Band 29, Heft 7

Background: The present study was conducted to translate and assess the validation of the measure of self-management of type 1 diabetes for adolescents that developed by Schilling et al [Schilling LS, Knafl KA, Grey M. Changing patterns of self-management in youth with type I diabetes. J Pediatr Nurs 2006;21:412–24]. Methods: The first stage of the study involved the translation of the measure of self-management of type 1 diabetes for adolescents into Persian based on the model proposed by Wild et al. in two versions [Wild D, Grove A, Martin M, Eremenco S, McElroy S, et al. Principles of good practice for the translation and cultural adaptation process for patient-reported outcomes (PRO) measures: report of the ISPOR task force for translation and cultural adaptation. Value Health 2005;8:94–104; Wild D, Eremenco S, Mear I, Martin M, Houchin C, et al. Multinational trials – recommendations on the translations required, approaches to using the same language in different countries, and the approaches to support pooling the data: the ISPOR patient-reported outcomes translation and linguistic validation good research practices task force report. Value Health 2009;12:430–40]. The translated versions were reviewed in consultation sessions with experts and the more appropriate items were selected and the final version was translated back into English in two versions and was then sent to the measure’s designer for confirmation. The content validity of the measure was then evaluated by a group of experts and found to be acceptable. The next stage evaluated the measure’s construct validity. This measure contains 52 items classified under five subscales. The confirmatory factor analysis was performed to assess the measure’s construct validity and was found to be acceptable. For evaluating the reliability of the measure, its internal consistency was assessed through calculating its Cronbach’s alpha and intra-class correlation. The measure’s consistency was measured through calculating its test-retest reliability. Results: The assessment of the measure’s content validity revealed a content validity index of 0.98. For the construct validity of the measure using the confirmatory factor analysis, the following figures were obtained: NFI=0.97, RMSA=0.001, AGFI=0.81, IFI=0.833, GFI=0.83. In the assessment of the measure’s reliability, the intra-class correlation showed an overall Cronbach’s alpha of 0.88. The test-retest showed a consistency of 0.73 for the measure. Conclusions: The validation of the 48-item measure revealed that it can be used in the population of Iranian adolescents with type 1 diabetes (8 items changed their subscales and 4 items were removed).

Background: This study aimed to evaluate the health-related quality of life (HRQoL) of adolescents with type 1 diabetes (T1DM) on the basis of the pediatric quality of life inventory™ (PedsQL™) generic and diabetes-specific modules, and to compare it to that of healthy peers. Methods: This retrospective case-control study involved 650 participants between ages of 13 and 19 years including 296 adolescents with T1DM from four diabetes centers and 354 healthy peers matched for age and gender from three different cities of the country. Participants completed the validated PedsQL™ for assessing the HRQoL. The analysis included an independent t-test to compare the means of the total and subscales of the PedsQL™ between boys and girls as well as between a healthy group and a group with T1DM. Gender differences in exercise, insulin therapy modalities were evaluated with the Pearson χ 2 -test. Results: Adolescents with T1DM have similar HRQoL in all domains when compared to their healthy counterparts. Females report worse HRQoL regardless of the presence of the disease. Insulin pump therapy facilitates better glycemic control and HRQoL. Regular exercise positively correlates with the generic HRQoL in both groups; however, it has no relationship with glycemic control. Conclusions: Optimal metabolic control and improved HRQoL are the eventual goals of diabetes management. Despite the difficulties, adolescents with diabetes can manage their disease well and live normal lives, similar to their healthy peers. Although diabetes-related problems exist, it seems that regular exercise and staying physically active, as well as promoting insulin pump therapy where it is applicable are related to favorable HRQoL.

Background: The objective of this study was to examine the cross-sectional relationship between homeostasis model assessment for insulin resistance (HOMA-IR) and serum 25-hydroxyvitamin D (25-OHD) level in Chinese children and adolescents. Methods: Anthropometric indices, lipid metabolic profile, and serum levels of glucose, insulin and 25-OHD were determined among 278 healthy prepubertal and pubertal, normal and overweight/obese children and adolescents aged 8–18 years between March 2014 and February 2015. Results: HOMA-IR was significantly different across vitamin D statuses (p<0.001), even after adjusting for body mass index (BMI) (p=0.035) and waist-to-height ratio (p=0.044); the difference was not significant between the vitamin D deficient and insufficient groups (p=0.120). HOMA-IR negatively correlated with serum 25-OHD level for all subjects (R 2 =0.148, p<0.001). Furthermore, they negatively correlated in the normal (R 2 =0.160, p<0.001) and overweight/obese (R 2 =0.086, p<0.001) groups, respectively. The regression lines of the two groups were parallel (p=0.669) but had a significantly different intercept (p<0.001). An association between HOMA-IR and BMI and serum 25-OHD level (R 2 =0.654, p<0.001) was demonstrated based on the stepwise multiple linear regression analysis of age, sex, pubertal maturation, BMI, waist-to-height ratio, triglyceride, cholesterol, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), 25-OHD and HOMA-IR. Conclusions: Our findings supported that lower vitamin D status is strongly associated with worse HOMA-IR.

Background: Obesity is an important risk factor for non-alcoholic fatty liver disease. Few studies have evaluated the association between vitamin D and non-alcoholic fatty liver disease in obese children. Therefore, we conducted a study to examine the relationship of vitamin D levels and hepatosteatosis in obese children. Methods: One hundred and eleven children with obesity participated in this study. Hepatosteatosis was diagnosed and graded using ultrasonography in all patients. Study participants were divided based on the presence of hepatosteatosis into two subgroups (hepatosteatosis and non-hepatosteatosis). Serum levels of 25-hydroxyvitamin D, calcium, phosphate, alkaline phosphatase, parathormone, and lipids were measured and compared. Results: Hepatosteatosis existed in 52% of obese children without chronic diseases. There was no statistically significant difference in the vitamin D level between the hepatosteatosis and non-hepatosteatosis groups. Alanine aminotransferase levels and the triglycerides-to-high density lipoprotein ratio were significantly higher, and the high density lipoprotein levels were significantly lower in the hepatosteatosis group compared to the non-hepatosteatosis group. Conclusions: Vitamin D deficiency is not directly related with hepatosteatosis. A high ALT level and a high triglycerides-to-HDL ratio and low HDL levels are more significant in hepatic steatosis in obese children.

Background: Pediatric thyroid nodules, while uncommon, have high malignancy risk. The objectives of the study were (1) to identify sonographic features predictive of malignancy; (2) to create a prediction model; and (3) to assess inter-observer agreement among radiologists. Methods: All available cases of thyroid nodules, surgically removed between 2000 and 2009. Three radiologists reviewed the sonographic images; 2 pathologists reviewed the tissue specimens. Adult prediction models were applied. Interobserver variability was assessed. Results: Twenty-seven subjects, mean age 13.1±3.4 years, were included. Nineteen nodules were differentiated thyroid carcinomas. On multivariate analysis, size was the only significant predictor of malignancy. On recursive partitioning analysis, size >35 mm with microcalcification and ill-defined margins yielded the best prediction model. Radiologist inter-observer agreement regarding malignancy was moderate (κ=0.50). Conclusions: Larger size, microcalcifications and ill-defined margins on ultrasound demonstrate the best predictive model for malignancy in the pediatric population. Experienced pediatric radiologists demonstrate moderate inter-observer agreement in prediction of malignancy.

Background: The essential role of thyroid hormones for normal brain development during a critical period of life is well established. Neonatal screening programs for congenital hypothyroidism (CH) enable early detection of patients and attainment of euthyroid status as quickly as possible. Adequate and accurate monitoring of thyroid function is necessary. In the study we aimed to determine the periodicity of thyroid function testing in the first year of life (3-month intervals versus <3-month intervals monitoring). Methods: We retrospectively analyzed charts of CH children from Macedonia detected on neonatal screening during a 3-year period (2011–2014). Needs for monthly thyroid monitoring were defined according to the recommendations: a dose change within a month of a previous control, values of T 4 /FT 4 not in the upper half of the reference range, and a high or very low thyroid-stimulating hormone (TSH) value. Results: Monthly thyroid testing was indicated in more than a third of CH patients during the first year of life. Children who needed more frequent monitoring intervals had a higher initial value of TSH (p=0.032) and a lower value of T 4 (p=0.038) than those requiring less frequent monitoring. The sex, birth weight, age of treatment onset, initial L-thyroxine dose, and L-thyroxine dose at 1-year of age in our study were not predictive factors for more frequent thyroid monitoring. Conclusions: Children with severe hypothyroidism at birth are potential candidates for more frequent thyroid monitoring during the first year of life, although the individual patient approach should not be avoided as variations in TSH values are very common.

Background: Congenital hypothyroidism (CH) is caused by thyroid gland (TG) dysgenesis or inadequate thyroid hormone biosynthesis in a structurally normal gland. Different etiologies are known to be associated with various clinical, biochemical and imaging markers and a subset of cases have an underlying genetic basis. Despite the presence of neonatal screening programs in the UAE, there is a lack of data on the disease etiology in the area. We aim to study the etiology of CH in our center and examine its relationship with the clinical, biochemical, genetic and radiological features. Methods: Patients with CH who were followed in our center between 2011 and 2014 are enrolled in the study. Data collected included gender, gestational age, history of CH in a first-degree relative, initial thyroid stimulating hormone (TSH) and thyroxine (T4) levels, imaging findings, associated disease/malformation and treatment details. Selected patients with associated systemic disease or familial CH underwent genetic testing. Results: Sixty-five patients were enrolled. Ten patients underwent genetic study: seven patients with associated congenital disease/malformation, one with a sibling and two with cousins with CH. Forty-nine subjects had technetium 99 and/or ultrasound scans. Dyshormonogenesis was diagnosed in two-thirds of the patients. Three patients of 10 tested had likely causative genetic mutations; two homozygous thyroid peroxidase (TPO) and one heterozygous thyroid stimulating hormone receptor (TSHR) missense mutations. Conclusions: Dyshormonogenesis is the commonest etiology in CH in the studied group. It is expected that genetic mutations are more prevalent in our region due to the nature of the CH etiology and the rate of high consanguinity rate.

Background: Dual oxidase 2 ( DUOX2 ) mutations are a cause of dyshormonogenesis (DH) and have been identified in patients with permanent congenital hypothyroidism (PH) and with transient hypothyroidism (TH). We aimed to elucidate the prevalence and phenotypical variations of DUOX2 mutations. Methods: Forty-eight Japanese DH patients were enroled and analysed for sequence variants of DUOX2 , DUOXA2 , and TPO using polymerase chain reaction-amplified direct sequencing. Results: Fourteen sequence variants of DUOX2 , including 10 novel variants, were identified in 11 patients. DUOX2 variants were more prevalent (11/48, 22.9%) than TPO (3/48, 6.3%) (p=0.020). The prevalence of DUOX2 variants in TH was slightly, but not significantly, higher than in PH. Furthermore, one patient had digenic heterozygous sequence variants of both DUOX2 and TPO . Conclusions: Our results suggest that DUOX2 mutations might be the most common cause of both PH and TH, and that phenotypes of these mutations might be milder than those of other causes.

Background: Osteogenesis imperfecta (OI) is characterized by bone fragility and short stature. Data about IGF-I/IGFBP-3 levels are rare in OI. Therefore IGF-I/IGFBP-3 levels in children with different types of OI were investigated. Methods: IGF-I and IGFBP-3 levels of 60 children (male n=38) were assessed in a retrospective cross-sectional setting. Results: Height/weight was significant different [height z-score type 3 versus type 4: p=0.0011 and weight (p≤0.0001)] between OI type 3 and 4. Mean IGF-I levels were in the lower normal range (mean±SD level 137.4±109.1 μg/L). Mean IGFBP-3 measurements were in the normal range (mean±SD 3.105±1.175 mg/L). No significant differences between OI type 3 and 4 children have been observed (IGF-I: p=0.0906; IGFBP-3: p=0.2042). Conclusions: Patients with different severities of OI have IGF-I and IGFBP-3 levels in the lower normal range. The type of OI does not significantly influence these growth factors.

Background: The aim of the study was to determine if physical activity (PA) is associated with bone health in children with Prader-Willi syndrome (PWS). Methods: Participants included 23 children with PWS (age: 11.0±2.0 years). PA, measured by accelerometry, was categorized into light, moderate, vigorous and moderate plus vigorous intensities. Hip, total body minus the head (body), bone mineral content (BMC), bone mineral density (BMD) and BMD z-score (BMD z ) were measured by dual X-ray absorptiometry. Separate hierarchical regression models were completed for all bone parameters, PA intensity and select covariates. Results: Moderate PA and select covariates explained the most variance in hip BMC (84.0%), BMD (61.3%) and BMD z (34.9%; p<0.05 for all). Likewise, for each body parameter, moderate PA and select covariates explained the most variance in body BMC (75.8%), BMD (74.4%) and BMD z (31.8%; p<0.05 for all). Conclusions: PA of at least moderate intensity appears important for BMC and BMD in children with PWS.

Background: The risk of developing type II diabetic nephropathy (DN) is lower in patients carrying the CNDP1 Mannheim polymorphism (homozygosity for the five leucine repeat), resulting in decreased activity of the histidine-dipeptide metabolizing enzyme carnosinase. The role of CNDP1 in other nephropathies is still unknown. Methods: To evaluate the impact of the CNDP1 Mannheim allele on pediatric chronic kidney disease (CKD), we prospectively followed the long-term clinical outcome of 272 children with non-diabetic kidney disease (glomerulopathies n=32, non-glomerular kidney disease n=240). Results: Renal failure progression was independent of CNDP1 genotype in the total cohort of CKD children. However, in patients with glomerulopathies, only 39% of patients homozygous for the CNDP1 Mannheim polymorphism attained the primary renal endpoint as compared to 77% of patients with any other CNDP1 genotype (p=0.06). Conclusions: Our findings in pediatric CKD patients suggest that the nephroprotective effect of the CNDP1 Mannheim variant is not restricted to patients with diabetic nephropathy.

Background: In adult women with polycystic ovary syndrome (PCOS) 17-OHP responses to human chorionic gonadotropin (hCG) stimulation are highly variable and inversely correlated with serum anti-Mullerian hormone (AMH) levels. The objective of this study was to determine whether adolescents with PCOS exhibit similar variable 17-OHP responsiveness to hCG and whether these responses are correlated to AMH levels. Methods: In a prospective study, adolescent PCOS (n=14) and normal controls (n=10) received 25 μg of hCG, intravenously. Blood samples were obtained before and 24 h afterwards for measurement of 17-OHP and basal AMH. Results: Variable 17-OHP responses to hCG were observed among PCOS girls similar to that observed in adults. There was no correlation between AMH and 17-OHP responses to hCG. Conclusions: Among adult and adolescent individuals with PCOS variable 17-OHP production appears to be characteristic of the disorder. In adolescent PCOS, 17-OHP responsiveness to hCG is not correlated to AMH.

Background: The objective of this study was to identify variables that might interfere with reaching the near final height (NFH) in Congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD). Methods: A cross-sectional study of 82 (24 males and 58 females) classic (23 salt-wasting form [SW] and 59 simple-virilizing form [SV]) CAH 21-OHD patients seen in our institution between 1989 and 2015 with 10.6 (0.5~25.5) years of follow-up who reached their NFH was conducted. The variables related to NFH were explored. Results: NFH (153.35±8.31) cm, (–1.9±1.1) SD was significantly lower than the normal population (p<0.001). The treated patients reached a significantly higher NFH (–1.7±1.1) SD than those untreated (–2.6±1.0) SD (p<0.05). Both of early treatment and late treatment group were taller than untreated group (p<0.001, p=0.013, respectively), and early treatment group had a taller height trend than late treatment group (p=0.089). A better height outcome was observed in patients with advantage in target height, good compliance, and low hydrocortisone dose by multivariate Cox regression analysis in 62 treatment patients. NFH and hydrocortisone dose was negatively correlated (r=–0.23, p=0.078) in treated group. Patients complicated by central precocious puberty (CPP) received gonadotropin-releasing hormone analogue (GnRHa) plus letrozole had increased NFH with height SD for bone age and Ht SD improved after treatment compare to no intervention group (p=0.001, p=0.035). Conclusions: Patients with classic 21-OHD have blunted final height, as compared with their target height and the population norm, not-treated even worse. Careful treatment adjustments have a favorable influence on growth. Alternative treatments, such as the use of puberty inhibitors GnRHa in addition to anti-estrogen therapy letrozole can somewhat improve NFH in children with 21-OHD complicated by CPP.

The Sertoli cell only syndrome (SCOS) is a rare genetic disorder with a variable phenotype ranging from a severe ambiguous genitalia to a normal male phenotype with infertility. SCOS is diagnosed on testicular histopathology as germ cells are absent without histological impairment of Sertoli or Leydig cells. The SRY positive XX male syndrome is usually diagnosed in adulthood during infertility investigations. Here, we report a rare case of 46,XX maleness with ambiguous genitalia due to Sertoli cell only syndrome (SCOS).

Primary hyperparathyroidism is very rare in children and adolescents. The management of a 12-year-old boy with renal calculi due to parathyroid adenoma is discussed. The single tumor after localization with sestamibi scintigraphy and SPECT-CT scan was excised with amelioration of symptoms. The case is reported due to the rarity of the disease and successful unilateral exploration. The association with hypopigmented areas of skin has also not been previously reported in literature.

Maleness associated with a 45,X karyotype is a rare condition in childhood. It is usually diagnosed in adult age because of infertility. We report a unique case of an unbalanced translocation t(Y;21) in a 14-year-old boy with 45,X karyotype referred because of short stature, thin habitus and puberty delay. Hormone analysis showed low serum levels of basal testosterone, insulin-like growth factor (IGF-I) and gonadotrophins. Diagnosis of GH deficiency and puberty delay were made. He was treated with human chorionic gonadotropin (hCG) and GH therapy, respectively, for 6 and 24 months.

Although propionic acidemia (PA) is a devastating inherited metabolic disease, with early diagnosis and advanced treatment strategies prognosis gets better and girls can survive to child-bearing ages. We share the detailed follow-up data of the pregnancy, successful labor with cesarean section and a healthy baby of a Turkish patient with PA.

Gonadotropin independent sexual precocity (SP) may be due to congenital adrenal hyperplasia (CAH), and its timing usually depends on the type of mutation in the CYP21A2 gene. Compound heterozygotes are common and express phenotypes of varying severity. The objective of this case report was to investigate the hormonal pattern and unusual genetic profile in a 7-year-old boy who presented with pubic hair, acne, an enlarged phallus, slightly increased testicular volume and advanced bone age. Clinical, hormonal and genetic studies were undertaken in the patient as well as his parents. We found elevated serum 17-hydroxyprogesterone (17-OHP) and androstenedione that were suppressed with dexamethasone, and elevated testosterone that actually rose after giving dexamethasone, indicating activity of the hypothalamic-pituitary-gonadal (HPG) axis. An initial search for common mutations was negative, but a more detailed genetic analysis of the CYP21A2 gene revealed two mutations including R341W, a non-classical mutation inherited from his mother, and g.823G>A, a novel not previously reported consensus donor splice site mutation inherited from his father, which is predicted to be salt wasting. However, the child had a normal plasma renin activity. He was effectively treated with low-dose dexamethasone and a GnRH agonist. His father was an unaffected carrier, but his mother had evidence of mild non-classical CAH. In a male child presenting with gonadotropin independent SP it is important to investigate adrenal function with respect to the androgen profile, and to carry out appropriate genetic studies.

Central diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS.