Journal of Pediatric Endocrinology & Metabolism最新文献

Objectives: The authors sought to assess whether the age of 18 reflects a true pathological inflection point that justifies transitioning between pediatric and adult paradigms of care with differentiated thyroid cancer (DTC).

Methods: A retrospective chart review was conducted for patients aged 12-24 undergoing hemithyroidectomy or total thyroidectomy for papillary or follicular thyroid carcinoma from 2010 to 2020.

Results: A total of 153 patients receiving surgery for DTC were assessed for pathological stage, nodal metastasis, and thyroid neoplasm characteristics. When comparing pathologic tumor staging of patients <18 vs. ≥18 years old, there was a significant relationship between age and pT stage (p=0.009), but not between age and pN stage (p=0.319). However, when comparing patients ≤15 vs. >15 years, there was a significant relationship between age and pT stage (p=0.015) and age and pN stage (p=0.016). Patients ≤15 years of age most commonly had stage pT2 tumors (48.9 %, n=22), whereas most >15 years had stage pT1 tumors (37.9 %, n=41). Of patients whose lymph nodes were analyzed, patients ≤15 years were most likely to have pN1b disease (31.1 %, n=14), while patients >15 years were most likely to have pN0 disease (33.3 %, n=36).

Conclusions: In this sample, separating children and adults at an age of 15, rather than 18, yielded more significant differences in risk of nodal involvement. Markers of invasive histology were more common in patients older than 15, while nodal involvement was more common in patients 15 and under.

Objectives: Immune checkpoint inhibitors (ICIs) are emerging treatment options for children with brain tumors, who are already at risk for developing endocrinopathies due to tumor location and treatment. Endocrine ICI-related adverse effects (irAEs) are common in adults but poorly characterized in the pediatric population. The aims of this study were to determine in pediatric brain tumor patients in a single institution (1) if endocrine surveillance took place before and after ICIs were initiated, and (2) the occurrence of endocrine irAEs.

Methods: This is a retrospective chart review of 22 pediatric brain tumor patients treated with ICIs at Children's Hospital Los Angeles between 2010 and 2022. We analyzed endocrine laboratory results, patient demographics, and treatment course.

Results: Most patients (82 %) received surveillance in at least one endocrine system before ICI treatment - all had thyroid function tested (100 %) whereas non-thyroid endocrine functions were seldomly assessed (6-22 %). Only those patients with surveillance prior to treatment had ongoing surveillance after ICI initiation - 100 % for thyroid function and 17-39 % for other endocrine systems. Hypothyroidism was the only endocrine problem diagnosed after ICI initiation, in two patients (9 %). Of note, most patients (68 %) expired during or shortly after ICI treatment.

Conclusions: This is one of the first institutional surveys of pediatric ICIs in a high-volume pediatric brain tumor center. Thyroid surveillance commonly occurred in pediatric patients, revealing diagnoses of hypothyroidism, which is consistent with adult data. However, little information is available for non-thyroid endocrine conditions, reflecting the need for comprehensive and systematic endocrine surveillance.

Background: Previous studies have shown that vitamin D deficiency is a risk factor for obesity in children and adolescents, but most focus on school-age children and adolescents, with little attention paid preschoolers.

Objectives: To explore the relationship between overweight or obesity in the context of vitamin D intake among preschool children in Beijing, and analyze the correlation.

Methods: A total of 51,640 preschoolers (26,775 boys; 24,865 girls), aged 1-6 years, were recruited for physical examination. Overweight or obesity was defined according to the World Health Organization Child Growth and Development Standards (2006 edition). Serum 25-hydroxy (OH) vitamin D levels were determined using standardized liquid chromatography-tandem mass spectrometry (LC-MS/MS), and vitamin D status was evaluated based on the Practice Guide on Clinical Issues Related to Vitamin D Nutrition in Chinese Children (2022).

Results: No significant change was observed in the incidence of overweight (7.72, 7.51, and 7.24 %) or obesity (2.75, 2.63, and 2.40 %) from 2021 to 2023. Among boys, 7.3 % were overweight and 2.8 % were obese. Among girls, 7.6 % were overweight and 2.3 % were obese. Vitamin D deficiency (2.10, 1.70, and 1.01 %) and insufficiency rate (24.09, 18.42, and 15.44 %) showed a decreasing trend. Deficiency or insufficiency was most common in children aged 36-59 months, and serum 25- (OH) vitamin D levels were significantly lower in winter compared to other seasons, with the highest levels in summer. Time spent outdoors was significantly less among children with vitamin D deficiency or insufficiency, and preschoolers who spent more than 2.94 h/day had higher serum vitamin D level. Serum 25- (OH) vitamin D levels were negatively correlated with body mass index (BMI), with overweight or obesity preschoolers showing significantly lower than their normal weight group. After adjusting for age, gender and season, family economic status, guardian educational level and time spent outdoors, the odds of vitamin D deficiency and insufficiency in overweight or obesity in preschoolers were 1.025 (95 % Cl: 1.002-1.174), 1.218 (95 % Cl: 1.099-1.708), respectively.

Conclusions: From 2021 to 2023, there was no significant change in the incidence of overweight or obesity among preschool children in Beijing. Furthermore, the rate of vitamin D deficiency or insufficiency decreased year by year. Vitamin D deficiency or insufficiency associates with factors such as age, season of the year, and time spent outdoors, and there is an association between overweight or obesity and vitamin D status among preschoolers.

Objectives: We describe a male with adrenal hypoplasia congenita (AHC) caused by a novel mutation in NR0B1, who was noted at 9 months of age to have central precocious puberty (CPP).

Case presentation: A 3-week-old full-term male presented with hypothermia and lethargy, and a 0.3 kg weight loss since birth. Labs were consistent with adrenal crisis, he was stabilized with stress dose hydrocortisone (HC), insulin, and antibiotics, and he was admitted to the Pediatric Intensive Care Unit. Subsequent labs revealed primary adrenal insufficiency with abdominal ultrasound remarkable for nonvisualization of the adrenal glands. Genetic testing identified a novel pathogenic c.707G>A [p.Trp236ter] nonsense variant in the DNA-binding domain of NR0B1 (DAX-1) confirming AHC. The patient was discharged with HC, fludrocortisone, and sodium supplementation with good tolerance and interval weight gain and normal electrolytes. At 9 months of age, the patient developed signs of precocious puberty, which failed to self-resolve or diminish with increased dosing of HC, and by the age of 15 months, he was treated with leuprolide acetate.

Conclusions: Historically, hypogonadotropic hypogonadism has been observed in 76 % of adolescent patients with AHC who have alterations in NR0B1. CPP has been infrequently described in AHC, and the natural history and management of CPP in this setting is not established. Our observations may contribute to the understanding of factors influencing normal and abnormal puberty in infants. Increased awareness of the possibility of CPP in AHC will aid clinicians in the earlier clinical and laboratory detection of this complication.

Objectives: The aim of the current study was to assess the natural course of partial remission (PR) phase of type 1 diabetes (T1D) and to highlight the putative association between vitamin D receptor (VDR) (Fok1) gene polymorphism and PR phase.

Methods: Ninety participants with newly diagnosed T1D were followed up for a total of 12 months. The VDR (Fok1) rs2228570 gene polymorphism was genotyped using allelic discrimination (AD) assay.

Results: Fifty-four patients (60 %) reached PR with an average duration of 5.63 ± 2.9 months. Among remitters, the frequency of CC "FF" genotype and allelic frequency of C "F" were significantly higher (p<0.001). Furthermore, participants expressing "CC" genotype had earlier onset of PR and spent a significantly longer duration in remission (p<0.001). Younger age (p<0.001; OR 41.6; CI 12.12-142.99), absence of DKA (p<0.001; OR 16, CI 4.36-50.74), higher C-peptide levels (p<0.001; OR 19.55; CI 6.52-58.63), and presence of CC "FF" genotype of VDR (p<0.001; OR 6.74; CI 2.41-18.86) best predicted the overall occurrence of PR.

Conclusions: Younger age, less extent of metabolic derangements, and expression of a CC "FF" genotype were found to influence the occurrence of PR. Data from the current study showed that the "C" allele could have a protective role on preserving residual β-cell mass and could predict both onset and duration of PR among newly diagnosed T1D. These findings support the growing concept of future tailored precision medicine.

Objectives: The study endeavored to evaluate the prolonged efficacy and safety of PEGylated rhGH (PEG-rhGH) administration in Chinese children diagnosed with growth hormone deficiency (GHD) over a 5-year period.

Methods: A retrospective analysis was conducted on children with GHD, who received a 0.2 mg/kg/week dose of PEG-rhGH between 2016 and 2023 in our department.

Results: The height standard deviation score (Ht SDS) exhibited a marked elevation post-PEG-rhGH administration (p<0.001), sustaining this enhancement beyond year 3, with increments recorded at 0.94±0.37, 1.49±0.48, 1.77±0.51, 2.12±0.65, and 2.15±0.58 across 5 years. Similarly, the height velocity (HV), insulin-like growth factor-1 standard deviation score (IGF-1 SDS), and bone age to chronological age ratio (BA/CA ratio) underwent significant augmentations (p<0.01). Remarkably, no signs of rapid bone maturation were detected during the 5-year observation. Among the participants, 31 patients (59.62 %) experienced adverse events, of which eight instances (15.38 %) were classified as treatment-related adverse events, but none were severe or unexpected. Additionally, high-density lipoprotein (HDL) levels rose while low-density lipoprotein (LDL) levels fell, both remaining within the standard range throughout the treatment phase.

Conclusions: Administering PEG-rhGH at a dosage of 0.2 mg/kg/week proved both effective and well-tolerated in treating prepubertal children with GHD. This regimen also demonstrated positive impacts on lipid metabolism over an extended treatment period.

Objectives: To study the urinary neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (β2M) levels as markers of tubular damage in children with type 1 diabetes (T1DM).

Methods: Forty T1DM children and 40 age-matched controls were enrolled. Subjects with coexisting kidney disorder, intake of oral glucose lowering drugs and syndromic diabetes mellitus were excluded. Fasting plasma glucose, glycated hemoglobin (HbA_1c), kidney function, urinary albumin-creatinine ratio (UACR), NGAL and β2M were measured and compared in cases and controls.

Results: The median (IQR) age of cases and controls was 10.6 (8, 14.2) and 10.7 (8.4, 13.7) years, respectively. Cases had disease duration of 4 (3, 6.8) years and HbA_1c 10.9 (9, 13.1) %. Microalbuminuria was seen in 14 (35 %). Median (IQR) levels of UACR were higher in cases than controls [19.38 (10.27, 35.26) and 6.49 (3.10, 11.65) µg/mg; p<0.001], similarly NGAL/creatinine [352.21 (191.49, 572.45) and 190.54 (125.91, 322.83) ng/mg; p=0.006], unlike β2M/creatinine [1.7 (0.43, 6.02) and 2.12 (1.05, 4.47) µg/mg; p=0.637]. Children with higher HbA_1c (≥10 %) had higher urinary ACR and tubular biomarkers than HbA_1c<10 % (p>0.05). Urinary ACR showed positive correlation with NGAL/creatinine (r=0.38, p=0.019) and β2M/creatinine (r=0.42, p=0.009).

Conclusions: Urinary biomarkers NGAL and β2M were elevated in the presence of normal urinary microalbumin levels suggestive of early tubular damage in T1DM.

Objectives: To generate normative data and validate the recently developed, gender-neutral, External Genitalia Score (EGS) in Indian preterm and term neonates and children up to 2 years of age with normal and atypical genitalia.

Methods: This observational study included 1,040 neonates born between 28 and 42 weeks of gestation and 152 children between 1 and 24 months of age. In addition, 50 children with disorders of sex development (DSD) were also enrolled in the study. The Prader stage/external masculinization score (EMS) (as applicable), anogenital ratio (AGR) and EGS were assessed for all neonates and children with typical and atypical genitalia.

Results: Median EGS values in newborn males with typical genitalia were 9.5 at 28-31 weeks, 10.5 at 32-33 weeks, 11 at 34 weeks and 11.5 in males at 35-42 weeks of gestation. For all females with typical genitalia, the EGS was 0. EMS and EGS showed a positive correlation in males with typical genitalia (r=0.421, p=0.000**) and all children with DSD (r=0.857, p=0.000**). Mean AGR in males and females with typical genitalia and those with DSD were 0.52±0.07, 0.31±0.05 and 0.47±0.13, respectively. EGS correlated with AGR in all males with typical genitalia (r=0.107, p=0.008**), and in all children with DSD (r=0.473, p=0.001**).

Conclusions: The EGS enables accurate, gender-neutral and comprehensive assessment of external genitalia in Indian neonates and children with typical and atypical genitalia/DSD. Evaluation for DSD is recommended in any child with EGS greater than 0 and ≤10th percentile for gestation or age (10.5 in a term neonate).

Objectives: Lipoid congenital adrenal hyperplasia (LCAH) is a rare autosomal recessive disease caused by mutations in the steroidogenic acute regulatory protein (STAR) gene, expressed in the adrenal and gonadal tissues. In classical LCAH, individuals with 46, XY chromosomes present with a female appearance of the external genitalia due to insufficient androgen production. In the non-classical form, a milder phenotype is observed with male external genitalia. Here, we present a non-classical LCAH diagnosis with a newly identified c.266T>A (p.Ile89Asn) likely pathogenic homozygous variant in a 46, XY infant.

Case presentation: A three-month-and-thirteen-day-old male proband presented with clinical features of cortisol and mineralocorticoid deficiencies. The manifestation of salt-wasting syndrome occurred relatively late, and although the external genitalia appeared male, there was a mild virilization defect. The combination of mild impairment in androgen production and severe salt-wasting syndrome is an intriguing finding in our patient. Peripheral blood samples were obtained from the patient and his family. The newly identified variant, determined by next-generation sequencing analysis, was confirmed by segregation analysis showing carrier status in both parents.

Conclusions: We aim to contribute to the literature by elucidating molecular mechanisms by presenting an atypical presentation and a newly identified variant.