Volume 34, Issue 8

Objectives Gonadotropin-releasing hormone analogs are the treatment of choice for central precocious puberty (CPP). This study characterizes patients treated with histrelin implant or leuprolide injection. Methods A US claims database was used to identify patients aged ≤20 years with ≥1 histrelin or leuprolide claim (index treatment) between April 2010 and November 2017 and continuous enrollment ≥3 months before and ≥12 months after the index treatment date. Results Overall, 4,217 patients (histrelin, n=1,001; leuprolide, n=3,216) were identified. The percentage of patients with CPP diagnosis was greater in the histrelin (96.5%) vs. leuprolide (68.8%; p<0.0001) cohort. In patients with CPP (histrelin, n=966; leuprolide, n=2,214), mean age at treatment initiation was similar for histrelin (9.0 ± 2.0 years) and leuprolide (9.1 ± 2.3 years), with >50% of patients aged 6–9 years. Mean treatment duration was significantly longer for histrelin (26.7 ± 14.8 months) vs. leuprolide (14.1 ± 12.1 months; p<0.0001), and was longer in younger patient groups. More patients switched from leuprolide to histrelin (12.3%) than vice versa (3.6%; p<0.0001). Median annual total treatment costs were slightly lower for the histrelin cohort ($23,071 [interquartile range, $16,833–$31,050]) than the leuprolide cohort ($27,021 [interquartile range, $18,314–$34,995]; p<0.0001). Conclusions Patients with CPP treated with histrelin had a longer duration of treatment, lower rates of index treatment discontinuation, and lower annual treatment costs vs. those treated with leuprolide.

Objectives Obesity is often the result of a high-calorie and unbalanced diet for a long time and can sometimes be associated with hyperphagia and eating disorders. Neurotensin (NT) is an anorexigenic peptide, which is secreted from the central nervous system and intestines, and increases intestinal fat absorption. In the literature, conflicting results regarding serum NT level in obesity and the relation of NT with metabolic parameters were reported. Besides, there is no data regarding the relation of NT with eating disorders or food preference in obese individuals. We aimed to evaluate the relation of serum NT level with metabolic parameters, hyperphagia, binge eating disorder (BED) and food preference in obese adolescents. Methods The study included 65 obese adolescents and 65 healthy controls. Anthropometric measurements, biochemical analyzes and body fat analyzes were performed in all cases. Hyperphagia score, presence of BED and three-day food intake records were also evaluated. Results NT level was significantly higher in obese adolescents than in controls and it was not associated with metabolic parameters, hyperphagia or food preference. In the obese group, NT level was not significantly different according to the presence of BED. Conclusions Serum NT level is high in obese adolescents; however, it is not associated with metabolic parameters, hyperphagia, BED or food preference.

Objectives Bone can act as an endocrine organ through the secretion of bone-specific hormones, i.e., osteokines. Recent research has demonstrated that lipocalin 2 (LCN2) secreted by osteoblasts are part of an important endocrine system that is finely tuned with other organs to ensure homeostatic balance and health. The aim of this study was to explore the association between bone and glucose metabolism in adolescents with obesity and type 2 diabetes mellitus (DM2). Methods The participants were 8 adolescents with DM2 (5 males, 3 females; age: 17.0 (14.0–20.0) years, median (interquartile range)), 14 adolescents with simple obesity (9 males, 5 females; age: 13.5 (12.4–15.5) years), and 15 controls (6 males, 9 females; age: 13.3 (11.0–15.0) years). Serum LCN2 and under-carboxylated osteocalcin (un-OC) levels were measured using enzyme-linked immunosorbent assays. Results The LCN2 levels were higher in patients with DM2 (58.1 (34.2–95.0) ng/mL; median (interquartile range)), but not in those with obesity (30.8 (23.1–38.3) ng/mL), when compared to the controls (18.2 (9.8–25.7) ng/mL). In the whole study group overall, serum LCN2 was positively correlated with the Model Assessment of Insulin Resistance score ( r =0.339, p=0.046) and body mass index ( r =0.580, p<0.0001), and negatively correlated with adiponectin ( r =−0.462, p=0.005). A multiple stepwise regression model showed that serum adiponectin was an independent predictor of serum LCN2. Conclusions The results of this study indicate that further investigations are warranted to determine whether LCN2 may act as a sensitive indicator of early-stage insulin resistance.

Objectives Hashimoto’s thyroiditis (HT) is the most common cause of goiter and acquired hypothyroidism in children and adolescents, especially in areas without endemic iodine deficiency. We aimed to evaluate the follow-up results of children and adolescents diagnosed with HT, including clinical, biochemical, and radiological findings and treatment approaches. Methods HT patients, who were diagnosed between 2012 and 2018 years in a single-center, were assessed retrospectively. Results Two hundred and twenty-four cases were included in the study, 75.9% of whom were girls (female/male ratio: 3.1) and 66.5% were pubertal. The median age of the cases at first admission was 12.5 (9.2–15) years. The median follow-up period of 196 patients, who continued their follow-up regularly, was 2.1 (0.7–4.8) years. When autoantibody levels were analyzed according to gender, mean anti-Tg levels were higher in girls (p=0.028), whereas anti-TPO levels were similar (p=0.372). A nodule was detected in the ultrasonographic follow-up of 29 (13%) patients. Papillary thyroid carcinoma was observed in 10.3% (n=3) of those with nodules. When the last ultrasonography findings of 188 patients with available radiological follow-up data were compared with their initial evaluation, the rate of heterogeneous parenchymal echogenicity increased significantly (p=0.008). The need for l -thyroxine dosage augmented over time. Conclusions Although HT is more common in adolescent girls, it can be encountered in both genders and at all ages in childhood. The incidence of malignancy was not higher in patients with nodules associated with HT than the reported incidences of malignancy in nodules not associated with HT.

Objectives Obesity is a growing problem in type 1 diabetes mellitus (T1DM) today. The aim of our study is to determine the frequency of overweight/obesity at the time of diagnosis and during follow-up in children with T1DM as well as review the conditions that may accompany. Methods A total of 315 patients with T1DM were retrospectively analyzed. The patients were divided into two groups as normal weight and overweight/obese. The two groups were compared in terms of age at diagnosis, birth weight, anthropometric measurements, insulin dose used and blood pressure measurements, and insulin, c-peptide, hemoglobin A1c, triglyceride, and high-density lipoprotein levels at the time of diagnosis and follow-up. Results The height, weight and body mass index standard deviation (BMI SD) scores, and c-peptide levels at the time of diagnosis of the overweight/obese group were higher than those with normal weight (p<0.001 and p = 0.008, respectively). The frequency of dyslipidemia and hypertension was higher in the overweight/obese group than in the normal weight group [18.2 vs. 5% (p = 0.015) and 10 vs. 1.5% (p = 0.003), respectively]. Conclusions In our study, the fact that the overweight/obese group had higher BMI and c-peptide and lower HDL values at the time of diagnosis can be evaluated as indicators that insulin resistance syndrome can accompany T1DM from the beginning (double diabetes). When determining the treatment and follow-up strategies of patients with T1DM, considering the risk of obesity and taking the necessary precautions is very important in terms of morbidity.

Objectives To evaluate anthropometric measures (AM) and insulin resistance (IR) association in adolescents aged 12–17 years and investigates how body mass index (BMI) interrelates with specific indicators of fat distribution in this association. Methods This analysis is from the Study of Cardiovascular Risks in Adolescents (ERICA) study, a national, cross-sectional study. AM was categorized by quartiles, and their means and 95% confidence intervals (95% CI) were estimated. The prevalence of IR was estimated for each AM according to the quartiles. The associations between AM and homeostatic model assessment of insulin resistance (HOMA-IR) levels were analyzed using Poisson models. Results 37,892 adolescents were included. IR prevalence tended to increase as quartiles increased for each AM. The association of BMI with IR persisted with the adjustment for others AM. The greatest reduction in the association’s strength was achieved with the adjustment by the waist circumference (WC) and the waist-to-height ratio (WHtR). Most other AM were also associated with IR. Conclusion AM has a positive association with the prevalence of IR, and the joint effect of BMI and central adiposity measures should be considered in cardiometabolic risk evaluation in adolescents.

Objectives Premature adrenarche may be associated with an intrauterine programmed metabolic syndrome which should be considered as a warning sign for coronary heart disease due to accelerated atherosclerosis, hypertension, type 2 diabetes mellitus (DM), and polycystic ovary syndrome. Methods Seventy-three patients with premature adrenarche were evaluated for metabolic parameters and aortic elasticity to evaluate the susceptibility to atherosclerosis and compared with a control group. The patients were examined in two groups as overweight and nonoverweight, and metabolic and cardiac parameters were also compared among these groups. Strain, distensibility, and stiffness index parameters were used to evaluate aortic elasticity. Results Biochemical parameters and cardiac measurements were not statistically different between patients and controls. They also did not differ between patients with normal weight and overweight groups. Atherogenic index and insulin resistance were closely related and a positive correlation between cholesterol and triglyceride, and ascending aortic stiffness was found. Conclusions The results may suggest that cholesterol and triglyceride-related arterial involvement is more involved in the pathogenesis of arterial stiffness. It can be considered that ‘being overweight’ or ‘having metabolic profile characterized by insulin resistance and dyslipidemia’ are the major coexisting factors influencing the vascular structure, rather than increased androgens and premature adrenarche itself.

Objectives Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by a deficiency in aldolase B that can result in hypoglycemia, nausea, vomiting, abdominal pain, liver and kidney dysfunction, coma, and even death. This study aims to represent the clinical features and molecular genetic analysis data of the patients diagnosed with HFI in our study population. Methods The medical records of the 26 patients with HFI were evaluated retrospectively. Age, gender, clinical findings, metabolic crises, and the results of molecular analyses were recorded. Results The patients with HFI had a good prognosis and the aversion to sugar-containing foods was the main complaint. Seven different variants were identified in the Aldolase B ( ALDOB ) gene in HFI patients. The most frequent mutations were p.Ala150Pro, p.Ala175Asp had a prevalence of 61 and 30%, respectively, in agreement with the literature and other known variants were found with minor frequencies c.360-363del4(3.8%), p.Asn335Lys(3.8%), and three novel mutations c.113-1_15del4 (3.8%), p.Ala338Val(7.6%), and p.Asp156His(3.8%) were identified at a heterozygous, homozygous, or compound heterozygous level. Conclusions This study results revealed three novel mutations in patients with HFI. On the basis of age of presentation, clinical symptoms, and metabolic crisis, there was no clear-cut genotype-phenotype correlation. This article also demonstrates the importance of screening suspected infants in cases of acute liver failure for prompt diagnosis and treatment of HFI.

Objectives Medium-chain (MCA) and long-chain acylcarnitine (LCA) blood concentrations play a significant role in the fatty acid (FA) oxidation process, especially during the first days of life. Identification of their abnormal concentrations, via expanded newborn screening, can lead to the diagnosis of FA oxidation disorders. This study aimed to demonstrate MCA and LCA concentrations in Dried Blood Spots (DBS) of full-term breastfed infants, in relation to their birth weight (BW) perinatally. Methods Breastfed full-term infants (n = 12,000, 6,000 males, 6,000 females) with BW 2,000–3,999 g were divided into four equal groups: Group A, 2,000–2,499 g, B 2,500–2,999 g, C 3,000–3,499 g, and D 3,500–3,999 g. Samples were collected as DBS and acylcarnitines were determined via a liquid chromatography tandem mass spectrometry method. Results MCA and LCA blood concentrations were determined significantly lower in group A (low birth weight infants) in both sexes. Infants with BW > 3,500 g (group D), were characterized by lower levels of C10, C10:1, C14, C14:1 acylcarnitines and higher levels of C16 and C18:1 acylcarnitines, as compared to the other groups of this study. Conclusions Concentration patterns in full-term breastfed newborns in relation to sex and mainly BW found in this study could be very helpful for neonatologists, especially for newborns of group A.

Objectives To analyse the prevalence and association between metabolic syndrome (MetS), clustered cardiometabolic risk (CCMR), obesity (body mass index [BMI], fat mass [FM] and waist circumference [WC]), and cardiorespiratory fitness (CRF); and to assess whether obesity (BMI, FM, and WC) acts as a mediator between CRF and MetS or CCMR. Methods This cross-sectional study included a subsample of the AFINA-te Study (n = 209; 11.51 ± 0.72 years old). BMI, FM, and WC were assessed. The Course-Navette test was used to assess CRF. MetS was calculated following the International Diabetes Federation (IDF) definitions, and assessed using WC, triglycerides (TGs), high density lipoprotein (HD), fasting glucose (FG), and systolic and diastolic blood pressures (SBP/DBP). CCMR was calculated based on the sex and age-specific z score. Results The prevalence of overweightness, obesity, MetS, and CCMR were 17.22, 1.44, 5.74, and 18.36%, respectively. After including BMI, FM, or WC into the model, the association between CRF and MetS was no longer significant, and the association between CRF and CCMR was only significant when it was mediated by BMI (β = −0.006; p = 0.026). The rest of the analysis of the mediation did not show a direct effect, although a significant indirect effect with a significant value for the Sobel test was observed (all p < 0.001). Conclusions BMI, FM, and WC act as full mediators in the association between CRF and MetS; FM and WC act as full mediators in the association between CRF and CCMR; and BMI acts as a partial mediator. The use of FM or WC as obesity variables is recommended.

Objectives Hyperinsulinism is the most common cause of recurrent hypoglycemia in infants, with transient and permanent forms. Currently, there are no effective tools to predict severity and time to resolution in infants with transient hyperinsulinism (tHI). Therefore, our objective was to assess whether early glucose trends predict disease duration in tHI. Methods A retrospective, pilot cohort of infants admitted with tHI was phenotyped for clinical and laboratory parameters. Blood glucose (BG) values were collected from the first documented hypoglycemia for 120 h (five days). Results In 27 neonates with tHI, the presence of fetal distress (p=0.001) and higher mean daily BG (p=0.035) were associated with shorter time to resolution of hypoglycemia. In a further sensitivity analysis that grouped the cohort by the presence or absence of fetal distress, we found that in neonates without fetal distress, lower mean daily glucose was associated with longer disease duration (R 2 =0.53, p=0.01). Conclusions Our pilot data suggests that predictors for disease duration of tHI may be elicited in the first week of life, and that tHI associated with fetal distress may represent a distinct clinical entity with a shorter time course.

Objectives Hyperglycemic hyperosmolar state (HHS) is one of the most severe acute complications of diabetes mellitus (DM) characterized by severe hyperglycemia and hyperosmolality without significant ketosis and acidosis. What is new? Since HHS in the pediatric population is rare and potentially life-threatening, every reported case is very valuable for raising awareness among healthcare professionals. Case presentation A 7-year-old boy with previously diagnosed Joubert syndrome was admitted due to vomiting, polydipsia and polyuria started several days earlier. He was severely dehydrated, and the initial blood glucose level was 115 mmol/L. Based on clinical manifestations and laboratory results, he was diagnosed with T1DM and HHS. The treatment with intravenous fluid was started and insulin administration began later. He was discharged after 10 days without any complications related to HHS. Conclusions Since HHS has a high mortality rate, early recognition, and proper management are necessary for a better outcome.

Objectives Wolfram syndrome (WS) is a rarely seen autosomal recessive multisystem neurodegenerative disorder caused by mutations in the WFS1 gene. Case Presentation Three sisters with WS had diabetes mellitus (DM) at 4 years of age and optic atrophy. In addition, the first case had hearing impairment, and the second case had diabetes insipidus and urinary incontinence. Linagliptin was administered to the first case as add-on therapy to intensive insulin treatment 15 years after the onset of DM, and her insulin need showed a dramatic decrease. The third case had a remission phase one month after the onset of DM. Conclusions Even in cases with the same mutation, symptoms and findings may widely vary in WS. Remission of diabetes has rarely been reported in WS. Also, this report describes the first trial of a dipeptidyl peptidase-4 inhibitor in a patient with WS which provided a decrease in exogenous insulin need.

Objectives Nutritional rickets may be a preventable cause of craniosynostosis. This potential association is under-recognised. A late diagnosis of craniosynostosis may result in reduced brain growth, raised intracranial pressure and long-term psychosocial problems. Case presentation We present four cases of craniosynostosis associated with nutritional rickets. Those who had delayed presentation underwent emergency craniotomy. Conclusions Treatment of nutritional rickets and early identification of craniosynostosis can reduce morbidity in these children.

Objectives Childhood obesity can lead to acute and chronic comorbidities and adult obesity, highlighting the need for prompt intervention. Families and caregivers play a vital role in treatment and when primary interventions fail, this may become a child protection issue. Case presentation We present two cases of severe childhood obesity where targeted lifestyle interventions failed to impact weight status. Both cases feature child welfare involvement with patients coming into the care of the local authority (under s20 of the Children Act 1989). Foster placement resulted in significant weight loss and improved BMI achieved through reduced portions, healthier choices, restricted calories to recommended daily intake for age and increased activity. Physical and emotional wellbeing benefits were observed and improvements in obesity related comorbidities. Conclusions Failure to reduce a child’s weight alone does not constitute a child protection issue. In severe cases, where maximum intervention has failed and when the child has obesity related comorbidites or at a higher risk of developing them, home environment change should be considered in the child’s best interest as a treatment for severe childhood obesity.