Leptin Concentration, Obesity, and Plasma Non-esterified Fatty Acid Levels in Children

The association between obesity and higher non-esterified fatty acid (NEFA) levels has been established in adults. In contrast, lower NEFA levels have been described in children with obesity although the reason behind this association remains unclear. Leptin, which regulates body weight and plays a role in lipolysis, could be involved in this relationship. We evaluated the influence of leptin in the association between obesity and NEFA concentrations in children, analyzing two cohorts including 684 6- to 8-year-olds and 836 12- to 16-year-old children, respectively. After adjusting by leptin, insulin levels remained significantly higher in adolescents with obesity as compared with levels in those without obesity. However, insulin levels showed no differences between prepubertal children with and without obesity. The significantly lower NEFA concentrations observed in 6- to 8-year-old girls with obesity disappeared when comparing NEFA levels between girls with and without obesity after adjusting by leptin. We report an influence of leptin levels on the association between obesity and insulin and NEFA in young children that is not observed in adolescents. Our findings add information about factors that may contribute to explain the lower NEFA levels described in prepubertal children with obesity.

Altered Cortisol Metabolism Increases Nocturnal Cortisol Bioavailability in Prepubertal Children With Type 1 Diabetes Mellitus

ObjectiveDisturbances in the activity of the hypothalamus-pituitary-adrenal axis could lead to functional alterations in the brain of diabetes patients. In a later perspective of investigating the link between the activity of the hypothalamus-pituitary-adrenal axis and the developing brain in children with diabetes, we assessed here nocturnal cortisol metabolism in prepubertal children with type 1 diabetes mellitus (T1DM).MethodsPrepubertal patients (aged 6–12 years) diagnosed with T1DM at least 1 year previously were recruited, along with matched controls. Nocturnal urine samples were collected, with saliva samples taken at awakening and 30 minutes after awakening. All samples were collected at home over 5 consecutive days with no detectable nocturnal hypoglycaemia. The State-Trait Anxiety Inventory (trait scale only) and Child Depression Inventory were also completed. Glucocorticoid metabolites in the urine, salivary cortisol (sF) and cortisone (sE) were measured by liquid chromatography–tandem mass spectrometry. Metabolic data were analysed by logistic regression, adjusting for sex, age, BMI and trait anxiety score.ResultsUrine glucocorticoid metabolites were significantly lower in T1DM patients compared to controls. 11β-hydroxysteroid dehydrogenase type 1 activity was significantly higher, while 11β-hydroxysteroid dehydrogenase type 2, 5(α+β)-reductase and 5α-reductase levels were all lower, in T1DM patients compared to controls. There was a significant group difference in delta sE level but not in delta sF level between the time of awakening and 30 minutes thereafter.ConclusionsOur findings suggest that altered nocturnal cortisol metabolism and morning HPA axis hyperactivity in children with T1DM leads to greater cortisol bioavailability and lower cortisol production as a compensatory effect. This altered nocturnal glucocorticoid metabolism when cortisol production is physiologically reduced and this HPA axis hyperactivity question their impact on brain functioning.

Suggested Cutoff Point for Testosterone by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) after Stimulation with Recombinant Human Chorionic Gonadotropin

The human chorionic gonadotropin (hCG) stimulation test that evaluates gonadal steroidogenesis is crucial in the assessment of patients with 46,XY disorders of sex development (DSD). This study aimed to determine a testosterone (T) cutoff level that indicates an adequate testicular function using LC-MS/MS after stimulation with recombinant human chorionic gonadotropin (rhCG) in a single dose. Nineteen prepubertal children with 46,XY DSD and normal T secretion were evaluated. T and dihydrotestosterone (DHT) levels were measured by liquid chromatography technique with tandem mass spectrometry (LC-MS/MS) before and 7 days after rhCG application at 250 µg. We suggest 0.89 ng/mL as the cutoff point for T after rhCG stimulation analyzed by LC-MS/MS.

Graves Disease in Childhood

Graves’ disease (GD) is an autoimmune disease caused by autoantibodies against thyroid stimulating hormone receptor (TSH-R), resulting in stimulation of thyroid gland and overproduction of thyroid hormones resulting in clinical manifestations. It is uncommon in children and is 6 times more prevalent in females. The symptomatology, clinical and biochemical severity are a function of age of onset of disease. Prepubertal children tend to present with weight loss and bowel frequency, associated with accelerated growth and bone maturation. Older children are more likely to present with the classical symptoms of thyrotoxicosis like palpitations, tremors and heat intolerance. Prepubertal children tend to have a more severe disease, longer duration of complaints and higher thyroid hormone levels at presentation than the pubertal and postpubertal children. The non-specificity of some of the symptoms in pediatric age group can lead to children being initially seen by other specialities before being referred to endocrinology. Management issues are decided based on patient’s priorities and shared decision making between patient and treating physician. Radioactive Iodine Ablation is preferred when there is relatively higher value placed on Definitive control of hyperthyroidism, Avoidance of surgery, and potential side effects of ATDs. Similarly Antithyroid drugs are chosen when a relatively higher value is placed on possibility of remission and avoidance of lifelong thyroid hormone treatment, Avoidance of surgery, Avoidance of exposure to radioactivity. Surgery is preferred when access to a high-volume thyroid surgeon is available and a relatively higher value is on prompt and definitive control of hyperthyroidism, avoidance of exposure to radioactivity and avoidance of potential side effects of ATDs. Continental differences with regards to management do exist; radio-iodine ablation being preferred in North America while Anti-thyroid drug treatment remains the initial standard care in Europe.

Increased hepcidin levels and non-alcoholic fatty liver disease in obese prepubertal children: a further piece to the complex puzzle of metabolic derangements

Introduction Several studies on obese youths and adults have reported increased hepcidin levels, which seems to be related to metabolic and iron metabolism alterations. The complete mechanisms involved in hepcidin increase remain to be elucidated, and particularly its role in the development of other known complications such as Nonalcoholic Fatty Liver Disease (NAFLD). NAFLD in prepubertal children might be of special interest in understanding the underlying mechanisms. Methods Anthropometric measurements, liver ultrasonography, lipid profile, liver function, oxidative stress, inflammatory state, and iron metabolism were studied in 42 obese prepubertal children and 33 healthy controls. We, therefore, evaluated the presence of possible correlations between Hepcidin and the other metabolic variables, and the possible association between NAFLD and iron metabolism. Results Hepcidin levels were significantly increased in the obese prepubertal children (p=0.001) with significant differences between obese children with and without NAFLD (p=0.01). Blood iron was lower in obese children (p=0.009). In the obese group, a negative correlation between hepcidin and both blood iron levels (p=0.01) and LagPHASE (p=0.02) was found. In addition, a positive association between hepcidin and NAFLD (p=0.03) was detected. Conclusions We suggest that an increase in hepcidin levels may represent an early step in iron metabolism derangements and metabolic alterations, including NAFLD, in prepubertal obese children.

Investigating whether serum IGF-1 and IGFBP-3 levels reflect the height outcome in prepubertal children upon rhGH therapy: LG growth study database

Serum insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3) levels can be used to monitor the safety of recombinant human growth hormone (rhGH) therapy. In this study, we evaluated the changes in serum IGF-I and IGFBP-3 levels during rhGH therapy as a marker of height outcome in prepubertal children. Totally, 705 prepubertal children with short stature were enrolled from the LG Growth Study Database. Data for three groups of subjects were obtained as follows: Idiopathic GH deficiency (IGHD; n = 486); idiopathic short stature (n = 66); small for gestational age (n = 153). Serum IGF-I and IGFBP-3 levels at the baseline and after the 1st and 2nd year of rhGH therapy, as well as the Δheight standard deviation score (SDS), were obtained. Δheight SDS after the 1st and 2nd year of rhGH therapy had notably increased compared to that at the baseline for all three groups. IGF-I and IGFBP-3 levels in all three groups were significantly increased compared to those at the baseline (p <0.001). Δheight SDS was positively correlated with ΔIGF-1 SDS after the 1st year of therapy, ΔIGFBP-3 SDS after the 2nd year of therapy in the IGHD group, and ΔIGF-I SDS and ΔIGFBP-3 SDS after the 2nd year of therapy (p < 0.05), regardless of whether the height at the baseline was a covariate. The increase in IGF-I and IGFBP-3 levels during rhGH therapy was related to the growth response in children with IGHD. Therefore, it may be valuable to measure the change in serum IGF-I and IGFBP-3 levels, especially the latter, during rhGH treatment to predict the growth response upon long-term treatment.

Effects of cyproheptadine on body weight gain in children with nonorganic failure to thrive in Taiwan: A hospital-based retrospective study

Failure to thrive (FTT) impairs the expected normal physical growth of children. This study aimed to evaluate the effects of cyproheptadine hydrochloride on growth parameters in prepubertal children with FTT. The medical records of prepubertal children who were newly diagnosed with FTT at China Medical University Hospital between 2007 and 2016 were retrospectively examined. The patients were divided into two groups depending on whether they had (T-group) or had not (NT-group) received cyproheptadine hydrochloride (0.3 mg/kg daily) for at least 14 days. The mean length of the treatment period was 97.22 days (range: 14–532 days). Weight, height, and body mass index were adjusted for age using the median values in the growth charts for Taiwanese boys and girls as the reference. A total of 788 patients aged 3–11 years were enrolled, 50 in the T-group and 738 in the NT-group. No statistically significant difference in the median age-adjusted weight value was noted between the T-group and NT-group during the follow up period. In the T-group, age-adjusted weight and body mass index were inversely associated with age (P <0.001, P <0.001) and positively associated with medication duration (P = 0.026, P = 0.04). Our findings underscore the positive association between cyproheptadine hydrochloride treatment and weight gain among prepubertal children. Further prospective clinical studies with a. longer and consistent treatment course is warranted.