Introduction: Puberty suppression using gonadotropin-releasing hormone agonists (GnRHa) is a reversible medical intervention that halts endogenous puberty, allowing transgender and gender-diverse (TGD) adolescents to avoid the development of secondary sexual characteristics that may cause psychological distress. This pause in pubertal progression provides time to explore gender identity or facilitates alignment with affirmed gender in those with an established identity. While widely used, long-term evidence on the efficacy and safety of GnRHa in this population remains limited. This systematic review aims to synthesize current data on the benefits and potential risks of GnRHa in TGD adolescents.Methods: We conducted a comprehensive literature search across PubMed, EMBASE, Cochrane Library, and other databases, covering studies published from February 2011 to February 2024. Eligible studies included adolescents under 18 with gender dysphoria or incongruence treated with GnRHa, reporting outcomes related to efficacy or side effects. Fifty-one studies met inclusion criteria, and data on physical health, mental health, bone density, fertility, and adverse events were extracted and assessed using the GRADE approach.Results: Of the 51 studies, 22 were rated as moderate to high-quality evidence. GnRHa effectively suppressed puberty and secondary sex characteristics. Effects on growth and body composition varied; bone mineral density declined during treatment, particularly in AMAB individuals. Mental health improved significantly, including reduced depression, anxiety, and suicidality—especially when GnRHa was followed by gender-affirming hormone therapy (GAHT). Quality of life improved over time, while body dissatisfaction often persisted during suppression and improved after GAHT or surgery. No moderate- or high-quality evidence was found on fertility, sexual function, or cancer risk.Conclusion: GnRHa is effective in halting puberty and improving mental health in TGD adolescents. However, key clinical and ethical considerations—such as bone health monitoring, fertility counseling, psychological support, and informed decision-making—must guide treatment. Long-term safety remains uncertain, particularly regarding skeletal health, reproductive outcomes and cancer risk. A precision medicine approach and co-produced longitudinal studies are essential to support safe, individualized care.Systematic review registration: https://www.crd.york.ac.uk, identifier CRD42024528334.

Crigler–Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in the following forms: CNS type 1 (CNS1), the more severe form with the complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. This narrative review aims to provide a detailed overview of CNS, highlighting its clinical significance and the need for new, more effective treatments. By summarizing current knowledge and discussing future treatments, this article seeks to encourage further research and advancements that can improve outcomes for CNS patients. The literature analysis showed that CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients responding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risk of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interventions.

Telemedicine (TM) has emerged as a valuable tool in managing pediatric type 1 diabetes (T1D), particularly during the COVID-19 pandemic when traditional in-person visits were limited. This narrative review examines the impact of TM on patient-provider relationships, glycemic control, and overall diabetes management in children and adolescents with T1D. Studies consistently demonstrate high levels of patient and provider satisfaction with TM, citing increased consultation frequency, reduced travel burdens, and lower associated costs. However, results regarding the effect of TM on glycemic control, as measured by HbA1c levels, are inconsistent. Some studies show significant reductions in HbA1c levels with TM use, while others report outcomes comparable to or less effective than traditional care. The effectiveness of TM also appears to be influenced by the concurrent use of advanced diabetes technologies, such as continuous glucose monitors and automated insulin delivery systems. Furthermore, TM’s impact on quality of life and other clinical outcomes beyond glucose management remains underexplored. Methodological limitations, including inconsistent randomization strategies and lack of long-term follow-up, hinder definitive conclusions. Despite these uncertainties, TM offers several advantages, such as improved accessibility and patient engagement, which may justify its broader implementation. Future research should focus on optimizing TM approaches to enhance glycemic control and quality of life, identifying the most effective strategies for specific patient groups, and addressing technological and economic barriers. This review highlights the need for comprehensive, long-term studies to fully understand TM’s potential in pediatric T1D management and its integration into standard care practices.

The COVID-19 pandemic has catalyzed the rapid expansion of telemedicine for managing chronic conditions such as type 1 diabetes (T1D) in children and adolescents. This narrative review aims to explore the role of telemedicine in pediatric T1D management by comparing its use before and after the pandemic. We conducted a comprehensive literature review covering studies published between 2000 and 2024, focusing on telemedicine applications in pediatric T1D care. The review includes clinical trials, systematic reviews, and observational studies examining telemedicine’s impact on glycemic control, patient satisfaction, and healthcare delivery. Results reveal that telemedicine has enhanced access to care, improved glycated hemoglobin (HbA1c) levels, and reduced diabetic ketoacidosis and hypoglycemic events. Patients and caregivers expressed high satisfaction, especially when using continuous glucose monitoring and insulin pump technologies integrated with telemedicine platforms. However, challenges such as digital literacy gaps, variability in healthcare provider training, and logistical issues like reimbursement policies persist. The pandemic highlighted the potential of telemedicine to supplement traditional in-person care, showing promise in enhancing patient outcomes and reducing healthcare burdens. Further research is needed to optimize telemedicine models for T1D, addressing barriers to implementation and exploring its long-term cost-effectiveness. This review underscores telemedicine’s evolving role as a complementary approach in managing pediatric T1D, advocating for the development of standardized care protocols to fully integrate digital health solutions into routine clinical practice.

Crigler-Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in two forms: CNS type 1 (CNS1), the more severe form with a complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients re-sponding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risks of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interven-tions.

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being.