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Objectives We conducted a scoping review and analyzed the medical literature on PubMed to assess any potential short-term and long-term benefits of pubertal induction in patients with Duchenne muscular dystrophy (DMD). Content We identified six articles from our research cumulatively reporting clinical data from 58 pediatric patients with DMD, of age between 12 and 17.7 years. All of them were on glucocorticoid therapy with variable duration and the longest follow-up of 11.7 years. In all patients, the induction protocol was successful (leading to appearance of secondary sexual characteristics); no secondary effects were reported by any analyzed studies. Three papers reported an objective improvement of patients’ quality of life, while in four there was a benefit on the bone profile. Summary DMD is an X-linked recessive genetic disorder that affects approximately 1 in 5,000 live-born male children. Because of early and chronic exposure to glucocorticoids, used as standards of care, pubertal development may be variable. While some boys experience a normal pubertal growth spurt, others have testosterone levels below the normal range for age and require pubertal induction therapy to achieve an adequate testicular volume, development of secondary sexual characteristics, and peak bone mass. When and how to use pubertal induction therapy in pediatric patients with DMD is still object of controversy. Outlook The reported evidence of testosterone therapy in patients with DMD is still limited to small cohort sizes, which suggest efficacy and psychosocial benefits.

Introduction The prevalence of overweight and obesity in childhood is a health challenge. This condition induces alterations in adipose tissue and metabolic disorders such as diabetes, dyslipidemia, and hypertension even in childhood and may also be associated with cancer development. Underlying mechanisms related to childhood cancer, such as leukemia and obesity, are not entirely understood. Content Considering this scenario, a systematic literature review was performed on the PubMed library. Studies that evaluate the association between overweight or obesity at diagnosis of childhood leukemia and the outcomes associated with this condition were included. Summary In some studies, a worse prognosis was observed in obese children compared to non-obese, which begs the question of how the adipose tissue environment may be involved with leukemia progression and its outcomes such as relapse, overall and event-free survival and infections. Outlook Obesity in children diagnosed with leukemia may be associated with poor outcomes during disease progression as reported in some studies. The remodeling and composition of adipose tissue, alterations in adipocytokines secretion, such as leptin, and inflammation that may trigger awakened oncogenes seem to be important players in cancer development and outcomes during treatment. Understanding if there is any relationship between adipose tissue and the development of childhood leukemia and its prognosis, as well as the biological mechanisms of this scenario, is important to contribute to improving the treatment protocols and survival, especially in obese children.

Introduction Recombinant human growth hormone (rhGH) therapy (GHT) for short stature resulting from growth hormone deficiency (GHD) is effective in promoting optimal growth velocity and achieving an appropriate final height. However, the specific metabolic changes in children during replacement GHT remain unclear. Content The study aimed to evaluate the effects of GHT on metabolism in children with GHD. This is a review of the literature published at PubMed/MEDLINE between January 2010 and August 2024, including original articles. The authors searched Medline using the following keywords: growth hormone therapy in children OR growth hormone treatment in children AND metabolism OR glycemia OR glycated hemoglobin OR insulin OR lipid profile OR blood pressure OR bone mineral density OR body mass index OR waist circumference OR hip circumference OR waist-to-hip ratio OR lean body mass OR visceral fat OR muscle strength OR physical activity OR exercise. Summary and Outlook GHT in children positively affects the lipid profile and body composition. Nevertheless, rhGH treatment may increase fasting glucose, glycated hemoglobin, and indices of insulin resistance. GHT in children has not been associated with an increased risk of diabetes. No changes in blood pressure during GHT were observed. The results of our review show that GHT impacts lipid profiles, carbohydrate metabolism, and body composition. Further studies are needed to clarify the molecular mechanisms by which GH regulates substrate metabolism.

Objectives Delayed puberty and osteoporosis are significant challenges in boys with Duchenne muscular dystrophy (DMD). The current International Care Considerations for DMD recommend bisphosphonate after first fracture and testosterone for delayed puberty from 12 years. This study aimed to investigate the current clinical practices of clinicians managing osteoporosis and testosterone treatment in DMD. Methods An online survey was circulated to paediatric clinicians involved in the management of bone health and puberty in DMD via patient groups (UK, USA, Italy, Israel). Results A total of 51/105 (48 %) responses were received. For osteoporosis, vertebral fracture of any grade (86 %) and long bone fracture (67 %) were the most common indications for starting bisphosphonates, with IV zoledronate being the most used agent (86 %). Approaches varied in managing bisphosphonate side effects, and transitioning care to adult specialists. Opinions differed on starting bisphosphonate before fracture. Fourty-nine clinicians managing pubertal disorders reported initiating testosterone for delayed puberty typically between 12 and 14 years, with majority prescribing intramuscular injections (96 %). Duration of testosterone therapy varied, with some using short-term courses and others continuing until adulthood. Conclusions This international survey highlights variability in the management of osteoporosis and delayed puberty in DMD. Recommendations on management of side-effects of IV bisphosphonate, osteoporosis therapy during transition, and longer-term treatment into adulthood is required. There is a need for further guidance on testosterone therapy, particularly in regard to monitoring after discontinuation and the threshold for re-initiation of treatment.

Objectives Growth hormone deficiency (GHD) diagnosis requires inadequate GH responses to two provocative tests, which are time-consuming and may cause side effects. Recent advancements in serum metabolomics offer potential novel biomarkers for medical conditions. This study investigated serum metabolomics in children with GHD to explore new diagnostic approaches and identify altered biological pathways. Methods We conducted a prospective study of 68 children (aged 3–18 years) undergoing growth hormone stimulation tests (GHST). Children with genetic syndromes, systemic illnesses, or end-stage renal disease were excluded. Untargeted metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS) identified 951 circulating metabolites (280 polar and 671 lipids). From the 68 children evaluated, 25 children were diagnosed with GHD, and 41 children served as controls. Two children exhibited a suboptimal GH peak during the first GHST but did not undergo a second confirmatory test. Results Significant differences were observed in 7 polar metabolites and 50 lipids between groups, but only phosphatidylserine (PS) (40:3) remained significant after false discovery rate correction. Cluster analysis revealed two lipid clusters significantly associated with GHD. Greater separation in metabolomic profiles was observed when a lower GH threshold was applied for diagnosis. Conclusions This study provides proof of concept for a unique lipidomics profile in children with GHD, highlighting its potential as a diagnostic tool. Larger-scale studies are required to validate these findings.

Objectives Growth hormone (GH) deficiency in children is characterized by impaired linear growth and reduced growth velocity, necessitating confirmation through two GH stimulation tests. At the time of diagnosis, approximately 4 % of children with GH deficiency exhibit concomitant adrenocorticotropic hormone (ACTH) deficiency, a prevalence that increases to 12 % over the course of follow-up. The insulin tolerance test is regarded as the gold standard for assessing both cortisol and GH secretion; however, its clinical application is constrained by potential risks and the requirement for close medical supervision. This study aims to evaluate the effect of the L-dopa stimulation test on cortisol secretion in pediatric patients with short stature. Methods This retrospective study included 138 children (65 females, 73 males) who underwent the L-dopa stimulation test for the assessment of GH deficiency at the Pediatric Endocrinology Clinic between January 2010 and December 2023. Serum cortisol concentrations were measured at the 90th and 120th min of the test. Patients with a peak cortisol response <18 μg/dL subsequently underwent a low-dose (1 μg) ACTH stimulation test to further evaluate adrenal function. Clinical, anthropometric, and biochemical data were extracted from medical records and subjected to statistical analysis. Results The mean age of the study cohort was 9.34 ± 3.79 years, with 65 (47.1 %) female and 73 (52.9 %) male patients. The mean height standard deviation score (SDS) was −2.62 ± 0.83, while the mean weight SDS was −1.81 ± 1.09. The mean peak GH response was 5.64 ± 4.0 ng/mL following the clonidine stimulation test and 7.29 ± 5.23 ng/mL following the L-dopa test. A total of 35 children exhibited a peak cortisol response <18 μg/dL during the L-dopa test. Among these, 35 underwent a low-dose (1 μg) ACTH stimulation test, and 7 patients (20 % of those tested; 5.1 % of the total cohort) were diagnosed with adrenal insufficiency, defined as a peak cortisol response <18 μg/dL. These patients were initiated on oral hydrocortisone therapy. Comparative analyses between patients with normal vs. impaired ACTH test responses (<18 μg/dL vs. ≥18 μg/dL) revealed no statistically significant differences in peak cortisol response to the L-dopa test, peak GH response to clonidine or L-dopa, age at presentation, gender, weight SDS, or height SDS. Conclusions The L-dopa stimulation test may represent a valuable adjunctive tool for the evaluation of cortisol sufficiency in children undergoing assessment for suspected GH deficiency. However, further prospective studies with larger sample sizes and standardized protocols are warranted to validate its diagnostic accuracy and clinical utility in detecting adrenal insufficiency.

Objectives Silver–Russell syndrome (SRS) is a rare imprinting disorder characterized by intrauterine and postnatal growth retardation. Its genetic etiology shows a heterogeneous distribution. This study aimed to evaluate the clinical characteristics of children diagnosed with SRS, their response to growth hormone therapy, and compare the data of genetically confirmed and clinically diagnosed SRS cases. Methods A total of 69 patients were included in the study. Genetically confirmed cases were considered Group 1, and cases with a clinical diagnosis according to the Netchine–Harbison scoring system were considered Group 2. The anthropometric data of the patients at birth, at the time of diagnosis, before and during the first year of growth hormone (GH) treatment, final height-SDS values of patients who reached final height, and accompanying comorbidities were recorded. Results In Group 1, 75.8 % had hypomethylation in the ICR1 region, 13.7 % had maternal uniparental disomy 7, 6.8 % had an IGF-2 mutation, and 3 % had a duplication in the 11p15 region. Central precocious puberty, gastroenterological, and neurologic comorbidities were found to be more frequent than those from other systems. Final height-SDS was −2.32 ± 1.57 (n=5) in Group 1 and −2.41 ± 0.86 (n=5) in Group 2. Conclusions 11p15 LOM was the most common genetic disorder in children with SRS in our case series. Gastroenterological problems and neurologic complications were observed frequently in these cases. Central precocious puberty was more commonly observed compared to the general population. The duration of treatment was the most critical factor in the success of GH therapy.

Objectives Male patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) are at risk of developing testicular adrenal rest tumors (TART), which are benign but an important cause of infertility. The limited medical infrastructure and lack of knowledge and awareness of 21OHD in Indonesia has contributed to missed or delayed diagnoses, leading to a reportedly low prevalence of 21OHD and an expected high rate of undiagnosed patients. In Indonesia, TART has not been widely reported, with only a single patient documented in a recent paper. This study aim was to define the potential risk factors for developing TART in Indonesian pediatric patients with 21OHD. Methods This cross-sectional study was conducted in 20 boys with genetically proven 21OHD (0–18 years old). All had pathogenic variants associated with 0 % or 0–1% residual enzymatic activity. Medical history, clinical characteristics, genetic analysis results, biochemical measurements, bone age, and scrotal ultrasonography (US) data were evaluated. Results In 5 of 20 patients (25 %), TART was detected by US. The patients with TART were mainly in puberty (p=0.014). Higher androstenedione levels and advanced bone age were associated with TART. Conclusions TART is an important complication in Indonesian patients with 21OHD presenting before or during puberty. Factors associated with TART are pubertal age and longstanding poor hormonal control. Early diagnosis and optimization of treatment may help to prevent TART development and consequently improve fertility in these patients.

Objectives Branched-chain organic acidemias (OAs) are inherited metabolic disorders resulting from enzyme deficiencies in the catabolic pathway of branched-chain amino acids, which could lead to mitochondrial dysfunction and oxidative stress. This study aimed to evaluate oxidative stress in OA patients using thiol-disulfide homeostasis (TDH) parameters. Methods 21 OA patients [methylmalonic acidemia (MMA), propionic acidemia (PA), and isovaleric acidemia] and 12 healthy controls participated in this study. TDH parameters such as native thiol, total thiol, and disulfide levels, in addition to Oxidative Stress Index, Total Antioxidant Status, and Total Oxidant Status were analyzed using spectrophotometry. Results The OA group had significantly lower native (p=0.004) and total thiol (p=0.006) levels compared to controls. When analyzing subgroups, native thiols were found to be lower in MMA (p=0.012) and in PA (p=0.008) with elevated disulfides in MMA (p=0.003) in comparison to both PA and controls. As compared to abnormal neurodevelopmental status, there was a statistically significant relationship with lower native thiols and a shift towards oxidative stress (p=0.004). Conclusions The parameters of the TDH are altered in patients with OA, especially in those with MMA and PA, indicating a significant level of oxidative stress. The neurodevelopmental outcome in OA may be exacerbated by this oxidative imbalance. The utilization of TDH as a biomarker may be a potential provider of oxidative status in OA patients and facilitate informing therapeutic strategies.

Objectives This study aims to highlight the rare yet significant cause of secondary hypertension in pediatric patients, specifically pheochromocytoma (PCC) and paraganglioma (PGL) and to discuss the diagnostic challenges and lessons learned from misdiagnosis in a pediatric case. Case presentation We present the case of an 8-year-old boy with a 2-year history of sustained hypertension, initially attributed to brainstem encephalitis. Despite antihypertensive therapy, his blood pressure remained elevated. After 2 years, symptoms such as diaphoresis and failure to thrive prompted further investigation. Biochemical tests revealed elevated urinary normetanephrine levels, and imaging identified a retroperitoneal mass. The diagnosis of retroperitoneal paraganglioma was confirmed, and surgical intervention resulted in the normalization of blood pressure and symptom resolution during the 1-year follow-up. Conclusions This case underscores the importance of considering rare causes of secondary hypertension, such as PGL, even in the absence of classic symptoms. Early biochemical testing, appropriate imaging, and multidisciplinary follow-up are essential for accurate diagnosis and optimal management in pediatric hypertension. Genetic testing is also crucial, particularly in pediatric cases where hereditary factors are prevalent.

Objectives Cushing’s syndrome (CS) in children is often caused by prolonged glucocorticoid use. Exogenous steroid administration, mainly oral and parenteral, commonly leads to iatrogenic CS, while topical corticosteroids’ role is less recognized. Here, we present seven pediatric cases of iatrogenic CS linked to topical glucocorticoids, resulting in adrenal insufficiency. Case presentation There were seven patients, aged 3–60 months, with diaper dermatitis (six patients) and scabies (one patient), all receiving topical clobetasol propionate for a median duration of 2 months (range: 0.5–3 months). Adrenal insufficiency was detected in all cases and treated with hydrocortisone at a median dose of 10 mg/m 2 /day (range: 7.5–50 mg/m 2 ). One infant also had hypercalcemia. Clinical findings and anthropometric measurements normalized during follow-up, with a median hypothalamic–pituitary–adrenal axis recovery time of 6 months (range: 4–9 months). Conclusions This study contributes valuable insights into the management of iatrogenic CS in pediatric patients and emphasizes the need for cautious prescribing practices to safeguard against adverse effects.

Objectives Wolcott–Rallison syndrome (WRS) is an autosomal recessive multisystemic genetic disorder caused by homozygous mutation in the eukaryotic translation initiation factor 2 alpha kinase 3 gene. It typically presents with neonatal onset insulin-dependent diabetes. Here, we report a 14-year-old male patient with WRS who presented with late-onset diabetes mellitus. Case presentation A 14-year-old male patient presented with acute liver failure secondary to acute gastroenteritis. On physical examination, signs of chronic malnutrition and muscle atrophy in the extremities were evident, accompanied by a waddling gait. Infectious, autoimmune, and metabolic diseases were excluded. Liver tests improved within 3 weeks with supportive treatment. Direct radiographs were consistent with multiple epiphyseal dysplasia. High blood glucose levels were observed at follow-up in the intensive care unit. At the 4-month follow-up, HbA1c increased to 55 mmol/mol (7.2 %) and basal insulin treatment was started at a dose of 0.4U/kg/day. Glycemic control was achieved after 6 months. Conclusions Diabetes typically manifests within the first 6 months of life, with a median age of 2.5 months, and has been observed in all patients with WRS reported in the literature. Our case is an interesting WRS patient whose diabetes started at the age of 14 years with a novel mutation.