Journal of Clinical Research in Pediatric Endocrinology最新文献

Introduction: The management of type 1 diabetes (T1D) in children aims to achieve an HbA1c of <7%, a good quality of life and a life similar to that of their peers. While the HbA1c <7% target may be difficult to achieve, it is possible that national programs, quality control programs and setting team targets can achieve significant reductions in HbA1c.

Methods: The records of children with T1D followed up in our department between 2020 and 2022 were analyzed. Children and their families received a comprehensive education including an 'Individual Treatment Plan', nutrition and carbohydrate counting. All HbA1c measured during follow-up were averaged for each child separately. Continuous glucose monitoring (CGM) data from the last visit was evaluated in terms of achieving CGM consensus targets. To assess the effect of CGM use and automated insulin delivery system (AID) use, subjects were divided into 3 groups as multiple dose insulin (MDI) and CGM users, non-AID pump users and AID users and evaluated.

Results: The 480 children included in the study had a mean HbA1c of 7.8±1.5% at the first visit. The median HbA1c value during the two-year follow-up was 7.1%. Of the participants, 43% had an HbA1c <7%. Evaluating cases by treatment modalities and glucose measurement methods revealed taht AID users having the lowest mean HbA1c (7±0.7%).

Conclusions: While diabetes technologies have significantly improved T1D treatment, we believe that holistic approaches focusing on patient behaviors, comprehensive education, teamwork, written individualized treatment plans, and tighter metabolic goals are effective in achieving better glycemic outcomes.

Background: Growth hormone deficiency (GHD) in children results in short stature and impaired bone health. While daily growth hormone (GH) injections are effective, they are associated with adherence challenges. Somatrogon, a long-acting recombinant human GH, allows weekly administration, potentially improving treatment compliance.

Methods: This retrospective cohort study included 39 prepubertal children with GHD treated with weekly Somatrogon at Al Jalila Children's Hospital, Dubai. Diagnosis was based on clinical, biochemical, and radiological criteria, including height standard deviation score (SDS) < -2.0, subnormal growth velocity, and subnormal peak GH in one stimulation test (<10 ng/mL) supported by low IGF-1 and/or abnormal MRI. Growth outcomes and bone health indices were assessed over 12 months using auxology, IGF-1 levels, and BoneXpert-derived Bone Health Index (BHI) SDS and Metacarpal Index (MCI) SDS.

Results: After 12 months of therapy, mean height SDS improved significantly from -2.16 ± 0.80 to -1.65 ± 0.71 (p < 0.001). IGF-1 SDS rose from -1.38 ± 1.02 to 0.88 ± 1.57 (p < 0.001). Adult predicted height and BHI SDS also improved significantly (p = 0.005 and p < 0.001, respectively). No significant changes were observed in bone age SDS or MCI SDS.

Conclusions: Weekly Somatrogon significantly improved linear growth, IGF-1 levels, and cortical bone health without advancing bone age in children with GHD. These findings support the efficacy of long-acting GH therapy and its potential to optimize growth and skeletal outcomes in clinical practice.

Sotos syndrome is a genetic disorder resulting from heterozygous pathogenic variants or deletions in the nuclear receptor-binding SET domain protein 1 (NSD1) gene. It is characterized by prenatal and postnatal overgrowth, macrocephaly, distinctive craniofacial features, learning disability, and advanced bone maturation. In contrast, Reverse Sotos syndrome, arises from duplications within the NSD1 gene, presenting with an opposite clinical phenotype, including microcephaly, developmental delay, short stature and delayed bone maturation. To date, the reverse clinical phenotype associated with the 5q35.2q35.3 microduplication encompassing the NSD1 gene has been reported in 43 cases. We present a novel case of a 4-year-11-month-old patient with a 5q35.2q35.3 duplication involving the NSD1 gene. The patient, exhibited clinical features of microcephaly, short stature, low-normal weight, delayed bone age, developmental delay, attention deficit hyperactivity disorder, alongside normal routine biochemical tests, nutritional parameters, and insulin-like growth factor-1 levels. Chromosomal microarray analysis (CMA) identified a 714.1 kb duplication in the 5q35.2q35.3 region, including NSD1. This case underscores the significance of NSD1 gene dosage alterations in manifesting a reverse clinical phenotype typified by microcephaly and short stature. Furthermore, it highlights the utility of CMA as a robust diagnostic tool for detecting microrearrangements and guiding clinical evaluation.

Objective: Progranulin (PGRN), a growth factor, modulates cell proliferation, wound repair, and inflammation. It involves glucose metabolism and is associated with insulin resistance and diabetes mellitus (DM). In the present study, we evaluate PGRN levels at admission and during follow-up in children with newly diagnosed type 1 diabetes mellitus (T1DM) in comparison with healthy controls.

Material and methods: A total of 49 children, 25 with T1DM (12F/13M) and 24 healthy controls (10F/14M) were recruited. The age, weight, height, body mass index (BMI), severity of acidosis, glucose, insulin, C-peptide, and diabetes-specific autoantibodies of children with newly diagnosed type 1 diabetes mellitus (T1DM) were examined. The PGRN was measured in children with T1DM at admission, first week of follow-up, and in healthy controls.

Results: There was no differences in age (11 ± 3.9 years vs 12.1 ± 3.1 years, p = 0.269) and BMI standard deviation score (SDS) (-0.11 ± 1.49 SD vs 0.10 ± 0.82 SD, p = 0.540) characteristics of children with T1DM and healthy controls. The basal PGRN levels of children with newly diagnosed T1DM were higher than those of controls (90.8 ± 17.3 ng/mL vs 30 ± 11.5 ng/mL, p < 0.001). In children with T1DM, basal PGRN at admission (90.8 ± 17.3 ng/mL) significantly declined (58.4 ± 16.9 ng/mL) in the first week (when glycemic regulation was achieved) (p <0.001).

Conclusion: These findings suggest that elevated PGRN levels in children with newly diagnosed T1DM may reflect both an acute inflammatory response to diabetic ketoacidosis and a persistent alteration in metabolic regulation, underscoring the potential role of PGRN as a biomarker in the early course of the disease.

Objective: This study aims to explore hormonal and neurodevelopmental influences on social cognition among individuals with Gender Dysphoria (GD), Congenital Adrenal Hyperplasia (CAH), and typically developing (TD) controls.

Method: Participants included 34 GD, 29 CAH, and 35 TD individuals. Social cognition was assessed using the Faces Test (FT), Reading the Mind in the Eyes Test (RMET), and Unexpected Outcomes Test (UOT). Psychiatric comorbidities were evaluated via the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-PL), depressive symptoms using the Children's Depression Inventory (CDI), autistic traits with the Autism Spectrum Screening Questionnaire (ASSQ), and ADHD symptoms through the ADHD Rating Scale.

Results: Psychiatric diagnoses were significantly more prevalent in the GD group, with Major Depressive Disorder (64.7%) and ADHD (50%) being the most common (p<0.001). TD participants showed moderately better performance on RMET (p=0.003) and UOT (p<0.001) compared to GD and CAH, while CAH individuals scored lower on FT (p=0.046). Regression analyses revealed depressive symptoms (B=-0.105, p=0.004) and CAH status (B=-2.221, p=0.003) predicted RMET scores, while GD (B=-3.232, p=0.022) and CAH (B=-7.974, p<0.001) predicted lower UOT performance. FT regressions were nonsignificant.

Conclusions: Findings highlight the interplay of hormonal and psychosocial factors in social cognition, emphasizing the need for nuanced, context-sensitive approaches to supporting social functioning and well-being in gender-diverse youth.

Objective: This study aimed to evaluate the prevalence of metabolic syndrome (MetS) in children with Type 1 Diabetes Mellitus (T1DM) and to determine the predictive value of simple anthropometric measurements-particularly neck circumference (NC) and waist circumference (WC)-in identifying MetS.

Methods: A total of 168 children (aged 6-18 years) with T1DM were included in this cross-sectional study. Anthropometric (NC, WC, BMI, TMI) and laboratory parameters (lipid profile, HbA1c) were recorded. MetS diagnosis was established according to the International Diabetes Federation (IDF) criteria. Receiver operating characteristic (ROC) curve analysis and LASSO regression were employed to identify key predictors.

Results: The prevalence of MetS was 8.9%. Children with MetS had significantly higher BMI, WC, NC, HC, and TMI values compared to non-MetS counterparts. ROC analysis revealed WC z-score had the highest discriminative power (AUC: 0.954), followed by NC z-score (AUC: 0.906). LASSO regression identified NC z-score and BMI percentile as the most robust predictors. A strong positive correlation was observed between NC and WC (r = 0.812, p <0.001), and NC showed a mild inverse correlation with HDL cholesterol.

Conclusion: NC and WC are simple, non-invasive, and reliable tools for early detection of MetS in pediatric T1DM patients. Their routine measurement could enhance risk stratification and guide preventive interventions targeting obesity and dyslipidemia. These findings support incorporating NC and WC into standard clinical assessments to improve long-term cardiometabolic outcomes in children with T1DM (i.e., NC z>1.04 or WC z >1.41 as actionable thresholds.

Osteoporosis in children is a rare condition, often associated with genetic factors. Monogenic forms of osteoporosis linked to the X chromosome are often related to mutations in the gene encoding plastin 3 (PLS3). PLS3 is a protein involved in actin bundle formation in the cytoskeletonWe present two brothers with recurrent peripheral fractures and vertebral compression fractures, both associated with low bone mineral density (BMD). The patients shared the same deletion (c.589_590) in PLS3 on Xq23, which was confirmed by next-generation sequencing. They were treated with zoledronic acid, calcium, and vitamin D, showing optimal improvement in bone mineral density, a reduction in bone fractures, and enhanced quality of life.

The transcription factor hepatocyte nuclear factor-4a plays a key role in insulin secretion and mutations in its encoding gene, HNF4A, have been associated with Monogenic diabetes (MODY 1) during adolescence or early adulthood and with transient hyperinsulinemic hypoglycemia during infancy. They are inherited as an autosomal dominant trait, therefore, HNF4A sequencing should be considered in every neonate presenting with macrosomia or persistent hypoglycemia after 24 hours from birth, especially when there is a family history of early-onset diabetes. Management of hyperinsulinism includes regular feeding, intravenous glucose and diazoxide, as first-line treatment. Blood glucose levels need regular monitoring to adjust treatment properly. Continuous glucose monitoring systems are not validated for neonates or patients with hyperinsulinism, so finger-prick blood tests are usually used before every meal. We present a case of diazoxide use in a female patient with neonatal hypoglycemia due to HNF4A mutation, where continuous glucose monitoring facilitated treatment decisions and detected hyperglycemia, as an adverse event early in the course. Notably, CGM use after hospital discharge contributed significantly to ongoing glucose monitoring and management. We recommend that further studies could establish CGM's usefulness as an adjunct in clinical care.

Resistance to thyroid hormone beta (RTHβ) is a rare condition typically caused by mutations in the THRβ gene, characterized by elevated thyroid hormones with non-suppressed TSH levels. We present a pediatric case of RTHβ associated with a novel THRβ variant, emphasizing diagnostic challenges and the importance of individualized treatment. A 6.5-year-old girl was evaluated for learning difficulties and tachycardia. Laboratory findings showed elevated free T3 and T4 with non-suppressed TSH. Pituitary MRI showed a 5x6 mm lesion, raising suspicion for TSHoma. Genetic testing of the THRβ gene was performed. A novel heterozygous THRβ variant (c.1376T>C; p.Phe459Ser) was identified in both the patient and her father. The mutation affects a highly conserved residue within the ligand-binding domain. Clinical and biochemical findings were consistent with RTHβ. Atenolol therapy was initiated to manage tachycardia with favorable response.This case highlights the potential for misdiagnosis of RTHβ as TSHoma and underscores the value of genetic testing in differentiating the two. The identification of a novel variant at codon 459 expands the mutational spectrum of THRβ and supports its role as a hotspot region relevant to RTHβ pathogenesis.