LH, Christiansen P, Main KM, Juul A, Jensen RB. Differentiation of Idiopathic Central Precocious Puberty From Premature Thelarche Using Principal Component Analysis. J Clin Endocrinol Metab 2024; 109:370-379. [PMID: 37698163 DOI: 10.1210/clinem/dgad535] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/31/2023] [Accepted: 09/08/2023] [Indexed: 09/13/2023]
Abstract
CONTEXT Nonprogressive premature thelarche (PT) is a self-limiting variant of early puberty, while idiopathic central precocious puberty (ICPP) is a disorder that causes progressive development of secondary sexual characteristics and often requires treatment. The diagnostic differentiation between these conditions is important but can be challenging since they often both initially present clinically with isolated breast development. OBJECTIVE To describe relevant clinical variables in a large cohort of girls referred for early puberty, and to evaluate clinical and biochemical parameters to distinguish between girls with ICPP and PT. METHODS This retrospective study included 1361 girls referred with signs of early puberty to a single, tertiary center from 2009 to 2019. We evaluated clinical presentation, medical history, growth velocity, bone age, hormonal serum concentrations, and gonadotropin-releasing hormone (GnRH) test results. RESULTS Central precocious puberty was diagnosed in 11% (ICPP: n = 143, organic CPP: n = 11) girls, whereas 8% (n = 91 girls) presented with PT. Receiver operating characteristic (ROC) analysis showed several biochemical and anthropometric markers as potential parameters to differentiate between ICPP and PT; however, none were individually adequate. Principal component analysis (PCA)-derived clinical and hormone profiles could predict girls with ICPP from girls with PT with a specificity of 90% and sensitivity of 84%, outperforming any single marker. CONCLUSION Differentiation of girls with ICPP and PT can be supported by individual clinical and biochemical parameters. However, dimension reduction of clinical and hormonal profiles by PCA improved the diagnostic value, which in the future may support the diagnostic process as a supplement to the GnRH test in evaluation of pubertal disorders.
Collapse
Affiliation(s)
- Amanda Cleemann Wang
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark
| | - Casper P Hagen
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark
- International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark
| | - Trine Holm Johannsen
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark
- International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark
| | - Andre Greger Madsen
- Medical Biochemistry and Pharmacology, Haukeland University Hospital, N-5020 Bergen, Norway
| | - Line Hartvig Cleemann
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark
- International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark
| | - Peter Christiansen
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark
- International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark
| | - Katharina M Main
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark
- International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark
| | - Anders Juul
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark
- International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark
| | - Rikke Beck Jensen
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, DK-2100 Copenhagen, Denmark
- International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark
- Department of Pediatrics, Copenhagen University Hospital-Herlev and Gentofte, DK-2730 Herlev, Denmark
| |
Collapse
|
|
10
|
Heo S, Shim YS, Lee HS, Hwang JS. Clinical course of peripheral precocious puberty in girls due to autonomous ovarian cysts. Clin Endocrinol (Oxf) 2024; 100:29-35. [PMID: 37386805 DOI: 10.1111/cen.14943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 05/20/2023] [Accepted: 06/16/2023] [Indexed: 07/01/2023]
Abstract
OBJECTIVE Peripheral precocious puberty (PPP) is the precocious development of secondary sexual characteristics without pulsatile gonadotropin-releasing hormone (GnRH) secretion. In girls, PPP suggests a hyper-oestrogenic state, such as autonomous ovarian cysts and McCune-Albright syndrome (MAS). We aimed to investigate PPP in girls with ovarian cysts, with or without MAS. DESIGN A retrospective study design was used. PATIENTS AND MEASUREMENTS The study included 12 girls diagnosed with ovarian cysts with PPP between January 2003 and May 2022. Pelvic sonography was performed in cases of vaginal bleeding or areolar pigmentation in PPP. The clinical characteristics, clinical course and pelvic sonographic findings of girls with ovarian cysts were investigated. RESULTS We found 18 episodes of ovarian cysts in the 12 girls. The median size of the ovarian cysts was 27.5 mm. Five of the girls were diagnosed with MAS. The median time to spontaneous regression was 6 months. Later, 4 out of 12 girls progressed to central precocious puberty (CPP), and three of them had a recurrence of ovarian cysts. Compared to the non-recurrent and recurrent groups, there was a difference in peak luteinizing hormone (LH) in the GnRH stimulation test and period to cyst regression. CONCLUSIONS Most ovarian cysts in PPP spontaneously disappear. However, this could be one of the findings of MAS. Some girls progress from PPP to CPP. Therefore, follow-up is necessary for ovarian cysts in patients with PPP. The recurrence of ovarian cysts may occur when spontaneous regression is prolonged.
Collapse
Affiliation(s)
- Seung Heo
- Department of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, Suwon, Korea
| | - Young Suk Shim
- Department of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, Suwon, Korea
| | - Hae Sang Lee
- Department of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, Suwon, Korea
| | - Jin Soon Hwang
- Department of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, Suwon, Korea
| |
Collapse
|
|
11
|
Zang S, Yin X, Li P. FTO-mediated m 6A demethylation regulates GnRH expression in the hypothalamus via the PLCβ3/Ca 2+/CAMK signalling pathway. Commun Biol 2023; 6:1297. [PMID: 38129517 PMCID: PMC10739951 DOI: 10.1038/s42003-023-05677-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 12/05/2023] [Indexed: 12/23/2023] Open
Abstract
N6-methyladenosine (m6A) plays a crucial role in the development and functional homeostasis of the central nervous system. The fat mass and obesity-associated (FTO) gene, which is highly expressed in the hypothalamus, is closely related to female pubertal development. In this study, we found that m6A methylation decreased in the hypothalamus gradually with puberty and decreased in female rats with precocious puberty. FTO expression was increased at the same time. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed that the m6A methylation of PLCβ3, a key enzyme of the Ca2+ signalling pathway, was decreased significantly in the hypothalamus in precocious rats. Upregulating FTO increased PLCβ3 expression and activated the Ca2+ signalling pathway, which promoted GnRH expression. Dual-luciferase reporter and MeRIP-qPCR assays confirmed that FTO regulated m6A demethylation of PLCβ3 and promoted PLCβ3 expression. Upon overexpressing FTO in the hypothalamic arcuate nucleus (ARC) in female rats, we observed advanced puberty onset. Meanwhile, PLCβ3 and GnRH expression in the hypothalamus increased significantly, and the Ca2+ signalling pathway was activated. Our study demonstrates that FTO enhances GnRH expression, which promotes puberty onset, by regulating m6A demethylation of PLCβ3 and activating the Ca2+ signalling pathway.
Collapse
Affiliation(s)
- Shaolian Zang
- Department of endocrinology, Shanghai Children's Hospital, School of medicine, Shanghai Jiao Tong University, 200062, Shanghai, China
| | - Xiaoqin Yin
- Department of endocrinology, Shanghai Children's Hospital, School of medicine, Shanghai Jiao Tong University, 200062, Shanghai, China.
| | - Pin Li
- Department of endocrinology, Shanghai Children's Hospital, School of medicine, Shanghai Jiao Tong University, 200062, Shanghai, China.
| |
Collapse
|
|
12
|
Ahn J, Lee Y, Gim S, Jeong H. Use of the Subcutaneous Triptorelin Stimulation Test for Diagnosis of Central Precocious Puberty. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1830. [PMID: 38002921 PMCID: PMC10669987 DOI: 10.3390/children10111830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/09/2023] [Accepted: 11/16/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND The gold standard gonadotropin-releasing hormone (GnRH) stimulation test uses the response to intravenously injected gonadorelin to diagnose central precocious puberty (CPP). However, gonadorelin is not always readily available. OBJECTIVE This study investigated the diagnostic efficacy of the subcutaneous triptorelin test and the optimal blood sampling time for diagnosis of CPP. METHODS This study retrospectively examined the medical records of 220 girls who had undergone either the triptorelin or gonadorelin test and compared their clinical characteristics. We retrospectively compared clinical parameters between girls diagnosed with CPP (n = 111) and idiopathic premature thelarche (IPT) (n = 109) using three different diagnostic methods: the gonadorelin, triptorelin 120 min, and triptorelin 180 min tests. The diagnostic ability of the stimulated luteinizing hormone (LH) concentration in the triptorelin test for CPP was evaluated using receiver operating characteristic (ROC) analysis. RESULTS The CPP group exhibited higher basal and peak gonadotropin levels, more advanced bone age, and a lower body mass index standard deviation score than the IPT group. In the gonadorelin test group, all girls with CPP exhibited a peak LH response 30-60 min after intravenous gonadorelin injection. In the triptorelin test group, most girls with CPP exhibited a peak LH response 60-180 min after subcutaneous triptorelin injection (n = 68). On the ROC curve, a peak LH concentration of ≥ 4.52 IU/L at 120 min had the highest CPP diagnostic accuracy, with sensitivity and specificity of 100% and 95.83%, respectively.
Collapse
Affiliation(s)
- Jungmin Ahn
- Department of Pediatrics, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Youngin Lee
- Department of Pediatrics, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Seongmin Gim
- Department of Pediatrics, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea
| | - Hwalrim Jeong
- Department of Pediatrics, School of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea
| |
Collapse
|
|
13
|
Abstract
Precocious puberty (PP) means the appearance of secondary sexual characters before the age of eight years in girls and nine years in boys. Puberty is indicated in girls by the enlargement of the breasts (thelarche) in girls and in boys by the enlargement of the testes in either volume or length (testicular volume = 4 mL, testicular length = 25 mm, or both). Two types of PP are recognized - namely central PP (CPP) and peripheral PP (PPP). This paper aims to describe the clinical findings and laboratory workup of PP and to illustrate the new trends in the management of precocious sexual maturation. Gonadotropin-releasing hormone (GnRH)-independent type (PPP) refers to the development of early pubertal maturation not related to the central activation of the hypothalamic-pituitary-gonadal (HPG) axis. It is classified into genetic or acquired disorders. The most common forms of congenital or genetic causes involve McCune-Albright syndrome (MAS), familial male-limited PP, and congenital adrenal hyperplasia. The acquired causes include exogenous exposure to androgens, functioning tumors or cysts, and the pseudo-PP of profound primary hypothyroidism. On the other hand, CPP is the most common and it is a gonadotropin-dependent form. It is due to premature maturation of the HPG axis. CPP may occur as genetic alterations, such as MKRN3, DLK1, or KISS1;as a part of mutations in the epigenetic factors that regulate the HPG axis, such as Lin28b and let-7; or as a part of syndromes, central lesions such as hypothalamic hamartoma, and others. A full, detailed history and physical examination should be taken. Furthermore, several investigations should be conducted for both types of PP, including the estimation of serum gonadotropins such as luteinizing and follicle-stimulating hormones and sex steroids, in addition to a radiographic workup and thyroid function tests. Treatment depends on the type of PP: Long-acting GnRHa, either intramuscularly or implanted, is the norm of care for CPP management, while in PPP, especially in congenital adrenal hyperplasia, the goal of management is to suppress adrenal androgen secretion by glucocorticoids. In addition, anastrozole and letrozole - third-generation aromatase inhibitors - are more potent for MAS.
Collapse
Affiliation(s)
- Ahmed Alghamdi
- Pediatric Endocrinology, Faculty of Medicine, Al Baha University, Al Baha, SAU
| |
Collapse
|
|
14
|
Najafi R, Heidarianpour A, Shokri E, Shokri B. Ameliorative effects of aerobic training in girls with precocious puberty: role of leptin and ghrelin. Sci Rep 2023; 13:15732. [PMID: 37735188 PMCID: PMC10575917 DOI: 10.1038/s41598-023-42828-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 09/15/2023] [Indexed: 09/23/2023] Open
Abstract
This study was an attempt to examine the changes in serum levels of ghrelin and leptin after 12-weeks of aerobic training and gonadotropin releasing hormone agonist (GnRH) treatment in girls with central precocious puberty. Thirty girls (6-8 years old) with precocious puberty who had received Triptorelin were randomly divided in two groups (medication and medication + training). Fifteen age-matched healthy girls (without precocious puberty) were also included as the control group. The medication + training group submitted an aerobic training program for 3 days/week with 20-75 min per day and 45-75% of maximum heart rate for 12-weeks. Serum levels of leptin, ghrelin, cholesterol, triglycerides and body mass index (BMI) were determined at baseline and 48 h after the last training session. The results indicated that leptin significantly decreased (p = 0.001) and ghrelin significantly increased (p = 0.001) in the medication + training group but no significant difference was observed in the ghrelin (p = 1) and leptin (p = 0.78) in the medication group. Leptin to ghrelin ratio indicated a decrease in medicine + training group (p = 0.028). Ghrelin were negatively correlated with leptin and BMI. The data indicated that aerobic training increased ghrelin and reduced leptin and leptin to ghrelin ratio but GnRH agonist treatment had no effect on plasma leptin and ghrelin levels.
Collapse
Affiliation(s)
- Ramyar Najafi
- Faculty of Sport Sciences, Bu-Ali Sina University, Hamedan, Iran
| | | | - Elnaz Shokri
- Faculty of Sport Sciences, Bu-Ali Sina University, Hamedan, Iran
| | - Behnaz Shokri
- Faculty of Sport Sciences, Bu-Ali Sina University, Hamedan, Iran
| |
Collapse
|
|
15
|
Kim SJ, Kim JH, Hong YH, Chung IH, Lee EB, Kang E, Kim J, Yang A, Rhie YJ, Yoo EG, Shin YL, Choi JH, Kim SY, Lee J. 2022 Clinical practice guidelines for central precocious puberty of Korean children and adolescents. Ann Pediatr Endocrinol Metab 2023; 28:168-177. [PMID: 37798893 PMCID: PMC10556443 DOI: 10.6065/apem.2346168.084] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 09/19/2023] [Indexed: 10/07/2023] Open
Abstract
The Committee of Central Precocious Puberty of Korean Pediatrics and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based 2022 clinical practice guidelines for central precocious puberty in Korean children and adolescents. These guidelines provide the grade of recommendations, which includes both the strength of recommendations and the level of evidence. In the absence of sufficient evidence, recommendations are based on expert opinion. These guidelines have been revised and supplement the previous guidelines "Clinical Guidelines for Precocious Puberty 2011," and are drawn from a comprehensive review of the latest domestic and international research and the grade of recommendation appropriate to the domestic situation. This review summarizes the newly revised guidelines into 8 key questions and 27 recommendations and consists of 4 sections: screening, diagnosis, treatment, and long-term outcome of central precocious puberty.
Collapse
Affiliation(s)
- Su Jin Kim
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, Korea
| | - Ji Hyun Kim
- Department of Pediatrics, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Yong Hee Hong
- Department of Pediatrics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - In Hyuk Chung
- Department of Pediatrics, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Eun Byoul Lee
- Department of Pediatrics, Catholic Kwandong University International St. Mary’s Hospital, Incheon, Korea
| | - Eungu Kang
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Jinsup Kim
- Department of Pediatrics, Hanyang University Medical Center, Hanyang University College of Medicine, Seoul, Korea
| | - Aram Yang
- Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Jun Rhie
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Eun-Gyong Yoo
- Department of Pediatrics, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Young-Lim Shin
- Department of Pediatrics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Jin Ho Choi
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Soo Young Kim
- Department of Family Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Jieun Lee
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, Korea
| | - Committee of Central precocious puberty of Korean Children and Adolescents on behalf of Korean Society of Pediatric Endocrinology (KSPE)
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, Korea
- Department of Pediatrics, Dongguk University Ilsan Hospital, Goyang, Korea
- Department of Pediatrics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Korea
- Department of Pediatrics, National Health Insurance Service Ilsan Hospital, Goyang, Korea
- Department of Pediatrics, Catholic Kwandong University International St. Mary’s Hospital, Incheon, Korea
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
- Department of Pediatrics, Hanyang University Medical Center, Hanyang University College of Medicine, Seoul, Korea
- Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Pediatrics, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Family Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| |
Collapse
|
|
16
|
Oh YR, Kim YJ, Oh KE, Park GH, Kang E, Nam HK, Rhie YJ, Oh S, Lee KH. Brain magnetic resonance imaging (MRI) findings in central precocious puberty patients: is routine MRI necessary for newly diagnosed patients? Ann Pediatr Endocrinol Metab 2023; 28:200-205. [PMID: 37798894 PMCID: PMC10556448 DOI: 10.6065/apem.2244192.096] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 12/29/2022] [Accepted: 03/06/2023] [Indexed: 10/07/2023] Open
Abstract
PURPOSE The overall incidence of central precocious puberty (CPP) has increased in recent decades, and brain magnetic resonance imaging (MRI) evaluations are recommended in cases of suspected brain lesions. This study aimed to investigate the prevalence of MRI abnormalities and to evaluate the need for routine brain MRI in patients with newly diagnosed CPP. METHODS This retrospective study reviewed the data of patients newly diagnosed with CPP who underwent routine pituitary MRI at Korea University Anam Hospital from March 2020 to September 2021. A total of 199 girls and 24 boys was enrolled in this study. Positive MRI findings were categorized as abnormal pituitary, nonpituitary incidental, and pathological. In addition, we investigated the incidence of MRI abnormalities and evaluated their associations with clinical and biochemical factors. RESULTS Positive brain MRI findings were observed in 84 patients (37.7%). Pituitary abnormalities were found in 54 patients (24.2%), with Rathke cleft cysts being the most common (16.1%). Incidental nonpituitary findings were observed in 29 patients (13.0%), while a pathological brain lesion (diagnosed as hypothalamic hamartoma) was observed in only 1 female patient (0.4%). No significant differences in sex or age were found in incidence of pituitary abnormalities or nonpituitary incidental findings. Compared with headache controls, significant associations were observed between abnormal pituitary findings on MRI and CPP (unadjusted odds ratio, 3.979; 95% confidence interval, 1.726-9.173). CONCLUSION True pathological findings were rare, even though the prevalence of abnormalities on pituitary MRI in patients with CPP was relatively high. Considering its cost-effectiveness, MRI screenings should be carefully considered in patients with CPP.
Collapse
Affiliation(s)
- Ye Rim Oh
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Yu Jin Kim
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Kyeong Eun Oh
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Gyu Hyun Park
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Eungu Kang
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Hyo-Kyoung Nam
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Young-Jun Rhie
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Saelin Oh
- Department of Radiology, Korea University College of Medicine, Seoul, Korea
| | - Kee-Hyoung Lee
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| |
Collapse
|
|
17
|
Choe Y, Cha JH, Kim YJ, Choi J, Lee K, Kim N, Na JY, Yang S. Rapid weight gain in early life is associated with central precocious puberty in girls, not in boys - a nationwide population-based study in Korea. Front Endocrinol (Lausanne) 2023; 14:1210995. [PMID: 37522114 PMCID: PMC10381025 DOI: 10.3389/fendo.2023.1210995] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 06/21/2023] [Indexed: 08/01/2023] Open
Abstract
OBJECTIVES This study aimed to investigate the effect of rapid weight gain (RWG) on the incidence of central precocious puberty (CPP) using nationwide population-based data. METHODS A total of 253,967 children (101,841 boys and 152,126 girls) who underwent regular health consultations under the National Health Insurance Service from 2007 to 2010 were followed up until the age of 10 years for boys and 9 years for girls. We calculated differences in the weight Z-scores from 4-6 months to 9-12 months (infancy) and from 9-12 months to 18-24 months or 30-36 months (toddlerhood) using the lambda-mu-sigma method. The population was subdivided into four groups: RWGinf/tod (infancy > + 0.67 standard deviation score [SDS], toddlerhood > 0 SDS), RWGinf (infancy > + 0.67 SDS, toddlerhood < 0 SDS), RWGtod (toddlerhood > + 0.67 SDS), and control (no RWG). The diagnosis of CPP was based on the diagnostic codes of the International Classification of Diseases 10th revision and the prescription of gonadotropin-releasing hormone agonists. The cumulative risk of CPP based on age was analyzed using Kaplan-Meier survival curves, and the association between the RWG groups and CPP was assessed using multivariate logistic regression analysis. RESULTS CPP was diagnosed in 268 boys and 9,225 girls. For the girls, the CPP-free probability was the highest in the control group, followed by the RWGtod, RWGinf, and RWGinf/tod groups (log-rank p < 0.001). However, the incidence of CPP did not vary significantly for the boys. Compared to the control group, the other groups had a higher risk of CPP in girls (RWGinf/tod: adjusted odds ratio [aOR] 1.35, 95%, confidence interval [95% CI] 1.13-1.62; RWGinf: aOR 1.25, 95% CI 1.13-1.38; and RWGtod: aOR 1.18, 95% CI 1.09-1.28). CONCLUSIONS This nationwide population-based study demonstrated that any RWG from birth to 3 years of age contributed to an increased risk of CPP in girls but not in boys. Girls who experienced RWG during both infancy and toddlerhood had the highest risk of developing CPP. These findings suggest that early detection and appropriate management of excessive weight gain in early life may be important for preventing CPP in girls.
Collapse
Affiliation(s)
- Yunsoo Choe
- Department of Pediatrics, Hanyang University Guri Hospital, Guri, Republic of Korea
| | - Jong Ho Cha
- Department of Pediatrics, Hanyang University Hospital, Seoul, Republic of Korea
| | - Yun Jin Kim
- Biostatistical Consulting and Research Lab, Medical Research Collaborating Center, Hanyang University, Seoul, Republic of Korea
| | - Jinjoo Choi
- Department of Pediatrics, Hanyang University Hospital, Seoul, Republic of Korea
| | - Kyeongmi Lee
- Department of Pediatrics, Hanyang University Hospital, Seoul, Republic of Korea
| | - Nayoung Kim
- Department of Pediatrics, Hanyang University Hospital, Seoul, Republic of Korea
| | - Jae Yoon Na
- Department of Pediatrics, Hanyang University Hospital, Seoul, Republic of Korea
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Seung Yang
- Department of Pediatrics, Hanyang University Hospital, Seoul, Republic of Korea
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
18
|
Pan C, Li C, Cheng S, Chen Y, Zhang J, Zhang Z, Zhang H, Liu L, Meng P, Yang X, Cheng B, Wen Y, Jia Y, Zhang F. The Effect of Secondary Sexual Characteristics Outset Time Abnormality on Addiction in Adults: a Mendelian Randomization Study. Int J Ment Health Addict 2023. [DOI: 10.1007/s11469-023-01037-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2023] Open
|
|
19
|
Brito VN, Canton APM, Seraphim CE, Abreu AP, Macedo DB, Mendonca BB, Kaiser UB, Argente J, Latronico AC. The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty. Endocr Rev 2023; 44:193-221. [PMID: 35930274 PMCID: PMC9985412 DOI: 10.1210/endrev/bnac020] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Indexed: 01/20/2023]
Abstract
The etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or functional brain alterations. All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP.
Collapse
Affiliation(s)
- Vinicius N Brito
- Discipline of Endocrinology & Metabolism, Department of Internal
Medicine, University of Sao Paulo Medical School, University of Sao
Paulo, Sao Paulo 01246 903, Brazil
| | - Ana P M Canton
- Discipline of Endocrinology & Metabolism, Department of Internal
Medicine, University of Sao Paulo Medical School, University of Sao
Paulo, Sao Paulo 01246 903, Brazil
| | - Carlos Eduardo Seraphim
- Discipline of Endocrinology & Metabolism, Department of Internal
Medicine, University of Sao Paulo Medical School, University of Sao
Paulo, Sao Paulo 01246 903, Brazil
| | - Ana Paula Abreu
- Division of Endocrinology, Diabetes and Hypertension, Department of
Medicine, Brigham and Women’s Hospital, Harvard Medical School,
Boston, MA 02115, USA
| | - Delanie B Macedo
- Discipline of Endocrinology & Metabolism, Department of Internal
Medicine, University of Sao Paulo Medical School, University of Sao
Paulo, Sao Paulo 01246 903, Brazil
- Division of Endocrinology, Diabetes and Hypertension, Department of
Medicine, Brigham and Women’s Hospital, Harvard Medical School,
Boston, MA 02115, USA
- Núcleo de Atenção Médica Integrada, Centro de Ciências da Saúde,
Universidade de Fortaleza, Fortaleza 60811 905,
Brazil
| | - Berenice B Mendonca
- Discipline of Endocrinology & Metabolism, Department of Internal
Medicine, University of Sao Paulo Medical School, University of Sao
Paulo, Sao Paulo 01246 903, Brazil
| | - Ursula B Kaiser
- Division of Endocrinology, Diabetes and Hypertension, Department of
Medicine, Brigham and Women’s Hospital, Harvard Medical School,
Boston, MA 02115, USA
| | - Jesús Argente
- Hospital Infantil Universitario Niño Jesús, Department of Endocrinology and
Department of Pediatrics, Universidad Autónoma de Madrid, Spanish PUBERE Registry,
CIBER of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, IMDEA
Institute, Madrid 28009, Spain
| | - Ana Claudia Latronico
- Discipline of Endocrinology & Metabolism, Department of Internal
Medicine, University of Sao Paulo Medical School, University of Sao
Paulo, Sao Paulo 01246 903, Brazil
| |
Collapse
|
|
20
|
Won EJ, Yi A, Ko YJ, Kim S, Kang SH, Park G, Jang SJ. Establishment of Korean Pediatric Reference Intervals for Estradiol using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry. Clin Biochem 2023; 113:52-58. [PMID: 36627011 DOI: 10.1016/j.clinbiochem.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 01/03/2023] [Accepted: 01/06/2023] [Indexed: 01/09/2023]
Abstract
BACKGROUND Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is a reliable and accurate method for measuring steroid hormone levels. There is an increasing need for sensitive and precise methods to measure estradiol in pediatric patients. Here, we established reference intervals for estradiol in healthy children using a UHPLC-MS/MS-based method for the first time in South Korea. METHODS Serum estradiol was measured using a Sciex Triple QuadTM 6500 + UHPLC-MS/MS (Sciex, Framingham, MA, USA). Reference intervals for estradiol were established according to the CLSI document EP28-A3c:2008. The reference intervals were validated using serum samples from 634 pediatric patients, including neonates, children, and adolescents. Among them, 389 specimens were used in analysis of the specimen acceptance time. Statistical analysis was performed using MedCalc (MedCalc, Ostend, Belgium) and Analyse-it (Analyse-it Software Ltd., Leeds, United Kingdom) software. RESULTS Reference intervals for boys (n = 297) were <16.6, <7.3, <19.0, <30.5, 7.6-96.5, and 10.6-134.4 pmol/L among those aged <1, 1-5, 6-9, 10-11, 12-14, and 15-17 years, respectively. Reference intervals for girls (n = 337) were <114.7, <24.2, <34.8, 8.0-177.0, 10.4-480.5, and 9.1-486.7 pmol/L among those aged <1, 1-5, 6-9, 10-11, 12-14, and 15-17 years, respectively. Overall, there was no effect of specimen acceptance time on estradiol measurements in boys or girls, except for that in the group aged 10-11 years. CONCLUSIONS The reference intervals for healthy children were validated using a UHPLC-MS/MS-based method. The highly analytical sensitive UHPLC-MS/MS method may be useful for estradiol determination in pediatric patients.
Collapse
Affiliation(s)
- Eun Jeong Won
- Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun, South Korea
| | - Ahram Yi
- Department of Laboratory Medicine, Green Cross Laboratories (GC Labs), Yongin, Gyeonggi, South Korea
| | - Young Jin Ko
- Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, South Korea.
| | - Serim Kim
- Department of Laboratory Medicine, Green Cross Laboratories (GC Labs), Yongin, Gyeonggi, South Korea
| | - Seong-Ho Kang
- Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, South Korea
| | - Geon Park
- Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, South Korea
| | - Sook-Jin Jang
- Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, South Korea
| |
Collapse
|
|
21
|
Cho AY, Shim YS, Lee HS, Hwang JS. Effect of gonadotropin-releasing hormone agonist monotherapy and combination therapy with growth hormone on final adult height in girls with central precocious puberty. Sci Rep 2023; 13:1264. [PMID: 36690835 PMCID: PMC9870989 DOI: 10.1038/s41598-023-28602-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 01/20/2023] [Indexed: 01/24/2023] Open
Abstract
This study aimed to compare clinical parameters, including final adult height (FAH), in girls with central precocious puberty treated with gonadotropin-releasing hormone agonists (GnRHa) with and without growth hormone (GH). This retrospective study reviewed data of 210 girls with precocious puberty who had reached FAH in a long-term trial of GnRHa treatment. The subjects were divided into the GnRHa treatment group (n = 188), and the combined GnRHa + GH treatment group (n = 22). Chronological age, bone age, height, height standard deviation score, predicted adult height (PAH), FAH, Tanner stage, and hormone levels were assessed during the treatment period. At the start of treatment, PAH was 156.35 ± 6.34 cm in the GnRHa monotherapy group and 150.41 ± 5.32 cm in the GnRHa + GH group (P < 0.001). At the end of treatment, PAH was 166.25 ± 5.26 cm in the GnRHa group and 164.07 ± 4.99 cm in the combined GnRHa + GH treatment group, which had increased compared to the start of treatment. The FAH in the GnRHa group and GnRHa + GH combination group were 161.07 ± 4.78 cm and 159.63 ± 3.8 6 cm, respectively, without significant difference. In addition, the height gain (FAH-PAH) was significantly higher in the GnRHa + GH group than the GnRHa group (9.22 ± 6.03 cm vs. 4.72 ± 5.01 cm, P < 0.001). In girls with central precocious puberty, the height gain in the FAH compared to PAH at the start of treatment was significantly higher with the GnRHa + GH combination treatment.
Collapse
Affiliation(s)
- Ah Young Cho
- Department of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, San 5, Wonchon-dong, Yeongtong-gu, Suwon, 443-721, Korea
| | - Young Suk Shim
- Department of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, San 5, Wonchon-dong, Yeongtong-gu, Suwon, 443-721, Korea
| | - Hae Sang Lee
- Department of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, San 5, Wonchon-dong, Yeongtong-gu, Suwon, 443-721, Korea.
| | - Jin Soon Hwang
- Department of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, San 5, Wonchon-dong, Yeongtong-gu, Suwon, 443-721, Korea
| |
Collapse
|
|
22
|
Tselebis A, Zabuliene L, Milionis C, Ilias I. Pandemic and precocious puberty - a Google trends study. World J Methodol 2023; 13:1-9. [PMID: 36684480 PMCID: PMC9850652 DOI: 10.5662/wjm.v13.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 11/29/2022] [Accepted: 01/11/2023] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Recent publications from several countries have reported that more young people (mainly girls) are experiencing precocious puberty (PP)/menarche during the coronavirus disease 2019 pandemic compared to the past. This variation is attributed to the stress of confinement, lack of exercise, obesity and disturbed sleep patterns. A common feature of the relevant papers, however, is the small number of reported cases of PP. Studies have shown that searches for diseases on the internet also reflect to some extent the epidemiology of these diseases.
AIM To estimate, through internet searches for PP, any changes in the epidemiology of PP.
METHODS We assessed in Google Trends searches for 21 PP-related terms in English internationally (which practically dwarf searches in other languages), in the years 2017-2021. Additionally, we assessed local searches for selected terms, in English and local languages, in countries where a rise in PP has been reported. Searches were collected in Relative Search Volumes format and analyzed using Kendall’s Tau test, with a statistical significance threshold of P < 0.05.
RESULTS Internationally, searches for three PP-related terms showed no noticeable change over the study period, while searches for eight terms showed a decrease. An increase was found over time in searches for nine PP-related terms. Of the 17 searches in English and local languages, in countries where a rise in PP has been reported, 5 showed a significant increase over time.
CONCLUSION Over the study period, more than half of the search terms showed little change or declined. The discrepancy between internet searches for PP and the reported increase in the literature is striking. It would be expected that a true increase in the incidence of PP would also be aptly reflected in Google trends. If our findings are valid, the literature may have been biased. The known secular trend of decreasing age of puberty may also have played a role.
Collapse
Affiliation(s)
- Athanasios Tselebis
- Department of Psychiatry, “Sotiria” General Chest Diseases Hospital, Athens GR-11527, Greece
| | - Lina Zabuliene
- Faculty of Medicine, Vilnius University, Vilnius LT-03101, Lithuania
| | - Charalampos Milionis
- Department of Endocrinology, Elena Venizelou General and Maternity Hospital, Athens GR-11521, Greece
| | - Ioannis Ilias
- Department of Endocrinology, Elena Venizelou General and Maternity Hospital, Athens GR-11521, Greece
| |
Collapse
|
|
23
|
Yoo E, Kim S, Jung HL, Shim JY, Shim JW, Kim DS, Kwak JH, Kim ES, Yang A. Impact of 6-month triptorelin formulation on predicted adult height and basal gonadotropin levels in patients with central precocious puberty. Front Endocrinol (Lausanne) 2023; 14:1134977. [PMID: 36875449 PMCID: PMC9982112 DOI: 10.3389/fendo.2023.1134977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 02/03/2023] [Indexed: 02/19/2023] Open
Abstract
BACKGROUND Triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist, is available in 1-, 3-, and 6-month formulations to treat central precocious puberty (CPP). The triptorelin pamoate 22.5-mg 6-month formulation recently approved for CPP offers greater convenience to children by reducing the injection frequency. However, worldwide research on using the 6-month formulation to treat CPP is scarce. This study aimed to determine the impact of the 6-month formulation on predicted adult height (PAH), changes in gonadotropin levels, and related variables. METHODS We included 42 patients (33 girls and nine boys) with idiopathic CPP treated with a 6-month triptorelin (6-mo TP) formulation for over 12 months. Auxological parameters, including chronological age, bone age, height (cm and standard deviation score [SDS]), weight (kg and SDS), target height (TH), and Tanner stage, were evaluated at baseline, and after 6, 12, and 18 months of treatment. Hormonal parameters, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol for girls or testosterone for boys, were analyzed concurrently. RESULTS The mean age at treatment initiation was 8.6 ± 0.83 (8.3 ± 0.62 for girls, 9.6 ± 0.68 for boys). The peak LH level following intravenous GnRH stimulation at diagnosis was 15.47 ± 9.94 IU/L. No progression of the modified Tanner stage was observed during treatment. Compared to baseline, LH, FSH, estradiol, and testosterone were significantly reduced. In particular, the basal LH levels were well suppressed to less than l.0 IU/L, and the LH/FSH ratio was less than 0.66. The bone age/chronological age ratio remained stable with a decreasing trend (1.15 at the start of treatment, 1.13 at 12 months, 1.11 at 18 months). PAH SDS increased during treatment (0.77 ± 0.79 at baseline, 0.87 ± 0.84 at the start of treatment, 1.01 ± 0.93 at six months, and 0.91 ± 0.79 at 12 months). No adverse effects were observed during treatment. CONCLUSION The 6-mo TP suppressed the pituitary-gonadal axis stably and improved the PAH during treatment. Considering its convenience and effectiveness, a significant shift to long-acting formulations can be expected.
Collapse
Affiliation(s)
- Eunjoo Yoo
- Department of Pediatrics, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Sinae Kim
- Biostatistics Collaboration Team, Research Core Center, National Cancer Center, Goyang, Republic of Korea
| | - Hye Lim Jung
- Department of Pediatrics, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Jung Yeon Shim
- Department of Pediatrics, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Jae Won Shim
- Department of Pediatrics, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Deok Soo Kim
- Department of Pediatrics, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Ji Hee Kwak
- Department of Pediatrics, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Eun Sil Kim
- Department of Pediatrics, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Aram Yang
- Department of Pediatrics, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
- *Correspondence: Aram Yang,
| |
Collapse
|
|
24
|
Kang S, Park MJ, Kim JM, Yuk JS, Kim SH. Ongoing increasing trends in central precocious puberty incidence among Korean boys and girls from 2008 to 2020. PLoS One 2023; 18:e0283510. [PMID: 36947549 PMCID: PMC10032490 DOI: 10.1371/journal.pone.0283510] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 03/09/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND Over the last few decades, there has been growing evidence of earlier onset and progression of puberty worldwide. This population-based longitudinal cohort study aimed to analyze the change in the annual incidence rate of central precocious puberty (CPP) among Korean children over the most recent decade, using the national registry data. METHOD The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) and insurance claims for gonadotropin-releasing hormone agonist (GnRHa) treatment were used to identify CPP patients who were using the Korean Health Insurance Review & Assessment Service (HIRA) database between 2008 and 2020. Patients who began GnRHa therapy before the age of 9 and 10 for girls and boys, respectively, were included in the study. RESULTS A total of 6,906 boys and 126,377 girls were diagnosed with CPP between 2008 and 2020. The annual incidence of CPP increased by 83.3 times in boys (from 1.2 to 100 per 100,000 persons) and by 15.9 times in girls (from 88.9 to 1414.7 per 100,000 persons). The age-specific annual incidence of CPP increased remarkably more in older children than in younger ones; the 2020 CPP incidence among 9-year-old boys and 8-year-old girls reached 705.2 and 7,967.3 per 100,000 persons, respectively. The annual prevalence of CPP in boys and girls increased from 2.7 to 206.5 (76.5 times) and from 141.8 to 3439.9 (24.3 times) per 100,000 persons, respectively. CONCLUSION Based on GnRHa treatment insurance claims, our study suggests that the annual incidence of CPP has substantially increased in Korea during the past 13 years. These findings highlight the importance of meticulous judgment by doctors in determining GnRHa treatment.
Collapse
Affiliation(s)
- Sinyoung Kang
- Department of Pediatrics, Samil Hospital, Daegu, Korea
| | - Mi Jung Park
- Dr. Park Mijung's Child Growth Clinic, Seoul, Korea
| | - Jung Min Kim
- Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Jin-Sung Yuk
- Department of Obstetrics and Gynecology, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Shin-Hye Kim
- Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea
| |
Collapse
|
|
25
|
Al-Hassan OA, Limbe MS, Warner J, Musa SA, Abdullah MA. Central precocious puberty in Sudan: 10 years' experience of paediatric endocrinology centres. Sudan J Paediatr 2023; 23:145-152. [PMID: 38380412 PMCID: PMC10876265 DOI: 10.24911/sjp.106-1652031727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 09/13/2023] [Indexed: 02/22/2024]
Abstract
Central precocious puberty (CPP) is frequently seen among cases presenting to our endocrine clinics. The purpose of this study was to have base line data on this condition with an attempt to point out any possible unique features of Sudan and to explore challenges faced in management and how that cultural and traditional practices may hamper care. Here, we are reporting the first data on this aspect from Sudanese subjects. Patients labelled as having CPP in Gafaar Ibnauf Children's Hospital and Soba University Hospital Endocrinology Clinics from January 2006 to 2016 are included in a descriptive hospital-based study which was conducted over 10 years in these two main paediatric endocrinology centres. Records of all patients with CPP were reviewed and challenges in diagnosis and management were identified. Most of the children with CPP presented late. Organic causes were more frequent among girls than what has been reported in the literature; in most boys, it was idiopathic. Almost half of the patients with underlying pathology were older than 6 years of age. Most cases including girls have an organic cause, thus magnetic resonance image should be done in all patients. Management of precocious puberty in a resource-limited country is faced with various challenges (e.g., expensive investigations and medications). We suggest establishing a unified protocol for managing these cases and creating collaboration between governmental, nongovernmental organisations and health services.
Collapse
Affiliation(s)
- Olivia A. Al-Hassan
- Department of Paediatric Endocrinology and Diabetes, Aladan Hospital, Kuwait
| | - Mary S. Limbe
- Department of Paediatric, Aga Khan University, Nairobi, Kenya
| | - Justin Warner
- Department of Paediatric Endocrinology, Noah’s Ark Children’s Hospital for Wales, Cardiff, United Kingdom
| | - Salwa A. Musa
- Department of Paediatrics and Child Health, Faculty of Medicine, Al-Neelain University, Khartoum, Sudan
- Department of Paediatric Endocrinology and Diabetes, Gafaar Ibnauf Children’s Hospital, Khartoum, Sudan
| | - Mohamed A. Abdullah
- Department of Paediatric Endocrinology and Diabetes, Gafaar Ibnauf Children’s Hospital, Khartoum, Sudan
- Department of Paediatrics and Child Health, Faculty of Medicine, University of Khartoum, Khartoum, Sudan
| |
Collapse
|
|
26
|
The Role of Genetics in Central Precocious Puberty: Confirmed and Potential Neuroendocrine Genetic and Epigenetic Contributors and Their Interactions with Endocrine Disrupting Chemicals (EDCs). ENDOCRINES 2022. [DOI: 10.3390/endocrines3030035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Despite the growing prevalence of central precocious puberty (CPP), most cases are still diagnosed as “idiopathic” due to the lack of identifiable findings of other diagnostic etiology. We are gaining greater insight into some key genes affecting neurotransmitters and receptors and how they stimulate or inhibit gonadotropin-releasing hormone (GnRH) secretion, as well as transcriptional and epigenetic influences. Although the genetic contributions to pubertal regulation are more established in the hypogonadotropic hypogonadism (HH) literature, cases of CPP have provided the opportunity to learn more about its own genetic influences. There have been clinically confirmed cases of CPP associated with gene mutations in kisspeptin and its receptor (KISS1, KISS1R), Delta-like noncanonical Notch ligand 1 (DLK1), and the now most commonly identified genetic cause of CPP, makorin ring finger protein (MKRN3). In addition to these proven genetic causes, a number of other candidates continue to be evaluated. After reviewing the basic clinical aspects of puberty, we summarize what is known about the various genetic and epigenetic causes of CPP as well as discuss some of the potential effects of endocrine disrupting chemicals (EDCs) on some of these processes.
Collapse
|
|
27
|
Peinkhofer M, Bossini B, Penco A, Giangreco M, Pellegrin MC, Vidonis V, Vittori G, Grassi N, Faleschini E, Barbi E, Tornese G. Reduction in pediatric growth hormone deficiency and increase in central precocious puberty diagnoses during COVID 19 pandemics. Ital J Pediatr 2022; 48:49. [PMID: 35346309 PMCID: PMC8960104 DOI: 10.1186/s13052-022-01238-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 03/08/2022] [Indexed: 01/14/2023] Open
Abstract
Abstract
Background
While several studies have been published so far on the effect of COVID-19 pandemic on health care for non-COVID-19 diseases, to date no study evaluated the impact of the COVID-19 pandemic on the entire field of pediatric endocrinology. This study aimed to evaluate differences in pediatric endocrine stimulation tests after the advent of COVID-19 pandemics.
Methods
Retrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 and 2020 in a tertiary center.
Results
Overall, 251 tests were performed on 190 patients in 2020, compared to 278 tests on 206 patients in 2019 (− 10% tests; − 8% children evaluated). A significant reduction was found in tests to diagnose growth hormone deficiency (GHD) (− 35%), while LHRH tests increased (+ 22%). A reduction of 30% in GHD diagnosis was observed. Central precocious puberty (CPP) diagnosis increased by 38% compared to 2019, mainly in females.
Conclusion
This study found a significant reduction of tests investigating GHD during COVID-19 pandemics. It also showed a clinically meaningful increase in cases of CPP in girls. These results suggest the need for families and pediatricians to monitor children’s growth during isolation and enlighten new perspectives towards conditions associated with lockdown restrictions as increased screen time, social isolation, and children’s anxiety as possible triggers of CPP.
Collapse
|
|
28
|
Development and Validation of Clinical Diagnostic Model for Girls with Central Precocious Puberty: Machine-learning Approaches. PLoS One 2022; 17:e0261965. [PMID: 35061754 PMCID: PMC8782515 DOI: 10.1371/journal.pone.0261965] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 12/14/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND A brief gonadotropin-releasing hormone analogues (GnRHa) stimulation test which solely focused on LH 30-minute post-stimulation was considered to identify girls with central precocious puberty (CPP). However, it was tested using traditional statistical methods. With advanced computer science, we aimed to develop a machine learning-based diagnostic model that processed baseline CPP-related variables and a brief GnRHa stimulation test for CPP diagnosis. METHODS We recruited girls suspected of precocious puberty and underwent a GnRHa stimulation test at Children Hospital 2, Vietnam, and Cathay General Hospital, Taiwan. Clinical data, bone age measurement, and 30-min post-stimulation blood test were used to build up the predictive model. The candidate model was developed by different machine learning algorithms that were mainly evaluated by sensitivity, specificity, the area under the receiver operator characteristic curve (AUC), and F1-score in internal and external validation data to classify girls as CPP and non-CPP at different time-points (0-min, 30-min, 60-min, and 120-min post-stimulation). RESULTS Among the 614 girls diagnosed with PP, 524 (85.3%) had CPP. The random forest algorithm yielded the highest value of F1-score (0.976), specificity (0.893), positive predicted value (0.987), and relatively high value of AUC (0.972) that contributed to high probability to identify CPP. The performance metrics of the 30-min post-stimulation diagnostic model including sensitivity and specificity surpassed those of the 0-minute model (0-min) and were equivalent to those of the model obtained 60-min and 120-min post-stimulation. Hence, our machine learning-based model helps shorten the stimulation test to 30 minutes after GnRHa injection, in general, it requires 120 minutes for a completed GnRHa stimulation test. CONCLUSIONS We developed a diagnostic model based on clinical features and a single sample 30-minute post-stimulation to identify CPP in girls that can reduce distress for children caused by multiple blood samplings.
Collapse
|
|
29
|
Soriano-Guillén L, Tena-Sempere M, Seraphim CE, Latronico AC, Argente J. Precocious sexual maturation: Unravelling the mechanisms of pubertal onset through clinical observations. J Neuroendocrinol 2022; 34:e12979. [PMID: 33904190 DOI: 10.1111/jne.12979] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/09/2021] [Accepted: 04/09/2021] [Indexed: 01/05/2023]
Abstract
Puberty is a crucial biological process normally occurring at a specific time during the lifespan, during which sexual and somatic maturation are completed, and reproductive capacity is reached. Pubertal timing is not only determined by genetics, but also by endogenous and environmental cues, including nutritional and metabolic signals. During the last decade, we have learned much regarding the essential roles of kisspeptins and the neuropeptide pathways that converge on these neurones to modulate kisspeptin signalling, as well as neurokinin B and dynorphin, the co-transmitters of Kiss1 neurones in the arcuate nucleus, and the effects of melanocortins on puberty. Indeed, melanocortins are involved in transmitting the regulatory actions of metabolic cues on pubertal maturation. Intracellular metabolic sensors, such as the AMP-activated protein kinase and the fuel-sensing deacetylase SIRT1, have been shown to contribute to puberty. Further understanding of these signals and regulatory circuits will help uncover the intimacies of the central control of puberty, as well as how alterations in metabolic status, ranging from undernutrition to obesity, affect the pubertal process. Precocious puberty is rare and has a clear female predominance. Central precocious puberty (CPP) is diagnosed when premature activation of the hypothalamic-pituitary axis occurs. Its causes are heterogeneous, with alterations of the central nervous system being of special interest, and with environmental factors also playing a role in some cases. During the last decade, several mutations in different genes (including KISS1, KISS1R, MKRN3 and DLK1) that cause CPP have been discovered. Loss-of-function mutations in MKRN3 are the most common monogenic cause of CPP known to date. Here, we review and update what is known regarding the genotype-phenotype relationship in patients with CPP.
Collapse
Affiliation(s)
- Leandro Soriano-Guillén
- Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain
- Department of Pediatrics, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
- Instituto de Investigación Fundación Jiménez Díaz, Madrid, Spain
| | - Manuel Tena-Sempere
- Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Córdoba, Spain
- Hospital Universitario Reina Sofía, Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Córdoba, Spain
- Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine and Turku Center for Disease Modeling, University of Turku, Turku, Finland
| | - Carlos E Seraphim
- Laboratory of Hormones and Molecular Genetics, LIM42, Developmental Endocrinology Unit, Department of Internal Medicine, Discipline Endocrinology and Metabolism, Faculty of Medicine, Clinicas Hospital, University of Sao Paulo, Sao Paulo, Brazil
| | - Ana C Latronico
- Laboratory of Hormones and Molecular Genetics, LIM42, Developmental Endocrinology Unit, Department of Internal Medicine, Discipline Endocrinology and Metabolism, Faculty of Medicine, Clinicas Hospital, University of Sao Paulo, Sao Paulo, Brazil
| | - Jesús Argente
- Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain
- Department of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- IMDEA Food Institute, CEIUAM+CSIC, Madrid, Spain
| |
Collapse
|
|
30
|
Choi KH, Park SC. An increasing tendency of precocious puberty among Korean children from the perspective of COVID-19 pandemic effect. Front Pediatr 2022; 10:968511. [PMID: 36090560 PMCID: PMC9454605 DOI: 10.3389/fped.2022.968511] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/03/2022] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION This study was conducted to investigate changes and new trends over the past 6 years by analyzing the current status of precocious puberty (PP) treatment and treatment costs in Korea between 2016 and 2021. MATERIALS AND METHODS Annual and monthly number of patients diagnosed with PP from 2016 to 2021 were reviewed using the data from Healthcare Bigdata Hub. Annual medical insurance expenses for the treatment of PP were also reviewed. The data were compared by the gender of the patients. RESULTS The number of patients diagnosed with PP rose from 86,352 in 2016 to 166,645 in 2021, while medical expenses rose from KRW 64,111,689,000 in 2016 to KRW 134,642,100,000 in 2021. The percentage of male PP patients increased from 9.21% in 2016 to 19.55% in 2021. CONCLUSION Increasing numbers of Korean patients diagnosed with PP. Consistent with the situation in other countries, the rapid increase in the number of cases since April 2020 appears to be a result of the COVID-19 pandemic. In Korea, this is considered a nationwide phenomenon. Also on the rise is the incidence of PP in males, which appears to be due to an increased awareness of the phenomenon. Further investigations are required to determine the possible causes in increasing prevalence of PP.
Collapse
|
|
31
|
Knific T, Lazarevič M, Žibert J, Obolnar N, Aleksovska N, Šuput Omladič J, Battelino T, Avbelj Stefanija M. Final adult height in children with central precocious puberty - a retrospective study. Front Endocrinol (Lausanne) 2022; 13:1008474. [PMID: 36531464 PMCID: PMC9757689 DOI: 10.3389/fendo.2022.1008474] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 11/14/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND/AIMS Central precocious puberty (CPP) is due to premature activation of the hypothalamic-pituitary-gonadal axis. It predominantly affects girls. CPP leads to lower final height (FH), yet the treatment benefit in girls between 6 and 8 years is equivocal. Our main goal was to evaluate the effects of gonadotropin-releasing hormone analog (GnRHa) on FH and identify factors that predict FH. METHODS In a retrospective study, children with CPP (12 boys, 81 girls) that reached FH were included. Their clinical data at diagnosis and up to their final height was compared by descriptive statistics among idiopathic (iCPP) (n=68) and non-idiopathic CPP (nCPP) and between GnRHa treated (n=48) and untreated (n=15) girls with iCPP. The treatment effect of body weight (BW) adjusted GnRHa dosing was evaluated. Univariate linear regression and step-wise multivariable regression including 48 girls with iCPP treated with GnRHa were performed to identify predicting factors for FH. RESULTS Children with idiopathic CPP (iCPP) reached higher FH (p=0.002) than children with non-idiopathic CPP. After the diagnosis, the treated group gained 7.0 cm more than the untreated group. Yet, attributable to individualized decision-making, the FH in both groups was comparable (161.5 cm in treated, 161.0 cm in untreated girls with iCPP), although the onset of menarche was 2.5 years earlier among untreated girls. BW-adjusted dosing suppressed peak luteinizing hormone (LH) below 4.5 IU/L in 95% of children; however, bone age further advanced during therapy in 38% of patients. Predicting factors revealed by multivariable regression were bone age at diagnosis, BMI SDS at diagnosis, LH basal, age at start and cessation of treatment, predicted adult height and target height. (R2 = 0.72). CONCLUSION Children with nCPP had worse FH outcome compared to iCPP despite similar CPP onset and therapeutic characteristics. Treatment by GnRHa using BW-adjusted dosing was effective in delaying menarche onset and reaching target height in girls with iCPP. Multiple factors affecting FH outcome indicated individualized decision-making regarding therapeutic intervention remains challenging. In the treated patients, among the factors that can be influenced, height at treatment cessation most significantly influenced the outcome.
Collapse
Affiliation(s)
- Taja Knific
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Melisa Lazarevič
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Janez Žibert
- Centre for Health Informatics and Statistics, Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia
| | - Nika Obolnar
- Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Nataša Aleksovska
- Department of Vascular Surgery, Izola General Hospital, Izola, Slovenia
| | - Jasna Šuput Omladič
- Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Tadej Battelino
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Magdalena Avbelj Stefanija
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
- *Correspondence: Magdalena Avbelj Stefanija,
| |
Collapse
|
|
32
|
Ziqin L, Xiaohui L, Xiaobo C. Precocious Puberty in Boys: A Study Based on Five Years of Data from a Single Center in Northern China. J Clin Res Pediatr Endocrinol 2021; 13:418-425. [PMID: 34013711 PMCID: PMC8638629 DOI: 10.4274/jcrpe.galenos.2021.2021.0033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
OBJECTIVE To evaluate the clinical features and etiology of precocious puberty (PP) in Chinese boys. METHODS In this study, data from boys who were referred for evaluation of PP from 2015 to 2020 at a tertiary hospital in Northern China were retrospectively analyzed. RESULTS Eighty-two boys were diagnosed with PP from 2015 to 2020. Sixty-two patients (75.6%) were diagnosed with central PP (CPP), and twenty patients (24.4%) were diagnosed with peripheral PP (PPP). In the CPP group, forty-nine cases were classified as idiopathic CPP, and thirteen patients had pathogenic CPP. The top three causes of PPP were congenital adrenal hyperplasia, germ cell tumors and familial male-limited PP. CONCLUSION The etiology of PP in males is diverse. The majority of CPP cases in Chinese boys are idiopathic rather than organic.
Collapse
Affiliation(s)
- Liu Ziqin
- Children’s Hospital Capital Institute of Pediatrics, Clinic of Endocrinology, Beijing, China,Graduate School of Peking Union Medical College, Capital Institute of Pediatrics, Beijing, China
| | - Li Xiaohui
- Graduate School of Peking Union Medical College, Capital Institute of Pediatrics, Beijing, China,Children’s Hospital Capital Institute of Pediatrics, Clinic of Cardiovascular Diseases, Beijing, China,* Address for Correspondence: Graduate School of Peking Union Medical College, Capital Institute of Pediatrics, Beijing, China E-mail:
| | - Chen Xiaobo
- Children’s Hospital Capital Institute of Pediatrics, Clinic of Endocrinology, Beijing, China
| |
Collapse
|
|
33
|
Wang C, Chen Q, Yuan K, He M, Zhu J, Fang Y, Hu J, Yan Q. The first central precocious puberty proteomic profiles revealed multiple metabolic networks and novel key disease-associated proteins. Aging (Albany NY) 2021; 13:24236-24250. [PMID: 34748517 PMCID: PMC8610109 DOI: 10.18632/aging.203676] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/28/2021] [Indexed: 12/12/2022]
Abstract
Though central precocious puberty (CPP) as a disease that seriously affects the development of a child is increasing year by year, treatment options remain limited and is the same as the 1980s’ method. These are mainly due to the complex pathogenesis of central precocious puberty. Therefore, systems biology approach to identify and explore the multiple factors related to the pathogenesis of central precocious puberty is necessary. Our data established the first proteome profile of CPP revealed 163 down-regulated and 129 were up-regulated differentially expressed proteins. These altered proteins were primarily enriched in three metabolic process including energy metabolism, amino acid metabolism and nitrogenous base metabolism. The identified altered members of the metabolic signaling are valuable and potential novel therapeutic targets of central precocious puberty.
Collapse
Affiliation(s)
- Chunlin Wang
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Qingqing Chen
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Ke Yuan
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Minfei He
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jianfang Zhu
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Yanlan Fang
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jianhong Hu
- Hailiang Hospital, Zhuji, Zhejiang Province, China
| | - Qingfeng Yan
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.,College of Life Science, Zhejiang University, Hangzhou, Zhejiang Province, China
| |
Collapse
|
|
34
|
Cheuiche AV, da Silveira LG, de Paula LCP, Lucena IRS, Silveiro SP. Diagnosis and management of precocious sexual maturation: an updated review. Eur J Pediatr 2021; 180:3073-3087. [PMID: 33745030 DOI: 10.1007/s00431-021-04022-1] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 02/17/2021] [Accepted: 03/08/2021] [Indexed: 12/12/2022]
Abstract
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.
Collapse
Affiliation(s)
- Amanda Veiga Cheuiche
- Post-graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Leticia Guimarães da Silveira
- Post-graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Leila Cristina Pedroso de Paula
- Post-graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.,Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | | | - Sandra Pinho Silveiro
- Post-graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. .,Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
| |
Collapse
|
|
35
|
Helvacıoğlu D, Demircioğlu Turan S, Güran T, Atay Z, Dağçınar A, Bezen D, Özturan EK, Darendeliler F, Yüksel A, Dursun F, Kılınç S, Semiz S, Abalı S, Yıldız M, Önder A, Bereket A. Cranial MRI Abnormalities and Long-term Follow-up of the Lesions in 770 Girls With Central Precocious Puberty. J Clin Endocrinol Metab 2021; 106:e2557-e2566. [PMID: 33765130 DOI: 10.1210/clinem/dgab190] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/20/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Central precocious puberty (CPP) may arise from central nervous system (CNS) lesions in a few affected girls. Recently, the incidence of girls with CPP has increased mostly in 6-8 year olds, in whom the necessity of magnetic resonance imaging (MRI) is debated. OBJECTIVE To investigate the frequency, long-term outcome and potential predictors of CNS lesions in a large cohort of girls with CPP. METHODS A multicenter cohort of 770 Turkish girls with CPP who had systematic cranial MRI between 2005 and 2017. Age at puberty onset was <6 years in 116 and 6-8 years in 654. CNS lesions were followed until final decision(6.2 ± 3.1 years). Potential predictors of CNS lesions were evaluated by univariate analyses. RESULTS A total of 104/770 (13.5%) girls had abnormal brain MRI. Of these, 2.8% were previously known CNS lesions, 3.8% had newly detected and causally related CNS lesions, 3.1 % were possibly, related and 3.8% were incidental. Only 2 (0.25%) neoplastic lesions (1 low grade glioma and 1 meningioma) were identified; neither required intervention over follow-up of 6 and 3.5 years respectively. Age at breast development <6 years (odds ratio [OR] 2.38; 95% CI 1.08-5.21) and the peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio >0.6 (OR 3.13; 95% CI 1.02-9.68) were significantly associated with CNS lesions. However, both patients with neoplastic lesions were >6 years old. CONCLUSION Although age and LH/FSH ratio are significant predictors of CNS lesions, their predictive power is weak. Thus, systematic MRI seems to be the most efficient current approach to avoid missing an occult CNS lesion in girls with CPP, despite the low likelihood of finding a lesion requiring intervention.
Collapse
Affiliation(s)
- Didem Helvacıoğlu
- Marmara University, School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Serap Demircioğlu Turan
- Marmara University, School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Tülay Güran
- Marmara University, School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Zeynep Atay
- Medipol University, School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Adnan Dağçınar
- Marmara University, School of Medicine, Department of Pediatric Neurosurgery, Istanbul, Turkey
| | - Diğdem Bezen
- Prof. Dr. Cemil Taşçıoğlu City Hospital, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Esin Karakılıç Özturan
- İstanbul University, İstanbul School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Feyza Darendeliler
- İstanbul University, İstanbul School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Ayşegül Yüksel
- Kocaeli Derince Education and Research Hospital, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Fatma Dursun
- Health Sciences University, Umraniye Education and Research Hospital, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Suna Kılınç
- Health Sciences University, Bağcılar Education and Research Hospital, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Serap Semiz
- Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Saygın Abalı
- Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Metin Yıldız
- Medeniyet University, Göztepe Education and Research Hospital, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Aşan Önder
- Medeniyet University, Göztepe Education and Research Hospital, Division of Pediatric Endocrinology, Istanbul, Turkey
| | - Abdullah Bereket
- Marmara University, School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Istanbul, Turkey
| |
Collapse
|
|
36
|
Wang G, Tang WY, Ji H, Wang X. Prenatal exposure to mercury and precocious puberty: a prospective birth cohort study. Hum Reprod 2021; 36:712-720. [PMID: 33367618 DOI: 10.1093/humrep/deaa315] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 10/19/2020] [Indexed: 11/15/2022] Open
Abstract
STUDY QUESTION Is in utero exposure to mercury associated with the risk of precocious puberty? SUMMARY ANSWER Prenatal exposure to high levels of mercury was associated with increased risk of precocious puberty, which was strengthened by concomitant maternal cardiometabolic conditions and adverse birth outcomes. WHAT IS KNOWN ALREADY The developing fetus is sensitive to mercury, a well-known endocrine disruptor which impacts the endocrine and reproductive system. STUDY DESIGN, SIZE, DURATION This study included 1512 mother-child pairs from the Boston Birth Cohort, a longitudinal cohort which recruited at birth and followed prospectively up to 21 years of age. PARTICIPANTS/MATERIALS, SETTING, METHODS Mother-child pairs, from a predominantly urban minority population, were enrolled from 2002 to 2013. Prenatal exposure was assessed by maternal mercury concentration in red blood cells (RBCs) collected at 1-3 days after delivery. Precocious puberty was defined based on International Classification of Disease codes. Cox proportional hazards models were applied to the association between maternal mercury concentrations and the risk of precocious puberty. MAIN RESULTS AND THE ROLE OF CHANCE The median (interquartile range) of maternal mercury concentrations among children with and without precocious puberty were 3.4 (1.9-4.6) µg/l and 2.0 (1.0-3.7) µg/l, respectively. Compared to those in the lowest tertile for mercury, the highest tertile was associated with increased risk of precocious puberty, with an adjusted hazard ratio (HR) of 2.41, 95% CI: 1.16-5.03. In addition, concomitant maternal cardiometabolic conditions and adverse birth outcomes strengthened the effects of mercury on the risk of precocious puberty. The highest risk of precocious puberty was observed among children who had adverse birth outcomes and whose mothers had high RBC-mercury concentrations along with cardiometabolic conditions, with an HR of 4.76 (95% CI: 1.66-13.60) compared to children with favorable profiles of all three risk factors. LIMITATIONS, REASONS FOR CAUTION Precocious puberty was defined based on medical records, not on a direct assessment, which may have led to underdiagnosis and the inability to make a subclassification. The study included a predominately urban, low-income, minority population and as such our findings may not be widely generalizable. WIDER IMPLICATIONS OF THE FINDINGS Prenatal Hg exposure was associated with an increased risk of precocious puberty. This risk was strengthened by concomitant maternal cardiometabolic conditions during pregnancy and adverse birth outcomes. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the NIH/National Institute of Environmental Health Sciences, NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.
Collapse
Affiliation(s)
- Guoying Wang
- Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Wan-Yee Tang
- Department of Environmental Health and Engineering, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.,Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Hongkai Ji
- Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Xiaobin Wang
- Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
37
|
Impact of the COVID-19 Pandemic on Seasonal Variations in Childhood and Adolescent Growth: Experience of Pediatric Endocrine Clinics. CHILDREN-BASEL 2021; 8:children8050404. [PMID: 34067734 PMCID: PMC8155986 DOI: 10.3390/children8050404] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/13/2021] [Accepted: 05/14/2021] [Indexed: 01/09/2023]
Abstract
Background: Children experience seasonal variations in growth whereby height increases most in spring and least in autumn, and weight increases least in spring and most in autumn. We hypothesized that activity restriction caused by efforts to contain the spread of coronavirus disease 2019 (COVID-19) would result in increased body mass index (BMI) in children, differing from conventional seasonal growth variations. Methods: We included 169 children who visited endocrine clinics of three hospitals in Korea at regular intervals under the same conditions for two years. Visit dates were D1 (January, 2019), D2 (July, 2019), D3 (January, 2020) before the COVID-19 outbreak, and D4 (July, 2020) during the pandemic. Differences in the z-score for height (HT), weight (WT), and BMI among time points and between spring seasons (i.e., S1–S3) were compared. Results: There were significant differences in BMIz among time points, which decreased from D1–D2 and increased from D2–D3 and D3–D4. WTz significantly increased from D2–D3 and D3–D4. BMIz values of S1 (spring 2019) and S3 (spring 2020) were −0.05 and 0.16, respectively, showing significant differences. WTz values between S1 and S3 were significantly different (−0.02 vs. 0.13). Conclusions: In 2019, there were conventional seasonal variations in BMIz, which declined in spring and increased in autumn, while in 2020, BMIz increased even in spring. The COVID-19 pandemic may have affected seasonal variations in the growth of children attending endocrine clinics.
Collapse
|
|
38
|
Wei Q, Wu M, Li YL, Rao R, Li S, Cen Q, Wu H, Lv L, Huang M, Ge YP, Lu ZL, Wen YP, Cao Y, Liu TT, Wang L. Physical deviation and precocious puberty among school-aged children in Leshan City: an investigative study. J Int Med Res 2021; 48:300060520939672. [PMID: 32865090 PMCID: PMC7469722 DOI: 10.1177/0300060520939672] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Objective We investigated physical deviation and precocious puberty among school-aged children in Leshan City, to provide a theoretical basis for the management of precocious puberty in children. Methods We selected 12 primary schools of Leshan City using a cluster random sampling method and conducted physical examinations among healthy students aged 4 12 years. A total of 11,000 students were recruited (5502 boys and 5498 girls). We measured body mass index (BMI), and participants were tested for precocious puberty according to the Tanner stages and standard maps. Nutritional status was also evaluated. Results Obese and overweight children accounted for a high proportion of participants; the prevalence of underweight was the lowest. The prevalence of obesity among boys was higher than that in girls. Precocious puberty was mainly observed in girls, particularly those age 7 years old. The prevalence of precocious puberty among overweight and obese children was higher than that in children with normal weight. Conclusion We identified a significant sex difference in precocious puberty among children in Leshan City. Overweight and obesity may be associated with precocious puberty.
Collapse
Affiliation(s)
- Qiong Wei
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Ming Wu
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Yu-Lin Li
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Rui Rao
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Song Li
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Qin Cen
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Hua Wu
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Li Lv
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Mao Huang
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Yu-Ping Ge
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Zhi-Li Lu
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Yao-Ping Wen
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Ying Cao
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Ting-Ting Liu
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| | - Li Wang
- Department of Pediatrics, The People's Hospital of Leshan, Sichuan, China
| |
Collapse
|
|
39
|
Luo X, Liang Y, Hou L, Wu W, Ying Y, Ye F. Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta-analysis. Clin Endocrinol (Oxf) 2021; 94:786-796. [PMID: 33387371 PMCID: PMC8248422 DOI: 10.1111/cen.14410] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 12/11/2020] [Accepted: 12/13/2020] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To investigate the long-term efficacy and safety of gonadotropin-releasing hormone analog (GnRHa) treatment in children with idiopathic central precocious puberty (CPP). METHOD The protocol was registered with International Prospective Register of Systematic Reviews (CRD42018102792). PubMed, EMBASE and the Cochrane Library were searched for eligible comparative and single-arm studies. RESULTS We identified a total of 98 studies that included 5475 individuals. The overall risk of bias of the eligible studies ranged from critical to moderate. The overall quality of evidence for each outcome ranged from very low to moderate. Evidence-based comparative studies showed that GnRHa treatment increase final adult height (FAH, cm; studies = 4, n = 242; mean difference [MD] = 4.83; 95% confidence interval [CI], 2.32 to 7.34; I2 = 49%) and decrease body mass index (BMI, kg/m2 ; studies = 3, n = 334; MD = -1.01; 95% CI, -1.64 to -0.37; I2 = 0%) in girls with idiopathic CPP compared with no treatment. The incidence of polycystic ovary syndrome (PCOS) did not significantly differ with and without GnRHa treatment (studies = 3, n = 179; risk ratio = 1.21; 95% CI, 0.46 to 3.15; I2 = 48%). The evidence for other long-term outcomes was very weak to deduce the effects of GnRHa treatment. Further, limited evidence is available on its effects in boys. CONCLUSION Compared with no treatment, evidence indicates that GnRHa treatment increase FAH and decrease BMI in girls with idiopathic CPP. GnRHa treatment did not evidently increase the risk of PCOS. However, evidence regarding other key long-term outcomes (such as infertility and malignant or metabolic diseases) was considered very weak to suggest the benefits or side effects of GnRHa treatment. Additional high-quality evidence is needed before firm conclusions can be drawn.
Collapse
Affiliation(s)
- Xiaoping Luo
- Department of PediatricsTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Yan Liang
- Department of PediatricsTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Ling Hou
- Department of PediatricsTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Wei Wu
- Department of PediatricsTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Yanqin Ying
- Department of PediatricsTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Feng Ye
- Department of PediatricsTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| |
Collapse
|
|
40
|
Abstract
Central precocious puberty (CPP) is due to the premature activation of the hypothalamic–pituitary–gonadal axis, which is responsible for the appearance of secondary sexual characteristics. It occurs before the age of 8 and 9 in girls and boys, respectively. CPP shows higher incidence in females than in males. Causes of CPP are similar in both sexes, but the idiopathic form is more frequent in girls, while organic forms are more frequent in males. Recent studies demonstrated a role of some genetic variants in the pathogenesis of CPP. The diagnostic evaluation based on accurate physical examination, assessment of the pituitary–gonadal axis, pelvic sonography in girls, and determination of bone age. Magnetic resonance of the central nervous system should be done in all boys and selected girls. Since the 1980s, pharmacologic treatment involves the use of gonadotropin-releasing hormone (GnRH) analogs. These drugs are characterized by few side effects and long-term safety. Many data are available on the outcome of GnRH analog treated female patients, while poor data are reported in boys. Adult height is improved in both sexes.
Collapse
|
|
41
|
Seo MY, Kim SH, Park MJ. Changes in anthropometric indices among Korean school students based on the 2010 and 2018 Korea School Health Examination Surveys. Ann Pediatr Endocrinol Metab 2021; 26:38-45. [PMID: 33819957 PMCID: PMC8026332 DOI: 10.6065/apem.2040100.050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 06/28/2020] [Indexed: 11/20/2022] Open
Abstract
PURPOSE This study sought to identify changes in anthropometric values among Korean school students by comparing the most recent nationwide data with previous data. METHODS Data from the Korea School Health Examination Survey 2018 were used. The study population consisted of 107,954 Korean school students ranging from the 1st grade in elementary school through the 3rd year of high school. The difference in height and weight values for each sex and school grade was analyzed by comparison with the Korea School Health Examination Survey 2010. RESULTS The mean heights of the 3rd-year high school students were 173.8 cm and 160.9 cm for boys and girls, respectively. The mean height of the 3rd-year high school students showed no difference between 2010 and 2018 for either sex. However, the mean height of the age group from the 3rd grade in elementary school through the 1st year in high school was significantly taller in 2018 compared to 2010 for both sexes. The mean weights of the 3rd-year high school students were 71.3 kg and 57.5 kg for boys and girls, respectively. The mean weight of students in 2018 was significantly higher compared to students in 2010 for most school grades. CONCLUSION Although no significant change was found in near-final height between 2010 and 2018 among high school seniors, the mean height during the growth spurt was significantly higher in 2018 compared to 2010. Weight was significantly higher in almost all school grades in 2018 compared to 2010.
Collapse
Affiliation(s)
- Moon Young Seo
- Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Shin-Hye Kim
- Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea,Address for co-correspondence: Shin-Hye Kim Department of Pediatrics, Inje University Sanggye Paik Hospital, 1342 Dongil-ro, Nowon-gu, Seoul 01757, Korea
| | - Mi Jung Park
- Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea,Address for correspondence: Mi Jung Park Department of Pediatrics, Inje University Sanggye Paik Hospital, 1342 Dongil-ro, Nowon-gu, Seoul 01757, Korea
| |
Collapse
|
|
42
|
Chae HW, Na JH, Kwon A, Kim HS, Lee YM. Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease. Eur J Pediatr 2021; 180:425-432. [PMID: 32914201 DOI: 10.1007/s00431-020-03804-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 09/02/2020] [Accepted: 09/07/2020] [Indexed: 12/23/2022]
Abstract
We retrospectively reviewed the data of 140 female pediatric patients with rare mitochondrial diseases (MDs) confirmed using muscle biopsy. We evaluated patients who were diagnosed with central precocious puberty (PP) with early pubertal development to determine whether PP is a clinical manifestation of MDs. We also examined the clinical, auxiological, laboratory, and radiological parameters after 1 year of gonadotropin-releasing hormone treatment for central PP. Among the 140 girls with MDs, 29 had early pubertal development and underwent endocrine evaluation. Ten (7.1%) patients were diagnosed with central PP; the prevalence of central PP was higher than was that previously thought. Patients with central PP exhibited bone age advancement over 1 year and increased sex hormone levels despite their young age at diagnosis. Serum estradiol levels were significantly higher in younger patients than in older patients (P = 0.004). Patients with central PP treated with gonadotropin-releasing hormone had favorable outcomes, and their pubertal development was suppressed for 1 year.Conclusion: Central PP may be a manifestation of endocrine dysfunction in young girls with MDs. What is Known: • The general characteristics of mitochondrial diseases include developmental delays and retarded growth. • Precocious puberty has rarely been suggested as a clinical manifestation of mitochondrial diseases. What is New: • Among the 140 girls with mitochondrial diseases, 10 (7.1%) were diagnosed with central precocious puberty. • Serum estradiol levels were significantly higher in younger patients than in older patients.
Collapse
Affiliation(s)
- Hyun-Wook Chae
- Department of Pediatrics, Gangnam Severance Hospital, Severance Children's Hospital, Yonsei University College of Medicine, 211 Eonjuro, Seodaemun-gu, Seoul, South Korea
| | - Ji-Hoon Na
- Department of Pediatrics, Gangnam Severance Hospital, Severance Children's Hospital, Yonsei University College of Medicine, 211 Eonjuro, Seodaemun-gu, Seoul, South Korea
| | - Ahreum Kwon
- Department of Pediatrics, Gangnam Severance Hospital, Severance Children's Hospital, Yonsei University College of Medicine, 211 Eonjuro, Seodaemun-gu, Seoul, South Korea
| | - Ho-Seong Kim
- Department of Pediatrics, Gangnam Severance Hospital, Severance Children's Hospital, Yonsei University College of Medicine, 211 Eonjuro, Seodaemun-gu, Seoul, South Korea
| | - Young-Mock Lee
- Department of Pediatrics, Gangnam Severance Hospital, Severance Children's Hospital, Yonsei University College of Medicine, 211 Eonjuro, Seodaemun-gu, Seoul, South Korea.
| |
Collapse
|
|
43
|
Time Points for Gonadotropin-Releasing Hormone Stimulation Test Results in Korean Children. J Clin Med 2021; 10:jcm10020252. [PMID: 33445515 PMCID: PMC7826683 DOI: 10.3390/jcm10020252] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 01/05/2021] [Accepted: 01/07/2021] [Indexed: 11/16/2022] Open
Abstract
The gold standard for the laboratory diagnosis of central precocious puberty is based on the measurement of luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation. We sought to investigate the laboratory data for GnRH stimulation testing using samples collected from Korean children at different time points. Sampling times were at the basal time point (0) and 15, 30, 45, 60, 90, and 120 min after GnRH stimulation. Pubertal response was defined as occurring when the peak LH concentration was 5 IU/L or more and rose to at least 2 times the basal LH concentration after GnRH stimulation. During the study period, 19,990 test results from 1958 Korean children (1841 females aged 1.3-8.9 years and 117 males aged 7.3-9.9 years) were obtained. Among the 1958 children, 1232 (62.9%) showed pubertal responses. The receiver operating characteristic curve that demonstrated the greatest area under the curve (AUC) among all examined time points was 45 min after GnRH stimulation in males (AUC 0.982, 95% CI 0.938-0.998) and 60 min in females (AUC 0.975, 95% CI 0.967-0.981). The combination of 45 min and 60 min showed the greatest AUC (0.996, 95% confidence interval 0.991-0.998), with a sensitivity level of 99.1% and a specificity of 100% for all children. The results of this study provide a possibility for a reduction in sampling time points (45 min and 60 min) to identify the presence of a pubertal response after GnRH stimulation in Korean children.
Collapse
|
|
44
|
Abstract
BACKGROUND Menarcheal age has been decreasing worldwide. However, few recent studies have observed trends in menarcheal age in larger populations, and the cutoff age for early menarche remains unclear. Therefore, we aimed to analyze recent trends of menarcheal age and to determine the cutoff age of early menarche based on nationally representative data. METHODS We conducted a cross-sectional study of 351,006 Korean girls aged 12-18 years who were born in 1988-2003 based on the data of the 2006-2015 Korea Youth Risk Behavior Survey. We identified the distribution of age at menarche using the complex sample Cox regression model. Trends in the prevalence of early menarche were determined using the complex sample linear model. RESULTS Ninety-five percent of all the participants reported they had experienced menarche. The mean menarcheal age was 13.0 years (95% confidence intervals [CIs], 12.92-13.04) for girls born in 1988 and decreased to 12.6 years (95% CI, 12.54-12.61) for girls born in 2003. The cutoff age (the 3rd percentile value) for early menarche was 10.5 years during the study period. The prevalence of early menarche significantly increased from 1.8% in 2006 to 3.2% in 2015 (P-for-trend < 0.001). Downward trends of menarcheal age were noted across all body mass index groups, and this trend was most prominent in the obese group. CONCLUSION We reported an ongoing downward trend in menarcheal age in Korean girls born in 1988-2003, decreasing by 0.4 years over the 15 years.
Collapse
Affiliation(s)
- Moon Young Seo
- Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Shin Hye Kim
- Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Anders Juul
- Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Mi Jung Park
- Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea.
| |
Collapse
|
|
45
|
Bigambo FM, Sun H, Yan W, Wu D, Xia Y, Wang X, Wang X. Association between phenols exposure and earlier puberty in children: A systematic review and meta-analysis. ENVIRONMENTAL RESEARCH 2020; 190:110056. [PMID: 32805251 DOI: 10.1016/j.envres.2020.110056] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/21/2020] [Accepted: 08/01/2020] [Indexed: 05/19/2023]
Abstract
OBJECTIVE To identify the association between phenolic chemicals and the risk of earlier puberty based on the available evidence by systematic review and meta-analysis. METHODS Databases PubMed, Web of Science, and Cochrane Library were searched and retrieved appropriate journal articles on the association between phenols exposure and earlier puberty in children published before February 14, 2020. Stata software version 12.0 and Excel were used for statistical analysis. RESULTS Nine studies were included in the meta-analysis with total subjects of 4737. All the subjects included in our studies were girls. The pooled estimate has shown the association between 2, 5- dichrolophenol exposure, and earlier puberty in children with effect size (ES) 1.13 (95% CI: 1.06, 1.20). Exposed to other types of phenolic chemicals such as bisphenol A, Triclosan, Benzophenone-3 were not statistically significant associated with the risk of earlier puberty in children with the overall pooled estimates of ES of 1.09 (95%CI: 0.88, 1.35), ES 1.05(95% CI: 0.96, 1.15), and ES 0.98 (95% CI: 0.88, 1.10) respectively. CONCLUSION Our results portray that phenols particularly 2, 5- dichlorophenol exposure might be associated with the risk of earlier puberty in children. Also, caution should be taken to other type of phenolic chemicals since in subgroup analysis some individual studies have shown a positive relationship between bisphenol A, Triclosan and Benzophenone-3 exposures, and the risk of earlier puberty in children. Future cohort studies should be conducted with more sample sizes to determine the relationship between 2, 5- dichlorophenol, and the risk of earlier puberty in children of all gender.
Collapse
Affiliation(s)
- Francis Manyori Bigambo
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Hanqing Sun
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Wu Yan
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Di Wu
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Yankai Xia
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Xu Wang
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Nanjing Children's Hospital Affiliated to Nanjing Medical University, 210008, Nanjing, China.
| | - Xinru Wang
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
| |
Collapse
|
|
46
|
Bräuner EV, Busch AS, Eckert-Lind C, Koch T, Hickey M, Juul A. Trends in the Incidence of Central Precocious Puberty and Normal Variant Puberty Among Children in Denmark, 1998 to 2017. JAMA Netw Open 2020; 3:e2015665. [PMID: 33044548 PMCID: PMC7550972 DOI: 10.1001/jamanetworkopen.2020.15665] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
IMPORTANCE There has been a worldwide secular trend toward earlier onset of puberty in the general population. However, it remains uncertain if these changes are paralleled with increased incidence of central precocious puberty (CPP) and normal variant puberty (ie, premature thelarche [PT] and premature adrenarche [PA]) because epidemiological evidence on the time trends in the incidence of these puberty disorders is scarce. OBJECTIVE To provide valid epidemiological data on the 20-year secular trend in the incidence rates of CPP and normal variant puberty. DESIGN, SETTING, AND PARTICIPANTS This population-based, 20-year cohort study used national registry data for all youth in Denmark registered with an incident diagnosis of CPP, PT, or PA in the Danish National Patient Registry from 1998 to 2017 (N = 8596) using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). We applied the maximum diagnostic age limit for precocious puberty (ie, onset of puberty before age 8 years for girls and age 9 years for boys) with and without a 12-month lag to address time from first contact to final registration in the Danish National Patient Registry. Data analysis was conducted in 2019. EXPOSURES Diagnosis of CPP, PT, or PA. MAIN OUTCOMES AND MEASURES The age-specific and sex-specific incidence rates of first-time diagnosis of CPP, PT, and PA were estimated using data from the Danish National Patient Registry from 1998 to 2017, and information about the total number of children at risk within the same age groups and sex from Statistics Denmark. Incidences were stratified according to immigration group (Danish origin, first-generation immigrant, second-generation immigrant). RESULTS Overall a total 8596 children (7770 [90.4%] girls; median [interquartile] age at diagnosis for boys, 8.0 [7.1-9.0] years; for girls, 8.0 [7.6-8.5] years) were registered with an incident diagnosis of CPP, PT, or PA, of whom 7391 (86.0%) had Danish origin (6671 [90.3%] girls), corresponding to 370 new cases in children with Danish origin per year. The 20-year mean annual incidence rates of CPP, PT, PA, and all 3 conditions per 10 000 girls with Danish origin were 9.2 (95% CI, 8.0 to 10.3), 1.1 (95% CI, 0.7 to 1.5), 1.3 (95% CI, 0.9 to 1.7), and 11.5 (95% CI, 10.3 to 12.8), respectively. For boys with Danish origin, the 20-year mean annual incidence rates per 10 000 boys were lower: 0.9 (95% CI, 0.6 to 1.2), 0.2 (95% CI, 0.1 to 0.4), and 1.1 (95% CI, 0.7 to 1.4) for CPP, PA, and the sum, respectively. There was a 6-fold increase in incidence for girls with Danish origin (from 2.6 per 10 000 to 14.6 per 10 000) and a 15-fold increase for boys with Danish origin (from 0.1 per 10 000 to 2.1 per 10 000). The 20-year mean incidence of CPP and PA among girls in the first-generation and second-generation immigrant groups were greater than that of girls with Danish origin. The incidence rate for CPP per 10 000 girls in the first-generation and second-generation groups were 13.7 (95% CI, 9.3 to 18.2) and 14.2 (95% CI, 4.6 to 23.9), respectively; the incidence rate for PA per 10 000 girls in the first-generation and second-generation groups were 2.0 (95% CI, 0.3 to 3.6) and 1.5 (95% CI, -1.6 to 4.7), respectively. No differences associated with immigration status were observed among boys. CONCLUSIONS AND RELEVANCE Our findings suggest that the annual incidence of CPP and normal variant puberty has substantially increased in Denmark during the last 20 years. These findings have implications for short-term and long-term health and potentially for the international classification of the reference age of puberty.
Collapse
Affiliation(s)
- Elvira V. Bräuner
- Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- The International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Alexander S. Busch
- Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- The International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Camilla Eckert-Lind
- Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- The International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Trine Koch
- Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- The International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Martha Hickey
- Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
| | - Anders Juul
- Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- The International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| |
Collapse
|
|
47
|
The Age Distribution among Children Seeking Medical Treatment for Precocious Puberty in Taiwan. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17186765. [PMID: 32957428 PMCID: PMC7559721 DOI: 10.3390/ijerph17186765] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/03/2020] [Accepted: 09/15/2020] [Indexed: 12/15/2022]
Abstract
Objective: Children with precocious puberty (PP) may have increased physiological and psychological problems. In this study, we aimed to explore the trend of parents seeking medical care for their children with precocious puberty. Methods: The Taiwan National Health Insurance Research Dataset (NHIRD) was used to estimate the prevalence (2000–2013) and incidence (2002–2013) of PP (ICD-9 code: 259.1) among boys aged 0–11 years and girls aged 0–10 years. The proportions of PP management within 1 year from the date of first diagnosis were also compared between two periods (2002–2007 and 2008–2012). The trends of PP prevalence or incidence were determined by join-point regression. Results: In 2000, 309 boys and 2706 girls had at least one visit for PP, the crude prevalence rates (per 10,000 persons) were 0.99 (95% confidence interval, 95% CI 0.87–1.14) and 13.56 (95% CI 13.01–14.13) in boys and girls, respectively. In 2013, the crude prevalence rates increased to 7.01 (95% CI 6.56–7.84) and 110.95 (95% CI 108.97–112.96) in boys and girls, respectively. A total of 2584 girls and 207 boys with incident PP cases were identified in 2002, and 7498 girls and 739 boys were identified in 2013. For girls, the incidence rates (per 10,000 person-years) were 16.17 (95% CI 15.55–16.80) and 70.23 (95% CI 68.65–71.83) in 2002 and 2013, respectively. For boys, the incidence rates were 1.09 (95% CI 0.95–1.24) and 5.72 (95% CI 5.32–6.15) in 2002 and 2013, respectively. The sex ratio (F:M) of the incidence of PP cases was 14.89 in 2002 and 12.28 in 2013. Conclusion: In this study, from 2000 to 2013, the frequency of visiting pediatric endocrinology outpatient clinics for precocious puberty increased in both genders. We advocate that it is important to pay increased attention to children’s health, environmental hormones, and diet. Researchers should consider how to survey precocious puberty and offer parents more education to avoid the waste of medical resources or delays in seeking medical care.
Collapse
|
|
48
|
Abstract
The relationship between obesity and puberty remains controversial. Whereas cross-sectional and longitudinal studies show a clear shift toward earlier puberty in obese girls, the trend in obese boys remains less obvious. Overweight boys mature earlier whereas obese boys mature later compared to healthy weight boys. Newer epidemiologic studies attempt to address these knowledge gaps. This review provides a detailed overview of the recent literature regarding secular trends in pubertal onset and tempo, and the connection with obesity. Additionally, this review summarizes potential mediators that permit obesity to promote early puberty. Other factors such as socioeconomic status, in utero exposures, nutritional, and even endocrine disrupting chemicals can cause perturbation of both metabolism and the endocrine axis that can ultimately have effects on pubertal development.
Collapse
|
|
49
|
Lee YB, Lee JA, Lee HL. Herbal Medicine for Idiopathic Central Precocious Puberty: A Systematic Review and Meta-Analysis. J Altern Complement Med 2020; 26:976-999. [PMID: 32654496 DOI: 10.1089/acm.2019.0312] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Introduction: Herbal medicine (HM) is widely used in East Asia to treat idiopathic central precocious puberty (ICPP). However, no systematic reviews of the efficacy and safety of HM for treatment of ICPP have been reported. Thus, this systematic review assessed the efficacy and safety of HM for ICPP. Most available clinical trials that investigated HM for ICPP were included in this review. Methods and analysis: Eleven databases, including Asian databases, were searched from the date of inception until June 2018. We included randomized controlled trials (RCTs) that assessed HM for ICPP. Results: Nine RCTs including 650 participants with ICPP, were included in this review. As a result of meta-analysis, response rate of HM group was 1.14 times higher compared with control group, with moderate level of evidence. Also, serum estradiol (E2) level was significantly lower in HM group compared to control group with moderate level of evidence. Notably, serum luteinizing hormone (LH) level (IU/L) and E2 level were significantly lower in HM group than triptorelin injection group with moderate level of evidence. Bone age index and uterine volume were also significantly lower in HM group than control group with very low level of evidence. The incidence of adverse events was lower in the HM group than control group, but it was not statistically significant. Conclusions: According to the results of the meta-analysis, it seems that HM treatment has a significant effect on the treatment of ICPP and can effectively reduce serum LH, E2 level, and bone age. In particular, as gonadotropin-releasing hormone analog therapy has a negative effect on the growth rate and final height if bone age ≥13 years, this study suggests that HM treatment may be helpful. Additional higher quality RCTs are needed to demonstrate the efficacy and safety of HM for treatment of ICPP.
Collapse
Affiliation(s)
- Yoo Been Lee
- Department of Pediatrics, College of Korean Medicine, Gachon University, Seongnam, Korea
| | - Ju Ah Lee
- Hwa-pyeong Institute of Integrative Medicine, Incheon, Korea
| | - Hye Lim Lee
- Department of Pediatrics, College of Korean Medicine, Daejeon University, Daejeon, Korea
| |
Collapse
|
|
50
|
Chung LY, Nam HK, Rhie YJ, Huh R, Lee KH. Prevalence of idiopathic scoliosis in girls with central precocious puberty: effect of a gonadotropin-releasing hormone agonist. Ann Pediatr Endocrinol Metab 2020; 25:92-96. [PMID: 32615688 PMCID: PMC7336263 DOI: 10.6065/apem.1938164.082] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 11/28/2019] [Indexed: 11/22/2022] Open
Abstract
PURPOSE Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis and occurs in children between 10 to 18 years old, during periods of growth spurts and puberty changes. In patients with central precocious puberty (CPP), due to early growth spurt, AIS is expected to develop before 10 years of age. Both AIS and CPP are more common in girls than in boys. The aim of this study was to determine the prevalence of AIS in girls with CPP and to evaluate the effect of treatment with gonadotropin-releasing hormone (GnRH) agonists on progression of scoliosis in these patients. METHODS We retrospectively reviewed medical records of 553 girls, 338 with CPP and 215 without CPP. Scoliosis angle was measured on the standing frontal radiograph of each patient according to the Cobb method. Patients with a Cobb angle of 10° or more were diagnosed with scoliosis. For girls with CPP, followup spine radiographs were collected 1 year after treatment with GnRH agonists. Progression of scoliosis before and after treatment was compared in terms of Cobb angle changes. RESULTS AIS was more prevalent in girls that were affected by CPP compared to controls without CPP (11.5% vs. 6.0%, CPP girls vs. non-CPP girls, respectively, P=0.031). The peak serum luteinizing hormone level positively correlated with Cobb angle (R2=0.015, P=0.023) in the CPP group. No progression of scoliosis was observed in CPP girls after one year of GnRH agonist treatment. Additionally, the prevalence of scoliosis decreased in CPP girls after 1 year of the treatment. CONCLUSION We report that the prevalence of AIS is higher in girls with CPP than in non-CPP patients. A regular follow-up schedule for spine radiographs should be considered to reduce the risk of progression. Furthermore, GnRH agonist treatment for CPP may have a suppressive effect on progression of AIS.
Collapse
Affiliation(s)
- Lindsey Yoojin Chung
- Department of Pediatrics, Myongji Hospital, Hanyang University College of Medicine, Ilsan, Korea
| | - Hyo-Kyoung Nam
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Young-Jun Rhie
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Rimm Huh
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Kee-Hyoung Lee
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea,Address for correspondence: Kee-Hyoung Lee, MD, PhD Department of Pediatrics, Korea University Anam Hospital, Korea University College of Medicine, Goryeodae-ro Seongbuk-gu, Seoul 02841, Korea Tel: +82-2-920-6604 Fax: +82-2-922-7476 E-mail:
| |
Collapse
|