Journal of Pediatric Endocrinology & Metabolism最新文献

Objectives: To determine the associations between various glucose and lipid-related indicators with elevated alanine aminotransferase (ALT) in pediatric population.

Methods: We analyzed the cross-sectional data of 3,771 Iranian children and adolescents aged 7-18 years using the fifth survey of a national school-based surveillance program. The predictive power of 11 different glucose and lipid-related indicators for predicting elevated ALT was examined using receiver operating characteristic (ROC) curve.

Results: In the total sample non-HDL-C, non-HDL-C/HDL-C, and TC/HDL-C showed the largest area under the curve (AUC) for elevated ALT detection, with 0.731 (cut-off, 129.5 mg/dL), 0.706, and 0.706, respectively. In girls, non-HDL-C had the highest predictive value (AUC, 0.741, cut-off, 129.5 mg/dL). Among boys, non-HDL-C/HDL-C and TC/HDL-C showed the largest AUC of 0.753 with optimum cut-off values of 2.63 and 3.63, respectively.

Conclusions: The findings of this study suggest that non-HDL-C, non-HDL-C/HDL-C, and TC/HDL-C can be predictors of elevated ALT in the pediatric population. These indices can be useful in large population-based studies for predicting children and adolescents at risk of fatty liver.

Objectives: The COVID-19 pandemic affected the mental health of children and adolescents in the general population, yet its impact on those with chronic conditions is relatively unknown. This study aimed to compare the incidences of comorbid mental disorders and substance misuse in children and adolescents with type 1 diabetes before and during the pandemic.

Methods: A total of 42,975 patients aged 6-18 years from the multicentre DPV (Diabetes Prospective Follow-up) registry were included. Multivariable regression models were applied to compare newly diagnosed comorbid mental disorders, adjusted for demographic and clinical variables, among them the number of medical visits, during the pre-pandemic period (09/2017-02/2020) and the COVID-19 pandemic period (03/2020-08/2022).

Results: Analysing both sexes together, there were no differences in the incidence rates of overall mental disorders between the pandemic and the pre-pandemic period. However, girls showed an increased incidence rate (odds ratio 1.2, CI 1.1-1.3) during the pandemic. Adolescent girls also displayed higher incidence rates of depression, eating disorders, and self-harm. Substance misuse declined overall during the pandemic (odds ratio 0.8, CI 0.7-0.9).

Conclusions: During the COVID-19 pandemic, we found higher incidence rates of overall mental disorders in girls, but not in boys and not in the total study population of children and adolescents with type 1 diabetes. Adolescent girls displayed increased incidence rates of depression, eating disorders, and self-harm. Substance misuse declined substantially. Clinicians should be aware of the high-risk group of adolescent girls during times of increased strain.

Objectives: Patients with Chiari malformation (CM) are prone to a variety of neurological sequelae, including benign intracranial hypertension (BIH). In these patients, BIH is attributed to impaired cerebrospinal fluid (CSF) flow due to anatomical abnormalities of the posterior fossa. Occasionally, patients with CM may require growth hormone therapy (GHT), which can increase the production of CSF. It is thought that patients with CM who undergo GHT are at high risk of BIH-associated symptoms (BIHAS). We describe the incidence of neurological symptoms in 34 patients with CM before and during GHT.

Methods: The database of a pediatric endocrinology center was queried for patients with CM who received GHT from 2010-22. Records were reviewed for adverse events. Demographic and radiological data were collected and analyzed. Patients with neoplastic disease, active inflammation, or acute trauma were excluded. CM diagnoses were independently assigned by a neuroradiology department. Patients were grouped based on the presence and nature of symptoms before and during GHT. Relationships between starting dose/BMI and occurrence of BIHAS/all GHT-associated symptoms were evaluated.

Results: GHT was not associated with new-onset or worsening of preexisting BIHAS in 33 out of 34 patients with CM. Five complex patients continued to have preexisting BIHAS, which did not worsen. Of the four patients who developed new-onset BIHAS during GHT, three patients' symptoms were attributed to other medical conditions. No patient permanently discontinued GHT due to BIHAS.

Conclusions: Growth hormone therapy is likely a safe treatment in patients with Chiari malformation and is unlikely to cause BIHAS.

Objectives: To investigate albumin (ALB) gene variations in patients suspected from familial dysalbuminemic hyperthyroxinemia (FDH).

Methods: Eight Turkish patients were included into the study. Clinical and laboratory characteristics of the subjects and their parents were evaluated and genetic analysis were performed.

Results: In genetic analysis, a previously reported heterozygous, c.725G>A variant was detected in exon seven of the ALB gene.

Conclusions: FDH is an asymptomatic condition however there is still a risk of misdiagnosis and unnecessary treatment. Therefore, if FDH is considered, initial ALB hotspot sequencing as a rapid and simple method is recommended instead of complex and expensive laboratory and imaging techniques.

Objectives: Somatrogon is a long-acting recombinant human growth hormone used to treat patients with paediatric growth hormone deficiency (pGHD). This global phase 3 study compared the efficacy and safety of once-weekly somatrogon with once-daily somatropin in children with GHD.

Methods: Prepubertal patients were randomized 1:1 to once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. The primary endpoint was height velocity (HV) at month 12; secondary endpoints included HV at month 6 and change in height standard deviation score (SDS) at months 6 and 12 and insulin-like growth factor 1 (IGF-1) SDS.

Results: This post hoc subgroup analysis focused specifically on Asian children (somatrogon: n=24 and mean age=7.76 years; somatropin: n=21 and mean age=8.10 years) across eight countries. Mean HV at month 12 was 10.95 cm/year (somatrogon) and 9.58 cm/year (somatropin); the treatment difference of 1.38 cm/year favoured somatrogon. The lower bound of the two-sided 95 % CI of the treatment difference (somatrogon-somatropin) was -0.20, similar to the overall study population (-0.24). Compared with the somatropin group, the somatrogon group had numerically higher HV at month 6 (8.31 vs. 11.23 cm/year); a similar trend was observed for height SDS and IGF-1 SDS at months 6 and 12. Safety and tolerability were similar between treatment groups; adverse events occurred in 83 % of somatrogon-treated children and 76 % of somatropin-treated children.

Conclusions: This subgroup analysis demonstrated that somatrogon efficacy and safety in Asian children were consistent with the overall study population, where once-weekly somatrogon was non-inferior to once-daily somatropin. Clinicaltrials.gov: NCT02968004.

Objectives: Phenylalanine hydroxylase (PAH) is predominantly a hepatic enzyme that catalyzes phenylalanine (Phe) into tyrosine, which is the rate-limiting step in Phe catabolism. Biallelic variants in the PAH gene cause PAH enzyme deficiency. Phenylketonuria (PKU) is an autosomal recessive disorder that causes neurologic, behavioral, and dermatological findings. PKU could be divided clinically into three types based on the blood Phe levels: classic phenylketonuria (cPKU), mild-moderate phenylketonuria (mPKU), and mild hyperphenylalaninemia (MHP). This study aimed to determine the phenotypic and genotypic characteristics of Turkish PKU patients in the eastern region of Türkiye.

Methods: Demographic characteristics, serum Phe levels, treatments, and PAH variants of 163 patients with PKU and hyperphenylalaninemia (HPA) were retrospectively evaluated. Blood Phe levels of the patients were analyzed with the high-performance liquid chromatography method. For PAH gene analysis, next-generation sequencing was performed.

Results: Of the 163 patients included in the study, 38 (23.3 %) had cPKU, 16 (9.8 %) had mPKU, and 109 (66.9 %) had MHP. Homozygous variants in the PAH gene were detected in 66 (40.5 %) of the patients, while compound heterozygous variants were detected in 97 (59.5 %) patients. Two novel and 35 recurrent variants in the PAH gene were detected. Of the two novel variants, one was missense (p.Phe351Leu) and the other was frameshift (p.Met276Cysfs*65). The most frequently detected variants were p.Thr380Met (18 %), p.Arg261Gln (16.8 %), and p.Ala300Ser (12.8 %). All patients with the homozygous c.1066-11G>A variant exhibited cPKU phenotype. The c.898G>T (p.Ala300Ser), c.1139C>T (p.Thr380Met), and c.1208C>T (p.Ala403Val) variants were statistically related to mild phenotype. On the other hand, c.592_613del (p.Tyr198Serfs*136), c.1028A>G (p.Tyr343Cys), and c.782G>A (p.Arg261Gln) variants were more frequently detected in the cPKU group.

Conclusions: Our study, conducted with patients from the eastern region of Türkiye, demonstrates the genetic heterogeneity in the Turkish population. Simultaneously, our research contributes to genotype-phenotype correlation and expands the genotypic spectrum by identifying novel variants.

Objectives: The most suitable biochemical markers for therapy adjustment in patients with congenital adrenal hyperplasia are controversial. 11-Oxygenated androgens are a promising new approach. The objective of this study was to investigate the diurnal rhythm of 11-ketotestosterone in children and adolescents in saliva and to correlate it with salivary 17-hydroxyprogesterone.

Methods: Fifty-one samples of steroid day-profiles from 17 patients were additionally analysed for 11-ketotestosterone, retrospectively. All patients were treated in our university outpatient clinic for paediatric endocrinology between 2020 and 2022. Steroid day-profiles of 17 patients could be examined. The cohort showed a balanced sex ratio. The median age was 13 years. The measurements for 17-hydroxyprogesterone were carried out during routine care by immunoassay. The measurements of 11-ketotestosterone were performed from frozen saliva samples using an implemented in-house protocol for liquid chromatography-tandem mass spectrometry (LC-MS/MS). The most important outcome were the absolute values for 11-ketotestosterone, their diurnal rhythmicity and the correlation with 17-hydroxyprogesterone.

Results: Both steroids show a circadian diurnal rhythm. 17-hydroxyprogesterone and 11-ketotestosterone correlate significantly. 11-Ketotestosterone showed a positive correlation with BMI at all times of the day.

Conclusions: 11-Ketotestosterone shows circadian rhythmicity in our cohort and correlates with 17-hydroxyprogesterone. These findings serve as an important basis for prospective research into 11-oxygenated androgens as therapeutic markers in paediatrics. However, 11-ketotestosterone appears to be very dependent on BMI.

Prompt diagnosis and early treatment are key goals to optimize the outcomes of children with growth hormone deficiency (GHD) and attain the genetically expected adult height. Nonetheless, several barriers can hinder prompt diagnosis and treatment of GHD, including payer-related issues. In Saudi Arabia, moderate-to-severe short stature was reported in 13.1 and 11.7 % of healthy boys and girls, respectively. Several access and payer barriers can face pediatric endocrinologists during the diagnosis and treatment of GHD in Saudi Arabia. Insurance coverage policies can restrict access to diagnostic tests for GHD and recombinant human growth hormone (rhGH) due to their high costs and lack of gold-standard criteria. Some insurance policies may limit the duration of treatment with rhGH or the amount of medication covered per month. This consensus article gathered the insights of pediatric endocrinologists from Saudi Arabia to reflect the access and payer barriers to the diagnostic tests and treatment options of children with short stature. We also discussed the current payer-related challenges endocrinologists face during the investigations of children with short stature. The consensus identified potential strategies to overcome these challenges and optimize patient management.

Objectives: Inactivating GNAS mutations result in varied phenotypes depending on parental origin. Maternally inherited mutations typically lead to hormone resistance and Albright's hereditary osteodystrophy (AHO), characterised by short stature, round facies, brachydactyly and subcutaneous ossifications. Paternal inheritance presents with features of AHO or ectopic ossification without hormone resistance. This report describes the case of a child with osteoma cutis and medulloblastoma. The objective of this report is to highlight the emerging association between inactivating germline GNAS mutations and medulloblastoma, aiming to shed light on its implications for tumor biology and promote future development of targeted surveillance strategies to improve outcomes in paediatric patients with these mutations.

Case presentation: A 12-month-old boy presented with multiple plaque-like skin lesions. Biopsy confirmed osteoma cutis, prompting genetic testing which confirmed a heterozygous inactivating GNAS mutation. At 2.5 years of age, he developed neurological symptoms and was diagnosed with a desmoplastic nodular medulloblastoma, SHH molecular group, confirmed by MRI and histology. Further analysis indicated a biallelic loss of GNAS in the tumor.

Conclusions: This case provides important insights into the role of GNAS as a tumor suppressor and the emerging association between inactivating GNAS variants and the development of medulloblastoma. The case underscores the importance of careful neurological assessment and ongoing vigilance in children with known inactivating GNAS variants or associated phenotypes. Further work to establish genotype-phenotype correlations is needed to inform optimal management of these patients.

Objectives: Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT.

Methods: We retrospectively analyzed the medical records of 19 pediatric CKD patients on dialysis with refractory sHPT who underwent sPTX at our institution between 2010 and 2020. All patients had clinical, radiological, and biochemical signs of renal osteodystrophy.

Results: One year after sPTX, parathyroid hormone (PTH) levels (median and interquartile range (IQR)) dropped from 2073 (1339-2484) to 164 (93-252) pg/mL (p=0.0001), alkaline phosphatase (ALP) levels from 1166 (764-2373) to 410 (126-421) IU/L (p=0.002), and the mean (±SDS) calcium-phosphate (Ca*P) product from 51±11 to 41±13 mg²/dL² (p=0.07). Postoperatively, all patients presented with severe hungry bone syndrome (HBS) and required intravenous and oral calcium and calcitriol supplementation. None of them had other postoperative complication. Histological findings had a good correlation with preoperative parathyroid ultrasound imaging (n: 15) in 100 % and with technetium-99m (^99mTc) sestamibi scintigraphy (n: 15) in 86.6 %. Clinical and radiological signs of bone disease improved in all patients.

Conclusions: Pediatric sPTX is effective and safe to control sHPT and calcium-phosphate metabolism in children with CKD on dialysis and may mitigate irreversible bone deformities and progression of cardiovascular disease.