Hormone Research in Paediatrics最新文献

Introduction: In 21-hydroxylase deficiency (21-OHD), impaired 21-hydroxylase activity causes 17-hydroxyprogesterone (17-OHP) accumulation and androgen excess, typically manifesting as hyperandrogenism. The POR gene encodes cytochrome P450 oxidoreductase (POR), the essential electron donor for all microsomal cytochrome P450 enzymes. While POR deficiency impairs multiple steroidogenic enzymes, its phenotypic impact on 21-OHD patients remains poorly characterized.

Case presentation: We report a male 21-OHD patient with homozygous CYP21A2 variant (c.293-13C>G) who presented atypically with absent hyperandrogenism and persistently low testosterone levels before puberty. Medication withdrawal revealed significantly elevated adrenocorticotropic hormone and 17-OHP, but only mildly elevated androstenedione (AD) and relatively low testosterone, suggesting impaired 17-OHP-to-AD conversion due to 17,20-lyase deficiency. Whole-exome sequencing identified a concurrent heterozygous pathogenic POR variant (c.1660C>T, p.Arg554Ter). The patient presented with delayed puberty during disease progression but achieved spontaneous puberty after 1.3 years of cumulative GnRH pump therapy, consistent with disease-related functional delayed puberty.

Conclusion: This 16-year follow-up case demonstrates that heterozygous POR variants may modulate the phenotype and hormonal profile in 21-OHD. These findings highlight the importance of whole-exome sequencing in atypical 21-OHD cases to identify potential modifiers of steroidogenic pathways.

Background: The transition from paediatric to adult healthcare is a critical period for young individuals with endocrine conditions. Despite numerous published recommendations, Europe still lacks recent, comprehensive, evidence-based, and practically applicable guidelines for endocrine healthcare transition.

Objective: The aim of the study was to develop European consensus guidance for transition from paediatric to adult care in endocrine conditions through a structured, evidence-based approach.

Methods: A systematic literature review identified 351 recommendations from 55 articles (2011-2023). Articles were included if they provided recommendations on the transition from paediatric to adult care for patients with endocrine diseases or general (non-disease-specific) transition guidance. The guidance was developed by a core multidisciplinary group (n = 7) and refined through focus groups with 18 experts from 10 European countries, representing both paediatric and adult care settings. Patient representatives have reviewed and approved it.

Results: The guidance includes recommendations across 11 domains: structure of transition service, patient empowerment, patient-professional relationship, multidisciplinary team organisation, healthcare provider education, timing and planning, care coordination, management of non-attendance, psychological support, parent/caregiver role, and readiness tools. Each recommendation was rated as either "recommend" (strong) or "suggest" (conditional) based on expert consensus and available evidence.

Conclusion: This ESE-ESPE guidance provides a comprehensive, practical framework for endocrine healthcare transition, applicable across different European healthcare settings. The recommendations emphasise structured programs, care coordination, and patient-centred approaches to optimise transition outcomes.

Background: Adolescents with type 1 diabetes (T1D) face barriers to moderate-to-vigorous physical activity (MVPA) such as uncertainty with self-management, limited access to supportive environments, and stigma related to living with diabetes. Opportunities for peer activities with T1D role model support are limited. To address this need, we tested iterative refinements of pilot Virtual Exercise Games for Youth with T1D (ExerT1D) for feasibility and acceptability.

Methods: The program included 6 versions: study 1 (1.1-1.4) included an active videogame, and study 2 (2.1-2.2) included a virtual reality active videogame. All versions included T1D exercise management education by clinicians and goal-setting guided by young adult coaches with T1D.

Results: Seventeen adolescents (median age 15.4 [IQR 14.6-16.4] years, 7 non-Hispanic white, 8 male, median HbA1c 8.1% [IQR 7.4%-11.1%]) enrolled. Participants rated the program, comfort, clinicians, coaches, and group cohesion high/very high. Motivation for the videogame was high . Building T1D and MVPA self-management skills was rated excellent at most sessions, as were peer interactions and enriched communication after adding immersive virtual reality in study 2. Transitions between VR apps caused delays of 19±6 minutes per 60min-90min session. Compared to baseline, HbA1c or Glucose Management Indicator (GMI) decreased over time in an exploratory analysis (d=-1.12, 90% CI [-1.78,-0.48]).

Conclusions: In a small cohort, the ExerT1D program facilitated a supportive environment for engaging diverse youth with T1D in an MVPA program led by T1D coaches. Larger studies are needed to assess the intervention's impact on engagement with physical activity, glycemic outcomes, and quality of life.

Objective: Silver-Russell syndrome (SRS) is a rare imprinting disorder characterized by growth retardation, early puberty, and poor pubertal growth, leading to short stature. We aimed to assess the outcome in terms of adult height (AH) and tolerance of combined treatment with recombinant human growth hormone (rhGH) and a gonadotropin-releasing hormone analogues (GnRHa) for children with SRS followed in a reference centre for rare disorders in France.

Patients and methods: This was a retrospective observational study that included children with molecularly confirmed SRS, aged 14 years and over, who received rhGH and GnRHa. We collected data on birth parameters, height and weight at the start of rhGH and at the start and end of GnRHa, bone age, and adult height, if reached.

Results: Thirty-nine children (17 girls and 22 boys) were analysed. The median age at the start of rhGH was 3.9 years (2.8;5.0) and that at the start of GnRHa was 10.0 years (9.3;11.0). AH was reached for 30 patients (76.9%): median AH standard deviation score (SDS) of -1.8 (-2.4;-1.1). There was no difference in AH between girls -2.1 SDS (-2.4;-1.5) and boys -1.4 SDS (-1.9;-1.2). Median pubertal height gain was 26.0 cm (23.0;29.0) for girls and 30.0 cm (28.0;34.0) for boys. Tolerance was good and there were few drug-related adverse effects.

Conclusion: Combined treatment with rhGH and GnRHa for children with SRS resulted in AH within standard references for more than half of our cohort and appears to be safe in this population.

Introduction: Youth and adults with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) are at risk for cognitive deficits and brain structural changes. Although factors inherent to CAH have been implicated in cognitive dysfunction, little is known about early developmental skills in these patients. Thus, we aimed to investigate development in younger children with CAH.

Methods: Cross-sectional study of 13 infants and toddlers (0.4-3.5 yrs) and 21 children (3.5-11 yrs) with classical CAH due to 21OHD. Infants and toddlers completed cognitive and motor skills screening (Bayley-4). Children also completed age-appropriate assessment of cognition (WISC-V Digit Span and Spatial Span subtests, NIH Toolbox-Version 2, WRAML-2 Design Memory subtest, CVLT-C) and motor skills (NIH Toolbox-Version 2). Their parents completed standardized reports of adaptive behavior and motor skills (Vineland-3). T-tests compared the CAH group (mean percentile, mean ± SD) with normative means.

Results: Infants and toddlers with CAH exhibited lower gross motor skills (27th percentile, 8.2±2.4, p=0.03) compared to the normative mean. Children with CAH exhibited decreased auditory working memory skills (WISC-V, 27th percentile, 8.2±1.8, p=0.01), and lower nonverbal learning skills (WRAML-2, 21st percentile, 7.6±3.4, p=0.02). Their parents reported lower adaptive behavior (Vineland-3, 30th percentile, 92.2±9.1, p=0.004) and overall motor skills (26th percentile, 90.3±11.4, p=0.006) than the normative mean.

Conclusions: Pediatric patients with CAH due to 21OHD exhibit distinct, age-dependent developmental deficits, with infants and toddlers displaying lower gross motor performance, and children exhibiting decreased auditory working memory and adaptive behavior skills. These findings suggest that early signs of developmental deficits in CAH may emerge at a younger age than previously recognized, emphasizing the role of clinical factors inherent to the disease.

Context: Evidence for growth hormone therapy in Indian hedgehog (IHH)-related short stature is limited.

Objective: To assess growth outcomes in children with heterozygous pathogenic IHH variants treated with recombinant human growth hormone (rhGH).

Methods: Retrospective cohort of 19 children with short stature carrying heterozygous deleterious IHH variants treated with daily rhGH (33-50 µg/kg/day); 10 attained adult height. Outcomes were height SD score (SDS), height velocity, and adult height SDS.

Results: At treatment start, median height SDS was -2.6 (IQR: -3.0; -2.2) and height velocity 5.1 cm/year (IQR: 4.3; 6.2). After 1 year, height velocity increased to 9.2 cm/year (IQR: 7.9; 10.3) and height SDS to -1.9 (IQR: -2.3; -1.6), with Δheight SDS 0.7 (IQR: 0.5; 1.0). Over a median of 4.0 years of therapy (IQR: 3.4; 5.7), total Δheight SDS was 1.2 (IQR: 0.8; 1.5), and 16/19 (84%) had height SDS ≥ -2.0 at last follow-up. At last follow-up, patients with predicted loss-of-function variants (n=6) showed higher height SDS than those with missense variants (n=13) [-0.8 (IQR: -0.9; -0.7) vs -1.7 (IQR: -1.9; -1.6)] and greater Δheight SDS [1.4 (IQR: 1.2; 1.9) vs 0.8 (IQR: 0.7; 1.3)]. Among those reaching adult height, adult height SDS was -1.7 (IQR: -1.9; -1.6) after a median of 5.8 years of therapy (IQR: 4.0; 7.3), with Δheight SDS 0.8 (IQR: 0.7; 1.4).

Conclusions: rhGH therapy was associated with clinically meaningful height gains, including adult height improvement, in children with IHH-related short stature; variant class may modify response.

Aims: Despite improvement in diabetes management, many adolescents with type 1 diabetes (T1D), especially those with disordered eating behaviors (DEB), struggle to reach glycemic targets and have higher HbA1c levels. We aimed to evaluate HbA1c and DEB trends in adolescents with T1D following insulin pump implementation.

Methods: This prospective longitudinal study, with 12 months follow-up, included adolescents (n=38) with T1D aged 10-20 years, who were assessed at baseline (prior to insulin pump implementation), and at 2-, 6-, and 12-months post-implementation. Data were collected from medical charts and self-reported questionnaires.

Results: HbA1c and DEB levels showed no significant changes over time. However, adolescents with DEB consistently had higher HbA1c levels than those without (P = 0.003). Both HbA1c and DEB were elevated in adolescents with body dissatisfaction, particularly those desiring thinner bodies (P = 0.012 and P < 0.001, respectively). HbA1c trends varied by insulin delivery method (P = 0.005), with the greatest reduction observed in users of hybrid closed-loop (HCL) systems (P = 0.04).

Conclusions: Despite insulin pump implementation, no significant overall changes were observed in HbA1c or DEB levels across the study period. However, adolescents using HCL systems showed reduced HbA1c, while levels remained elevated among those with DEB. Both HbA1c and DEB were higher in adolescents with body dissatisfaction, particularly those desiring thinner bodies. These findings highlight the need for targeted support during the adoption of diabetes technologies. Larger studies are warranted to guide effective interventions for this high-risk population.

Introduction: 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 K_ATP channel variants may respond to oral sulphonylurea instead of insulin. The study aimed 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 to 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.

Conclusion: 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 K_ATP-related NDM.

Introduction: 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. The objective of this study was to evaluate the long-term efficacy and safety of weekly PEG-rhGH in ISS children.

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/week with dose adjustment (up to 0.4 mg/kg/week) 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 of ΔHT SDS were 1.52, 1.24, and 1.07 for PEG-rhGH 0.2/0.2 mg/kg/week, 0.1/0.2 mg/kg/week, and 0/0.2 mg/kg/week groups, respectively. The 0.2/0.2 mg/kg/week group maintained significantly greater height improvements. HV was highest in the 0/0.2 mg/kg/week group (9.16 ± 1.33 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.