Hormone Research in Paediatrics最新文献

Background: Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes presenting before 6 months of age. It may be permanent (PNDM) or transient (TNDM). Individuals with KATP channel variants may respond to oral sulphonylurea instead of insulin.

Aim: To review the presentation, genotype, phenotype, management and outcomes of patients diagnosed with NDM in Ireland over 19 years.

Methods: Data on Irish NDM cases from 2006-2024 were collated through Paediatric Endocrinologists nationally and electronic databases. Analyses were performed using SPSS, with ethical approval obtained.

Results: Nineteen cases were identified: twelve PNDM and seven TNDM. Age at diagnosis ranged from 1 day to 11 months. Among PNDM cases, KCNJ11 (n=6), EIF2AK3 (n=3) and INS (n=1) variants were identified, while two lacked a genetic diagnosis. Six TNDM cases had 6q24 methylation defects, and one had an ABCC8 variant. Genetic diagnosis informed familial risk and prompted changes to a parent's medical management. Sulphonylurea therapy was most effective when initiated early.

Conclusions: This national case series highlights the genetic and phenotypic spectrum of NDM in Ireland. Early genetic diagnosis enables precision therapy, with timely sulphonylurea initiation improving outcomes in KATP-related NDM.

Background: Idiopathic short stature (ISS) is characterized by short stature without identifiable underlying disorders. Long-acting PEGylated recombinant human growth hormone (PEG-rhGH) has emerged as a promising treatment option for ISS children.

Objective: To evaluate the efficacy and safety of weekly PEG-rhGH in ISS children during the extension study.

Methods: This multicenter, open-label, uncontrolled extension study (extension phase) followed the initial 52-week trial (main phase). All subjects received once-weekly PEG-rhGH at 0.2 mg/kg/wk with dose adjustment (up to 0.4 mg/kg/wk) based on height velocity (HV) and insulin-like growth factor-1 (IGF-1) standard deviation score (SDS). The primary endpoint was change in height SDS (ΔHT SDS) from baseline; secondary endpoints mainly included HV, changes in bone age/chronological age ratio, IGF-1 SDS and average annual prescribed dose. Safety was evaluated through adverse events and clinical findings.

Results: Of 280 children enrolled in extension study, 268 completed 52-week treatment. This analysis included results up to week 104, representing 52-week extension phase following the 52-week main phase. At week 104, the least squares means (LSM) of ΔHT SDS were 1.517, 1.242 and 1.067 for PEG-rhGH 0.2/0.2 mg/kg/wk, 0.1/0.2 mg/kg/wk and 0/0.2 mg/kg/wk groups, respectively. The 0.2/0.2 mg/kg/wk group maintained significantly greater height improvements. HV was highest in the 0/0.2 mg/kg/wk group (9.158±1.334 cm/year), reflecting typical first-year catch-up growth. Mean IGF-1 SDS remained within 2SDS during 2 years.

Conclusion: Once-weekly PEG-rhGH in children with ISS showed sustained efficacy over 2 years in all assessed height-based outcomes. Treatment remained safe and well-tolerated with no new safety signals.

Introduction: Achondroplasia is a rare skeletal dysplasia characterized by severe disproportionate short stature. Vosoritide is currently the only approved therapy. The CrescNet registry is a network of primary and specialized pediatric tertiary centers that aims to improve early detection of growth disorders in Europe. In 2021, an achondroplasia-specific data collection module was set up within CrescNet to enhance data collection among children with achondroplasia and assess the impact of interventions. Here, we describe the module setup and report preliminary real-world outcomes of vosoritide treatment over 3 years.

Methods: The module was established in 10 of 11 countries participating in CrescNet. Achondroplasia-specific data were collected, including developmental milestones, interventions (such as limb-lengthening surgery, treatment with vosoritide and growth hormone), complications, and health-related quality of life, alongside standard anthropometric measurements (eg height, weight, etc). Pseudonymized data were sent to the CrescNet central database, Leipzig University Hospital, Germany, for analysis by age and treatment status.

Results: As of May 2025, 486 participants from 32 tertiary centers were enrolled. Data from 73 untreated and 186 vosoritide-treated individuals with genetically documented achondroplasia were analyzed. In vosoritide-treated individuals, mean height standard deviation score, referenced to an untreated European achondroplasia population, significantly increased from baseline at 1, 2, and 3 years after vosoritide initiation (P≤0.0001).

Conclusions: The module facilitates the collection of real-world data to improve understanding of the natural history of achondroplasia and outcomes associated with interventions. Growth data from vosoritide-treated individuals were consistent with clinical trial findings and published real-world data. Longer-term follow-up is ongoing.

Introduction: As an alternative to commercial automated insulin delivery (AID) systems open-source AID (OS-AID) technologies such as Loop had growing interest among people with type 1 diabetes (T1D). This study aims to evaluate the six-month glycemic outcomes of children using the Loop iOS.3 system.

Methods: A total of fifty children aged 2-18 years with a minimum 6-month T1D duration, initiated Loop OS-AID between May 2023 and May 2024. Data from continuous glucose monitoring and insulin delivery were collected and analyzed at baseline, 3 months, and 6 months. Primary outcomes included time in range (TIR, 3.9 - 10mmol/L [70-180 mg/dL]), time above range (TAR), time below range (TBR), glucose management indicator (GMI), and HbA1c.

Results: TIR improved significantly from 68.3% at baseline to 72.7% at 6 months (p=0.003). The proportion of participants with TIR >70% increased from 46% to 66% (p=0.012). The mean HbA1c value showed a significant decrease from baseline to month 6 (53 mmol/mol [7.0%] vs. 49 mmol/mol [6.6%], p=0.006), although HbA1c measurements were available for a limited number of participants. TAR1 > 10mmol/L (180 mg/dL) decreased (2 vs 17.1 p <0.001), while TAR2 >13.8mmol/L (250mg/dl) showed a slight, non-significant reduction (5 vs 4 p=0.363). TBR1 <3.9mmol/L (70mg/dL) and TBR2 <3mmol/L (54mg/dL) remained stable (3 vs 3, p1=0.474; 0.7 vs 0.9, p2=0.560). The basal insulin ratio dropped significantly (40.3% vs 19.7%, p <0.001), suggesting a shift in dosing dynamics due to the algorithm's automatic correction bolus strategy.

Conclusion: Use of the Loop OS-AID system resulted in improved glycemic outcomes without increased risk of hypoglycemia or DKA (Diabetic ketoacidosis). These findings support Loop as a safe and effective alternative for pediatric T1D management. Further large-scale and longer-term studies are warranted.

Background: Long-term glucocorticoid (GC) therapy is a leading cause of growth retardation in children with chronic renal and rheumatic diseases. While recombinant human growth hormone (rhGH) is used to counteract these effects, its efficacy relative to spontaneous catch-up growth following GC withdrawal remains inadequately quantified. This study aimed to compare the efficacy of rhGH treatment against spontaneous catch-up growth in children with GC-induced short stature.

Methods: This retrospective, non-randomized controlled study was conducted at a single tertiary children's hospital, including patients treated between 2010 and 2020. We established a treatment group of 34 children (23 with nephrotic syndrome [NS]) with GC-induced short stature who received rhGH therapy (0.15-0.2 IU/kg/day, approx. 0.05-0.067 mg/kg/day) for at least one year. A historical control group comprised 20 children with NS who exhibited short stature after GC cessation and were monitored for spontaneous catch-up growth for 6-12 months. The primary outcome was the annualized growth velocity after one year. Secondary outcomes included changes in height standard deviation score (SDS), bone age (BA), IGF-1 SDS, and IGF-binding protein 3 (IGF-BP3) levels.

Results: The primary analysis focused on patients with NS. The mean annualized growth velocity in the rhGH-treated NS subgroup (n=23) was significantly higher than in the control group (n=20) (10.48 ± 2.58 cm/year vs. 5.79 ± 0.49 cm/year, P < 0.001). Within the entire rhGH treatment cohort (n=34), after one year of therapy, the height SDS significantly improved (P < 0.001). The discrepancy between bone age and chronological age narrowed from 2.61 ± 1.64 years at baseline to a median of 1.0 year (IQR: 0.45, 2.6) post-treatment (P < 0.001). Serum IGF-1 SDS increased significantly from -1.45 ± 0.82 to 1.12 ± 0.95 (P < 0.001). rhGH therapy was well-tolerated.

Conclusion: In children with Nephrotic Syndrome and GC-induced short stature, rhGH treatment results in a significantly greater improvement in growth velocity compared to spontaneous catch-up growth alone. It effectively enhances linear growth and normalizes the GH-IGF-1 axis with a favorable safety profile.

Objective: Since the first description of Turner Syndrome (TS), both genotypic spectrum and phenotypic presentation have evolved. This study aims to examine trends in this evolution over the past three decades and provides an overview of current genetic and clinical features in a large nationwide multicenter cohort of girls with TS.

Patients and methods: We analyzed data from growth hormone (GH)-treated girls with TS included in BELGROW, the national GH registry of the BELux Society for Pediatric Endocrinology and Diabetology, between 1985-2022. Karyotype, age at diagnosis, and phenotype were studied in 716 girls. Two periods were compared: 1991-2002 (Group 1, n=250) and 2003-2017 (Group 2, n=270).

Results: The annual number of girls with TS starting GH remained stable (mean n=19/year). In the entire cohort, monosomy 45,X was the most frequent karyotype (44%), followed by structural anomalies of the X chromosome (27%), 45,X/46,XX mosaicism (13%), triple X mosaicism (4%), 45,X/46,XY or complex Y anomalies (6%), and others (6%). The proportion of 45,X decreased between the two periods (46% to 38%, p<0.05). Overall, median age at diagnosis was 6.4 years with 7.6% of girls diagnosed prenatally, 24% before age 1, 49% in childhood, and 19% after 12 years. Prenatal diagnoses increased from 2.5% (Group 1) to 15% (Group 2) (p<0.001). Girls with a 45,X karyotype were diagnosed earlier than girls with other genotypes (median 2.2 vs 8 years, p<0.001). Skeletal (73%), neurosensory (60%), and cardiac (29%) systems were most affected. Skeletal and cardiac malformations were more frequent in girls with a 45,X karyotype (p<0.05 and p<0.01, respectively).

Conclusion: Genotype distribution and timing of TS diagnosis have significantly changed since 1991 while the annual number of girls starting GH therapy has remained stable. A 45,X karyotype is associated with earlier diagnosis and more comorbidities.

Introduction: Improving outcomes for transition-aged patients with type 1 diabetes (T1D) requires understanding glycemic trajectories and modifiable factors. We evaluated longitudinal glycated hemoglobin (HbA1c) trends, target attainment, and associated factors in Korean youth with T1D.

Methods: This retrospective cohort included 354 patients diagnosed before age 14 years with HbA1c data at three or more distinct ages between 15 and 22 years, followed at Seoul National University Children's Hospital 1999-2024. Linear mixed-effects models assessed factors associated with HbA1c trajectory.

Results: Mean HbA1c declined from 9.0% (75 mmol/mol) at age 15 years to 8.2% (66 mmol/mol) at age 22 years (-0.103% [-1.1 mmol/mol] per year, p < 0.001). Older age, male sex, continuous glucose monitoring (CGM) use, and parental college education were independently associated with lower HbA1c over time (all p < 0.05). At age 22 years, there were no CGM users in the 2006-2015 cohort, whereas 25.2% used CGM in the 2016-2024 cohort. At this age, 19.6% achieved HbA1c < 7% (53 mmol/mol), whereas 24.8% remained at ≥ 9%. Among those with HbA1c ≥ 9% at age 15 years, nearly half remained ≥ 9% at age 22 years, while approximately one-tenth improved to < 7%.

Conclusions: Although glycemic control improved with age, a substantial proportion of adolescents and young adults with T1D failed to meet HbA1c targets. Given that CGM use was a key factor associated with better control, increasing CGM uptake alongside tailored support may improve outcomes during the transition to adulthood.

Introduction: MED12 is a causative gene for congenital malformation syndromes. The association between MED12 variants 46,XY disorders/differences of sex development (DSD) remains unclear, although several variant-positive patients exhibited genital abnormalities.

Case presentation: Three siblings manifested hypomasculinized genitalia, including hypospadias and cryptorchidism, with normal or mildly increased gonadotropin levels. Two patients showed normal spontaneous puberty. Whole exome sequencing identified a maternally-derived hemizygous MED12 variant (c.3064A>G, p.Met1022Val). One patient lacked typical clinical features of MED12-associated malformation syndromes.

Conclusion: MED12 variants may be associated with 46,XY DSD with or without congenital malformation syndromes through testicular dysfunction and defective genital formation during fetal development.

Pediatric endocrinology has made remarkable advances over recent decades, transforming the lives of countless children and families. Yet, major challenges persist. Many rare and complex endocrine disorders remain difficult to diagnose, monitor, and treat effectively. Disparities in access to specialized care, limited research investment, and fragmented health systems continue to create inequities in outcomes across regions and populations. This document arises from the collective effort of the European Society for Paediatric Endocrinology (ESPE) to highlight these unmet medical needs and to chart a path forward. It underscores the necessity of harmonized diagnostic standards, innovative research, and sustainable policies that support both patients and professionals. By identifying key barriers and proposing strategic directions, ESPE aims to foster collaboration among clinicians, researchers, policymakers, and patient communities. Only through coordinated action can we ensure that every child with an endocrine disorder receives equitable, timely, and high-quality care-regardless of where they live.

Introduction: Obesity in childhood and adolescence represents one of the most challenging public health problems of our century, and is associated with significant morbidity and mortality, as well as increased public health costs. To address the obesity epidemic more effectively, the World Health Organization suggests the development and implementation of reliable e-Health systems (digital technologies, such as electronic health records (EHRs), clinical decision support systems (CDSS) and mobile health tools) that would monitor the daily behavior objectively. Our objective was to determine the effectiveness of BigO system in the prevention and management of childhood obesity.

Methods: Our study was part of the four-year European BigO project (http://bigoprogram.eu, Horizon2020, No.727688). One thousand seven hundred and twenty-seven (n=1727) children and adolescents (mean age ± SD: 12.6 ± 2.4; 898 males, 829 females) were studied prospectively following approval by the local Ethics Human Research Committee. The data collection system included the BigO technology platform, which interfaces with a Smartphone and Smartwatch, and records data objectively (using inertial sensors and GPS) for each patient. Data were transmitted to BigO servers to extract behavioral indicators. Participants used the BigO system for at least 4 weeks. Subsequently, they entered a personalized lifestyle intervention program of diet, physical exercise and sleep for 6 months and used the system again for 4 weeks.

Results: Subjects were classified as having obesity (n=1277, 73.9%), overweight (n=413, 23.9%) or normal BMI (n=37, 2.1%) according to WHO cut-off points. At the end of the study, the proportion of subjects with obesity decreased, while the proportion of subjects with overweight and normal BMI increased. The BigO system monitored the daily behavior of all subjects objectively and effectively, and provided detailed information on their diet, physical activity and sleep habits, as well as the availability of exercise facilities in their communities and their living conditions.

Conclusion: These novel e-health applications and digital technologies were effective at collecting and analyzing objective data about the daily behavior of children and adolescents with overweight and obesity. Therefore, they may be useful to use in clinical practice and to design public health policies to address the epidemic of childhood obesity.