Hormone Research in Paediatrics最新文献

{"title":"Short Stature and Response to Growth Hormone Treatment in CUL3-Related Neurodevelopmental Disorder.","authors":"Petra Loid, Anu Närhi, Shabir Hussain, Mari Muurinen, Outi Mäkitie","doi":"10.1159/000547715","DOIUrl":"10.1159/000547715","url":null,"abstract":"<p><strong>Introduction: </strong>Recent research has expanded the spectrum of genetic causes for growth failures. Patients with CUL3-related neurodevelopmental disorder (NDD) present with variable phenotypic manifestations, and growth retardation has been observed in some of these patients.</p><p><strong>Case presentation: </strong>We present two families with NDD and variable degree of short stature. The proband in Family 1 had short stature (-3.0 SDS), developmental delay, learning difficulties, and autism spectrum disorder. Whole exome sequencing (WES) revealed a novel likely pathogenic heterozygous nonsense CUL3 variant c.420C>G, p.Tyr140Ter. The variant was also identified in her non-identical twin sister, who presented with short stature and NDD, and in their father, who had NDD and epilepsy but normal height. The proband and her sister were treated with growth hormone (GH) with good response. The proband and his brother in Family 2 presented with short stature during childhood, NDD, and facial dysmorphism. WES identified a heterozygous likely pathogenic nonsense CUL3 variant c.442C>T, p.Arg148Ter in the proband and his brother. The variant was inherited from their mother, who had facial dysmorphism and hypertension but normal height.</p><p><strong>Conclusion: </strong>CUL3-related NDD can be associated with growth retardation. We observed a good response to GH therapy in 2 of our patients with short stature. Our finding expands the spectrum of disease-causing variants in CUL3 and demonstrates variable intra-familial clinical expressivity.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-7"},"PeriodicalIF":2.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired Generalized Lipodystrophy with Extensive Autoimmune Involvement: A Case Report and Review of the Literature.","authors":"Asma Deeb, Rasha Hassan Beck, Umama Fatima, Husna Yoosuf","doi":"10.1159/000547714","DOIUrl":"10.1159/000547714","url":null,"abstract":"<p><strong>Introduction: </strong>Acquired generalized lipodystrophy (AGL) is a rare condition characterized by body fat loss and, usually, metabolic syndrome with or without associated autoimmune diseases. Clinical phenotypes of AGL are heterogenous, making diagnosis and management challenging. Here, we present a case of AGL with a unique and dominant autoimmune phenotype that prompts discussion of this rare disorder, the prolonged clinical course, and its optimal management.</p><p><strong>Case presentations: </strong>A two and a half-year-old girl presented with thinning of her arms and legs and vitiligo. She subsequently developed alopecia at age four and Graves' disease at age twelve with associated Graves' eye disease. By age fourteen, she developed Addison's disease and typical features of severe AGL with fat loss from the extremities and buttocks, venomegaly, muscle hypertrophy, and acanthosis nigricans. She had mild dyslipidemia but normal fasting insulin, HbA1c, and leptin levels. Although her parents were consanguineous, next-generation sequencing of a targeted but comprehensive lipodystrophy gene panel was negative. The negative genetics, clinical features, and presence of autoimmune diseases favored a diagnosis of AGL.</p><p><strong>Conclusion: </strong>This case is unusual in that (i) it was associated with several autoimmune diseases (Graves' disease, Addison's disease, vitiligo, and alopecia); (ii) leptin levels were normal despite lipodystrophy; (iii) her Graves' disease was associated with severe eye disease. Given the distinct but unusual phenotype (multiple autoimmune diseases associated with generalized lipodystrophy in the absence of hypoleptinemia) and parental consanguinity, despite negative targeted gene sequencing, our patient's AGL may have been due to a novel, autosomal recessive genetic variant. Whole-genome sequencing would be useful in this case to try to determine a genetic cause to provide new insights into AGL and the underlying autoimmune mechanisms.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finding Early Biomarkers to Prevent Unfavorable Long-Term Health Outcomes after Premature Adrenarche: A Multicenter Prospective Cohort Study Protocol.","authors":"Philipp Augsburger, Oili Niskanen, Jarmo Jääskeläinen, Christa E Flück, Jani Liimatta","doi":"10.1159/000547606","DOIUrl":"10.1159/000547606","url":null,"abstract":"<p><strong>Introduction: </strong>Adrenarche is a prepubertal developmental phase in humans characterized by increasing levels of adrenal androgens in circulation. While its regulation and biological significance remain poorly understood, the earlier onset of adrenarche - referred to as premature adrenarche (PA) - raises concerns about potential long-term health risks, including metabolic syndrome and polycystic ovary syndrome. Our study aimed to elucidate the regulatory mechanisms underlying adrenarche and PA, specifically investigating whether PA represents a benign variation of normal development, or a disorder associated with increased risks of unfavorable metabolic and reproductive outcomes in adulthood.</p><p><strong>Methods: </strong>This study employs a longitudinal design to track a well-characterized cohort of children with PA alongside age-matched healthy controls, following them from adrenarche through puberty into early adulthood. Conducted across two independent research centers in Kuopio, Finland, and Bern, Switzerland, the study involves detailed phenotypic assessments, including comprehensive medical histories and body composition analyses. Biological samples undergo multi-omics profiling - encompassing transcriptomics and metabolomics - using advanced techniques such as liquid and gas chromatography tandem-mass spectrometry and RNA sequencing. This integrated approach aims to identify biomarkers predictive of adverse health outcomes in PA, with candidate biomarkers and regulatory factors further validated through in vitro adrenal cell model studies.</p><p><strong>Conclusion: </strong>This study provides the first comprehensive, longitudinal comparison of PA and healthy controls across critical developmental milestones. By elucidating the molecular factors that regulate the maturation of the zona reticularis, it seeks to resolve the longstanding mystery of adrenarche. Furthermore, by differentiating benign developmental variations from PA cases linked with long-term health risks, the findings could refine current diagnostic criteria and enable early identification of children at risk. Ultimately, this research paves the way for more accurate diagnoses, targeted interventions, and improved long-term health outcomes.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Insights into the Pathophysiology and Management of Obesity in Childhood and Adolescence.","authors":"Evangelia Charmandari, Sabine E Hannema, Evelien F Gevers","doi":"10.1159/000547229","DOIUrl":"10.1159/000547229","url":null,"abstract":"","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-2"},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Childhood Obesity on Growth: Interpretation of Growth Hormone Provocation Tests.","authors":"Feneli Karachaliou, Jouly Maltezou, Vassiliki Bekiou, Eleni Tsintzou, Aristofania Simatou","doi":"10.1159/000547492","DOIUrl":"10.1159/000547492","url":null,"abstract":"<p><strong>Background: </strong>Obesity during childhood can significantly impact growth and puberty.</p><p><strong>Summary: </strong>Obese children show accelerated linear growth during pre-puberty, possibly due to early estrogenization, normal/high IGF1 levels, high leptin levels, and the action of insulin on the IGF1 receptor. Obesity also affects puberty, leading to both earlier onset of puberty in girls and alteration in pubertal timing in boys, combined with reduced growth spurts. Leptin has been identified as the most significant link between obesity and pubertal onset. During puberty, increased estrogen levels antagonize the growth-promoting actions of leptin and accelerate bone maturation, leading to earlier epiphyseal closure. Spontaneous and stimulated GH secretion is markedly reduced in obesity due to hypothalamic, pituitary, and peripheral factors. The blunted GH response to stimuli may lead to an overdiagnosis of growth hormone deficiency (GHD) in obese, short-statured children.</p><p><strong>Key messages: </strong>While obese children may be taller during childhood, they have reduced growth spurts during puberty due to accelerated epiphyseal closure, and final heights are similar or even compromised compared to the genetic potential. GH secretion, both spontaneous and stimulated, is decreased, and therefore, the differential diagnosis of GHD versus an obesity-related decrease in GH secretion remains a problem of great practical importance. Data on the effects of obesity on GH levels are limited, and weight-status-adjusted cutoffs for GH stimulation tests have not been set and validated as yet. This review summarizes our knowledge on the underlying mechanisms, by which obesity affects growth and puberty and data on its impact on GH stimulation tests.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Growth Prediction Model from Mid-Puberty to Near Adult Height in Adolescents with Idiopathic Isolated Growth Hormone Deficiency Treated with Growth Hormone.","authors":"Joeri Vliegenthart, Maria A J de Ridder, Jan Maarten Wit, Ardine M J Reedijk, Raoul D Oude Engberink, Erica L T van den Akker, Danielle C M van der Kaay","doi":"10.1159/000547488","DOIUrl":"10.1159/000547488","url":null,"abstract":"<p><strong>Introduction: </strong>Recombinant human growth hormone (rhGH) treatment of children with idiopathic isolated growth hormone deficiency (IIGHD) typically results in catch-up growth for several years followed by a period of normal growth. The effect of rhGH treatment on late pubertal height gain in adolescents with IIGHD has remained unclear. This study aimed to develop and validate a prediction model for height gain from mid-puberty to near adult height (NAH) in patients with IIGHD, treated with rhGH.</p><p><strong>Methods: </strong>Data from the Dutch National Registry of Growth Hormone Treatment in Children were used, focusing on 151 patients who received rhGH treatment until NAH. Predictors included age, bone age, Tanner stage, and target height SDS minus height SDS at mid-puberty. Validation was performed in 33 males and 7 females who had a normal GH response in a GH stimulation test at mid-puberty and continued rhGH until NAH.</p><p><strong>Results: </strong>The model explained 48% of the variance for males (residual SD 4.16 cm) and 18% for females (residual SD 3.64 cm). Validation showed a mean (SD) difference of 1.48 (2.36) cm for males and 3.57 (2.66) cm for females between predicted and attained NAH.</p><p><strong>Conclusion: </strong>For females, explained variance was insufficient to reliably predict height gain. For GH sufficient males, the model can be used to assess efficacy of continuing or discontinuing rhGH treatment at mid-puberty in future studies.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to \"Invited Mini Review Metabolic Bone Disease of Prematurity: Overview and Practice Recommendations\" - Limitations to Utilization of Practice Guideline in Acutely Ill and Medically Complex Neonates.","authors":"Rochelle Sequeira Gomes","doi":"10.1159/000547292","DOIUrl":"10.1159/000547292","url":null,"abstract":"","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-2"},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Unusual Liver and Kidney Involvement in Congenital Hyperinsulinism with <italic>HNF1A</italic> Mutation: A Case Report.","authors":"Evelina Maines, Arianna Maiorana, Maria Chiara Cardellini, Aldo Naselli, Annalisa Cuccu, Francesca Tota, Giuliana Marchiò, Francesca Rivieri, Francesca Romana Lepri, Giovanni Piccoli, Massimo Soffiati, Roberto Franceschi","doi":"10.1159/000547127","DOIUrl":"10.1159/000547127","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocyte nuclear factor-1α (HNF-1α) and hepatocyte nuclear factor-4α (HNF-4α) are transcription factors highly expressed in β-cells, hepatocytes, intestinal epithelial cells, and renal tubular cells. Variants in both HNF1A and HNF4A gene have been linked to maturity-onset diabetes of youth (MODY) and congenital hyperinsulinism (HI). To date, the association between HI, renal tubulopathy, and hepatopathy has been described only in patients with HNF-4α deficiency. HI due to HNF-1α deficiency has not been linked to extra-pancreatic features.</p><p><strong>Case presentation: </strong>Our patient presented neonatal onset of HI and hepatomegaly, cholestasis, echographic features of liver steatosis, and renal tubulopathy (glycosuria, phosphaturia, aminoaciduria, uricosuria, proteinuria) from the first month of life. The molecular analysis revealed a heterozygous maternal variant c.4432G>A (p.Gly1478Ar) in the ABCC8 gene and a heterozygous maternal variant c.1859C>T (Thr620Ile) in HNF1A gene. We describe an 8-month follow-up and discuss possible pathogenetic mechanisms linking HNF1A-HI and features of extra-pancreatic involvement.</p><p><strong>Conclusion: </strong>Our case describes a likely association between HI due to HNF-1α deficiency with liver and kidney involvement. Further cases are needed to validate our hypothesis and to establish if a genotype-phenotype correlation exists in case of extra-pancreatic involvement, as for the known HNF4A mutation-specific phenotype.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype, Phenotype Characteristics and Long-Term Follow-Up of Patients with Vitamin D-Dependent Rickets Type IA: A Nationwide Multi-Centre Retrospective Cross-Sectional Study.","authors":"Atilla Cayir, Huseyin Demirbilek, Ayberk Türkyılmaz, Serap Turan, Abdullah Bereket, Feyza Darendeliler, Mehmet Nuri Özbek, Serkan Bilge Koca, Edip Unal, Deniz Okdemir, Ihsan Esen, Erdal Eren, Ruken Yıldırım, Semra Cetinkaya, Kadriye Cansu Sahin, Ahmet Anık, Ayse Sena Dönmez, Ayşe Pınar Öztürk, Elvan Bayramoglu, Muammer Buyukinan, Fatih Gurbuz, Korcan Demir, Suna Kılınç, Gonul Buyukyilmaz, Sare Betul Kaygusuz, Gamze Çelmeli, Beray Selver Eklioglu, Sezer Acar, Fatma Dursun, Ihsan Turan, Beyhan Özkaya, Erdal Kurnaz, Rıza Taner Baran, Behzat Özkan","doi":"10.1159/000546497","DOIUrl":"10.1159/000546497","url":null,"abstract":"<p><strong>Introduction: </strong>Vitamin D-dependent rickets type IA (VDDR1A) is an autosomal recessive disorder characterized by defects in the biosynthesis of its active form 1,25-dihydroxyvitamin D due to mutations in the CYP27B1 gene, which encodes for 1α-hydroxylase. The present study aimed to evaluate the clinical characteristics, molecular genetic aetiology, and long-term outcomes of a large nationwide cohort of children with VDDR1A from Turkey.</p><p><strong>Methods: </strong>In this multi-centre retrospective cross-sectional study, we collected clinical characteristics, laboratory features, molecular genetic analysis results, and long-term follow-up of a nationwide cohort of patients with VDDR1A using a web-based research network, CEDD-NET, for paediatric endocrinology research.</p><p><strong>Results: </strong>In total, 118 patients (57 F, 61 M) with VDDR1A were recruited. The median age of the diagnosis was 1.7 years (0.2-18.3 years). The most common presenting complaints were skeletal deformity (n = 61), short stature (n = 45), and delay in walking (n = 42). The most common mutation was a splice-donor-site mutation (c.195+2T>G) (n = 42), followed by a 7-bp duplication 1319-1325dupCCCACCC (Phe443Profs*24) (n = 25), and two missense mutations p.K192E (c.574A>G) (n = 17) and c.1474C>T (p.R492W) (n = 12). The novel c.195+2T>C and c.1215_1215+2delTGTinsCGA splice-site and c.1144C>A missense variants were firstly described in our cohort.</p><p><strong>Conclusion: </strong>The most common four mutations accounted for the underlying aetiology of VDDR1A in approximately 81% of the cohort, indicating Turkey may serve as a mutational hotspot or exhibit a founder effect for these variants. Our large cohort's results suggested no clear and clinically meaningful phenotype-genotype relationship in VDDR1A.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Arginine Vasopressin Deficiency (Central Diabetes Insipidus) in Neonates and Infants.","authors":"Hannah Pearlstein, Allie Dayno, Jessica Zook, Julia Crowley, Craig Alter, Iris Gutmark-Little, Shana E McCormack","doi":"10.1159/000547155","DOIUrl":"10.1159/000547155","url":null,"abstract":"<p><strong>Background: </strong>Arginine vasopressin deficiency (AVP-D), previously called central diabetes insipidus (central DI), is the inability to concentrate urine despite elevated serum osmolality (i.e., volume depletion) related to inadequate production of the posterior pituitary hormone vasopressin. Without treatment, which typically consists of fluids and pharmacologic vasopressin analogs, AVP-D can quickly lead to hypernatremia and dehydration. Management of AVP-D in neonates and infants is particularly challenging for many reasons: their inability to communicate thirst, their limited renal concentrating capacity, the obligate fluids required for nutrition that may cause hyponatremia with anti-diuretic therapy, the lack of FDA-approved formulation of vasopressin analog in this age, the potential need for growth-related adjustments in nutrition, fluids, and vasopressin analogs, and a limited evidence base. Despite these challenges, multiple groups have reported experiences with the available pharmacologic options, including alternative formulations of desmopressin (buccal, standard oral tablet, orally disintegrating tablet [melt], subcutaneous) and thiazide diuretics.</p><p><strong>Summary: </strong>The objective of this mini-review was to provide pragmatic guidance on the options for long-term outpatient management of AVP-D in neonates and infants.</p><p><strong>Key messages: </strong>Management of AVP-D in neonates and infants necessitates special considerations. For each affected patient and family, weighing the relative merits and drawbacks of each approach is critical to identify the most appropriate option, which may also change over time.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}