Journal of Pediatric Endocrinology & Metabolism最新文献

Objectives: Hybrid closed-loop (HCL) systems improve glycemic control in type 1 diabetes mellitus (T1D), but their effectiveness in young, poorly controlled populations is not established and requires study.

Methods: A pre-post study was performed using electronic health records of patients 3-24 years with baseline HbA1c≥9 % prescribed HCL within the New York City Health+Hospitals System assessing HbA1c levels and hospitalizations before and after HCL initiation and factors associated with achieving HbA1c<9 % after HCL initiation.

Results: Of 47 children and adolescents who met inclusion criteria, 4.68 % female, 95.72 % non-White, and 82.22 % covered by public insurance, with a baseline average HbA1c 10.6 % (2.28 IQR). The most prevalent pump type was Omnipod 5 (70.21 %). The HbA1c was significantly lower in the postperiod than baseline (HbA1c before=median 10.6 (IQR2.28), HbA1c after=median 9.33 (IQR 2.97), difference 1.00 (IQR 1.64), p<0.05) with a decrease in median diabetes-related hospitalizations (preperiod 1.00 (IQR 1.00), postperiod 0.00 (IQR 1.00), difference -1.00, IQR 2, p<0.05). Lower baseline HbA1c levels made reaching HbA1c<9 % more likely. Multivariable analysis showed that the odds of having HbA1c of <9 % was 2.1 times less likely for every one point increase in baseline HbA1c and 12.5 times less likely for those with a pump at (p<0.05).

Conclusions: HCL therapy improved glycemic control and decreased diabetes-related hospitalizations in youth with poorly controlled T1DM. Higher baseline HbA1c levels predicted less success with HCL therapy so those who stand to benefit most benefit least.

Objectives: Testicular adrenal rest tumours (TARTs) are a common cause of infertility in males with congenital adrenal hyperplasia (CAH). Ovarian adrenal rest tumours (OARTs) and polycystic ovaries (PCO) can impair ovarian function in female patients with CAH. We aim to detect gonadal changes in children and adolescents with CAH.

Methods: This study was conducted on 50 CAH patients (30 females and 20 males) with 21-hydroxylase deficiency (21-OHD), with a mean age of 10.35 ± 2.36 years. Testicular ultrasonography and pelvic magnetic resonance imaging (MRI) were done in males and females respectively. Glucocorticoid doses and biochemical data were obtained from the patients' medical records.

Results: TARTs were detected in 10/20 male patients (50 %). There was a significant relation between presence of TARTs, body mass index (BMI) standard deviation score (SDS), and bone age (p=0.017 and 0.023; respectively). There was no significant relation between presence of TARTs, laboratory parameters, or treatment received (p>0.05). Of those subjected to genetic analysis, 48 % had I2 splice (c.290-13A/C>G) followed by P30L (c.89C>T) (40.7 %). P30L (c.89C>T) was the most common allele among the patients with TARTs (42.9 %). There was no significant relation between presence of TARTs, the genotype, alleles, or the genotype groups (p>0.05). Only one female patient had radiological evidence of bilateral polycystic ovaries and none had OARTs.

Conclusions: The prevalence of TARTs in our study was high (50 %). Screening for TARTs in males with CAH is crucial; however, routine ovarian imaging in CAH females is not indicated unless ovarian dysfunction is present.

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: To evaluate the long-term effectiveness of weekly vs. daily growth hormone (GH) administration in children with GH deficiency.

Methods: This study, part of the "LG Growth Study", included a total of 996 children with GH deficiency (773 receiving daily GH and 193 receiving weekly GH). Anthropometric data were collected at baseline and every 12 months; clinical and laboratory data were collected at baseline and throughout the study.

Results: At baseline, the weekly GH group was older, shorter in mid-parental height (MPH), and had more pubertal boys compared to the daily GH group (age: 8.46 ± 3.44 vs. 7.46 ± 2.89 years, p<0.001; MPH: -0.88 ± 0.73 SD vs. -1.02 ± 0.84 SD, p=0.044; pubertal boys: 34.0 vs. 16.9 %, p=0.006). Height velocity and change in height SDS during the first 12 months were higher in the daily GH group (height velocity: 9.06 ± 1.72 vs. 8.67 ± 1.98 cm/year, p=0.028; height SDS change: 0.78 ± 0.39 vs. 0.61 ± 0.41, p<0.001). However, height SDS at 24 and 48 months were similar between groups. No significant differences in overall height velocity, annualized treatment continuation rate, and safety profile were observed over 48 months.

Conclusions: Weekly GH therapy appears to be an effective and safe alternative to daily GH treatment in children with GH deficiency over a 4-year period. Further research with larger sample sizes and longer follow-up is needed to confirm these findings and assess the extended safety and effectiveness of LAGH.

This study is to evaluate the efficacy and safety of aromatase inhibitors (AIs) in the treatment of short stature in male children and adolescents. Pooled estimates of final or near-final height, predicted adult height (PAH), bone age, and potential side effects were calculated using a random-effects model or fixed-effects model. Our search identified 11 studies with a total of 463 participants. AI was associated with a significant increase in final or near-final height (weight mean difference (WMD)=3.61 cm, 95 % CI: 0.96, 6.26; p<0.001) and PAH (WMD=2.52 cm, 95 % CI: 0.32, 4.72; p=0.025) compared to other treatment. The use of AI showed an increased risk of minor side effects (risk ratio (RR)=2.90, 95 % CI: 1.15, 7.33; p=0.025), but no severe adverse effects were reported. Subgroup analysis, stratified by patient disease, revealed that AI significantly enhanced final or near-final height in both patients with idiopathic short stature (ISS) and those with constitutional delay of growth and puberty (CDGP). AIs may contribute to height increase in male children and adolescents with short stature, without significantly advancing bone age. However, the increased risk of minor side effects indicates the need for careful monitoring during AI therapy.

The average age of diagnosis of Prader-Willi syndrome (PWS) in most countries is less than 6 months of age. With the current medical knowledge of the benefits of growth hormone for infants with PWS, including improved cognitive function and improved psychomotor development, parents of infants with PWS want growth hormone therapy initiated as soon as possible. But the current recommendations to perform overnight polysomnography prior to initiation of growth hormone treatment often delays the initiation of therapy. We submit that overnight polysomnography for young infants (<6 months of age) is not necessary prior to growth hormone treatment, as there are no findings on polysomnography in this age group that should delay or prevent the initiation of growth hormone therapy.

Growth hormone deficiency (GHD) diagnosis still lacks a gold standard or ideal diagnostic marker. Unlike other epigenetic mechanisms, non-coding RNAs regulate post-transcriptional levels. The information on non-coding RNAs in the field of GHD is limited. Therefore, this study aimed to explore the role of hsa_circ_0002473 as a competitive endogenous RNA for has-miR-4645-3p in attenuating the inhibitory effect of has-miR-4645-3p on SSTR2. In this study, we screened three significantly expressed circular RNAs (circRNAs) in five children with GHD, and selected the highest expressed hsa_circ_0002473 as the study object, and screened has-miR-4645-3p, which is the most likely to bind to hsa_circ_0002473, according to the microRNA (miRNA)-circRNA regulatory network, to study the role and mechanism of has-miR-4645-3p as a competitive endogenous RNA of has-miR-4645-3p on GH3 cells. Somatostatin receptor 2 (SSTR2) inhibits GH3 cell proliferation, and miRNA binding to SSTR2 inhibits the latter expression. Both bioinformatics and dual-luciferase reporter analyses showed targeting relationships between hsa_circ_0002473 and has-miR-4645-3p and between has-miR-4645-3p and SSTR2. We constructed the hsa_circ_0002473/has-miR-4645-3p axis and transfected it into GH3 cells and found that overexpression of hsa_circ_0002473 inhibited the proliferation and growth hormone (GH) secretion of GH3 cells, and that hsa-miR-4645-3p promoted the proliferation and GH secretion of GH3 cells by targeting SSTR2. Co-culture revealed that the inhibitory effect of hsa_circ_0002473 was reversed by has-miR-4645-3p. In conclusion, our findings suggest that hsa_circ_0002473 can act as a competitive endogenous RNA for has-miR-4645-3p to regulate GH3 cell proliferation and secretion by targeting SSTR2.

Purpose: Existing literature lacks data on a subgroup exhibiting psychiatric symptoms below the DSM-5 diagnostic threshold within DSD cases. Our study aims to assess parental knowledge, attitudes toward DSD, and parental perceptions of emotional and behavioral states through a transdiagnostic perspective.

Methods: The study was conducted with a total of 35 parents of children with DSD. Two groups were established via k-means clustering, based on psychiatric symptomatology levels, derived from The Strength and Difficulties Questionnaire - Parent Form and The Revised Children's Anxiety and Depression Scale - Parent Form: with one group exhibiting lower reported psychiatric symptoms (LPS=27) and the other demonstrating higher psychiatric symptoms (HPS=8) by parents.

Results: Our study found that many parents were hesitant to disclose DSD diagnoses to their children, believing them to be too young to comprehend the information (42.9 %) and that they were unaware of the available support that could be provided by the medical team in disclosing the diagnosis (25.7 %). Our study found no differences in DSM-5 diagnoses between HPS and LPS groups (p>0.05), with ADHD being the most prevalent diagnosis (21.7 %) and a significant overrepresentation of children with a discrepancy between assigned gender at birth and gender upbringing in the HPS group compared to the LPS group (p<0.001).

Conclusions: Our study emphasizes the necessity of a transdiagnostic approach in psychiatry to move beyond binary conceptualizations and better understand the complexities of individuals with DSD.

Objectives: Steroid 5α-reductase type 2 deficiency (5α-RD2) is an autosomal recessive disorder caused by mutations in the SRD5A2 gene. This condition is characterized by reduced enzymatic activity of the 5α-reductase type 2 enzyme. Individuals with mutations in the SRD5A2 gene may exhibit various symptoms of under-masculinization in 46, XY individuals. We conducted a comprehensive analysis of the SRD5A2 gene in a patient with disorder of sex development (DSD).

Case presentation: We describe a patient with a homozygous Gly183Ser variant in the SRD5A2 gene. Their sibling also carries this variant in homozygosity, while both parents have it in a heterozygous state. The patient presents with predominantly female traits and was raised as a girl. Although the siblings exhibit distinct phenotypic characteristics, both have assumed a male gender identity.

Conclusions: This study reveals different phenotypes for the two siblings, highlighting the complexity of establishing a genotype-phenotype correlation in the SRD5A2 gene. It is noteworthy that the Gly183Ser variant seems to be more prevalent among individuals of African descent, aligning with our patient's ethnic background.

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.