Despite the optimization of replacement therapy, adrenal crises still represent life-threatening emergencies in many children with adrenal insufficiency.
We summarized current standards of clinical ...practice for adrenal crisis and investigated the prevalence of suspected/incipient adrenal crisis, in relation to different treatment modalities, in a group of children with adrenal insufficiency.
Fifty-one children were investigated. Forty-one patients (32 patients <4 yrs and 9 patients >4 yrs) used quartered non-diluted 10 mg tablets. Two patients <4 yrs used a micronized weighted formulation obtained from 10 mg tablets. Two patients <4 yrs used a liquid formulation. Six patients >4 yrs used crushed non-diluted 10 mg tablets. The overall number of episodes of adrenal crisis was 7.3/patient/yr in patients <4yrs and 4.9/patient/yr in patients >4 yrs. The mean number of hospital admissions was 0.5/patient/yr in children <4 yrs and 0.53/patient/yr in children >4 yrs. There was a wide variability in the individual number of events reported. Both children on therapy with a micronized weighted formulation reported no episode of suspected adrenal crisis during the 6-month observation period.
Parental education on oral stress dosing and switching to parenteral hydrocortisone when necessary are the essential approaches to prevent adrenal crisis in children.
Context: Obesity and iron deficiency are two of the most common nutritional disorders worldwide. Several studies found higher rates of iron deficiency in obese than in normal-weight children. ...Hepcidin represents the main inhibitor of intestinal iron absorption, and its expression is increased in adipose tissue of obese patients. Leptin is able, in vitro, to raise hepcidin expression.
Objectives: Aims of this work were 1) to assess the association between poor iron status and obesity, 2) to investigate whether iron homeostasis of obese children may be modulated by serum hepcidin variations, and 3) to assess the potential correlation between leptin and serum hepcidin variations.
Methods: Iron status and absorption as well as hepcidin, leptin, and IL-6 levels were studied in 60 obese children and in 50 controls.
Results: Obese children showed lower iron and transferrin saturation (both P < 0.05) and higher hepcidin levels (P = 0.004) compared with controls. A direct correlation between hepcidin and obesity degree (P = 0.0015), and inverse correlations between hepcidin and iron (P = 0.04), hepcidin and transferrin saturation (P = 0.005), and hepcidin and iron absorption (P = 0.003) were observed. A correlation between leptin and hepcidin (P = 0.006) has been found. The correlation remained significant when adjusted for body mass index, sex, pubertal stage, and IL-6 values.
Conclusions: We propose that in obese patients, increased hepcidin production, at least partly leptin mediated, represents the missing link between obesity and disrupted iron metabolism.
Increased hepcidin production, at least partly leptin mediated, can represent the missing link between obesity and disrupted iron metabolism in childhood obesity.
Neck ultrasound (nUS) is the cornerstone of clinical management of thyroid nodules in pediatric patients, as well as adults. The current study was carried out to explore and compare the diagnostic ...performance of the main US-based risk stratification systems (RSSs) (i.e., the American College of Radiology (ACR), European (EU), Korean (K) TI-RADSs and ATA US RSS criteria) for detecting malignant thyroid lesions in pediatric patients. We conducted a retrospective analysis of consecutive children and adolescents who received a diagnosis of thyroid nodule. We included subjects with age <19 years having thyroid nodules with benign cytology/histology or final histological diagnosis. We excluded subjects with (a) a previous malignancy, (b) a history of radiation exposure, (c) cancer genetic susceptibility syndromes, (d) lymph nodes suspicious for metastases of thyroid cancer at nUS, (e) a family history of thyroid cancer, or (f) cytologically indeterminate nodules without histology and nodules with inadequate cytology. We included 41 nodules in 36 patients with median age 15 years (11–17 years). Of the 41 thyroid nodules, 29 (70.7%) were benign and 12 (29.3%) were malignant. For both ACR TI-RADS and EU-TIRADS, we found a sensitivity of 41.7%. Instead, for both K-TIRADS and ATA US RSS, we found a sensitivity of 50%. The missed malignancy rate for ACR-TIRADS and EU-TIRADS was 58.3%, while that for K-TIRADS and ATA US RSS was 50%. The unnecessary FNA prevalence for ACR TI-RADS and EU-TIRADS was 58.3%, while that for K-TIRADS and ATA US RSS was 76%. Our findings suggest that the four US-based RSSs (i.e., ACR-TIRADS, EU-TIRADS, K-TIRADS, and ATA US RSS) have suboptimal performance in managing pediatric patients with thyroid nodules, with one-half of cancers without indication for FNA according to their recommendations.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Background Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of ...puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls. Results Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin). Conclusions The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.
Puberty is a critical process characterized by several physical and psychological changes that culminate in the achievement of sexual maturation and fertility. The onset of puberty depends on several ...incompletely understood mechanisms that certainly involve gonadotropin-releasing hormone (GnRH) and its effects on the pituitary gland. The role of makorin ring finger protein 3 (MKRN3) in the regulation of pubertal timing was revealed when loss-of-function mutations were identified in patients with central precocious puberty (CPP), which to date, represent the most commonly known genetic cause of this condition. The
MKRN3
gene showed ubiquitous expression in tissues from a broad spectrum of species, suggesting an important cellular role. Its involvement in the initiation of puberty and endocrine functions has just begun to be studied. This review discusses some of the recent approaches developed to predict MKRN3 functions and its involvement in pubertal development.
A polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood ...and childhood obesity. Aims of this study were i) to analyse in a large group of obese children the role of the interaction of not-genetic factors such as BMI, waist circumference (W/Hr) and insulin resistance (HOMA-IR) in exposing the association between the I148M polymorphism and ALT levels and ii) to stratify the individual risk of these children to have liver injury on the basis of this gene-environment interaction.
1048 Italian obese children were investigated. Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M variant genotyped.
Children carrying the 148M allele showed higher ALT and AST levels (p = 0.000006 and p = 0.0002, respectively). Relationships between BMI-SDS, HOMA-IR and W/Hr with ALT were analysed in function of the different PNPLA3 genotypes. Children 148M homozygous showed a stronger correlation between ALT and W/Hr than those carrying the other genotypes (p: 0.0045) and, therefore, 148M homozygotes with high extent of abdominal fat (W/Hr above 0.62) had the highest OR (4.9, 95% C. I. 3.2-7.8, p = 0.00001) to develop pathologic ALT.
We have i) showed for the first time that the magnitude of the association of PNPLA3 with liver enzymes is driven by the size of abdominal fat and ii) stratified the individual risk to develop liver damage on the basis of the interaction between the PNPLA3 genotype and abdominal fat.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Delayed puberty is a common reason of pediatric endocrinological consultation. It is often a self-limited (or constitutional) condition with a strong familial basis. The type of inheritance is ...variable but most commonly autosomal dominant. Despite this strong genetic determinant, mutations in genes implicated in the regulation of hypothalamic–pituitary–gonadal axis have rarely been identified in cases of self-limited delayed puberty and often in relatives of patients with congenital hypogonadotropic hypogonadism (i.e.,
FGFR1
and
GNRHR
genes). However, recently, next-generation sequencing analysis has led to the discovery of new genes (i.e.,
IGSF10, HS6ST1, FTO
, and
EAP1
) that are implicated in determining isolated self-limited delayed puberty in some families. Despite the heterogeneity of genetic defects resulting in delayed puberty, genetic testing may become a useful diagnostic tool for the correct classification and management of patients with delayed puberty. This article will discuss the benefits and the limitations of genetic testing execution in cases of delayed puberty.
DLK1 gene is considered a molecular gatekeeper of adipogenesis. DLK1 mutations have been reported as a cause of central precocious puberty associated with obesity and metabolic syndrome with ...undetectable DLK1 serum levels. We investigated the association between DLK1 circulating levels with clinical and biochemical parameters in obese adolescents and healthy controls.
Sixty-five obese adolescents and 40 controls were enrolled and underwent a complete clinical examination and biochemical assessment for glucose homeostasis and DLK1 plasma levels.
We observed lower DLK1 levels in cases compared to controls. Moreover, we found a negative correlation between DLK1 and HOMA-IR and a direct correlation with insulin-sensitivity index.
Our findings suggest that DLK1 might be involved in metabolic derangement in obese children.
PDF
