Journal of Clinical Research in Pediatric Endocrinology最新文献

{"title":"Real-World Efficacy of Weekly Somatrogon on Growth and Bone Health in Pediatric Growth Hormone Deficiency: A 12-Month Retrospective Cohort Study.","authors":"Mohammad Hosny Awad, Reham Ghanim, Rania Eladl, Zulf Mughal, Manal Mustafa","doi":"10.4274/jcrpe.galenos.2025.2025-6-24","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-6-24","url":null,"abstract":"<p><strong>Background: </strong>Growth hormone deficiency (GHD) in children results in short stature and impaired bone health. While daily growth hormone (GH) injections are effective, they are associated with adherence challenges. Somatrogon, a long-acting recombinant human GH, allows weekly administration, potentially improving treatment compliance.</p><p><strong>Methods: </strong>This retrospective cohort study included 39 prepubertal children with GHD treated with weekly Somatrogon at Al Jalila Children's Hospital, Dubai. Diagnosis was based on clinical, biochemical, and radiological criteria, including height standard deviation score (SDS) < -2.0, subnormal growth velocity, and subnormal peak GH in one stimulation test (<10 ng/mL) supported by low IGF-1 and/or abnormal MRI. Growth outcomes and bone health indices were assessed over 12 months using auxology, IGF-1 levels, and BoneXpert-derived Bone Health Index (BHI) SDS and Metacarpal Index (MCI) SDS.</p><p><strong>Results: </strong>After 12 months of therapy, mean height SDS improved significantly from -2.16 ± 0.80 to -1.65 ± 0.71 (p < 0.001). IGF-1 SDS rose from -1.38 ± 1.02 to 0.88 ± 1.57 (p < 0.001). Adult predicted height and BHI SDS also improved significantly (p = 0.005 and p < 0.001, respectively). No significant changes were observed in bone age SDS or MCI SDS.</p><p><strong>Conclusions: </strong>Weekly Somatrogon significantly improved linear growth, IGF-1 levels, and cortical bone health without advancing bone age in children with GHD. These findings support the efficacy of long-acting GH therapy and its potential to optimize growth and skeletal outcomes in clinical practice.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Opposite Phenotype of Sotos Syndrome: 5q35.2q35.3 Microduplication Syndrome.","authors":"Kübra Şen Küçük, Aydan Mengübaş Erbaş, Zehra Manav Yiğit, Ahmet Anık","doi":"10.4274/jcrpe.galenos.2025.2025-6-8","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-6-8","url":null,"abstract":"<p><p>Sotos syndrome is a genetic disorder resulting from heterozygous pathogenic variants or deletions in the nuclear receptor-binding SET domain protein 1 (NSD1) gene. It is characterized by prenatal and postnatal overgrowth, macrocephaly, distinctive craniofacial features, learning disability, and advanced bone maturation. In contrast, Reverse Sotos syndrome, arises from duplications within the NSD1 gene, presenting with an opposite clinical phenotype, including microcephaly, developmental delay, short stature and delayed bone maturation. To date, the reverse clinical phenotype associated with the 5q35.2q35.3 microduplication encompassing the NSD1 gene has been reported in 43 cases. We present a novel case of a 4-year-11-month-old patient with a 5q35.2q35.3 duplication involving the NSD1 gene. The patient, exhibited clinical features of microcephaly, short stature, low-normal weight, delayed bone age, developmental delay, attention deficit hyperactivity disorder, alongside normal routine biochemical tests, nutritional parameters, and insulin-like growth factor-1 levels. Chromosomal microarray analysis (CMA) identified a 714.1 kb duplication in the 5q35.2q35.3 region, including NSD1. This case underscores the significance of NSD1 gene dosage alterations in manifesting a reverse clinical phenotype typified by microcephaly and short stature. Furthermore, it highlights the utility of CMA as a robust diagnostic tool for detecting microrearrangements and guiding clinical evaluation.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Course of Progranulin Levels at Admission and During Early Period of Insulin Treatment in Children with Newly Diagnosed Type 1 Diabetes Mellitus.","authors":"Ayse Sena Donmez, Atilla Cayir, Esra Laloglu, Alev Lazoglu Ozkaya, Esra Dişci, Serap Kilic Kaya, Kamber Kaşali, Serkan Bilge Koca, Huseyin Demirbilek","doi":"10.4274/jcrpe.galenos.2025.2025-3-9","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-3-9","url":null,"abstract":"<p><strong>Objective: </strong>Progranulin (PGRN), a growth factor, modulates cell proliferation, wound repair, and inflammation. It involves glucose metabolism and is associated with insulin resistance and diabetes mellitus (DM). In the present study, we evaluate PGRN levels at admission and during follow-up in children with newly diagnosed type 1 diabetes mellitus (T1DM) in comparison with healthy controls.</p><p><strong>Material and methods: </strong>A total of 49 children, 25 with T1DM (12F/13M) and 24 healthy controls (10F/14M) were recruited. The age, weight, height, body mass index (BMI), severity of acidosis, glucose, insulin, C-peptide, and diabetes-specific autoantibodies of children with newly diagnosed type 1 diabetes mellitus (T1DM) were examined. The PGRN was measured in children with T1DM at admission, first week of follow-up, and in healthy controls.</p><p><strong>Results: </strong>There was no differences in age (11 ± 3.9 years vs 12.1 ± 3.1 years, p = 0.269) and BMI standard deviation score (SDS) (-0.11 ± 1.49 SD vs 0.10 ± 0.82 SD, p = 0.540) characteristics of children with T1DM and healthy controls. The basal PGRN levels of children with newly diagnosed T1DM were higher than those of controls (90.8 ± 17.3 ng/mL vs 30 ± 11.5 ng/mL, p < 0.001). In children with T1DM, basal PGRN at admission (90.8 ± 17.3 ng/mL) significantly declined (58.4 ± 16.9 ng/mL) in the first week (when glycemic regulation was achieved) (p <0.001).</p><p><strong>Conclusion: </strong>These findings suggest that elevated PGRN levels in children with newly diagnosed T1DM may reflect both an acute inflammatory response to diabetic ketoacidosis and a persistent alteration in metabolic regulation, underscoring the potential role of PGRN as a biomarker in the early course of the disease.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Cognition in Adolescents With Gender Dysphoria and Congenital Adrenal Hyperplasia: A Preliminary Investigation of Biological vs. Experiential Gender Effects.","authors":"Begum Yulug-Tas, Burcu Ozbaran, Ipek Inal-Kaleli, Nurhak Dogan, Arzu Jalilova, Samim Ozen, Sezen Kose, Damla Goksen, Sukran Darcan, Tezan Bildik","doi":"10.4274/jcrpe.galenos.2025.2025-3-16","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-3-16","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore hormonal and neurodevelopmental influences on social cognition among individuals with Gender Dysphoria (GD), Congenital Adrenal Hyperplasia (CAH), and typically developing (TD) controls.</p><p><strong>Method: </strong>Participants included 34 GD, 29 CAH, and 35 TD individuals. Social cognition was assessed using the Faces Test (FT), Reading the Mind in the Eyes Test (RMET), and Unexpected Outcomes Test (UOT). Psychiatric comorbidities were evaluated via the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-PL), depressive symptoms using the Children's Depression Inventory (CDI), autistic traits with the Autism Spectrum Screening Questionnaire (ASSQ), and ADHD symptoms through the ADHD Rating Scale.</p><p><strong>Results: </strong>Psychiatric diagnoses were significantly more prevalent in the GD group, with Major Depressive Disorder (64.7%) and ADHD (50%) being the most common (p<0.001). TD participants showed moderately better performance on RMET (p=0.003) and UOT (p<0.001) compared to GD and CAH, while CAH individuals scored lower on FT (p=0.046). Regression analyses revealed depressive symptoms (B=-0.105, p=0.004) and CAH status (B=-2.221, p=0.003) predicted RMET scores, while GD (B=-3.232, p=0.022) and CAH (B=-7.974, p<0.001) predicted lower UOT performance. FT regressions were nonsignificant.</p><p><strong>Conclusions: </strong>Findings highlight the interplay of hormonal and psychosocial factors in social cognition, emphasizing the need for nuanced, context-sensitive approaches to supporting social functioning and well-being in gender-diverse youth.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association with Metabolic Syndrome in Children Diagnosed with Type 1 Diabetes Mellitus: A Cross-sectional Study.","authors":"Serpil Albayrak, Murat Karaoglan, Mehmet Keskin, Ahmet Yildirim","doi":"10.4274/jcrpe.galenos.2025.2025-2-11","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-2-11","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the prevalence of metabolic syndrome (MetS) in children with Type 1 Diabetes Mellitus (T1DM) and to determine the predictive value of simple anthropometric measurements-particularly neck circumference (NC) and waist circumference (WC)-in identifying MetS.</p><p><strong>Methods: </strong>A total of 168 children (aged 6-18 years) with T1DM were included in this cross-sectional study. Anthropometric (NC, WC, BMI, TMI) and laboratory parameters (lipid profile, HbA1c) were recorded. MetS diagnosis was established according to the International Diabetes Federation (IDF) criteria. Receiver operating characteristic (ROC) curve analysis and LASSO regression were employed to identify key predictors.</p><p><strong>Results: </strong>The prevalence of MetS was 8.9%. Children with MetS had significantly higher BMI, WC, NC, HC, and TMI values compared to non-MetS counterparts. ROC analysis revealed WC z-score had the highest discriminative power (AUC: 0.954), followed by NC z-score (AUC: 0.906). LASSO regression identified NC z-score and BMI percentile as the most robust predictors. A strong positive correlation was observed between NC and WC (r = 0.812, p <0.001), and NC showed a mild inverse correlation with HDL cholesterol.</p><p><strong>Conclusion: </strong>NC and WC are simple, non-invasive, and reliable tools for early detection of MetS in pediatric T1DM patients. Their routine measurement could enhance risk stratification and guide preventive interventions targeting obesity and dyslipidemia. These findings support incorporating NC and WC into standard clinical assessments to improve long-term cardiometabolic outcomes in children with T1DM (i.e., NC z>1.04 or WC z >1.41 as actionable thresholds.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"X-linked Osteoporosis due to <i>PLS3</i> Pathogenic Variant: Case Report on Zoledronic Acid Treatment in Siblings.","authors":"María Camila Velandia-Avendaño, María Paula Sarmiento-Ramón","doi":"10.4274/jcrpe.galenos.2025.2025-4-2","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-4-2","url":null,"abstract":"<p><p>Osteoporosis in children is a rare condition, often associated with genetic factors. Monogenic forms of osteoporosis linked to the X chromosome are often related to mutations in the gene encoding plastin 3 (PLS3). PLS3 is a protein involved in actin bundle formation in the cytoskeletonWe present two brothers with recurrent peripheral fractures and vertebral compression fractures, both associated with low bone mineral density (BMD). The patients shared the same deletion (c.589_590) in <i>PLS3</i> on Xq23, which was confirmed by next-generation sequencing. They were treated with zoledronic acid, calcium, and vitamin D, showing optimal improvement in bone mineral density, a reduction in bone fractures, and enhanced quality of life.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 1 Diabetes Mellitus and Transfer from Pediatric to Adult Care: A Single-Center Experience.","authors":"Betül Yiğit Yalçın, Ummahan Tercan, Melek Yildiz, Hülya Hacısahinogulları, Gülşah Yenidünya Yalın, Nurdan Gül, Ozlem Soyluk Selcukbiricik, Ayşe Kubat Üzüm, Sukran Poyrazoglu, Firdevs Baş, Kubilay Karşıdağ, İlhan Satman, Feyza Darendeliler","doi":"10.4274/jcrpe.galenos.2025.2025-1-21","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-1-21","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Type 1 diabetes mellitus (T1D) necessitates lifelong management, and a standardized transition protocol with multidisciplinary support can help ease the shift from pediatric-focused healthcare to adult care systems.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;Our objective was to assess the sociodemographic data, clinical features, and laboratory parameters that may influence the transition period and post-transition process among patients with T1DM and to compare results between two different transition models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrospectively analyzed 64 T1D patients who transitioned to the adult outpatient clinic at Istanbul University, Istanbul Faculty of Medicine. Patients were followed up between 2001 and 2022, completed their pediatric follow-up, and participated in the shift from pediatric to adult outpatient care. Demographic data, clinical and metabolic parameters before and after the transition, the presence of diabetic complications and comorbidities, and treatment modalities were analyzed. These patients were transferred to adult care with two different transition models: in model 1, the transition was performed in a single meeting, whereas in model 2, it was performed over a period of 4-6 months. Due to pandemic-related disruptions, a few patients were transferred following telephone consultations and were excluded from model comparisons. The differences between the outcomes of the transition models were also examined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Sixty-four patients were included in the analysis (43.7% female, age at diagnosis 9.4±3.9 years). At their last pediatric visit, the participants had a mean age of 19.4 ± 1.2 years (range 16.6-21.9). The mean age at transfer to adult care was 20.2 ± 1.4 years (17.7-23.1), and the mean age at the most recent adult visit was 23.2 ± 4.2 years (18.4-39.5). The median time in adult care follow-up was 3.3 (range 0.3-20.9) years. The mean body mass index (BMI) decreased from 24.1 ± 1.7 kg/m² at transition to 23.6 ± 3.5 kg/m² during adult follow-up. Although the mean BMI fell slightly, obesity prevalence rose from 1.6 % to 9.6 %, reflecting a right-shift in the BMI distribution. Annual routine diabetes-care visits decreased from 3.0 ± 0.9 visits per year during pediatric follow-up to 2.1 ± 1.8 visits per year in adult care (p=0.009). The mean HbA1c level was significantly lower in adults (8.9% vs. 8.3%; p=0.007). Total insulin doses were significantly higher at transition than at the last adult care visit (0.95 vs 0.75 IU/kg/day; p=0.009). Basal insulin ratio was higher in adulthood (43.1% vs. 52.8%; p&lt;0.0001). The use of continuous subcutaneous insulin infusion (CSII) therapy in adult care was higher (4.7% vs. 12.5%, p=0.11). The frequency of autoimmune thyroiditis and coeliac disease did not differ between adult and pediatric care. Although the frequency of microvascular and macrovascular complications increased in adult care, there was no statistically sig","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diazoxide and Continuous Glucose Monitoring as Treatment in a Neonate with Hyperinsulinemic Hypoglycemia due to HNF4A Mutation.","authors":"Georgia Sotiriou, Stilianos Xinias, Valentina Diamantidou, Anny Mertzanian, Meropi Dimitriadou, Amalia Sertedaki, Athanasios Christoforidis","doi":"10.4274/jcrpe.galenos.2025.2025-4-12","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-4-12","url":null,"abstract":"<p><p>The transcription factor hepatocyte nuclear factor-4a plays a key role in insulin secretion and mutations in its encoding gene, <i>HNF4A</i>, have been associated with Monogenic diabetes (MODY 1) during adolescence or early adulthood and with transient hyperinsulinemic hypoglycemia during infancy. They are inherited as an autosomal dominant trait, therefore, <i>HNF4A</i> sequencing should be considered in every neonate presenting with macrosomia or persistent hypoglycemia after 24 hours from birth, especially when there is a family history of early-onset diabetes. Management of hyperinsulinism includes regular feeding, intravenous glucose and diazoxide, as first-line treatment. Blood glucose levels need regular monitoring to adjust treatment properly. Continuous glucose monitoring systems are not validated for neonates or patients with hyperinsulinism, so finger-prick blood tests are usually used before every meal. We present a case of diazoxide use in a female patient with neonatal hypoglycemia due to <i>HNF4A</i> mutation, where continuous glucose monitoring facilitated treatment decisions and detected hyperglycemia, as an adverse event early in the course. Notably, CGM use after hospital discharge contributed significantly to ongoing glucose monitoring and management. We recommend that further studies could establish CGM's usefulness as an adjunct in clinical care.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel <i>THRβ</i> Variant in a Child With Resistance to Thyroid Hormone β: Diagnostic and Therapeutic Challenges.","authors":"Gözde Gürpınar, Duygu Gamze Aracı","doi":"10.4274/jcrpe.galenos.2025.2025-6-7","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-6-7","url":null,"abstract":"<p><p>Resistance to thyroid hormone beta (RTHβ) is a rare condition typically caused by mutations in the <i>THRβ</i> gene, characterized by elevated thyroid hormones with non-suppressed TSH levels. We present a pediatric case of RTHβ associated with a novel <i>THRβ</i> variant, emphasizing diagnostic challenges and the importance of individualized treatment. A 6.5-year-old girl was evaluated for learning difficulties and tachycardia. Laboratory findings showed elevated free T3 and T4 with non-suppressed TSH. Pituitary MRI showed a 5x6 mm lesion, raising suspicion for TSHoma. Genetic testing of the <i>THRβ</i> gene was performed. A novel heterozygous <i>THRβ</i> variant (c.1376T>C; p.Phe459Ser) was identified in both the patient and her father. The mutation affects a highly conserved residue within the ligand-binding domain. Clinical and biochemical findings were consistent with RTHβ. Atenolol therapy was initiated to manage tachycardia with favorable response.This case highlights the potential for misdiagnosis of RTHβ as TSHoma and underscores the value of genetic testing in differentiating the two. The identification of a novel variant at codon 459 expands the mutational spectrum of <i>THRβ</i> and supports its role as a hotspot region relevant to RTHβ pathogenesis.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of Idiopathic Hypogonadotropic Hypogonadism.","authors":"A Kemal Topaloğlu, Leman Damla Kotan","doi":"10.4274/jcrpe.galenos.2025.2025-6-23","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2025.2025-6-23","url":null,"abstract":"<p><p>Idiopathic hypogonadotropic hypogonadism (IHH) comprises a group of disorders characterized by deficient secretion or action of gonadotropin-releasing hormone (GnRH), leading to impaired pubertal development and infertility. Traditionally, IHH is classified into Kallmann syndrome (KS), associated with anosmia, and normosmic IHH (nIHH), in which olfactory function is preserved. The condition exhibits marked genetic heterogeneity. Advances in next generation sequencing have significantly expanded the genetic landscape of IHH, with pathogenic variants identified in over 60 genes, accounting for up to 50% of cases. Oligogenic inheritance is increasingly recognized, occurring in 10-20% of individuals. The potential for spontaneous or treatment-induced clinical recovery in a subset of patients, along with phenotypic overlap with constitutional delay of growth and puberty (CDGP), presents additional diagnostic challenges. Despite these complexities, genetic studies of IHH have provided critical insights into fundamental neuroendocrine processes, most notably the recent elucidation of the KNDy (Kisspeptin, Neurokinin B, Dynorphin) neurons as the GnRH pulse generator. These discoveries have also informed the development of targeted therapies, exemplified by the recent FDA approval of fezolinetant, a neurokinin B receptor antagonist, for the treatment of menopausal vasomotor symptoms.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}