Hormone Research in Paediatrics最新文献

Introduction: Multidisciplinary care can improve glycemic outcomes in individuals with type 1 diabetes (T1D). Yet, prior studies suggest limited utilization of team-based care and either no reimbursement or inadequate reimbursement for diabetes and nutritional education, mental health, and social support as well as remote services. We sought to evaluate multidisciplinary care services offered by pediatric diabetes centers to understand whether current practices are sustainable.

Methods: The Pediatric Endocrine Society Diabetes Special Interest Group collaborated with the T1DX-Quality Improvement Collaborative to survey US pediatric diabetes centers on care delivery practices and resources for new onset and ongoing care, introduction of technology, and telehealth focusing on team-based approaches.

Results: We analyzed responses from 31 centers, mostly academic, from 16 states and Washington DC representing all geographical regions providing care for 45,759 youth with T1D who had at least one visit in 2022. Most centers (74%) provided initial diabetes education in the inpatient setting using clinic-employed staff. The majority initiated CGMs at or close to diagnosis and offered insulin pump therapy within the first year. All but one center encouraged communication with diabetes teams between visits. Less than half of practices estimated that at least 50% of their youth with T1D received mental health services and assessments for social concerns annually. Telehealth was utilized by all centers. Many centers indicated suboptimal reimbursement, and 87% operated at a budget deficit.

Conclusion: Despite the commitment of pediatric diabetes centers to provide high-quality multidisciplinary care, many youth with T1D may not receive the services as frequently as recommended. These services are often unreimbursed. We advocate for alternative reimbursement models for clinical workflows that support the delivery of individualized, multidisciplinary care aligned with best practices shown to improve clinical outcomes and quality of life for youth with T1D. Examples include expansion of telemedicine and remote monitoring, non-face-to-face acute and routine care, navigation of technology, supplies and services, engagement and coordination of community-based resources among others. Such models would promote equitable, needs-based care while enabling centers to operate efficiently.

Background: It is not known whether the extent of pubertal development influences the treatment effects in very young transgender people undergoing puberty suppression (PS) and gender-affirming hormone therapy (GAHT). This study aimed to investigate how anthropometric parameters and body composition change according to birth-assigned sex and affirmed gender during PS and GAHT.

Methods: This retrospective study included data from 201 adolescents starting PS under 15yr at a national gender service (139 trans boys and 62 trans girls). Data from 127 of them who subsequently received GAHT were available. Height, weight, BMI, total lean, fat and muscle mass (LM, FM and MM) were collected using Tanita body composition analyzer.

Results: 'In puberty' trans boys (Tanner stage 2-3), total FM increased on PS (2.49 kg, 95% CI 1.66;3.33) similarly to LM (2.41 kg, 95% CI 1.85;2.97), while in 'completing puberty' trans boys (Tanner stage 4-5) the increase of total FM (1.80 kg, 95% CI 1.21;2.39) was higher than total LM (0.97 kg, 95% CI 0.63;1.30). 'In puberty' trans boys showed increasing mean FM z-scores from baseline after 3 years of PS (from 0.70 to 1.2). Mean LM z-scores decreased in both 'in puberty' (from 0.98 to 0.5) and 'completing puberty' (from 1.16 to 0.80) trans boys. During GAHT, 'in puberty' trans boys showed a greater increase of total LM and MM (respectively 6.28 kg, 95% CI 3.54;9.02 and 6.08 kg, 95% CI 3.64;8.51). Both groups 'in puberty' and 'completing puberty' trans boys did not show a further increase in total FM. In contrast, 'completing puberty' trans girls showed the greatest increase of total FM during PS (4.27 kg, 95% CI 1.50;7.03). MM and LM % decreased throughout PS in all trans girls, whereas body composition only changed slightly during GAHT.

Conclusions: The effect of PS on body composition is more pronounced in 'in puberty' trans adolescents, and 'in puberty' trans boys are more responsive to GAHT, showing greater increases in MM and LM. In trans girls, the most significant increase in FM, along with reduction in LM and MM, occurs during PS, whereas no substantial changes were observed during subsequent GAHT. This suggests that any effect on physical performance may depend on pubertal development at the start of intervention.

Background: Despite guidelines emphasizing the importance of a structured pediatric-to-adult healthcare transition (HCT) for individuals with congenital adrenal hyperplasia (CAH), significant gaps remain in understanding the transition experiences and long-term outcomes of this population. This scoping review examines existing research on HCT for emerging adults with CAH.

Summary: PubMed, Scopus, and Embase databases were systematically searched to identify research exploring the HCT of individuals with CAH. Eighteen studies met the inclusion criteria. Findings were categorized as: (1) HCT readiness and communication, (2) HCT programs and outcomes, and (3) HCT experiences and considerations. Barriers hindering effective HCT include clinician shortages, distance to specialty care centers, and socioeconomic challenges. Knowledge gaps include patient and parent perspectives, a lack of validated transition readiness measures, insufficient long-term health outcome data, intervention research, and data on self-management skills. Addressing these gaps is essential to enhancing patient outcomes and continuity of care.

Key messages: This review highlights the importance of strategies, including effective communication, structured HCT programs, and transition readiness measures, to improve outcomes for individuals with CAH. Challenges, such as inconsistent metrics, logistical barriers, and high rates of care dropout, demonstrate the need for further research, tailored interventions, and advocacy to optimize HCT practices.

Introduction: 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.

Case presentation: 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.

Conclusion: 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.

Introduction: 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.

Case presentations: 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.

Conclusion: 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.

Introduction: 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.

Methods: 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.

Conclusion: 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.

Background: Obesity during childhood can significantly impact growth and puberty.

Summary: 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.

Key messages: 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.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.