Hormone Research in Paediatrics最新文献

Introduction: Associated conditions, especially being born small for gestational age (SGA), have been reported with a higher prevalence in patients with differences in sexual development (DSD) compared to the general population. Our objective was to analyze the prevalence of SGA in a cohort of DSD patients evaluated at a single tertiary pediatric center, and to examine its association with sex chromosome constitution, molecular diagnosis, and clinical phenotype.

Methods: Gestational age, birth weight, and birth length were evaluated to assess prenatal growth and the prevalence of SGA. DSD patients were classified according to karyotype. Among 46,XY DSD patients, perinatal data were further analyzed based on molecular diagnosis and the presence or absence of gonadal dysgenesis.

Results: Overall, 642 DSD patients were included: 202 (31.5%) with chromosomal DSD, 218 (33.9%) with 46,XX DSD, and 222 (34.6%) with 46,XY DSD. SGA prevalence was 30.2%, 7%, and 27.5%, respectively. In the 46,XY DSD group, a molecular diagnosis was achieved in 35% of patients. SGA was more frequent in 46,XY DSD subjects without molecular diagnosis and without gonadal dysgenesis.

Conclusion: A high prevalence of SGA was observed among individuals with sex chromosome DSD, consistent with the literature, whereas a lower prevalence was found among those with 46,XX DSD, as expected in the Latin American population. The frequency of SGA in the 46,XY DSD group reinforces the association between SGA and DSD in the 46,XY DSD, particularly in patients without a clear molecular diagnosis and without specific disorders of undervirilization. Factors involved in early embryonic growth, development, and gonadal differentiation may mediate the association between being born SGA and DSD in humans. Further studies are needed to clarify the etiological diagnosis.

Introduction: Patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency require lifelong glucocorticoid treatment, often at supraphysiologic doses, which increases their risk for obesity starting in early childhood and osteoporosis later in life. While obesity and inflammation have been shown to negatively impact bone health in the general population, the relationship between bone mineral density (BMD) and abdominal adiposity in youth with CAH remains unclear. We examine the association between BMD, adiposity, inflammation, and adrenal androgens in youth with CAH.

Methods: Thirty-five youth with CAH (12.33 ± 3.20 years; 12 males) and 38 age- and sex-matched controls (12.70 ± 2.83 years; 14 males) underwent dual-energy X-ray absorptiometry for BMD, MRI for abdominal adiposity (visceral adipose tissue [VAT] and subcutaneous adipose tissue [SAT]), and bone age X-ray. Linear regression models assessed associations between whole body and lumbar spine areal BMD height-adjusted Z-score (LS aBMD_HAZ), adiposity, hormones, and inflammatory markers, adjusting for GC dose and BMI-z.

Results: Adiposity measures were significantly higher in CAH patients (SAT, VAT, total % body fat, Ps <0.01). LS aBMD_HAZ negatively correlated with SAT (β = -1.21; 95% CI: -2.17, -0.24; p = 0.014), VAT (β = -0.38; 95% CI: -0.77, 0.02; p = 0.061), and total % body fat (β = -0.63; 95% CI: -1.23, -0.03; p = 0.039) in youth with CAH, independent of BMI-z and GC dose. In controls, only VAT (β = -0.39; 95% CI: -0.77, -0.01; p = 0.044) was negatively associated with LS aBMD_HAZ. Areal BMD_HAZ remained within normal limits for both groups, but in CAH patients, LS aBMD_HAZ declined with age. No associations were found between BMD_HAZ and adrenal hormones or MCP-1.

Conclusion: Adiposity negatively impacts BMD in CAH youth, independent of BMI and GC dose, potentially increasing the risk of osteoporosis in adulthood. Further research is needed to explore strategies to mitigate these effects.

Introduction: The rate of malignancy (ROM) among pediatric studies using the Bethesda System is 39.5% and 41.5% for atypia of undetermined significance/follicular lesion of undetermined significance and for suspected follicular neoplasm, respectively. Data reported on the basis of Bethesda System showed lower ROM in adults with indeterminate nodules (30.5% and 28.9%, respectively). Studies on adults based on the Italian Society of Anatomic Pathology and Cytology (SIAPEC) classification, report a ROM of 4-20.8% for TIR3a and 28-60.3% for TIR3b category, showing greater sensitivity in detecting malignancy. To date, very few performance data are available about SIAPEC classification in pediatric age.

Methods: Multicentre retrospective data were collected from 44 pediatric subjects with thyroid nodules.

Results: The distribution of cytological categories after fine-needle aspiration biopsy (FNAB) was 26 TIR3a and 18 TIR3b. Surgical approach was performed in 8/26 subjects with TIR3a and 18/18 subjects with TIR3b with a total ROM of 53.8% (12.5% for TIR3a, 72.8% for TIR3b). Total FNAB accuracy for the indeterminate cytologic category was 77%.

Conclusion: The reported data seem to confirm a greater sensitivity of SIAPEC classification to identify malignancy within the indeterminate category also in pediatric age and not only in adulthood. This finding may orient clinicians toward clinical follow-up for the indeterminate TIR3a group and toward surgical approach with total thyroidectomy in the indeterminate TIR3b group, although this indication should be confirmed in further national multicenter studies including larger cohorts.

Background: Inequities in the clinical care and health outcomes of youth and young adults (YYAs) with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) are well-established. Systemic and institutional racism and barriers, as well as implicit biases underlie these inequities in the USA.

Summary: This article offers a broad overview and analysis of disparities in clinical care and outcomes among YYAs with T1D and T2D, framed within an ethical context. We argue that achieving ethical care requires centering assessments of patient and family needs within the realities of their lived experiences, as well as structural barriers and challenges. We examine the impact of structural racism and implicit bias on clinical care and explore how factors such as non-English language communication, literacy, numeracy, nutrition, school nursing services, access to diabetes technology and medications, and insurance disparities influence diabetes management and outcomes. The article concludes with a call to action and concrete recommendations to address and reduce these inequities.

Key messages: Clinicians can play a pivotal role in reducing diabetes-related healthcare disparities by adopting an ethical approach that centers upon lived experiences of YYA with diabetes thereby identifying opportunities for more equitable care.

Growth hormone (GH) therapy is a cornerstone in managing pediatric growth disorders, yet individual responses vary significantly despite standardized protocols. This variability underscores the need for a comprehensive predictive framework to guide clinical decisions and optimize outcomes. Key determinants of growth response include the underlying diagnosis and degree of GH sensitivity, with conditions like severe GH deficiency typically responding better than disorders such as idiopathic short stature, small for gestational age, or Turner syndrome. Patient-specific factors - including age at treatment initiation, bone age delay, mid-parental height, and auxological parameters - further shape therapeutic outcomes. Definitions of poor response remain debated, typically relying on first-year height gain or height velocity metrics. A suboptimal response should prompt reassessment of the diagnosis and therapeutic strategy. Emerging therapies offer promising alternatives and adjuncts aimed at improving adherence, targeting specific etiologies, and enhancing outcomes. Despite early success, these interventions require further validation regarding long-term efficacy, safety, and cost-effectiveness. Together, these innovations reflect a broader shift toward mechanism-driven, personalized therapy in pediatric endocrinology.

Introduction: Automated insulin delivery (AID) systems offer superior glycaemic control compared to non-AID in children with type 1 diabetes, yet their performance during real-life challenges, such as summer camps with physical activity, remains underexplored. This study evaluated AID efficacy based on time range (70-180 mg/dL), comparing AID systems against sensor-augmented pump therapy (SAP) during a summer camp in children with type 1 diabetes.

Methods: Data were collected from a 14-day diabetes camp (July 2024) involving 26 children (mean + SD age 10 ± 1.3 years), using Medtronic MiniMed 780G (n = 13), mylife CamAPS FX (n = 7), or SAP (n = 6). Continuous glucose monitoring (CGM)-derived metrics for the two AID systems and SAP were compared by means of t tests or Mann-Whitney U tests (p ≤ 0.05).

Results: Both AID systems showed a similar time in range over the camp (primary endpoint, 75.5 ± 7.5% for MiniMed 780G vs. 71.1 ± 11.16% for CamAPS FX; p = 0.30). No significant differences were found for other glycaemic metrics or insulin dosage. Overnight, MiniMed 780G had less time below 54 mg/dL (0.0% [IQR: 0.0; 0.0%]) than CamAPS FX (0.4% [IQR: 0.0; 0.7%]; p = 0.024). SAP had significantly lower time in range than both AID systems (75.0% [IQR: 70.0; 81.0%] vs. 56.0% [IQR: 55.0; 66.0%]; p = 0.006). A positive correlation was found between coefficient of variation and the total number of steps (r = 0.39; p = 0.0459).

Conclusions: Despite the camp's challenges, both AID systems were safe and effective, meeting recommended CGM-derived treatment targets. Furthermore, AID systems showed superior glycaemic control compared to SAP.

Introduction: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder, typically diagnosed within the first 6 months of life. While NDM is well recognized globally, data from India regarding its clinical characteristics, treatment strategies, and long-term outcomes are scarce. We describe the molecular characterization, clinical phenotype, and follow-up of children with NDM, managed at a tertiary care pediatric diabetes clinic in northern India over the last 2 decades.

Methods: Data from children diagnosed with NDM between January 2005 and December 2024 were retrospectively analyzed. Genetic testing was performed using standard protocols.

Results: Thirty-two patients (10 females) with NDM, median age at diagnosis 13.2 (range: 1.6-36.5) weeks, were identified. Twenty-four patients had diabetic ketoacidosis at diagnosis. Pathogenic genetic variants were confirmed in 25 children, including KCNJ11 (11/25), the INS gene (4/25), and EIF2AK3 (3/25). An empirical sulfonylurea trial was initiated in 22 infants with good response in 13 (12 with variants in the KCNJ11 or ABCC8 genes). HbA1c levels among this cohort were significantly better than other genetic variants (41 [38, 45] vs. 75 [52, 81] mmol/mol). At a median follow-up of 6.6 years, the mean HbA1c was 56.33 ± 18.55 mmol/mol with two deaths (both EIF2AK3 gene related).

Conclusions: This study highlights the genetic heterogeneity of NDM in the North Indian population and emphasizes the significance of early genetic testing for personalized management. Empirical sulfonylurea trials proved successful in specific cases, considering that genetic testing is delayed in resource-limited settings.

Introduction: Genetic analysis is essential for diagnosing, treating, and predicting complications in neonatal diabetes mellitus (NDM) but is unavailable in some regions. Sulfonylureas are effective for NDM caused by KCNJ11 or ABCC8 mutations, which are among the most common genetic causes; therefore, they are often given before genetic testing. Unfortunately, in certain ethnicities, this mutation rarely occurs. This report presents a case of NDM with a heterozygous INS gene missense mutation and positive pancreatic autoantibodies in a single individual.

Case presentation: A three-month-old boy, born to non-consanguineous parents, presented with diabetic ketoacidosis and bronchopneumonia. Initial management included intravenous insulin and antibiotics, followed by sulfonylurea and detemir insulin. The patient demonstrated a good response at 5 months of age, but by 11 months, glucose control deteriorated with increased HbA1c, positive pancreatic autoantibodies, and declining C-peptide levels over 10 months, necessitating a transition from sulfonylurea to basal - bolus insulin regimen. Genetic testing at age 4 years identified a heterozygous missense mutation in the INS gene (c.325T>C, p.Cys109Arg), confirming a diagnosis of permanent NDM.

Conclusion: In settings where genetic testing is limited, cautious sulfonylurea use based on clinical algorithms is recommended. Regular monitoring of sulfonylurea response, pancreatic autoantibodies, and β-cell function is essential to guide therapy adjustments.