Frequency of Ambiguous Genitalia in 14,177 Newborns in Turkey.

CONTEXT: Limited data are available on the exact incidence of disorders of sex development (DSD) with genital ambiguity at birth. OBJECTIVE: To determine frequency of ambiguous genitalia in newborns. DESIGN: Prospective multicenter study. SETTING: Three tertiary care hospitals. PATIENTS OR OTHER PARTICIPANTS: All 14,177 babies born during the study period were included. MAIN OUTCOME MEASURES: All newborns were examined at birth; data on weeks of gestation, birth weight, and length were collected. A structured questionnaire was used for data collection. Quigley and Prader scales were used for phenotypic grading. Clinical and genetic investigations were performed. RESULTS: Eighteen babies with ambiguous genitalia were found among 14,177 newborns (1.3/1000). Fifteen newborns had 46,XY DSD, one had 46,XX congenital adrenal hyperplasia, and one had 45,X/46,XY mixed gonadal dysgenesis. Karyotype analysis was not done in one baby who died in the neonatal period. The ratio of prematurity was higher in the DSD group (44% vs 11%; P < 0.001) and the ratio of small for gestational age was also higher in the DSD group (22% vs 5%; P = 0.007). Eight babies with DSD had mothers who had additional medical conditions, such as preeclampsia, depression, insulin resistance, and gestational diabetes mellitus. CONCLUSION: The frequency of ambiguous genitalia was higher than in previous studies, but, as with any experiment, the finding should be met with caution because this study was conducted in tertiary care hospitals. In addition, lower birth weight in the DSD group supports the hypothesis that early placental dysfunction might be important in the etiology of male genital anomalies.

Determinants of Increased Aortic Diameters in Young Normotensive Patients With Turner Syndrome Without Structural Heart Disease.

Factors associated with aortic dilation and dissection in patients with Turner syndrome (TS) remain unclear. We assessed magnetic resonance imaging-based aortic diameters at nine predefined anatomic positions and examined associations of increased aortic diameters with B-type natriuretic peptide (BNP), A-type NP (ANP), growth hormone treatment, insulin-like growth factor 1 (IGF1), and estrogen status. Forty-seven patients with TS aged 7.3-21 years and 34 healthy peers were enrolled in this study. Aortic diameters were higher in patients with TS at three positions than in controls (p < 0.05). History of GH treatment, pubertal status, and serum estradiol levels were not associated with increased aortic diameters. Patients with TS had higher plasma BNP and ANP levels than controls. BNP and IGF1 were independently associated with the increase in aortic diameters in TS at three positions of the ascending aorta (R2 = 0.361-0.458, p < 0.05 for all). At two positions of the descending aorta, only BNP emerged as an independent variable (R2 = 0.130-0.139, p < 0.05). We conclude that young, normotensive patients with TS had greater aortic diameters at several positions than healthy controls. BNP and IGF1 were independently associated with increased aortic diameters in TS.

Evaluation and Treatment Results of Ovarian Cysts in Childhood and Adolescence: A Multicenter, Retrospective Study of 100 Patients.

STUDY OBJECTIVE: To investigate the characteristics of children with ovarian cysts and evaluate treatment strategies. DESIGN: Retrospective study. SETTING: Eight pediatric endocrinology clinics, Turkey. PARTICIPANTS: A total of 100 children and adolescents with ovarian cysts. INTERVENTIONS: Patient data collected via retrospective chart review. Patients were stratified according to age into 4 groups (newborns, 1-12 months, 1-8 years, and 8-18 years). MAIN OUTCOME MEASURES: Special emphasis was given to torsion and tumor cases, concomitant diseases, treatment modalities, and problems during follow-up. RESULTS: Most newborns and infants were asymptomatic with the cysts being discovered incidentally; in girls ages 1-8, symptoms were common, including breast budding (47.1%, 16 of 34) and vaginal bleeding (29.4%, 10 of 34). Girls older than 8 years mostly presented with abdominal pain (31.6%, 12 of 38) and menstrual irregularity (21.1%, 8 of 38). Most of our patients were diagnosed with a simple ovarian cyst, but 9 patients were found to have ovarian tumors. Ovarian torsion was detected in 7 patients; 5 with large and 2 with small cysts (<20 mm). Two patients had central precocious puberty (CPP) at presentation and 5 patients developed CPP during follow-up. The surgical intervention rate was high (38%, 38 of 100), but was associated with earlier treatment year, and this association remained significant after adjusting for confounders (P = .035). CONCLUSION: Most girls have simple cysts, which have a favorable prognosis without intervention; however, there might be coexisting pathologies or complications such as tumors, torsion, and CPP; hence these patients should be evaluated accordingly and treated with a multidisciplinary approach.

Sonography and Magnetic Resonance Imaging Characteristics of Testicular Adrenal Rest Tumors.

BACKGROUND: The aim of this study was to describe the gray-scale and color Doppler ultrasonography (US) and magnetic resonance (MR) imaging features of testicular adrenal rest tumors (TART) in patients with congenital adrenal hyperplasia. MATERIAL/METHODS: Forty-one patients with congenital adrenal hyperplasia were evaluated by gray-scale and color Doppler ultrasonography. Totally eighteen adrenal rest tumors in 9 patients were diagnosed TART on US and MR imaging. Gray-scale and color Doppler US and MR findings of the patients were documented. RESULTS: A total of eighteen masses were evaluated in nine patients. The mean age of these patients was 14.3±4.5 (range 10.1-23.3) years. US revealed hypoechoic lesions around the mediastinum testis with hypervascularity dispersing in ten patients and hypovascularity in two patients. In six patients, the lesions were hyperechoic with poor vascularity. Lesions exhibited homogeneous (n=8) and heterogeneous (n=10). Testicular microlithiasis was present in 4 of 9 patients with TART. Doppler ultrasound showed normal testicular vessels passing through the mass which were undisturbed, not displaced and not change in caliber. MRI features were the following: all lesions were hypointense on T2- and hyperintense (n=12) and isointense (n=6) on T1-weighted images. All masses revealed homogeneous contrast enhancement on postcontrast T1-weighted images. CONCLUSIONS: Ultrasonography and MRI are good methods for detecting and monitoring TART. US is the first preferable modality because it is quick and cheap than MRI. Bilateral mostly hypoechoic lesions depicted around the mediastinum testis with no mass effect is highly suggestive for the diagnosis of testicular adrenal rest tissues on ultrasonography. Normal testicular vessels coursing through the lesions undisturbed and not change in caliber is described specific for this kind of tumors.

Diagnosis and management of pediatric adrenal insufficiency.

BACKGROUND: Adrenal insufficiency (AI) is a wellknown cause of potentially life-threatening disorders. Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function, leading to varying degrees of glucocorticoid (GC) deficiency. Iatrogenic AI induced by exogenous GCs is the most common cause of AI. The criteria for the diagnosis and management of iatrogenic AI, neonatal AI, and critical illness-related corticosteroid insufficiency (CIRCI) are not clear. DATA SOURCES: We reviewed the recent original publications and classical data from the literature, as well as the clinical, diagnostic and management strategies of pediatric AI. RESULTS: Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI, neonatal AI, and CIRCI are provided. Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI, GC treatment has to be tailored to highly suggestive clinical symptoms and signs. Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy. It is mainly the delay in treatment that is responsible for mortality in adrenal crisis. CONCLUSIONS: Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.

Rare Causes of Primary Adrenal Insufficiency: Genetic and Clinical Characterization of a Large Nationwide Cohort.

CONTEXT: Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management. OBJECTIVE: The objective of the study was to investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology. DESIGN: A structured questionnaire was used to evaluate clinical, biochemical, and imaging data. Genetic analysis was performed using Haloplex capture and next-generation sequencing. Patients with congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune adrenal insufficiency, or obvious syndromic PAI were excluded. SETTING: The study was conducted in 19 tertiary pediatric endocrinology clinics. PATIENTS: Ninety-five children (48 females, aged 0-18 y, eight familial) with PAI of unknown etiology participated in the study. RESULTS: A genetic diagnosis was obtained in 77 patients (81%). The range of etiologies was as follows: MC2R (n = 25), NR0B1 (n = 12), STAR (n = 11), CYP11A1 (n = 9), MRAP (n = 9), NNT (n = 7), ABCD1 (n = 2), NR5A1 (n = 1), and AAAS (n = 1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c.IVS3ds+1delG in MRAP. Several important clinical and molecular insights emerged. CONCLUSION: This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (eg, mineralocorticoid replacement), predicting comorbidities (eg, neurological, puberty/fertility), and targeting clinical genetic testing in the future.

An easily missed diagnosis: 17-alpha-hydroxylase/17,20-lyase deficiency.

The CYP17A1 gene encodes the enzyme P450c17, which mediates both 17α-hydroxylase and 17,20-lyase activities and is essential for production of cortisol and sex steroids. Loss-of-function mutations of this gene cause 17α-hydroxylase/17,20-lyase deficiency, characterized by hypertension, hypokalemia and sexual infantilism. A 6-year-old phenotypically female patient presented with hypertension and hyperpigmentation. Her blood test results showed low cortisol and high adrenocorticotropic hormone (ACTH), progesterone, deoxycorticosterone and gonadotropin levels and were consistent with the diagnosis of 17α-hydroxylase/17,20-lyase deficiency. Her karyotype was 46XY. Genetic studies of the patient revealed a novel homozygous point mutation, c.1307G>A, within the coding sequence of the CYP17A1 gene. 17α-hydroxylase/17,20-lyase deficiency should be considered in the differential diagnosis of hypertension in children and adolescents, and physical examination of these patients should be done very carefully.

Epidemiologic Features of Type 1 Diabetic Patients between 0 and 18 Years of Age in Istanbul City.

OBJECTIVE: To evaluate the epidemiologic, clinical and laboratory characteristics of a group of children with type 1 diabetes mellitus (T1DM) living in a Turkish city. METHODS: The records of 395 (boys/girls: 199/196) children with newly diagnosed T1DM hospitalized in the years 1985-2004 were evaluated retrospectively. The data were assessed by gender and age subgroups (≤5, 6-10 and ≥11 years). RESULTS: Mean age of children at diagnosis was 8.1±4.1 years. At T1DM onset, the number of children ≤5, between 6-10 and ≥11 years old was 110 (27.9%), 147 (37.2%) and 138 (34.9%), respectively. The patients were mostly diagnosed at ages 6-8 years (24.1%), followed by cases aged 3-5 years (22.0%). Polyuria and polydipsia were the most common symptoms (94.7%). Mean duration of symptoms was 21.5±18.6 days. Although the patients mostly presented in autumn (30.7%), no season-related significant differences were found. The frequency of ketoacidosis was relatively high (48.5%). When compared to boys, the girls experienced higher rates of ketoacidosis (55.1% vs. 41.7%, p=0.042); had a higher frequency of anti-thyroid peroxidase antibodies (11.7% vs. 4.2%, p=0.049) and higher insulin requirement (0.89±0.41 vs. 0.77±0.36 IU/kg, p=0.005). Cases with a family history of T1DM were more likely to have anti-endomysial antibodies (42.9% vs. 8.1%, p=0.027) and higher initial blood glucose levels (510.5±145.0 vs. 436.1±156.5 mg/dL, p=0.005). CONCLUSION: The findings possibly indicate a decreasing age of T1DM onset. The high frequency of ketoacidosis at presentation is noteworthy. Girls had higher rates of ketoacidosis, higher frequency of anti-thyroid antibodies and higher insulin requirements as compared to boys. Patients with a family history of T1DM had higher initial glucose levels and higher frequency of anti-endomysial antibodies.

Increased arterial stiffness in young normotensive patients with Turner syndrome: associations with vascular biomarkers.

OBJECTIVES: Factors contributing to arteriopathy in patients with Turner syndrome (TS) remain unclear. We assessed arterial stiffness in young, normotensive patients with TS and correlated arterial stiffness with vascular biomarkers, GH treatment and oestrogen exposure. Sixty-one patients with TS (mean age, 12·6 years; range 6·6-21·3 years) were matched for age and sex with 61 healthy peers. Associations between arterial stiffness and high-sensitivity C-reactive protein (hsCRP), B-type natriuretic peptide (BNP), atrial NP (ANP), plasma aldosterone/plasma renin activity (PRA), IGF1 and IGFBP3 were examined after adjusting for well-established confounders of vascular disease. RESULTS: Carotid intima media thickness standard deviation score (SDS), arterial stiffness index SDS and incremental modulus of elasticity SDS were higher, and distensibility coefficient SDS was lower in patients with TS. The duration of GH treatment and oestrogen exposure was not associated with indices of arterial stiffness. TS patients had higher hsCRP, BNP and ANP. Plasma aldosterone/PRA, IGF1 and IGFBP3 were similar in patients and controls. Multivariable regression analyses (R(2) = 0·200-0·668, P < 0·01) showed that BNP was associated with all indices of arterial stiffness. We found that hsCRP was associated with distensibility coefficient SDS (ß = -0·16, P < 0·01). TS was independently associated with increased arterial stiffness (ß = 0·420-3·424, P < 0·001 for all, R(2) = 0·06-0·31). CONCLUSIONS: Young, normotensive TS patients had increased arterial stiffness than that of healthy peers. BNP, and possibly hsCRP, was independently associated with arterial stiffness in TS. Further research will determine any causal inference of these relationships.

Associations of size at birth and postnatal catch-up growth status with clinical and biomedical characteristics in prepubertal girls with precocious adrenarche: preliminary results.

CONTEXT: The causes of polycystic ovarian syndrome (PCOS) in girls with precocious adrenarche (PA) remain unclear. OBJECTIVE: Our goal was to compare the clinical, biochemical, and ultrasound characteristics of girls with PA whose size at birth was appropriate for gestational age (AGA) vs those born small for gestational age (SGA). PCOS-associated metabolic and morphological correlates were examined. DESIGN: Glucose tolerance, ACTH stimulation, and transabdominal ultrasounds were examined in 56 AGA and 31 SGA girls with PA. Bone age and hormonal profiles were determined. SGA girls were divided into 2 groups by catch-up growth (CUG) status. Subgroups were compared. RESULTS: Chronological age, Tanner stage for pubarche, ovarian volume, and uterine volume were similar between the groups. SGA girls had lower body mass index and higher bone age-adjusted post-corticotropin cortisol. We found increased body mass index-adjusted mean serum insulin, reduced insulin sensitivity, and reduced IGF-binding protein-1 in SGA girls. Multicystic ovaries were more common in SGA girls (odds ratio [OR] = 9.69, 95% confidence interval [CI] = 3.34-28.15; P < .001). SGA girls without CUG had a higher incidence of multicystic ovaries than CUG counterparts (OR = 8.4, 95% CI = 1.4-19.3; P = .027). Being born SGA (OR = 43.4, 95% CI = 6.9-84.7; P = .001] and exaggerated 17-hydroxyprogesterone response (OR = 15.8, 95% CI = 1.7-49.8; P = .015) were associated with multicystic ovaries. CONCLUSIONS: Significant differences in hormone levels, insulin sensitivity, and ovarian maturity were found in prepubertal girls with PA who were SGA. Longitudinal follow-up will help determine whether these factors contribute to a specific PCOS phenotype in SGA girls with PA.

Z-score reference values for height in Turkish children aged 6 to 18 years.

OBJECTIVE: Standard deviation score or Z-score reference charts are used in some countries in preference to percentile charts and are considered as better tools in assessing children with measurements outside the accepted limits of normality. Growth data for Istanbul children have previously been reported as percentiles; hence, the aim of this study is to present these data in Z-score reference tables. Data on secular trend in height in Turkish children will also be presented. METHODS: Height and weight data based on a total of 11 664 height and 11 655 weight measurements in 1100 boys and 1020 girls between 6 and 18 years of age obtained by biannual visits to schools were analyzed. All children came from well-to-do families and were all healthy. All measurements were made by two trained technicians. The LMS method was used in the analyses. The results were expressed as Z-score values for age. RESULTS: Heights of the boys and girls in all age groups were close to the updated USA growth references and showed an upward trend from previous data on Turkish children. CONCLUSIONS: Height growth in Turkish school-age children of high socioeconomic level conforms to the updated growth data for USA children and also shows a secular trend. The data also point to the importance of updating local growth data periodically.

Comparative analysis of glucoinsulinemic markers and proinflammatory cytokines in prepubertal children born large-versus appropriate-for gestational age.

Children born large for gestational age (LGA) may be at risk for development of obesity and insulin resistance (IR). The reciprocal relationship of adipokines and proinflammatory cytokines is suggested to play a putative role in fine tuning of insulin secretory dynamics. To evaluate serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, insulin-like growth factor-1 (IGF-1), and IGF-binding protein-1 (IGFBP-1) concentrations in idiopathic LGA-born children to appropriate for gestational age (AGA) and idiopathic LGA-born children at prepubertal ages and investigate their associations with IR, evaluated by homeostasis model assessment-IR (HOMA-IR), we conducted a cross-sectional study to compare 40 (19 females) idiopathic LGA-born prepubertal children [mean ± SD age 6.1 ± 2.5 years] and 49 (25 females) (5.4 ± 1.8 years) AGA-born BMI-matched peers with respect to anthropometric and laboratory data. Both groups were further divided into subgroups as being obese/overweight (OW) and non-OW, and the analyses were repeated. LGA-born children were taller and heavier than AGA-born children (p < 0.001). Fasting insulin, HOMA-IR, and leptin were higher in LGA-born children than in AGA-born counterparts (p < 0.001). Serum TNF-α levels were lower and IL-6 levels were significantly higher in LGA- than in AGA-born children (p < 0.001). In the LGA group, TNF-α was correlated with HOMA-IR (r = -0.49, p = 0.002). LGA-born non-OW children had higher serum insulin concentrations and HOMA-IR than AGA-born counterparts. Multivariate regression analysis revealed that HOMA-IR was best explained by (R (2) = 0.517) birth weight SDS (ß = +0.418, p = 0.002), leptin (ß = +0.620, p = 0.000), and TNF-α (ß = -0.374, p = 0.003) in LGA-born children. Idiopathic LGA-born children have significantly lower TNF-α and higher IL-6 levels than AGA-born children. Reduced TNF-α levels are associated with increased IR.

Sitting height and sitting height/height ratio references for Turkish children.

UNLABELLED: Sitting height (SHt) measurements and sitting height/height (SHt/Ht) ratio are important criteria in the diagnosis of growth problems and particularly in the diagnosis of dysproportionate growth. It is known that body proportions are related to genetic influences and show variations among different populations. This study aimed to provide reference data on SHt and SHt/Ht ratios for Turkish children of ages 6-18 years. SHt measurements were performed on a sample of 1,100 boys and 1,020 girls between 6 and 18 years of age attending primary and secondary schools located in six different districts of Istanbul city. Criteria advanced by WHO for establishing reference standards for growth were observed in the study design. The sample consisted of a mixture of children measured only once and those measured at follow-up over different periods of time. Parallel to increase in Ht, SHt increased with age. Mean value for SHt/Ht ratio was 55-56% at ages 6 to 8.5 years in both sexes. In girls, this value started to decrease at age 11.5 years and remained between 53% and 54% thereafter. In the boys, a decrease to 52-53% was noted in the SHt/Ht ratio after age 12 years. In both sexes, SHt/Ht ratio decreased with puberty, demonstrating that growth in trunk length exceeded growth in limb length in midpubertal ages. These changes occurred at an earlier age in the girls. Values obtained for SHt/Ht ratios in Turkish children were high as compared to Dutch children and low as compared to Chinese children. CONCLUSION: This study, by providing reference data on sitting height and sitting height/height ratios in Turkish children of ages between 6 and 18 years, will be useful in the diagnosis and follow-up of children with growth problems. This study also supports the view that body proportions are influenced by genetic makeup.

Pelvic ultrasound findings in prepubertal girls with precocious adrenarche born appropriate for gestational age.

BACKGROUND: Precocious adrenarche (PA) refers to the clinical onset of excess androgen in girls before the age of 8. It is associated with an increased risk of functional ovarian hyperandrogenism after puberty. PA may be associated with polycystic ovary syndrome (PCOS). We compared pelvic ultrasound (US) findings of girls with PA born appropriate for gestational age (AGA) to healthy body mass index (BMI)-matched peers to determine whether US findings in AGA-born PA girls are associated with PCOS antecedents. SUBJECTS AND METHODS: We conducted a cross-sectional study on 56 AGA-born girls with PA (6·9 ± 0·6 years) and 33 BMI-matched prepubertal AGA-born peers (7·1 ± 1·0 years). Hormonal data, homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISIcomp ) and pelvic US findings were compared. Associations of pelvic US findings with clinical and metabolic data were investigated. RESULTS: Precocious adrenarche girls had greater height and bone age-adjusted uterine length (UL; P = 0·01) and UL standard deviation score (SDS) (P = 0·02) than BMI-matched peers. Mean ovarian volume (MOV), MOV SDS, uterine volume, uterine cross-sectional area and ovarian morphology were similar between the groups (P > 0·05). MOV and MOV SDS correlated with ISIcomp (r = -0·683, P < 0·001; r = -0·760, P < 0·001; respectively). Correlations of pelvic US findings with other biochemical data did not reach significance (P > 0·05). Multivariate regression analysis revealed that in girls with PA, ISIcomp had the most significant effect on MOV SDS (R(2) = 0·731, ß = -4·784, P = 0·001). CONCLUSIONS: Appropriate for gestational age-born PA girls have greater UL measurements than AGA-born BMI-matched peers. In AGA-born girls with PA, decreasing insulin sensitivity is strongly and independently associated with an increase in MOV. Longitudinal follow-up of our cohort after menarche will allow us to establish how many AGA-born girls with PA will ultimately develop PCOS.

Netherton syndrome associated with growth hormone deficiency.

Netherton syndrome (NS) is a rare autosomal recessive disorder characterized by ichthyosiform scaling, hair abnormalities, and variable atopic features. Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS. Growth retardation is a classic feature of NS, but growth hormone (GH) deficiency with subsequent response to GH therapy is not documented in the literature. It is proposed that a lack of inhibition of proteases due to a deficiency of LEKTI in the pituitary gland leads to the overprocessing of human GH in NS. Herein we report three patients with NS who had growth retardation associated with GH deficiency and responded well to GH therapy.

Reduced atherogenic indices in prepubertal girls with precocious adrenarche born appropriate for gestational age in relation to the conundrum of DHEAS.

CONTEXT: An association between low birth weight, insulin resistance (IR), dyslipidemia, and atherogenesis has been shown in girls with precocious adrenarche (PA). OBJECTIVE: To evaluate whether girls with PA born appropriate for gestational age (AGA) have increased risk for metabolic complications at initial evaluation. DESIGN/METHODS: We conducted a cross-sectional study on 69 AGA born girls with PA (mean (±s.d.) age 7.1±1 years) and 45 body mass index (BMI)- and waist circumference (WC)-matched prepubertal peers born AGA (mean (±s.d.) 7.5±1.9 years). A standard 2-h oral glucose tolerance test with insulin sampling was performed. Fasting plasma lipids and high-sensitivity C-reactive protein were analyzed, and blood pressure was recorded. Insulin sensitivity (IS) index (ISIcomp), homeostasis model assessment of IR, and atherogenic index (AI) (triglycerides/high-density lipoprotein cholesterol) were calculated. SETTING: The study was performed at University Hospital. RESULTS: AI was significantly lower in girls with PA than in controls (P<0.001), and it was correlated with BMI SDS (r=0.44, P=0.001) and WC (r=0.39, P=0.001). The significant correlation of AI with ISIcomp (r=-0.38, P=0.001) disappeared after correcting for BMI (r=-0.185, P=0.16). Multivariate regression analysis revealed that DHEAS was the only significant parameter influencing AI in girls with born AGA (R (2)=0.475 ß=-0.018, P=0.0001). CONCLUSIONS: Metabolic screening in prepubertal AGA born girls with PA may yield favorable lipid profiles. AI in girls with PA is increased in relation to decreasing IS and increasing BMI and WC. DHEAS seems to have the most significant effect on AI.

Frequency and severity of ketoacidosis at onset of autoimmune type 1 diabetes over the past decade in children referred to a tertiary paediatric care centre: potential impact of a national programme highlighted.

AIMS: To assess the frequency and severity of diabetic ketoacidosis (DKA) at disease onset in children newly diagnosed with autoimmune type 1 diabetes (T1D) in Istanbul in the last decade. Also, to evaluate the potential contribution of the national diabetes awareness programme (NDAP) initiated in 2010. METHODS: Four hundred and one consecutive children (mean ± standard deviation, age 8.1 ± 4.1 years) with a diagnosis of autoimmune T1D were evaluated retrospectively with respect to demographic, clinical, and laboratory data in relation to DKA at disease onset. The possible impact of NDAP on the rate of DKA at disease onset in the last 2 years was also evaluated by comparing the data related to the time intervals before and after the onset of the programme. The results were evaluated at 95% confidence interval and significance was granted for p ≤ 0.05. RESULTS: The overall frequency of DKA at disease onset was 44.2%, with a significant trend for decline in rate of DKA at disease onset in the last decade (p=0.0001). There were no significant differences in proportions of newly diagnosed T1D patients with severe or moderate DKA over time. Mean body mass index standard deviation score tended to increase in the last decade, but not significantly (p=0.09). When the time intervals before and after the onset of NDAP were evaluated, there was a more than two-fold decrease in rate of DKA (from 49.3% to 23.9%) (p<0.0001). CONCLUSIONS: The frequency of a DKA event at onset of T1D is still high in Istanbul children despite a decreasing trend in the last decade. NDAP may significantly contribute to the reduction in rate of DKA.

Are metabolic syndrome antecedents in prepubertal children associated with being born idiopathic large for gestational age?

INTRODUCTION: Being born large for gestational age (LGA) is a risk factor for development of metabolic syndrome (MS) in adolescents and adults. OBJECTIVE: To evaluate prepubertal children born idiopathic LGA to non-obese mothers without gestational diabetes or glucosuria with respect to the presence of MS antecedents. PATIENTS AND METHODS: We conducted a cross-sectional study to compare 40 (19 F) LGA-born prepubertal children of a mean age of 6.1 ± 2.5 yr and 49 (25 F) appropriate for gestational age (AGA)-born body mass index (BMI)-matched peers of a mean age of 5.4 ± 1.8 yr with respect to their anthropometric data, blood pressure measurements, fasting serum glucose and insulin levels, homeostasis model assessment-insulin resistance (HOMA-IR), and lipids and atherogenic index (AI) [triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)]. HOMA-IR > 2.5 was used to define IR. HDL-C ≤ 40 mg/dL and TG ≥ 110 mg/dL were used to define dyslipidemia. Both groups were further divided into subgroups as obese and non-obese according to their BMI percentiles and the analyses were repeated. RESULTS: Non-obese LGA children had higher waist circumference (WC) standard deviation scores (SDSs) than BMI-matched AGA-born peers (p = 0.024). There were no significant differences between pooled, obese and non-obese subgroups of LGA-born children and their AGA counterparts with respect to dyslipidemia and IR. AI was higher in non-obese LGA children than in AGA counterparts (p = 0.028). CONCLUSIONS: Non-obese idiopathic LGA-born children have higher AIs than AGA-born counterparts in the absence of IR. WC seems to be a good clinical screening tool in identifying at risk of non-obese LGA children. Further studies are needed to evaluate MS antecedents in idiopathic LGA-born children.