Journal of Pediatric Endocrinology & Metabolism最新文献

Objectives: Kisspeptin plays a major role in the onset of puberty by stimulating the gonadotropin-releasing hormone (GnRH) neurons. The aim of this study was to investigate whether GnRH inhibits kisspeptin secretion via a negative feedback mechanism and potential associations between kisspeptin levels and other hormones of importance for pubertal onset.

Methods: Thirteen girls with suspected central precocious puberty underwent a GnRH stimulation test twice in a randomized, placebo-controlled manner. Blood was sampled up to 150 min after an IV injection of either Relefact LHRH^® or saline. The levels of kisspeptin, acylated ghrelin, ultrasensitive oestradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), insulin and glucose were analysed.

Results: Baseline kisspeptin levels ranged from 9.9 to 201.6 pg/mL. Neither area under the curve for kisspeptin levels nor peaks were significantly lower after the GnRH injection compared to placebo. Baseline kisspeptin and glucose levels tended to be associated (rho=0.55, p=0.051) but no other associations were found between kisspeptin and other hormones.

Conclusions: Basal levels of kisspeptin vary widely in young girls. We found no evidence of a negative feedback mechanism of GnRH on kisspeptin in this small pilot study. The suggested association between kisspeptin and glucose levels needs further investigations.

Objectives: Because patients with type 1 diabetes mellitus (T1DM) have persistent and profound limitations in immune functions, immune response to vaccines may diminish. The aim of our study was to compare the antibody to Hepatitis B surface antigen (anti-HBs) serologies of children with T1DM, at the time of T1DM diagnosis, who were vaccinated according to the vaccination schedule with the anti-HBs serologies of healthy children. And to investigate the relationship between anti-HBs levels and the accompanying variables of these patients.

Methods: Anti-HBs and Hepatitis B surface antigen (HBs Ag) results of 214 children with T1DM and 210 healthy children were recorded retrospectively. Seropositivity rates for anti-HBs were compared between T1DM and control groups and the odds of seropositivity were examined. Clinical and laboratory data of T1DM patients were investigated according to anti-HBs seropositivity.

Results: Anti-HBs seropositivity rates and titers in the T1DM group were significantly lower than those in the healthy group. According to anti-HBs status among T1DM patients; no difference was found in terms of gender, BMI, presence of comorbidities, presence of autoantibodies and lipid profiles. Diagnosis age and HbA1c levels of anti-HBs negative group were higher than anti-HBs positive group in patients diagnosed with T1DM. However, neither age nor HbA1c level was found to significantly change the odds of the seropositivity for anti-HBs in T1DM patients after adjustment.

Conclusions: We recommend that children diagnosed with T1DM should have anti-HBs serology tested at the time of diagnosis and seronegative patients should have additional hepatitis B vaccination.

Objectives: This study aimed to assess differences in insulin-like growth factor 1 (IGF-1) levels following the transition from somatropin to lonapegsomatropin in patients with pediatric growth hormone deficiency (GHD). Secondary objectives included the evaluation of dose titrations based on IGF-1 levels, changes in annualized height velocity (AHV) and body mass index (BMI), and assessing reported adverse effects associated with lonapegsomatropin therapy.

Methods: A single-center, retrospective review was conducted including patients diagnosed with pediatric GHD initially treated with somatropin who transitioned to lonapegsomatropin between January 1, 2022, and December 31, 2023.

Results: Fourteen patients (median age: 9 years) were included. The median somatropin dose was 0.18 mg/kg/week (range, 0.09 to 0.29) at the time of transition and patients were initiated on a median lonapegsomatropin dose of 0.23 mg/kg/week (range, 0.15 to 0.26). This resulted in an IGF-1 increase of 2.3 SDS post-switch. Dose adjustments were made based on IGF-1 levels. Five patients required immediate dose reductions; four of these required further adjustments due to persistent elevation. There were no serious adverse effects reported.

Conclusions: Lonapegsomatropin may be a favorable option to reduce injection burden for those with pediatric GHD, though the manufacturer's recommended starting dose of 0.24 mg/kg/week may require individualization. Careful monitoring and dose adjustment based on IGF-1 levels are necessary to maintain safety and efficacy.

Objectives: The gonadotropin-releasing hormone (GnRH) provocation test is crucial for diagnosing central precocious puberty (CPP). However, due to its invasion and high cost, it is essential to find a simpler biomarker. This study aimed to investigate the feasibility of fasting insulin (FINS) and insulin-like growth factor-1 (IGF-1) as potential biomarkers for diagnosing girls with CPP and to analyze their effects on puberty development.

Methods: From May 2023 to June 2024, we retrospectively analyzed 145 girls in the growth clinic of the Third Affiliated Hospital of Zhengzhou University, including 80 CPP girls as the case group and 65 normal growth and development girls as the control group. Collect their growth and development parameters and blood samples. The levels of FINS, IGF-1, and sex hormones were detected and compared between the two groups.

Results: Compared with the control group, girls in the CPP group showed higher levels of FINS, IGF-1, and IGF-1 standard deviation score (IGF-1 SDS) (p<0.001). Multivariate logistic regression analysis showed that the risk of CPP increased with the increase of FINS, IGF-1, and IGF-1SDS levels [OR=1.141, 95 % CI=(1.029-1.265), p<0.05; OR=1.062, 95 % CI=(1.011-1.116), p<0.05; OR=1.610, 95 % CI=(1.029-2.520), p<0.05]. The areas under the curve of FINS, IGF-1, IGF-1SDS, and their combination in the diagnosis of CPP were 0.759, 0.716, 0.707, and 0.777, respectively.

Conclusions: Elevated FINS and IGF-1 levels in girls with CPP indicate their potential as effective biomarkers for early screening and diagnosis of CPP.

Objectives: Neonatal severe hyperparathyroidism (NSHPT) is a rare condition characterized by inactivating mutations in the calcium-sensing receptor (CaSR) gene, leading to significant hypercalcemia and related complications.

Case presentation: We present a case of a six-day-old male infant with weakness, jaundice, and hypotonia, later diagnosed with NSHPT due to a known homozygous CaSR mutation (c.242T>A; p.I81K). Initial laboratory findings revealed markedly elevated serum calcium levels and high parathyroid hormone levels which were compatible with primary hyperparathyroidism. After initial management, bisphosphonates were administered, resulting in the patient remaining normocalcemic for 11 months, although hyperparathyroidism persisted. Then, due to the ongoing hyperparathyroidism, cinacalcet was added and continued for nine months. Finally, a total parathyroidectomy was performed. Postoperatively, the patient developed hypoparathyroidism, necessitating long-term supplementation with calcium and calcitriol. By the last follow-up at 3 years, the patient exhibited normal growth parameters and no neurodevelopmental deficits.

Conclusions: This case underscores the importance of early diagnosis and intervention in NSHPT and highlights the critical role of medical treatment, surgical management and long-term follow-up in optimising patient outcomes. Continued research is essential to enhance understanding and treatment strategies for NSHPT.

Objectives: The prevalence and predisposing factors to metabolic dysfunction-associated fatty liver disease (MAFLD) in children with type 1 Diabetes (T1D) living in developing countries are unknown.

Methods: A cross-sectional study was conducted in children with T1D. The presence of liver fat and tissue stiffness were assessed by ultrasonography and shear-wave elastography (SWE), respectively. The SWE values were correlated to body mass index (BMI), glycemic control, disease duration, and gamma-glutamyl transferase (GGT). Healthy non-obese children (n=36) were recruited as controls.

Results: One hundred children with T1D were grouped (Group A-C) according to the disease duration (<5, 5-10, and >10 years, respectively). The mean diabetes duration and glycated hemoglobin were 5.9 ± 4.0 years and 8.2 ± 0.55 %, respectively. The mean SWE values were significantly higher in the patient groups compared to controls (5.07 ± 0.67, 5.27 ± 0.65, 5.16 ± 0.50, vs. 4.80 ± 0.82 kPa, p-value 0.006). The liver stiffness based on SWE showed a positive but weak relationship with BMI, diabetes duration, glycemic control, and GGT levels. A significantly higher number of children with T1D had MAFLD [9(20 %), 7(24.1 %), 7(26.9 %), vs. 1(3 %), p-value <0.001] based on ultrasonography.

Conclusions: Children with T1D showed higher liver stiffness values than controls. A weakly positive relationship of liver stiffness was observed with BMI, duration of diabetes, glycemic control, and serum GGT. Approximately one-fourth of children with diabetes showed sonographic evidence of hepatic steatosis. Larger studies are needed to ascertain the effects of obesity, diabetes duration, and metabolic control on the prevalence and progression of MAFLD in children with T1D.

Objectives: Differences of sex development (DSD) refer to various congenital conditions affecting the urogenital and hormonal systems. Accurate diagnosis and personalized management are crucial for supporting patients through complex decisions, such as those related to gender identity.

Methods: This study represents the first comprehensive investigation into DSD in Iran, analyzing patient's clinical and genetic data between 1991 and 2020. Karyotype analysis was performed on 69 patients without a molecular diagnosis, with sex chromosome DSD excluded. Presence of SRY gene evaluated in all sex reversal patients. Whole exome sequencing (WES) was used for 26 undiagnosed patients, revealing pathogenic variants in WT1, NR5A1, DHX37, AR, CYP17A1, and LHCGR genes.

Results: The most common diagnosis was testicular TDSD, identified in 42 patients (60.86 %), with the SRY gene being the primary cause in 36 of these patients. The study highlights the importance of genetic analysis in identifying novel and rare gene variants, particularly within the steroid hormone and gonad differentiation pathways, for both 46, XY and 46, XX DSD.

Conclusions: These findings emphasize the need for genetic analysis in providing personalized patient care and tailored counseling to help individuals navigate complex decisions, including those involving gender identity.

Objectives: There is limited research on thyroid function in pediatric patients with cystic fibrosis (pwCF). This study aimed to determine the frequency of thyroid dysfunction in children and adolescents with CF and to evaluate iodine deficiency and selenium status in pwCF.

Methods: Sixty-two CF patients and 62 control subjects were evaluated. The anthropometric measurements, nutritional status, FEV1(Forced-expiratory-volume in 1 s) percentage, thyroid function tests (TSH, FT4, FT3), urinary iodine and selenium levels, hospitalization status in the last six months, antibiotic usage, and colonization status with staphylococcus or pseudomonas were assessed for the cases.

Results: The mean age of the patient group was 10.84 ± 4.04 years. All CF patients were receiving multivitamin supplementation. Malnutrition was present in 50 % of patients, bacterial colonization in 29 %, FEV1 decrease in 38.5 %, subclinical hypothyroidism (SH) in 12.9 %, iodine deficiency in 87 % and exocrine pancreatic insufficiency in 100 %. T3 levels were found to be higher in pwCF. No significant difference was found between malnutrition and FEV1 and urinary iodine and selenium levels. Compared to the control group, pwCF had lower urinary iodine levels.

Conclusions: To the best of our knowledge, our study is one of the few in the literature to investigate urinary selenium levels alongside iodine in PwCF. Further research is needed to clarify and interpret elevated urinary selenium levels in this context. It was shown that iodine deficiency and the rate of SH were relatively high in pwCF. However, it was still thought that correcting iodine deficiency in these patients could improve thyroid dysfunction associated with CF.

Objectives: To develop a clinical model for predicting the occurrence of Central Precocious Puberty based on the breast development outcomes in chinese girls.

Methods: This is a retrospective study, which included a total of 1,001 girls aged 6-9 years old who visited the outpatient clinic of Beijing Children's Hospital from January 2017 to October 2022 for "breast development". Participants were categorized into pubertal development (PD) cohort and simple premature breast development (PT) according to the criteria, and information was collected and tested for relevant indicators. After dealing with missing data, logistic regression, LASSO regression and random forest were used to screen the variables, and support vector machine models were built with SMOTE oversampling and ten-fold cross-validation to assess the effectiveness of the models in the training and validation sets.

Results: A total of 1,001 girls were included in the analysis, of whom 369 (36.9 %) were diagnosed with PD and 632 (63.1 %) with PT. Body mass index (BMI), bone age (BA), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), uterine diameter, and ovary volume were identified as the final predictor variables by three variable screening methods. The AUC of the constructed disease diagnostic model was 0.9457 in the developmental cohort and 0.8357 in the external validation group, and sensitivity analyses revealed that the performance of the constructed models with different variable selection strategies was similar.

Conclusions: A disease diagnostic model was developed that may help predict a girl's risk of diagnosing central precocious puberty.

Objectives: The association of celiac disease (CD) in type 1 diabetes mellitus (T1DM) is well-established, yet variation exists in screening practices. This study measures the accuracy of early screening with tissue transglutaminase immunoglobulin A (TTG-IgA) and endomysial antibody (EMA) in newly diagnosed T1DM.

Methods: This is a retrospective study of children with T1DM between 2013 and 2019 with early CD screening and follow-up. Data elements included anthropometrics, serologies, blood pH, bicarbonate, and Hemoglobin A1c. Celiac serologies were analyzed using chi-square and receiver operating characteristic curves to calculate optimal levels for predicting CD.

Results: A total of 1,292 children met inclusion criteria with 142 having positive celiac serologies; 47 (33.1 %) of whom were subsequently diagnosed with CD - an incidence of 3.6 %. All subjects with positive EMA and TTG-IgA ≥8 times upper limit of normal were diagnosed with CD. Gastrointestinal symptoms, BMI, and thyroid disease were not statistically significant variables in this cohort, although there was a trend toward CD in lower BMI patients and higher TTG IgA in those with markedly elevated HgbA_1c.

Conclusions: Early celiac screening in T1DM is reliable and promotes timely CD diagnosis and treatment. Although transient positive celiac serologies were noted, the degree of TTG-IgA elevation and EMA positivity are strong predictors of coexisting CD. Larger prospective studies using these assays will further define the risk stratification algorithm that is needed for our T1DM community.