Journal of Clinical Research in Pediatric Endocrinology最新文献

Objective: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population.

Methods: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D’ and R² values in SNP paired combinations.

Results: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799.

Conclusion: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

Background: Excessive iodine intake triggers the Wolff-Chaikoff effect resulting in downregulation of thyroid hormone synthesis to prevent hyperthyroidism. Failure to escape the Wolff-Chaikoff effect can be seen especially in (premature born) infants and may result in prolonged iodine induced hypothyroidism. We describe a rare case of a preterm infant who developed severe iodinated contrast induced hypothyroidism after the use and prolonged stasis of enteral iodinated contrast media (ICM). In addition a systematic literature search was performed to evaluate all available data on this complication.

Methods: A systematic literature search was performed in PubMed and Embase. Studies describing the effect of enteral ICM on thyroid function were considered eligible. The primary outcome was to determine the frequency of contrast induced hypothyroidism in infants after administration of enteral ICM.

Results: The premature infant in our center developed severe iodinated contrast induced hypothyroidism after enteral ICM. In total, only two studies met our eligibility data, reporting eight patients. Out of these eight patients, four premature infants developed a contrast induced hypothyroidism after enteral administration of ICM.

Conclusion: Data on severity, length and frequency of contrast induced hypothyroidism after exposure to enteral ICM is very scarce. The herein reported case and literature search illustrate the potential severity of the complication and underline the necessity of future studies on this topic. We recommend standardized monitoring of thyroid function after exposure to enteral ICM in newborns to prevent delayed diagnosis of severe contrast induced hypothyroidism until evidence based recommendations can be made.

Objective: To study the national incidence of admission for diabetic ketoacidosis (DKA) in Thai children and adolescents with type 1 diabetes (T1D) and characterize risk factors for DKA admission.

Methods: Admission records of children and adolescents with T1D during the years 2015-2019 were retrieved from the Thai health coverage system of all schemes. Hospitalization was categorized according to patients' age groups (<1, 1-5, 6-12 and 13-17 years), sex and geographical regions (Bangkok, Central, Northeast, North and South). DKA admission incidence and rate were calculated and compared among subgroups.

Results: The annual incidences of T1D and DKA admissions progressively increased over the study period (T1D: 12.0 to 15.0, p<0.001 and DKA: 4.8 to 7.3 per 100,000 child-years, p<0.001). About half of DKA admissions (52%) were recurrent episodes. DKA admission rate was 1.49 admissions/patient. The incidence of DKA admission was greatest in individuals aged 13-17 years (13-17 years: 10.3; 6-12 years: 6.3; 1-5 years: 1.7; and <1 year: 0.6 per 100,000 child-years, p<0.001). DKA admission incidence was greater in females than males (7.6 vs. 4.3 per 100,000 child-years, p<0.001). Among 5 geographical regions, greatest percentage of recurrent DKA (57%), rate of increased annual incidence of DKA admission (3.8 to 7.8 per 100,000 child-years), and DKA admission rate (1.64 admissions/patient) were found in the Northeast region.

Conclusions: During the years 2015-2019, rising annual incidences of T1D and DKA admissions among Thai youth were observed. Individuals older than 6 years, being females, and resided in the Northeast region had higher risk for DKA hospitalization.

Schimke Immuno-Osseous Dysplasia (SIOD) (MIM:242900) is an ultra-rare autosomal recessive pan-ethnic pleiotropic disease. Typical findings of this syndrome are steroid-resistant nephrotic syndrome, cellular immunodeficiency and spondyloepiphyseal dysplasia and facial dysmorphism. Biallelic variants in the SMARCAL1 gene cause SIOD. The five-and-half-year-old female patient was evaluated because of short stature, dysmorphism, hypercalcemia, hypophosphatemia and elevated FSH levels. Karyotype analysis and array-CGH testing were normal. Clinical Exome Sequencing was performed via next-generation sequencing to analyze genes associated with hypophosphatemia. No pathogenic variant was detected. The subsequent detection of proteinuria during her follow-up for cross-fused ectopic left kidney ultimately facilitated the diagnosis of SIOD, although no obvious spondyloepiphyseal dysplasia was detected. Re-analysis of CES revealed a novel homozygous c.2422_2427+9delinsA pathogenic variant in the SMARCAL1. One hundred twenty-five SIOD cases from 38 literature reporting SMARCAL1 gene pathogenic variants were reviewed to investigate whether hypercalcemia, hypophosphatemia and elevated FSH levels had been previously reported in SIOD patients. This review revealed that this was the first time these findings had been reported in a SIOD patient. This report expands not only the phenotypic but also genotypic spectrum of SIOD.

Objective: Endocrine abnormalities may represent the only clinical manifestation of primary mitochondrial disorders. This study aimed to evaluate the endocrinological characteristics of mitochondrial disease in our cohort.

Methods: A total of twenty-six pediatric patients diagnosed with mitochondrial disease were categorized on the basis of their specific genetic abnormalities. The auxologic data, pubertal development, and, based on their clinical symptoms, hormonal profiles were obtained.

Results: Twelve of the cohort of 26 patients (46%) were female. In 15 of the patients (57.6%), their mitochondrial disease (MD) was caused by nuclear DNA mutations (nDNA group). Four patients had Leigh syndrome, 2 patients had LHON syndrome, 2 patients had MELAS, and 1 patient had KSS clinical phenotype. The median age at diagnosis was 2.91 (0.59-16.8) years, and the median age at first endocrinologic evaluation was 4.62 (1.26-18) years. The mean height SDS was -1.34 ± 2.12, and the mean BMI SDS was -0.82 ± 1.96 for all patients. Of the 26 patients, 6 (23%) had a range of hormonal deficits. Ovarian insufficiency, central adrenal insufficiency, central hypothyroidism, diabetes mellitus, and critical illness-related adrenal insufficiency were all observed. Three of the patients were initially monitored in the endocrine clinic for hormone deficiencies but it was later determined that the hormonal abnormalities were caused by underlying mitochondrial disease.

Conclusion: Individuals diagnosed with mitochondrial disease, particularly those with specific genetic abnormalities, are considered a high-risk group for developing hormonal deficits. Endocrine diseases could be one of the primary mitochondrial disorders' early warning symptoms.

Children with diabetes need consistent care across all environments, including school, where they spend significant time.Turkey's Diabetes at School Program, initiated in 2010, has made substantial progress in integrating diabetes care into the school system. The program's achievements include government support, annual awareness activities, communication between diabetes teams and schools, policy implementation, and training for school staff. A recent meeting of Provincial Health Service Officers highlighted ongoing efforts and future directions for the program, emphasizing the importance of continuous support for children with diabetes in educational settings. Key outcomes of this meeting include designated caregivers for children with diabetes at school, optional administration of insulin by trained staff, mandatory diabetes education for teachers, and health-conscious policies for school activities. The program's success is attributed to the collaborative efforts of teachers, healthcare professionals, and government officials. Ensuring robust support for children with diabetes in schools is vital for their well-being and academic success.

Objective: Children with PTEN hamartoma tumor syndrome (PHTS) are at increased risk for developing thyroid abnormalities, including differentiated thyroid carcinoma (DTC). The Dutch PHTS guideline recommends ultrasound surveillance starting from age 18. Since the literature describes PHTS patients who developed DTC before age 18, the Dutch PHTS expertise centre has initiated annual ultrasound surveillance starting from age 12. The purpose of this study was to identify the yield of thyroid ultrasound surveillance in children.

Methods: A retrospective single centre cohort study was conducted. Pediatric PHTS patients who received thyroid ultrasound surveillance before age 18 between 2016-2023 were included. Patients' medical records have been reviewed. Primary outcomes included prevalence and time to develop thyroid nodules ≥10mm, nodular growth, goiter, thyroiditis and DTC. Descriptive statistics and Kaplan-Meier analyses were performed.

Results: Forty-three patients were included. Two patients (5%) were diagnosed with DTC at ages 12 and 17. Both DTCs were identified as minimally invasive follicular carcinoma at stages pT3NxMx and pT1NxMx respectively. A total of 84% were diagnosed with thyroid abnormalities at a median age of 12 years (range 9-18). Most common findings were benign, including nodular disease (74%), goiter (30%) and autoimmune thyroiditis (12%). Nodular growth was observed in 14 patients (33%) resulting in (hemi)thyroidectomy in 7 patients (16%).

Conclusion: Thyroid ultrasound surveillance resulted in the detection of DTC in 2/43 PHTS patients before age 18. These findings support the recommendation to initiate thyroid ultrasound surveillance in children at least from age 12, preferably within an expertise centre.

Autosomal recessive hypophosphatemic rickets (HR) type 2 (ARHR2) is a rare form of HR caused by variant of the gene encoding ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Our patient presented with a history of unsteady gait and progressively bowing legs that had commenced at the age of 1 year. Laboratory tests revealed an elevated level of fibroblast growth factor 23 (FGF23), hypophosphatemia, and a high urine phosphate level. Radiography revealed the typical features of rickets. Next-generation sequencing identified a previously reported c.783C>G (p.Tyr261Ter) and a novel c.1092-42A>G variant in the ENPP1 gene. The patient was prescribed oral phosphates and active vitamin D and underwent guided growth of both distal femora and proximal tibiae commencing at the age of 3 years. No evidence of generalized arterial calcification was apparent during follow-up, and growth rate was satisfactory.

Most cases associated with Hereditary Severe Insulin Resistance Syndrome (H-SIRS) are linked to mutations in the insulin receptor (INSR) gene. Patients with H-SIRS typically manifest symptoms of hyperinsulinemia, insulin resistance, and diabetes mellitus. Other symptoms include impaired glucose regulation, hyperandrogenism, and the presence of acanthosis nigricans (AN). In this report, we present two cases of H-SIRS in female children exhibiting various symptoms, such as hyperinsulinemia, fasting hypoglycemia, postprandial hyperglycemia, overweight, fatty liver, hyperandrogenism, and varying degrees of AN. One patient also presented with mental retardation. Gene sequencing identified specific mutations in the INSR gene for both patients: c.2663A > G (p.Tyr888Cys) and c.38_61del (p.Pro13_Ala20del). These mutations have the potential to disrupt the interaction between INSR and insulin, leading to abnormal insulin signaling, insulin resistance, and various clinical manifestations.

Objective: To determine inequalities in access to diabetes technologies and the effect of socioeconomic factors on families with children with type 1 diabetes.

Methods: In this multicenter cross-sectional study, parents of children with type 1 diabetes completed a questionnaire about household sociodemographic characteristics, latest HbA1c values, continuous glucose monitoring (CGM) and insulin pump use of children, the education and working status of parents. These characteristics were compared between technology use (only-CGM, only-pump, CGM+pump, no technology use).

Results: Among 882 families, only-CGM users, only-pump users, and CGM+pump users compared with no technology users, adjusting for age, sex, region, education levels, number of working parents, and household income. Children living in the least developed region had lower odds of having only-CGM (OR=0.20, 95%CI 0.12-0.34) and having CGM+pump (OR=0.07, 95%CI 0.03-0.22) compared with those living in the most developed region. Children with parents who had not finished high school had lower odds of having only-CGM (Mothers: OR=0.36, 95%CI 0.19-0.66; fathers: OR=0.32, 95%CI 0.18-0.60) or both CGM+pump (OR=0.27, 95%CI 0.11-0.64; fathers: OR=0.34, 95%CI 0.15-0.79) rather than no-technology compared to children whose parents has a university degree. Every $840 increase in the household income increased the odds by 5% for having only-CGM (OR=1.05, 95%CI 1.02-1.09) and CGM+pump (OR=1.05, 95%CI 1.01-1.08).

Conclusion: Socioeconomic factors such as education, regions, and income were associated with inequality in access to technologies. The inequalities are more prominent in access to CGM while CGM had a bigger contribution to glycemic control.