Hormone Research in Paediatrics最新文献

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, clinical decision support systems, 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 4-year European BigO project (http://bigoprogram.eu, Horizon2020, No. 727688). Overall, 1,727 (n = 1,727) 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 = 1,277, 73.9%), overweight (n = 413, 23.9%), or normal BMI (n = 37, 2.1%) according to WHO cutoff 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.

Introduction: Caring for youth with type 1 diabetes (T1D) can be challenging for caregivers. Diabetes technology can improve glycemic outcomes and reduce the burden for youth with T1D. Little is known about the emotional challenges caregivers experience in relation to each step of the diabetes technology journey. Using qualitative methods, this study aimed to understand the emotional barriers caregivers encounter along the diabetes technology journey and to explore caregivers' attitudes toward diabetes technology, diabetes burden, and diabetes-specific family conflict using patient-reported outcomes surveys.

Methods: Nine virtual workshops were held with caregivers of Black and Hispanic/Latino youth aged 2-17 years old with T1D managed with diabetes technology to elicit emotional barriers to the use of diabetes technology. All sessions were recorded and analyzed using an inductive approach. Caregivers also completed validated surveys regarding diabetes technology attitude, diabetes burden, and updated diabetes-specific family conflict.

Results: Emotional challenges with each step of the diabetes journey included: 1) mistrust of the device leading to fear, 2) anxiety related to possible device malfunctions, and 3) frustration with device visibility and diabetes technology troubleshooting. Most caregivers (88%) reported low diabetes burden, positive attitude towards diabetes technology (95% CI [17.6-20.2]), and low diabetes-specific family conflict (95% CI [15.2-39.5]).

Conclusion: This study identified key emotional barriers caregivers face during the diabetes technology journey for youth with T1D. Proactively addressing emotional barriers to the adoption and use of diabetes technology may ultimately lead to greater adoption and use.

Introduction: Obesity in childhood and adolescence is a significant public health issue, associated with increased morbidity, mortality, and healthcare costs. The search for effective strategies to combat obesity has spurred the development of e-health technologies, which objectively record behavioral data and correlate them with factors that increase body mass index (BMI). The aim of our study was to assess the dietary habits of children and adolescents with overweight and obesity in Greece.

Methods: Eight hundred eighty (n = 880) children and adolescents (mean age ± standard deviation: 12.226 ± 1.972 years, 453 males, 427 females) participated in the study prospectively. Based on BMI, subjects were classified as having obesity (n = 658, 74.8%) and overweight (n = 222, 25.2%) according to the International Obesity Task Force (IOTF) cut-off points. Participants' medical history and anthropometric data were collected, and caregivers completed the self-administered ToyBox food frequency questionnaire.

Results: Boys were more likely to have obesity (78.4% vs. 71%, p = 0.011) and girls were more likely to have overweight (29% vs. 21.6%, p = 0.011). The consumption of cereal without added sugar was higher across both BMI categories than the consumption of cereal with added sugar (p = 0.016). In both groups, the majority of participants consumed more than 115 g of meat and poultry (p = 0.019) with an increased frequency of 2-4 times per week (p = 0.034). Boys consumed more water, light beverages, vegetables, meat, fried potatoes, and chocolate spread than girls (p < 0.05).

Conclusions: These findings provide information on the dietary habits of children with overweight and obesity in our country, and may help develop guidelines for the prevention and treatment of childhood obesity.

Increasingly children and adolescents are being identified in early-stage type 1 diabetes (T1D), defined as two or more islet autoantibodies without hyperglycemia (above diagnostic threshold) or reliance on intensive insulin therapy. They require clinical monitoring and care. Healthy lifestyle education is recommended in guidelines, however evidence synthesis to inform clinical practice is lacking. Therefore, this review summarizes current evidence on nutrition, lifestyle to delay progression to stage 3 T1D; and proposes lifestyle strategies for children and adolescents with early-stage T1D. Specifically, we suggest a key focus on reducing beta-cell stress, promoting a healthy gut microbiome and establishing healthy lifestyles and relationships with food, prior to the introduction of intensive insulin therapy. As secondary prevention of T1D is an emerging research area and randomized controlled trials are scarce, evidence has been largely drawn from prospective cohort studies and routine clinical care for stage 3 T1D. A balanced and varied diet, limiting intake of foods containing high amounts of saturated fat and added sugar, and moderate levels of physical activity, are likely beneficial for overall health in children and adolescents with early-stage T1D. Low glycemic index (GI) diets may be protective against progression to stage 3 T1D.

Introduction: Turner syndrome (TS) is a complex genetic condition requiring lifelong, multidisciplinary care. International consensus guidelines exist, but the organisation of paediatric TS services in the UK has not been systematically explored.

Methods: A structured electronic survey was distributed to paediatric endocrinology centres across the UK with responses collected from June 2023 to February 2024. The survey collected information on service configuration, staffing, multidisciplinary team (MDT) composition, transition pathways, use of consensus guidelines, and engagement with patient registries and support societies.

Results: Responses were received from 20 UK tertiary centres. Six out of 20 centres operated a dedicated TS clinic. MDTs were limited in most centres to paediatric endocrine consultants and nurse specialists, and shared care models for outreach patients were common. Transition practices varied, with 45% of centres using TS-specific pathways, 45% using general endocrine transition pathways, and 10% without a transition pathway. Awareness of international TS guidelines, the Turner Syndrome Support Society, and the i-TS registry was high, but active engagement varied.

Conclusion: Significant variability exists in UK paediatric TS service models. Centres without dedicated clinics were generally smaller with fewer patients. Geographic challenges may exacerbate inequalities for outreach patients. While some centres offer best practice examples, improvements in MDT availability, transition planning, and registry engagement are needed to align more closely with international care recommendations.