Hormone Research in Paediatrics最新文献

Introduction: Short stature is a common clinical feature of Turner syndrome (TS) and Noonan syndrome (NS). Growth hormone (GH) treatment increases height in patients with TS and NS. We aimed to assess treatment patterns and costs in a real-world setting of GH-treated patients with TS and NS in the USA.

Methods: Patients with TS (aged 4 to <14 years) or NS (aged ≤18 years) were included in this retrospective analysis using the Komodo Health claims database. The study period from January 1, 2016, to September 30, 2022, included ≥6 months pre-index (baseline) and ≥1 year post-index (follow-up); the index date was the first (TS) or latest of two visits (NS) with diagnostic coding for the condition. Data were analyzed descriptively.

Results: Among 2,530 patients with TS (mean age [SD] 8.4 [3.0] years) and 1,119 patients with NS (mean age 7.0 [4.4] years), 36% and 16% initiated GH treatment during follow-up, respectively. Of these patients, 48%/41% were early initiators (started ≤6 months post-index), 66%/70% had high adherence (≥80% of GH treatment days covered), and 56%/52% had long persistence (treated ≥2 years). Mean GH treatment duration was 24.9 (15.9) and 17.6 (10.1) months for patients with TS and NS, respectively. Median (IQR) total all-cause costs per patient/year were USD 10,232 (USD 2,850-USD 36,590) and USD 17,937 (USD 5,616-USD 47,552), respectively.

Conclusion: Of the few patients on GH therapy, less than half were initiated on treatment early after their TS or NS diagnosis. Greater awareness regarding early diagnosis and treatment of TS and NS is needed.

Introduction: Given the rising prevalence of childhood obesity, it is critical to understand the metabolic consequences of excess adiposity in youth. In particular, investigating alterations in glycolysis and the tricarboxylic acid (TCA) cycle in youth with obesity are essential for elucidating the underlying mechanisms contributing to metabolic dysregulation in this population.

Methods: Forty-eight adolescents and young adults aged 15-24 years had plasma obtained after a 12-h fasting to measure levels of glucose, insulin, and TCA cycle intermediates: pyruvate, lactate, fumarate, malate, α-ketoglutarate, cis/trans aconitate, and isocitrate. Additionally, participants underwent an assessment of liver proton-density fat fraction (PDFF) and a 3-h oral glucose tolerance test (OGTT).

Results: Nineteen youth without obesity (BMI 21.5 ± 0.5 kg/m2) and twenty-nine youth with obesity (BMI 37.3 ± 1.7 kg/m2) were enrolled in the study. Youth with obesity showed higher plasma concentrations of lactate (p = 0.015) and pyruvate (p = 0.096) and lower plasma concentrations of fumarate (p = 0.022), malate (p = 0.009), cis/trans aconitate (p = 0.03), and citrate/isocitrate (p = 0.012). PDFF was directly correlated with lactate (r = 0.46, p = 0.027). Adipose tissue insulin resistance was not associated with biomarkers of glycolysis.

Conclusion: The metabolomic analysis revealed distinct characteristics between adolescents with and without obesity, thus demonstrating lower rates of aerobic glucose utilization in youth with obesity, which may contribute to the development of insulin resistance, type 2 diabetes, and cardiovascular disease.

Introduction: We wanted to establish the etiologic cause of diabetes in a female subject with mild hyperglycemia since childhood, that suddenly worsened in her late 40s. We retrieved the proband's laboratory data from the age of 5 years. We assessed type 1 diabetes autoantibodies and performed genetic screening by clinical exome.

Case presentation: The proband showed stable hyperglycemia not requiring pharmacological therapy for 42 years. The proband's fasting plasma glucose increased from 120 to 130 mg/dL (6.1-7.2 mmol/L) to 150-159 mg/dL (8.3-8.8 mmol/L) at the age of 47 years. Four type 1 diabetes autoantibodies resulted repeatedly negative. A spontaneous glucokinase pathogenic variant (c.645C>A, p. Tyr215Ter) and a NEUROD1 variant (c.616dupC, p.His206ProfsTer38) were identified in the proband. Her mother, who carries the NEUROD1 variant, was diagnosed with diabetes by OGTT (120' = 211 mg/dL) when 77 years old. NEUROD1, a low penetrance maturity onset diabetes of the young (MODY) gene, is known to regulate gene transcription of GCK and SLC2A2, encoding for GLUT2, a functional partner of GCK in glucose sensing of the β cell.

Conclusions: We conclude that the low penetrance NEUROD1 variant is likely responsible of the peculiar trajectory of fasting glucose in a subject who presented with classical metabolic phenotype associated with glucokinase haploinsufficiency from childhood to adulthood.

Introduction: Transition from pediatric to adult care present challenges for patients with chronic diseases. The objective of the study was to identify factors associated with metabolic control in childhood-onset type 1 diabetes (T1D) following transfer to adult care. Additionally, we aimed to characterize sociodemographic parameters and to compare these data with those of the general population.

Methods: Contact of 281 patients transferred from pediatric to adult care between 1998 and 2021 yearly by questionnaire to provide information regarding their current hemoglobin A1c (HbA1c), type of care, type of therapy, occupational situation, living situation, marital status, and parental status. Data were analyzed using a mixed cross-sectional longitudinal approach.

Results: A total of 205 patients responded at least once (mean age: 27.7 years). Women were more frequently treated with pump therapy than men (p < 0.05). HbA1c levels reported by men did not significantly differ from those reported by women before and after transfer. Individuals employed in academic jobs after transfer had significantly lower HbA1c levels before and after transfer than those in nonacademic jobs, while the differences between individuals who were in vocational training and those pursuing studies were most pronounced (7.4 ± 1.0%, 57 ± 13 mmol/mol vs. 7.0 ± 0.8%, 53 ± 15 mmol/mol, p < 0.05). Moreover, among individuals aged 30-40, those with T1D exhibited a lower prevalence of having children (38.0% vs. 52.7%) and being married (40.5% vs. 55.3%) compared to general population.

Conclusions: Psychosocial life circumstances that are considered more stable in early adulthood, such as being a parent and working in academic occupation, were positively associated with metabolic control.

Introduction: Overweight and obesity in adolescence represents a major health concern globally, owing to the associated increased morbidity and mortality in adulthood. The prevalence of overweight and obesity in adolescents in Greece is 41% and is the highest among European countries. The aim of our study was to assess the effectiveness of a multidisciplinary, personalized lifestyle intervention program of diet, sleep, and exercise in the management of overweight and obesity in adolescence.

Methods: Five hundred and forty-four (544) adolescents (mean age ± standard deviation: 12.29 ± 2.10 years; 328 females, 216 males) were studied prospectively for 1 year. Participants were classified as having severe obesity (n = 192 35.3%), obesity (n = 107, 19.7%), overweight (n = 161, 29.6%), or normal body mass index (BMI) (n = 84, 15.4%) according to the International Obesity Task Force (IOTF) cut-off points. All subjects received multidisciplinary, personalized advice on diet, sleep, and exercise at frequent intervals for a period of 1 year. Detailed clinical evaluation and laboratory investigations were performed at the beginning and the end of the study.

Results: Adolescents with obesity and severe obesity had significantly higher systolic and diastolic blood pressure, as well as a more adverse cardiometabolic profile compared with their overweight and normal BMI counterparts. At the end of the study, obesity rates decreased by 15%, severe obesity rates by 33.8% and a significant improvement in most cardiometabolic risk factors was noted.

Conclusion: These findings indicate that a multidisciplinary, personalized, lifestyle intervention program is effective at reducing the prevalence of overweight and obesity in adolescence.

Introduction: β-human chorionic gonadotrophin (β-hCG) secreting tumors causing gonadotropin-independent precocious puberty (GIPP) are rare. This case underscores the diagnostic difficulties presented by these tumors.

Case presentation: A 10.8-year-old boy was referred with rapidly advancing puberty. He had Tanner stage 5 pubic hair, macropenis, accelerated growth and bone age. Suppressed gonadotropins with elevated testosterone and β-hCG levels led to diagnosis of GIPP. Cranial imaging for the source of β-hCG identified a 7-mm pituitary adenoma; however, resection of the pituitary lesion and petrosal sinus and cerebrospinal fluid β-hCG measurements did not support this. A testicular biopsy and spermatic venous β-hCG levels due to testicular calcifications indicated no evidence of testicular secretion. PET/CT demonstrated mild fluorodeoxyglucose uptake in the thymic region. Excisional biopsy was consistent with thymic hyperplasia. During follow-up, β-hCG levels fluctuated between 100 and 154 mIU/mL, with serial imaging (cranial, thoraco-abdomino-pelvic magnetic resonance imaging) remaining unremarkable. At sixth year of follow-up, β-hCG surged to 2,039 mIU/mL, at which time, thoracic CT revealed a 5 cm mass in the mediastinum. The mass was resected and pathology was consistent a mixed germ cell tumor.

Conclusion: The source of β-hCG may remain obscure for a long time in β-hCG-mediated GIPP. Ongoing surveillance is essential in similar cases.

Introduction: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in children. At least 10 monogenic causes and 28 syndromes have been reported to be associated with CHI. The aim of this study was to evaluate epidemiologic data and genetic background of persistent nonsyndromic CHI in Slovakia.

Methods: Based on data from the nationwide Diabgene database of children with persistent hyperinsulinemic hypoglycaemia, 28 children were diagnosed with nonsyndromic CHI during the years 2005-2024. DNA analysis of the most common CHI genes was performed. Epidemiology of CHI was calculated using Slovak demographic data.

Results: The overall incidence of nonsyndromic CHI in Slovakia over the last 20 years was 1:39,804 live births. In 2024, the prevalence was 1:161,802 children younger than 19 years. A genetic cause was identified in 9 children (32%), the most common was CHI due to mutation in ABCC8 gene (n = 4), followed by the KCNJ11 (n = 2), HNF4A (n = 2), and HK1 (n = 1) genes. In diazoxide-unresponsive CHI (n = 6), 5 children had a mutation in the ABCC8 or KCNJ11 genes and one in the HK1 gene. Four children had the focal form based on the paternally inherited recessive mutation and underwent pancreatic surgery.

Conclusion: Nonsyndromic CHI is a rare disease with nationwide incidence in Slovakia of 1:39,804. Diazoxide-unresponsive CHI accounts for 21% of all the cases. A genetic cause was identified in 32% (100% in diazoxide-unresponsive) of children; mutations in the ABCC8 gene were the most prevalent. The type of mutation determines the most appropriate management strategy, including pancreatic surgery.