Band 29, Heft 12

Background: The diagnosis of non-alcoholic fatty liver disease (NAFLD) is usually based on liver ultrasonography and serum alanine aminotransferase (ALT) levels. However, the serum ALT level is not sensitive for detecting NAFLD. If more serum markers are available, serum analysis may play a more important role in the diagnosis of NAFLD. Methods: Here, we have investigated whether vascular endothelial cadherin (VE-cad) and thrombomodulin (TM) are markers of NAFLD in children. After an examination of liver ultrasonography, 90 children were divided into a lean control group (n=32), an overweight/obese NAFLD group (group-NAFLD, n=34) and an overweight/obese non-NAFLD group (group-SOO, n=24). Results: Two overweight/obese groups had similar obesity. However, serum VE-cad and TM levels were increased in group-NAFLD but not group-SOO. When data from all children were pooled, serum VE-cad and TM levels were positively correlated to body-mass index (BMI) and serum ALT levels. Conclusions: In conclusion, VE-cad and TM are markers of pediatric NAFLD.

Background: The aim of the study was to investigate the association among elevated serum ferritin, metabolic syndrome (MetS) and ‘elevated alanine aminotransferase (ALT) levels beyond healthy-range limits’ in children and adolescents. Methods: We analyzed data from 4855 subjects (2579 male) aged 10–19 who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) (2007–2012). Results: The prevalence of MetS and ‘elevated ALT’ tended to increase with an increase in the serum ferritin quartile (p-value for trend: all <0.05). The odds ratios (ORs) for MetS in serum ferritin quartile-Q4 compared to ferritin quartile-Q1 was 1.59 (1.01, 2.55) in females after adjusting for age, body mass index (BMI), and insulin resistance. The ORs for ‘elevated ALT’ in ferritin quartile-Q4 compared to ferritin quartile-Q1 were 4.45 (2.18, 9.10) in male and 3.10 (1.70, 5.66) in female subjects after adjusting for other covariates. Conclusions: The independent association between elevated serum ferritin and MetS (or ‘elevated ALT’) begins in children and adolescents.

Background: Excessive use of fructose has been incriminated as a risk factor for hepatic steatosis. Procollagen type III N-terminal peptide (P3NP) is a marker for steatohepatitis. Thus, we aimed to assess fructose intake in obese children and its relation to nonalcoholic fatty liver disease (NAFLD) and P3NP. Methods: Fifty-five obese children were compared to 30 controls. All were subjected to dietary fructose and anthropometric assessment, fasting blood sugar (FBS), fasting insulin (FI) and homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, uric acid, alanine aminotransferase (ALT), P3NP and abdominal ultrasound. Results: Patients had higher fructose intake which was associated with increased NAFLD grade. There was an increase in P3NP with increased NAFLD grade. P3NP correlated positively with fructose intake (processed sources and total) and caloric intake. Conclusions: High fructose intake is associated with NAFLD and P3NP may serve as a marker of NAFLD in obese children with a proposed cutoff value of 8.5 ng/mL.

Background: Central diabetes insipidus (CDI) is a heterogeneous disease caused by arginine vasopressin deficiency; its management implies a profound understanding of the pathophysiology and the clinical spectrum. The aim of the study was to describe the clinical characteristics that indicate organicity in children and adolescents with central diabetes insipidus treated at the Department of Endocrinology from The Child Health’s Institute during 2001 to 2013. Methods: Cross-sectional, retrospective study. 79 cases of patients diagnosed with CDI (51 males and 28 females) from 1 month to 16 years of age were reviewed. For the descriptive analysis, measures of central tendency and dispersion were used; groups of organic and idiopathic CDI were compared using χ 2 -test and t-test. A p-value<0.05 was considered significant. Results: The average age of patients was 8.1±4.2 years. Organic causes were intracranial tumors, 44 (55.7%), Langerhans cell histiocytosis (LCH), 11 (13.9%) and cerebral malformations in 7 (8.9%) patients, while the idiopathic group was 14 (17.7%) patients. Regarding clinical characteristics suggestive of organicity, headache (p=0.02) and visual disturbances (p=0.01) were found statistically significant. The anterior pituitary hormonal abnormalities were documented in 34 (52.3%) organic CDI patients. Furthermore, we did not find a significant difference in the average daily dose of desmopressin between patients with permanent vs. transitory CDI (0.81±0.65 vs. 0.59±0.62; p=0.363). Conclusions: The main clinical features suggestive of organicity in pediatric patients with central diabetes insipidus were headache and visual disturbances; furthermore, anterior pituitary hormonal abnormalities suggest an underlying organic etiology.

Background: The objective of the study was to analyze salivary flow rate, urea concentration, and buffer capacity in adolescents with type 1 diabetes mellitus (type 1 DM) in two different stages. Methods: This study was performed on adolescents (14–19 years), allocated between two groups: type 1 DM group comprised 32 adolescents with type 1 DM, and non-type 1 DM group comprised 32 nondiabetics. The adolescents in type 1 DM group were evaluated at a baseline (T0) and after 15 months (T1), and those in non-type 1 DM group were only evaluated at T0. Diabetic status was determined by glycosylated hemoglobin (GHb) and capillary glucose tests. Measurement of salivary flow was performed by means of stimulated saliva (SSFR) collection. The buffer capacity (BC) was determined, and analysis of urea salivary concentration was performed using the colorimetric method. Results: At T0, there were significant differences between diabetics and nondiabetics for SSFR and BC (p<0.05). In diabetics, SSFR was 0.790 mL/min in T0 and 0.881 mL/min in T1 (p>0.05). BC at T0 was 4.8, and at T1, it was 3.9 (p=0.000). Urea concentration mean value had a significant decrease at T1 (28.13) compared with T0 (34.88) (p=0.013). There was a negative correlation between SSFR and urea salivary concentration at both T0 (r=−0.426, p≤0.05) and T1 (r=−0.601, p≤0.01). Conclusions: In adolescents with type 1 DM, hyposalivation at T0 was associated with an increase in urea salivary concentration. At T1, hyposalivation was associated with a reduction in BC, and an increase in salivary urea.

Background: The adequacy of cortisol response in non-classical congenital adrenal hyperplasia (NCCAH) has not been fully elucidated. The aim was to evaluate cortisol response to adrenocorticotropin (ACTH) stimulation test in children and adolescents with NCCAH and heterozygotes for CYP21A2 gene mutations. Methods: One hundred and forty-six children and adolescents, mean age 7.9 (0.7–17.5) years with clinical hyperandrogenism, were evaluated retrospectively. Thirty-one subjects had NCCAH, 30 were heterozygotes for CYP21A2 gene mutations, while 85 showed normal response to ACTH test. Results: Baseline cortisol levels did not differ among NCCAH, heterozygotes, and normal responders: 15.75 (5.83–59.6) μg/dL vs. 14.67 (5.43–40.89) μg/dL vs. 14.04 (2.97–34.8) μg/dL, p=0.721. However, NCCAH patients had lower peak cortisol compared to heterozygotes and control group: 28.34 (12.25–84.40) vs. 35.22 (17.47–52.37) μg/dL vs. 34.92 (19.91–46.68) μg/dL, respectively, p=0.000. Peak cortisol was <18 μg/dL in 7/31 NCCAH patients and in one heterozygote. Conclusions: A percentage of 21.2% NCCAH patients showed inadequate cortisol response to ACTH stimulation. In these subjects, the discontinuation of treatment on completion of growth deserves consideration.

Background: Vitamin D deficiency is a widely recognized public health problem. Efficacy of a recently developed micellized form of vitamin D3 has not been studied. Hence, we undertook this study to compare its efficacy with the conventionally used fat-soluble vitamin D3. Methods: In this open-labeled nonrandomized pilot study, we recruited 180 healthy children, aged 13–14 years in two groups and supplemented Group A (60 children) with 60,000 IU of fat-soluble vitamin D3/month with milk and Group B (120 children) with 60,000 IU/month of water miscible vitamin D3 under supervision for 6 months. Serum 25(OD)D, parathyroid hormone (PTH), calcium, phosphate, and alkaline phosphatase (ALP) levels were evaluated before and after supplementation in 156 children (54 in Group A and 102 in Group B) who completed the study. Results: We observed a significantly greater increase in the serum 25(OH)D levels in group B as compared to group A (31.8±9.1 ng/mL vs. 23.7±10.4 ng/mL; p<0.001). All children in group B achieved adequate levels of serum 25(OH)D (>20 ng/mL) as against 83.3% children in group A. Serum PTH and ALP levels declined considerably in both the groups following supplementation. Conclusions: Vitamin D supplementation significantly increased the serum 25(OH)D levels in both groups. Miscible form of vitamin D3 appears to be better in achieving higher levels of serum 25(OH)D than that observed with a similar dose of fat-soluble vitamin D3. Further studies with different dose regimens are required to establish its efficacy over the conventionally used fat-soluble vitamin D3.

Background: In congenital adrenal hyperplasia (CAH), adjusting hydrocortisone dose during childhood avoids reduced adult height. However, there are currently no CAH-specific charts to monitor growth during treatment. Our objective was to elaborate growth reference charts and bone maturation data for CAH patients. Methods: We conducted a retrospective observational cohort study, in 34 French CAH centers. Patients were 496 children born 1970–1991 with genetically proven 21-hydroxylase deficiency. Their growth and bone maturation data were collected until age 18 together with adult height, puberty onset, parental height, and treatment. The mean (SD) heights were modeled from birth to adulthood. The median±1 SD and ±2 SDs model-generated curves were compared with the French references. A linear model for bone maturation and a logistic regression model for the probability of short adult height were built. Results: Growth charts were built by sex for salt wasting (SW) and simple virilizing (SV) children treated before 1 year of age. In girls and boys, growth was close to that of the general French population up to puberty onset. There was almost no pubertal spurt and the mean adult height was shorter than that of the general population in girls (−1.2 SD, 156.7 cm) and boys (−1.0 SD, 168.8 cm). Advanced bone age at 8 years had a strong impact on the risk of short adult height (OR: 4.5 per year advance). Conclusions: The 8-year bone age is a strong predictor of adult height. It will help monitoring the growth of CAH-affected children.

Background: Several studies have pointed out the existence of cardiac dysfunction in patients with type 1 diabetes mellitus (DM) even in the absence of ischemic, valvular, or hypertensive heart disease. The present study evaluated cardiac dysfunction and the relationship between severity of disease and degree of cardiac dysfunction in children with type 1 DM. Methods: In this prospective study, 31 patients with type 1 DM and 33 sex- and age-matched healthy children were evaluated with conventional echocardiography and tissue Doppler echocardiography (TDE). A correlation between cardiac functions and glycated hemoglobin (HbA 1C ) was examined. Results: TDE results indicated that mitral valve early diastolic annular peak flow rate (E′), mitral valve systolic flow rate (S′), ratio of mitral valve early diastolic peak flow rate to mitral valve early diastolic annular peak flow rate (E/E′), and left ventricular (LV) myocardial performance index (MPI) were higher, and LV ejection time (ET) was shorter in patients with type 1 DM (p<0.05). In addition, tricuspid valve E′ and right ventricular (RV) MPI were higher, while RV ET and tricuspid E/E′ were lower in patients with type 1 DM compared to healthy children (p<0.05). Conclusions: Although conventional echocardiography revealed no difference between patients with type 1 DM and healthy children, TDE showed dysfunctions of both ventricles. This state is closely related to degree of blood glucose level control. These findings signify diagnostic value of TDE in the early detection of cardiac effects among patients with type 1 DM.

Background: The objective of the study was to analyze the association of apelin gene ( APLN ) single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM). Methods: A total of 1966 subjects were enrolled in this study, including 168 cases (first batch), 330 cases (second batch), and 1468 nondiabetic controls. The SNPs in the HapMap-HCB of APLN were detected using Sequenom MassARRAY SNP technology and included rs2281068, rs3115757, rs2235309, and rs2235310. The related clinical characteristics with glucose metabolism were tested, including the fasting blood glucose (FPG), insulin (INS), C-peptide, glycosylated hemoglobin (HbA 1c ), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). Results: A correlation between rs3115757 and rs2281068 and diabetes was observed in first batch. Thus, we compared the SNPs (rs3115757 and rs2281068) between the cases and controls after more cases were enrolled. In addition, the results showed a significant correlation between APLN rs2281068 and diabetes (p<0.05). However, age, BMI, WC, blood pressure, and serum markers in T2DM had no relationship with APLN rs2281068. Conclusions: The SNP rs2281068 in APLN is significantly related to diabetes mellitus in a Chinese population.

Neonatal diabetes is a rare form of monogenic diabetes characterised by persistent hyperglycaemia during the first 6–9 months of age. About half of the cases of neonatal diabetes are transient forms resulting from mutations in the genes in the imprinted region of chromosome 6q24 and the other half are permanent forms. Activating mutations in the potassium ATP (K ATP ) channels encoded by the genes KCNJ11 and ABCC8 are responsible for the majority of permanent neonatal diabetes mellitus (PNDM). Mutations in K ATP channels can be associated with Developmental delay, Epilepsy and Neonatal Diabetes (DEND) syndrome. Intermediate DEND (iDEND) syndrome is a rare mild form of DEND syndrome. Successful transition from insulin to sulphonyl urea (SU) agents in patients with PNDM due to KCNJ11 mutations and in patients with intermediate DEND syndrome due to KCNJ11 mutation have been reported in the literature. To our knowledge, the successful transition of PNDM with DEND due to ABCC8 mutation has only been reported only once before in the literature. We report the successful transition from insulin to SU in two Iraqi siblings with PNDM due to ABCC8 mutation, one with iDEND.

Background: Gonadal dysgenesis with an apparently normal 46,XX karyotype is a rare cause of hypergonadotrophic hypogonadism. Tall stature is not a widely recognized association. Case report: A 15-year-old girl presented with primary amenorrhoea. Examination showed a non-dysmorphic girl of normal intellect with no breast development (Tanner stage B1P4A1) who was tall compared with her parents: height standard deviation score (SDS) +1.56 vs. midparental height of +0.23 SDS, and slim build (weight −0.13 SDS). Investigations showed a 46,XX karyotype, elevated gonadotropins (FSH 119 and LH 33.7 IU/L), serum estradiol <5 pmol/L, uterine length 3.75 cm with cylindrical shape, and absent ovaries on ultrasound. Initially, a 364055-bp deletion on Xp21.2 was reported on array CGH. However, repeat analysis using BlueGnome CytoChip ISCA 4x180k v2.0 array was normal. With oral ethinyl estradiol induction puberty progressed to B4P4A2 but aged 18.4 years, the patient was remarkably tall with height SDS +2.88, weight SDS +0.97. Conclusions: Caution is needed in interpreting small changes with array CGH, particularly with the older assays. We postulate that the genetic change causing 46,XX gonadal dysgenesis in our patient may have also resulted in unsuppressed somatic growth. More critical height assessment, including parental height measurement, of future patients with 46,XX gonadal dysgenesis is recommended in order to determine whether or not a true association with tall stature may be present in certain cases.

Prolactinomas are a rare subset of brain tumors in pediatrics. We report a child with a prolactin secreting macroadenoma which was refractory to initial treatment with a dopamine antagonist. Given the location of her tumor she was ineligible for surgical resection. Temozolomide (200 mg/m 2 ×5 days each month) was administered with a dramatic and prolonged response in tumor size, prolactin level, and symptoms, with no side effects from treatment. We demonstrate the benefit of temozolomide in the treatment of a pediatric patient with prolactinoma.