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Introduction Data on adult height (AHt) in individuals with non-classical congenital adrenal hyperplasia (NCCAH) are inconsistent. Methods We conducted a retrospective study of 109 females diagnosed with NCCAH at age

To evaluate the effect of nutritional supplementation on height, weight and body composition in short and lean male preadolescents.A randomised, double-blinded, placebo-controlled trial of nutritional supplementation of short and lean prepubertal 10-14.5-year-old boys. Primary outcomes included Δheight-SDS and Δweight-SDS. Secondary outcomes included changes in body composition and BMI-SDS.Of 160 boys enrolled, 126 (80%) completed 6 months' intervention. Baseline age, height-SDS, weight-SDS, BMI-SDS, body composition and dietary intake were similar in the formula and placebo groups. 'Good' formula consumers (intake of ≥50% of the recommended dose, n = 30) gained significantly more in weight-SDS, BMI-SDS, fat-free-mass and muscle mass (p 0.05) than did 'poor' consumers (n = 35) and the placebo group (n = 61). Only in the formula group, positive dose-response correlations were found between consumption of the formula and changes in the outcome parameters examined, including Δheight-SDS (r = 0.301, p = 0.015). Boys aged11.4 years who were 'good' formula consumers maintained their Δheight-SDS, while Δheight-SDS declined in 'poor' consumers and the placebo group of the same age (p = 0.033).Intervention with a multi-nutrient, protein-rich formula was effective in increasing weight-SDS, fat-free-mass, muscle mass and BMI-SDS in short and lean prepubertal male adolescents. Good consumption of the formula prevented Δheight-SDS decline in the older participants.

Aim The COVID‐19 pandemic prompted the rapid development of remote medical services. During lockdown periods, children's growth data were obtained from parents’ home assessments. This study aimed to assess the accuracy of home height and weight measurements and analyse their utility in clinical decision‐making. Methods A retrospective, single‐centre observational study. Children aged 3–18 years were measured for weight and height at home using guidance provided to parents on proper measurements techniques before subsequent professional re‐evaluation at our endocrine institution clinic. The two sets of measurements were compared and analysed according to various clinical parameters. Results Height measurements at home and in the clinic were comparable (diff = 0.1 ± 1.3cm, p = 0.42) amongst the 107 children (mean age 10.2 ± 3.7, 56.1% males) participating in the study, except in overweight and obese children where they were significantly higher in the clinic (diff = 0.86 ± 1.48cm, p = 0.018). Weight and BMI were significantly higher in the clinic (diff = 0.45 ± 0.8kg and diff = 0.3 ± 0.6kg/m2, p

Background Type 1 diabetes (T1D) contributes to altered lipid profiles and increases the risk of cardiovascular disease (CVD). Youth with T1D may have additional CVD risk factors within the first decade of diagnosis. Aim To examine risk factors for dyslipidemia in young subjects with T1D. Methods Longitudinal and cross-sectional retrospective study of 170 young subjects with T1D (86 males; baseline mean age 12.2 ± 5.6 years and hemoglobin A1c 8.4% ± 1.4%) were followed in a single tertiary diabetes center for a median duration of 15 years. Predictors for outcomes of lipid profiles at last visit (total cholesterol [TC], triglycerides [TGs], low-density lipoprotein-cholesterol [LDL-c], and high-density lipoprotein-cholesterol [HDL-c]) were analyzed by stepwise linear regression models. Results At baseline, 79.5% of the patients had at least one additional CVD risk factor (borderline dyslipidemia/dyslipidemia [37.5%], pre-hypertension/hypertension [27.6%], and overweight/obesity [16.5%]) and 41.6% had multiple (≥ 2) CVD risk factors. A positive family history of at least one CVD risk factor in a first-degree relative was reported in 54.1% of the cohort. Predictors of elevated TC: family history of CVD (β[SE] = 23.1[8.3], P = 0.006); of elevated LDL-c: baseline diastolic blood pressure (DBP) (β[SE] = 11.4[4.7], P = 0.003) and family history of CVD (β[SE] = 20.7[6.8], P = 0.017); of elevated TGs: baseline DBP (β[SE] = 23.8[9.1], P = 0.010) and family history of CVD (β[SE] = 31.0[13.1], P = 0.020); and of low HDL-c levels: baseline DBP (β[SE] = 4.8[2.1], P = 0.022]). Conclusion Our findings suggest that elevated lipid profiles are associated with DBP and a positive family history of CVD. It is of utmost importance to prevent and control modifiable risk factors such as these, as early as childhood, given that inadequate glycemic control and elevation in blood pressure intensify the risk of dyslipidemia.

Introduction: Adequate nutrition plays an important role in linear growth throughout childhood, including puberty. However, not all children are willing or able to consume an adequate balanced diet daily. We aimed to evaluate the 1-year effectiveness and safety of nutritional supplementation on linear growth, weight gain, and changes in body composition in short and lean peripubertal boys. Methods: A one-year, 2-phase multicenter interventional study comprising 1-6 months of a double-blinded intervention with nutritional formula or placebo, followed by 6-12 months of an open-label extension with the nutritional formula for all participants. Results: The outcomes of the double-blinded intervention were reported previously. A total of 79/98 (81%) boys, aged ≥10 years, Tanner stages 1-3, completed the open-labeled extension-phase. For this phase, a significant dose-response correlation (P

Objective: The need for personalization of the reference values of thyroid function tests has been previously suggested. We aimed at determining TSH reference values in a large cohort of children according to age, sex, BMI, and ethnicity. Design: A population-based cohort study. Methods: The study cohort included 75 549 healthy children aged 5–18 years. Data analyzed included age, gender, TSH, FT4 levels, BMI and ethnicity. Multivariate logistic regression analysis examined the associations between the study parameters. Results: TSH in the Jewish population is lower than in the non-Jewish population (median: 2.1 IU/L (IQR: 1.5) vs 2.2 IU/L (IQR: 1.5), P < 0.0001). TSH is significantly affected by BMI for children defined as underweight, normal weight, overweight or obese, levels increased as weight diverged from the normal range (median levels: 2.1 IU/L (IQR: 1.4), 2.0 IU/L (IQR: 1.3), 2.1 IU/L (IQR: 1.4), 2.4 (IQR: 1.5), respectively, P < 0.001). The 2.5 percentile is affected by gender and BMI (P < 0.02 and P < 0.001, respectively), while the 97.5 percentile is affected by ethnic origin and BMI (P < 0.001 for both). New TSH reference intervals (RI) adjusted according to BMI and ethnicity are suggested. Comparison of the old and new RI demonstrate the significance of RI personalization: 25.1% of the children with TSH levels above the old RI are within the new RI, while 2.3% of the children who were in the old RI are below the new RI. Conclusions: TSH reference values in children are affected by BMI and ethnicity. Reference values should be individualized accordingly to improve future clinical decision-making and treatment.

Context Data is needed regarding the effect of SARS-CoV-19 infection on young people with established type 1 diabetes. Identifying the disease outcomes, short and long-term sequelae may help to establish an evidence-based prevention and education policy for sick days management and DKA prevention. Objective This work aims to describe clinical manifestations of SARS-CoV-2 infection in children, adolescents, and young adults with established type 1 diabetes (T1D) and explore the effects of COVID-19 on glycemic control and disease course. Methods An observational study was conducted at 3 pediatric diabetes clinics in Israel between mid-March 2020 and mid-March 2021. Included were young people with established T1D, age younger than 30 years, who tested positive for SARS-CoV-2 (quantitative real-time polymerase chain reaction). Data were collected from medical files, diabetes devices, and COVID-19 questionnaire. Outcome measures were analyzed by the presence/absence of clinical symptoms (symptomatic/asymptomatic) and by age group (pediatric, Results Of 132 patients, mean age 16.9 ± 5.3years, with COVID-19–confirmed infection, 103 (78%) had related symptoms; the most common were headaches, fatigue, fever, and loss of sense of smell. All had a mild disease course, but 4 required hospitalization and 2 cases were directly related to COVID-19 infection (pleuropneumonia in a patient with immunodeficiency syndrome, 1 case of diabetic ketoacidosis). Logistic regression analysis showed that age (odds ratio [OR] = 1.11; 95% CI, 1.01-1.23; P = .033), elevated glucose levels (OR = 5.23; 95% CI, 1.12-24.41; P = .035), and comorbidities (OR = 8.21; 95% CI, 1.00-67.51; P = .050) were positively associated with symptomatic infection. Persistent symptoms occurred in 16.5% of the cohort over a median of 6.7 months; age (OR = 1.14; 95% CI, 1.01-1.29; P = .030) and elevated glucose levels (OR = 3.42; 95% CI, 1.12-10.40; P = .031) were positively associated with persistent symptoms. Usually, no change was reported in glucose levels (64%) except for a temporary deterioration in glycemic control during the short infection period. Conclusion Young people with established T1D experience mild COVID-19 infection. Elevated glucose levels during COVID-19 infection and older age were associated with prolonged disease course.

Poor glycemic control in children with type 1 diabetes (T1D) may hinder sexual development and the associated growth spurt. This study aims to identify factors that may affect the timing of puberty, total pubertal growth (TPG), and final height (F-Ht) in boys with T1D.This was a retrospective longitudinal study of 68 boys diagnosed with T1D during 1996 to 2009, who were prepubertal at diagnosis and had completed puberty at the time of data collection. Data were accessed regarding anthropometric measurements, Tanner stage, and glycosylated hemoglobin (HbA1c) levels from diagnosis to F-Ht. F-Ht was compared to parental height and Israeli National Health Survey data.The mean F-Ht standard deviation score (F-Ht-SDS) was lower than the mean Ht-SDS at diagnosis (P .006) but similar to the mean target height SDS (P = .3) and to values from the national survey (P = .12). Mean HbA1c levels in the year preceding pubertal onset were associated with the age at onset of puberty (R = 0.33, P = .009) and inversely with TPG (R = -0.3, P = .03). Mean HbA1c levels during puberty were inversely associated with TPG (R = -0.26, P = .035) and F-Ht (R = -0.28, P = .02). Boys who presented with diabetic ketoacidosis at diagnosis were shorter than those who did not throughout the follow-up.We found associations of age of pubertal onset, pubertal growth spurt, and F-Ht with target height and glycemic control before and during puberty. Targeted interventions to achieve optimal metabolic control during these time periods are needed for normal, timely puberty and for achieving optimal adult height within the genetic target height.背景: 1型糖尿病(T1D)儿童血糖控制不良可能会阻碍性发育和生长发育。本研究旨在确定可能影响T1D男孩青春期发育时间、总青春期发育(TPG)和最终身高(F-Ht)的因素。 方法: 这是一项回顾性纵向研究, 研究对象为1996年至2009年间被诊断为T1D的68名男孩, 他们在被诊断时处于青春期前, 在数据收集时青春期结束。获取从诊断到F-Ht的人体测量、Tanner分期和糖化血红蛋白(HbA1c)水平的数据。将F-Ht与父母身高和以色列国民健康调查数据进行比较。 结果: 诊断时F-Ht标准差得分(F-Ht-SDS)低于Ht-SDS平均值(P0.006), 与靶高度SDS平均值(P=0.3)和全国普查值(P=0.12)相近。青春期开始前一年的平均HbA1c水平与青春期开始年龄呈正相关(R=0.33, P=0.009), 与TPG呈负相关(R= -0.3, P=0.03)。青春期平均HbA1c水平与TPG(R=-0.26, P=0.035)和F-Ht(R=-0.28, P=0.02)呈负相关。在诊断时以糖尿病酮症酸中毒为起病的男孩在整个随访过程中的身高要比那些没有酮症酸中毒的男孩要矮。 结论: 我们发现青春期开始年龄、青春期生长增速期和F-Ht与青春期前和青春期期间的目标身高和血糖控制相关。在这些时间段内实现最佳代谢控制的针对性干预对于在遗传目标身高范围内达到最佳成人身高是必要的。.

To compare clinical outcomes of 3 treatment regimens-glucocorticoids (GCs), oral contraceptives (OCs), or a combination of both-administered to adolescents and young women diagnosed in childhood with nonclassical congenital adrenal hyperplasia (NCCAH), who had been treated with GCs until their adult height was achieved.A retrospective study of medical records of 53 female patients with NCCAH followed in 3 tertiary pediatric endocrinology institutes. The 3 treatment groups were compared for the prevalence of hirsutism and acne, standardized body mass index (BMI)-standard deviation score (SDS), and androgen levels at the attainment of adult height (baseline), 1-year later, and at the last documented visit.At baseline, there were no significant differences among groups in BMI-SDS, androgen levels, hirsutism prevalence, acne, or irregular menses. From baseline to the last visit, the rate of hirsutism declined significantly only in the OC group (37.5% vs 6.2%, respectively; P = .03). The rate of acne declined in the combined group (50% vs 9%, respectively; P = .03) with a similar tendency in the OC group (50% vs 12.5%, respectively; P = .05). No significant changes were observed in BMI-SDS for the entire cohort or any subgroup during follow-up. A significant rise in androstenedione (P.001), testosterone (P.01), and 17-hydroxyprogesterone (P.01) levels was observed only in the OC group.In girls diagnosed in childhood with NCCAH, who require treatment for hyperandrogenism following completion of linear growth, management should be tailored individually using a patient-centered approach. Treatment with OCs might be better than that with GCs for regression of hirsutism and acne. The long-term effects of elevated levels of androgens associated with this treatment regimen should be further studied.

Given the large number of false-positive growth hormone deficiency (GHD) diagnoses from a single growth hormone (GH) stimulation test in children, 2 different pharmacologic tests, performed on separate days or sequentially, are required. This study aimed to assess the reliability and safety of a combined arginine-clonidine stimulation test (CACST).This was a retrospective, single-center, observational study. During 2017-2019, 515 children aged8 years underwent GH stimulation tests (CACST: n = 362 or clonidine stimulation test [CST]: n = 153). The main outcome measures used to compare the tests were GH response (sufficiency/deficiency) and amplitude and timing of peak GH and safety parameters.Population characteristics were as follows: median age of 12.2 years (interquartile range [IQR]: 10.7, 13.4), 331 boys (64%), and 282 prepubertal children (54.8%). The GHD rate was comparable with 12.7% for CACST and 14.4% for CST followed by a confirmatory test (glucagon or arginine) (P = .609). Peak GH was higher and occurred later in response to CACST compared with CST (14.6 ng/mL [IQR: 10.6, 19.4] vs 11.4 ng/mL [IQR: 7.0, 15.8], respectively, P.001; 90 minutes [IQR: 60, 90] vs 60 minutes [IQR: 60, 90], respectively, P.001). No serious adverse events occurred following CACST.Our findings demonstrate the reliability and safety of CACST in detecting GHD in late childhood and adolescence, suggesting that it may replace separate or sequential GH stimulation tests. By diminishing the need for the second GH stimulation test, CACST saves time, is more cost-effective, and reduces discomfort for children, caregivers, and medical staff.

CONTEXT Management of GH-treated children with idiopathic short stature (ISS) with early puberty and adolescents in midpuberty at initiation of treatment is challenging. OBJECTIVE To assess the effect of combined GH/GnRHa therapy during puberty on achieved adult height (AHt) in these children with ISS and to determine whether outcome depended on sex and pubertal status at initiation of GH therapy. DESIGN Retrospective, single-center observational study from 2003-2018. SETTING Tertiary endocrine center. PATIENTS One hundred ninety-two GH-treated children with ISS; 58 of 192 were treated by GH/GnRHa during puberty; 31 of 58 were prepubertal (19 girls) and 27 of 58 pubertal (19 girls) at initiation of GH. MAIN OUTCOME MEASURES AHt, gain-in-height standard deviation score (SDS), AHt vs predicted adult height (PAHt), AHt vs target height (THt). RESULTS Most boys and girls attained AHt SDS within the normal range (-0.73 ± 0.60 and -0.85 ± 0.65, respectively). Treatment modality, pubertal status, and sex were tested for their joint effect on growth outcome measures. Combined GH/GnRHa therapy increased AHt vs PAHt (P < 0.001) and AHt vs THt (P = 0.035). Prepubertal status at onset of GH treatment increased AHt (P = 0.049), gain-in-height SDS (P < 0.001), AHt vs PAHt (P < 0.001), and AHt vs THt (P = 0.042). Female sex increased AHt vs PAHt (P < 0.001). CONCLUSIONS Our study demonstrated a beneficial effect of combined GH/GnRHa therapy in increasing AHt outcome in children with ISS with early/normal puberty and in adolescents naive to GH treatment who are in midpuberty at initiation of therapy. This effect was more pronounced in the prepubertal group and in girls. Prospective randomized controlled trials are needed to assess whether GnRHa can increase AHt in GH-treated children with ISS.

Context Central precocious puberty (CPP) may be the first presentation of nonclassical congenital adrenal hyperplasia (NCCAH) in girls. Data on the prevalence and the clinical phenotype of CPP associated with NCCAH are sparse. Objectives To study the clinical and laboratory characteristics that could differentiate idiopathic CPP from CPP associated with NCCAH and to determine the prevalence of NCCAH among girls with CPP. Design Case-control study. Setting Tertiary pediatric endocrinology institute. Participants and methods From 2008 to 2017, 147 girls who had undergone stimulation tests with gonadotropin-releasing hormone and ACTH were diagnosed with CPP; of these, seven (4.8%) were eventually diagnosed with NCCAH. These seven patients together with 30 girls who presented with CPP during 1984 to 2008 and were later diagnosed with NCCAH comprised the NCCAH group. Demographic, anthropometric, clinical, and laboratory data were compared between the NCCAH group and the 140 girls with idiopathic CPP (ICPP group). Results No between-group differences were found in height, weight, body mass index, bone age, and Tanner stage. Mean basal levels of androstenedione, dehydroepiandrosterone-sulphate, and 17-hydroxyprogesterone were significantly higher in the NCCAH group, although ranges overlapped between the groups, and stimulated cortisol level was higher in the ICPP group. Conclusion NCCAH was found in 4.8% of girls presenting with true CPP over 10 years, and no single parameter could differentiate between the diagnoses. Thus, in girls with true CPP from populations in which NCCAH is prevalent, assessment of adrenal androgens is required, and ACTH test should be considered.

Introduction: The diagnosis of childhood growth hormone deficiency (GHD) requires a failure to respond to 2 GH stimulation tests (GHSTs) performed with different stimuli. The most commonly used tests are glucagon stimulation test (GST) and clonidine stimulation test (CST). This study assesses and compares GST and CST’s diagnostic efficacy for the initial evaluation of short children. Methods: Retrospective, single-center, observational study of 512 short children who underwent GHST with GST first or CST first and a confirmatory test with the opposite stimulus in cases of initial GH peak Results: Population characteristics include median age of 9.3 years (interquartile range 6.2, 12.1), 78.3% prepubertal, and 61% boys. Subnormal GH response in the initial test was recorded in 204 (39.8%) children: 148 (45.5%) in GST first and 56 (30%) in CST first, p < 0.001. Confirmatory tests verified GHD in 75/512 (14.6%) patients. Divergent results between the initial and confirmatory tests were more prevalent in GST first than CST first (103/148 [69.6%] vs. 26/56 [46.4%], p < 0.001) indicating a significantly lower error rate for the CST first compared to the GST first. In multivariate analysis, the only significant predictive variable for divergent results between the tests was the type of stimulation test (OR = 0.349 [95% CI 0.217, 0.562], p < 0.001). Conclusions: Screening of GH status with CST first is more efficient than that with GST first in diagnosing GHD in short children with suspected GHD. It is suggested that performing CST first may reduce the need for a second provocative test and avoid patients’ inconvenience of undergoing 2 serial tests.

Background: Data on the course of puberty and pubertal growth in boys with Type 1 diabetes (T1D) are sparse. Objectives: To study the course of puberty, pubertal growth and final height in boys with T1D as well as possible factors affecting these. Methods: In this retrospective longitudinal study, 68 boys diagnosed with T1D between 1996-2009 who were pre-pubertal at diagnosis and had completed puberty served as the cohort. Collected were data on anthropometric measurements, Tanner stage, and HbA1c levels from diagnosis to final height (F-Ht). F-Ht was compared to parental height and to the data of the national health survey Results – In the study cohort final height-SDS was lower than that at diagnosis. It was similar to parental Ht-SDS as well as to that of the national health survey (p=0.126). F-Ht was inversely related to average HbA1c during puberty (R=-0.27, p=0.045). Boys who presented with diabetic ketoacidosis at diagnosis were shorter than those who did not throughout the entire follow-up. Age at onset of puberty was significantly related to the age of maternal menarche (R=0.44, p=0.01) and to HbA1c levels in the year preceding puberty onset (R=0.36, p=0.01). Total pubertal growth was inversely related to HbA1c levels in the year preceding onset of puberty (average R=-0.3, p=0.03) Conclusions: Boys with T1D diagnosed before puberty achieve final height similar to that of their parents and that of the general population. Diabetic ketoacidosis at the diagnosis is associated with diminished F-Ht. Age of pubertal onset and F-Ht are affected by genetic factors as well as by glycemic control before and during puberty. These results emphasize the importance of tight metabolic control in adolescents, to enable growth within the genetic target.

Background Few studies have evaluated the impact of diabetic ketoacidosis (DKA) at diabetes onset on long-term glycemic control in patients with type 1 diabetes (T1D). Objective We aimed to determine any differences in long-term glycemic control between children/adolescents with T1D presenting with DKA at diabetes onset and those without. Methods This retrospective study comprised 335 patients diagnosed with T1D from September 2007 to December 2012, among which 132 (39.4%) presented with DKA. Variables compared between patients with DKA at onset and those without: yearly hemoglobin A1c (HbA1c) levels, daily insulin dose, yearly rates of severe hypoglycemia and DKA, percent of patients achieving target HbA1c levels. Results After the first year of diabetes, the mean daily insulin dose and HbA1c level were significantly higher in the group with DKA at onset (0.74 ± 0.26 vs 0.69 ± 0.27 units/kg/d, P = .049, and 7.85 ± 1.13% vs 7.49 ± 0.94%, P = .01, respectively), despite similarity of therapy (multiple daily injections or continuous subcutaneous insulin infusion), with a similar but not statistically significant trend subsequently. Mean HbA1c since onset was significantly higher in the DKA group (8.08 ± 0.95% vs 7.86 ± 0.95%, P = .025). A significantly higher percentage of patients in the group without DKA at onset achieved a mean level of HbA1c since onset within glycemic targets (32% vs 20.5%, P = .02). In the DKA group, the frequency of subsequent DKA episodes per diabetes years was significantly higher (P = .042). Conclusions DKA at diagnosis was associated with less favorable long-term glycemic control as assessed by HbA1c and the rate of DKA episodes. T1D patients presenting with DKA may therefore need stricter treatment and tight follow-up.

Aim This study explored whether using the suggested diagnostic serum basal level of 17-hydroxyprogesterone (6.0 nmol/L) would lead to underdiagnosis of nonclassical congenital adrenal hyperplasia. Methods We retrospectively studied 123 patients with nonclassical congenital adrenal hyperplasia, defined as an adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone level of more than 45 nmol/L. Of these 13 had basal 17-hydroxyprogesterone levels of less than 6.0 nmol/L and 110 exceeded that level. The 42 controls had idiopathic premature pubarche. Clinical and laboratory data were reviewed and compared. Results There were no differences between patients with 17-hydroxyprogesterone levels of

Context: Central precocious puberty (CPP) may be the first presentation of non-classical congenital adrenal hyperplasia (NCCAH) in girls. Data on the prevalence and the clinical phenotype of CPP associated with NCCAH are sparse. Objectives: To study the clinical and laboratory characteristics that could differentiate idiopathic CPP from CPP associated with NCCAH and to determine the prevalence of NCCAH among girls with CPP. Design: Case-control study. Setting: Tertiary pediatric endocrinology institute. Participants and Methods: From 2008 to 2017, 147 girls who had undergone stimulation tests with gonadotropin-releasing hormone and Synacthen were diagnosed with CPP, of whom 7 (4.8%) were eventually diagnosed with NCCAH. These 7 patients together with 30 girls who presented with CPP in1984-2008 and were later diagnosed with NCCAH comprised the NCCAH group. Demographic, anthropometric, clinical, and laboratory data were compared between the NCCAH group and the 140 girls with idiopathic CPP (ICPP group). Results: No between-group differences were found in height, weight, body mass index, bone age, and Tanner stage. Mean basal levels of androstenedione, DHEAS, and 17-OHP were significantly higher in the NCCAH group, although ranges overlapped between the groups, and stimulated cortisol level was higher in the ICPP group. Conclusions: NCCAH was found in 4.8% of girls presenting with true CPP over a 10-year period, and no one parameter could differentiate between the diagnoses. Thus, in girls with true CPP from populations in which NCCAH is prevalent, assessment of adrenal androgens is required and ACTH test should be considered. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

To assess clinical variables, including early thyroid scintigraphy, in predicting the outcome (permanent vs transient) in term infants with congenital hypothyroidism (CH).In a retrospective study, 142 full-term infants with CH diagnosed between 2000 and 2012 were categorized into three groups: agenesis/ectopic thyroid and permanent CH; eutopic thyroid and permanent CH; and eutopic thyroid and transient CH. All underwent early thyroid scintigraphy and were under regular follow-up in our tertiary Pediatric Endocrine Institute.Thyroid scan showed agenesis/ectopic thyroid in 58 (41%) and eutopic thyroid in 84 (59%) infants. Imaging findings were similar in eutopic-permanent and eutopic-transient groups. At initial evaluation, TSH levels were higher in the agenesis/ectopic group than in the eutopic-permanent and eutopic-transient groups (71.5 ± 11.2 mIU/L vs 49.1 ± 27.9 mIU/L and 42.5 ± 29.1 mIU/L, respectively; P0.001). Higher l-T4 doses were required from the third month in the agenesis/ectopic than in the eutopic-permanent group (P0.001) and from the sixth month in the eutopic-permanent than in the eutopic-transient group (P0.01). Initial TSH63.5 mU/L (P0.001) and l-T4 dose4.6 μg/kg/d at age6 months (P0.001) were found to be predictors for an agenesis/ectopic gland using receiver operating characteristic analysis, as was an l-T4 dose2.2 μg/kg/d at age6 months (P0.01) for permanent CH in patients with a eutopic gland.Although early thyroid scintigraphy is reliable in predicting permanent CH when detecting agenesis or ectopic gland, it cannot differentiate between permanent and transient CH in cases with a eutopic thyroid. Confirmatory TSH at diagnosis and the l-T4 dose through treatment may better distinguish between permanent and transient CH.

Objective Patients with Turner syndrome (TS) are at increased risk for metabolic disorders. We aimed to delineate the occurrence and evolution of metabolic comorbidities in TS patients and to determine whether these differ in 45,X monosomy and other karyotypes. Methods A longitudinal and cross-sectional retrospective cohort study was conducted in a tertiary pediatric endocrine unit during 1980–2016. Ninety-eight TS patients, 30 with 45,X monosomy were followed from childhood to early adulthood. Outcome measures included weight status, blood pressure (BP), glucose metabolism, and lipid profile. Results Longitudinal analysis showed a significant change in body mass index (BMI) percentiles over time [F(3,115) = 4.8, P = 0.003]. Age was associated with evolution of elevated BP [systolic BP: odds ratio (OR) = 0.91, P = 0.003; diastolic BP: OR = 0.93, P = 0.023], impaired glucose metabolism (HbA1c: OR = 1.08, P = 0.029; impaired glucose tolerance: OR = 1.12, P = 0.029), and abnormal lipid profile (cholesterol: OR = 1.06, P = 0.01; low-density lipoprotein cholesterol: OR = 1.07, P = 0.041; high-density lipoprotein cholesterol: OR = 1.07, P = 0.033). The occurrence of metabolic comorbidities was similar in 45,X monosomy and other karyotypes. Coexistence of multiple metabolic comorbidities was significantly higher in 45,X monosomy [F(1,72) = 4.81, P = 0.032]. BMI percentiles were positively correlated with metabolic comorbidities (occurrence and number) in each patient (r = 0.35, P = 0.002 and r = 0.383, P = 0.001, respectively). Conclusion Our longitudinal study provides unique insights into the evolution of weight gain and metabolic disorders from childhood to early adulthood in TS patients. Since overweight and increasing age aggravate the risk for metabolic comorbidities, careful surveillance is warranted to prevent and control obesity already from childhood. The more prominent clustering of metabolic comorbidities in 45,X monosomy underscores the importance of a more vigorous intervention in this group.

Aim: To investigate the effect of growth hormone (GH) therapy on appetite-regulating hormones and to examine the association between these hormones and the response to GH, body composition, and resting energy expenditure (REE). Methods: Nine pre-pubertal children with idiopathic short stature underwent a standard meal test before and 4 months following initiation of GH treatment. Ghrelin, GLP-1, leptin, and insulin levels were measured; area under the curve (AUC) was calculated. Height, weight, body composition, REE, and insulin-like growth factor levels were recorded at baseline and after 4 and 12 months. Results: Following 4 months of GH therapy, food intake increased, with increased height-standard deviation score (SDS), weight-SDS, and REE (p p = .045) and fasting GLP-1 (p = .038), and an increase in fasting insulin (p = .043). Ghrelin levels before GH treatment were positively correlated with the changes in weight-SDS (fasting: r = .667, p = .05; AUC: r = .788, p = .012) and REE (fasting: r = .866, p = .005; AUC: r = .847, p = .008) following 4 months of GH therapy. Ghrelin AUC at 4 months was positively correlated with the changes in height-SDS (r = .741, p = .022) and fat-free-mass (r = .890, p = .001) at 12 months of GH treatment. Conclusions: The reduction in ghrelin and GLP-1 following GH treatment suggests a role for GH in appetite regulation. Fasting and meal-AUC ghrelin levels may serve as biomarkers for predicting short-term (4 months) changes in weight and longer term (12 months) changes in height following GH treatment. The mechanisms linking GH with changes in appetite-regulating hormones remain to be elucidated. Abbreviations: SDS: standard deviation score; REE: resting energy expenditure; SMT: standard meal test; AUC: area under the curve; ISS: idiopathic short stature; SGA: small for gestational age; FFM: fat-free-mass; FM: fat mass; EER: estimated energy requirements; DRI: dietary reference intakes; IQR: inter-quartile range

Central precocious puberty (CPP) may have clinical implications in adulthood.To assess the prevalence of obesity, metabolic outcome (hyperlipidemia, diabetes, and hypertension), and malignancy rate of former CPP women between the third and fifth decades of life.This was a case control study of a historical cohort using the computerized database of a health management organization.The setting was the Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, and Clalit Health Services.The study group comprised of 142 CPP women aged 27-50 years [100 GnRH analog (GnRHa) treated; 42 untreated]. The control group comprised of 413 women randomly matched for age, year of birth, and community clinic (283 for the GnRHa treated; 130 for the untreated).Extracted from the database were demographic data, medical history, medications dispensed, recorded anthropometric measurements, vital signs, and laboratory data.At young adulthood, body mass index (percentile and distribution) of treated and untreated former CPP women was comparable to that of their respective controls. Elevated body mass index at presentation was a risk factor for obesity in adulthood in the GnRHa-treated group (r = 0.257; P = .01). The prevalence of metabolic comorbidities (16 vs 13.4%; 21.4 vs 24.6%) and malignancy rate (1.0 vs 1.5%; 4.8 vs 1.5%) were similar in the former CPP women and their controls, with no significant difference between CPP groups.CPP (treated or untreated) is not associated with increased risk of obesity, metabolic derangements, or cancer morbidities in young adulthood. The finding that the health status of former CPP women is similar to that of the general population is reassuring.

Patients with type 1 diabetes (T1D) are exempt from conscript military service, but some volunteer for national service.To evaluate the effect of national service (military or civil) on metabolic control and incidence of acute diabetes complications in young adults with T1D.Clinical and laboratory data of 145 T1D patients were retrieved from medical records. The cohort comprised 76 patients volunteering for national service and 69 non-volunteers. Outcome measures were HbA1c, body mass index-standard deviation scores (BMI-SDS), insulin dosage, and occurrence of severe hypoglycemia or diabetic ketoacidosis (DKA).Metabolic control was similar in volunteers and non-volunteers: mean HbA1c at various time points was: 7.83 ± 1.52% vs. 8.07% ± 1.63 one year before enlistment age, 7.89 ± 1.36% vs. 7.93 ± 1.42% at enlistment age, 7.81 ± 1.28% vs. 8.00 ± 1.22% one year thereafter, 7.68 ± 0.88% vs. 7.82 ± 1.33% two years thereafter, and 7.62 ± 0.80% vs. 7.79 ± 1.19% three years thereafter. There were no significant changes in HbA1c from baseline throughout follow-up. BMI and insulin requirements were similar and remained unchanged in volunteers and controls: mean BMI-SDS one year before enlistment age was 0.23 ± 0.83 vs. 0.29 ± 0.95, at enlistment age 0.19 ± 0.87 vs. 0.25 ± 0.98, one year thereafter 0.25 ± 0.82 vs. 0.20 ± 0.96, two years thereafter 0.10 ± 0.86 vs. 0.15 ± 0.94, and three years thereafter 0.20 ± 0.87 vs. 0.16 ± 0.96. Mean insulin dose in U/kg/day one year before enlistment age was 0.90 ± 0.23 vs. 0.90 ± 0.37, at enlistment age 0.90 ± 0.28 vs. 0.93 ± 0.33, one year thereafter 0.86 ± 0.24 vs. 0.95 ± 0.33, two years thereafter 0.86 ± 0.21 vs. 0.86 ± 0.29, and three years thereafter 0.87 ± 0.23 vs. 0.86 ± 0.28. There were no episodes of severe hypoglycemia or DKA in either group.Our data indicate that during voluntary national service young adults with T1D maintain metabolic control similar to that of non-volunteers.

Bone age (BA) indicates more clearly than chronologic age how far an individual has progressed toward full maturity, and predicts the potential for further growth. Single or serial skeletal age estimations help to confirm the diagnosis of normal puberty and normal pubertal variants such as constitutional delay of growth and puberty, premature therlache, and precocious adrenarche. BA can aid in the clinical workup of children whose sexual maturation is early or delayed. Although BA is considered a qualitative rather than quantitative measure, it serves to round out the clinical picture, providing information without which diagnosis could not be achieved.

Prognostic factors for pediatric differentiated thyroid cancer (DTC) are not well established.The objective of the study was to retrospectively compare the postoperative risk-stratification systems: American Thyroid Association (ATA) risk categories, Schneider Children's Medical Center of Israel (SCMCI) score, and the response to initial therapy as predictors for disease outcome.Fifty-four DTC patients, median age at diagnosis 13.9 years (range 1.9-17 y), followed up for a median of 8.8 years (range 2.6-20.5 y) were stratified into prepubertal (n = 9), pubertal (n = 25), and postpubertal (n = 20) groups. All patients underwent total/near-total thyroidectomy; 48 received radioiodine therapy. The extent of DTC was evaluated by applying the ATA risk categories and the novel SCMCI score. Postoperative risk stratifications (low/intermediate/high) were determined using histopathological, laboratory, and imaging findings. Response to initial therapy (complete/acceptable/incomplete) was based on stimulated thyroglobulin and imaging results during the first 2 years of follow-up.The risk for recurrent/persistent disease, as assessed by the postoperative ATA risk-stratification system and the SCMCI score and by the response to initial therapy, was higher in the prepubertal group (P.001, P = .002, and P = .02, respectively). Outcome prediction by the risk-stratification systems was applicable: ATA risk categories, P = .014, R(2) = 0.247, predictive ability 80.4%; SCMCI score, P.001, R(2) = 0.435, predictive ability 86.3%; and response to initial therapy stratification, P.001, R(2) = 0.789, predictive ability 96.1%. The proportion of variance explained by the ATA risk categories (0.25), SCMCI score (0.44), and response to initial therapy (0.79) indicated that the latter was the most precise predictor and that the SCMCI score reflected the disease outcome better than ATA risk categories.Our data confirm that the postoperative pediatric ATA stratification system and the novel SCMCI score are suitable for predicting the risk of recurrent/persistent disease in this population. The response to initial therapy classification performed 1-2 years after the initial therapy may be more appropriate for guiding surveillance recommendations.

Diabet. Med. 29, e170–e175 (2012) Abstract Aims To determine whether the frequency and severity of diabetic ketoacidosis and the clinical characteristics of children at diagnosis of Type 1 diabetes mellitus have changed over the past decades among patients under surveillance of a tertiary paediatric centre. Methods In three time-periods, 75 (1986–1987), 86 (1996–1997) and 245 (2006–2007) patients at mean age 10.1 ± 4.7 years (0.6–20.0) were diagnosed with new-onset Type 1 diabetes. Data on clinical characteristics and laboratory evaluation at diagnosis retrieved from the patients’ files . Comparative analysis was performed between the three time periods. Results The frequency of diabetic ketoacidosis at diagnosis was 40% in 1986–1987, 41.8% in 1996–1997 and 29.4% in 2006–2007; the last rate was significantly lower (P = 0.04). No significant differences in the proportions of patients with severe or moderate diabetic ketoacidosis were found over time. Mean weight standard deviation score significantly increased from −0.72 ± 1.8 in 1986–1987 to −0.27 ± 1.2 in 2006–2007 (P

To assess the interrelationship between extent of adrenarche at presentation in girls with precocious adrenarche (PA) born appropriate for gestational age and their growth pattern, pubertal course and adult height.We reviewed clinical and laboratory data from medical charts of 85 girls with PA aged 5.0 to 8.8 years at referral, stratified in 3 subgroups according to bone age (BA) minus chronological age (CA) ≤0 years; 0BA minus CA1 year; BA minus CA1 year.Extent of pubarche and dehydroepiandrosterone-sulfate levels were greatest in the BA-CA1 subgroup (P=.02, P=.008, respectively), who also were taller at diagnosis (P=.002) and during childhood (P=.01). In all subgroups, pubertal onset was within normal range; menarche occurred earlier than in control subjects (P.02); all attained adult height within their mid-parental height range. Predicted adult height was overestimated in girls with BA ≤CA (P=.04) and underestimated with BA-CA1 (P.001).Although a more pronounced adrenarche and BA advancement at diagnosis in girls with PA born appropriate for gestational age had an impact on their pre-pubertal growth pattern, it was not associated with early and rapid progression of puberty or reduced adult height. This reassuring clinical course indicates that PA is a benign condition, irrespective of the extent of adrenarche at presentation. Adult height prediction is unreliable in PA.

Microdeletion syndromes include numerous syndromic phenotypes associated with intellectual disability and dysmorphic features. We report on a patient with a novel microdeletion of chromosomal region 3p11.2-p12.1 containing POU1F1, chromatin-modifying protein 2B (CHMP2B), and vestigial-like 3 (VGLL3) genes. Our patient was diagnosed as having a neonatal multiple pituitary hormone [growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin] deficiency. In addition to the typical findings associated with these hormonal deficiencies, she exhibited clinical features resembling those of Laron syndrome (frontal bossing, saddle nose, small chin, blue sclera, and acromicria), with moderate intellectual disability. She also displayed an unusual growth pattern characterized by unresponsiveness to high doses of GH replacement therapy during infancy and early childhood and an accelerated growth rate beginning at the age of 4.5 years. Insulin-like growth factor (IGF)-1 levels were consistently extremely low or undetectable. Extensive medical and genetic analysis ruled out primary and secondary GH insensitivity. The distinct phenotype and the peculiar growth pattern observed in this affected patient, not reported to have been observed in other cases with POU1F1 gene inactivity, suggest that the other two deleted genes play a possible role in the development of this syndrome. This hypothesis may be supported by the fact that both the CHMP2B and VGLL3 genes are expressed in the liver and the growth plate, the two main target organs of the GH/IGF-1 axis. The homozygous deletion of the CHMP2B gene, previously associated with frontotemporal dementia, may contribute to the intellectual disability observed in this patient.

Background: Significant idiopathic bone age (BA) advancement is defined as BA >2 SD above the mean chronological age (CA) with no underlying etiology. BA advancement due to endocrinopathies is associated with early puberty and compromised adult height (AHt), necessitating treatment. The natural history of idiopathic BA advancement is not well-established. Aim: To determine the pattern of growth and puberty, and validity of AHt prediction in idiopathic BA advancement. Methods: Fifty-five prepubertal patients (20 boys aged 6.7 ± 2.2 years, 35 girls aged 6.4 ± 2.0 years) evaluated between 1985 and 2008 were found to have idiopathic BA advancement. Assessed during follow-up were: BA, height (Ht), weight (Wt), pubertal course and predicted AHt (PAHt). Attained AHt was compared to PAHt and to midparental Ht (MPHt). Results: Throughout follow-up, BA-SDS (SD score) significantly declined (p < 0.001), Ht-SDS significantly decreased (p = 0.006) and Wt-SDS did not change. Pubertal onset, duration and growth were within the normal range. Attained AHts did not differ significantly from MPHts (boys: 172 ± 6.7 vs. 171 ± 6.1 cm; girls: 160.5 ± 6.5 vs. 159.0 ± 6.8 cm). PAHts using the ‘accelerated’ tables of Bayley and Pinneau were accurate. Conclusion: Idiopathic BA advancement differs from BA advancement with underlying endocrinopathy in evolution of BA progression (decline in BA-SDS), growth pattern, validity of AHt prediction and uncompromised AHt. This indicates that it requires minimal clinical monitoring and usually does not mandate treatment.

Familial type 1 diabetes mellitus (T1D) comprises parent-offspring and sib-pair subgroups.To compare the demographic and clinical characteristics in the two subgroups at diagnosis and evaluate the differences between index cases and second affected family members.Retrieved from our institutional registry of new T1D cases for the years 1979-2008 were a cohort of 194 familial cases (87 parent-offspring, 107 sib-pairs); 133 sporadic cases matched by age, gender, and year of diagnosis were selected as controls. Extracted from their medical files were demographic data, family background, clinical and laboratory findings.The parent-offspring subgroup was characterized by male preponderance (p = 0.009). At diagnosis parents were significantly older than their offspring (p0.001) and probands were significantly younger than their affected siblings (p = 0.03). Clinical symptoms and metabolic decompensation were similar in the familial subgroups. Diabetic ketoacidosis (DKA) rate and hemoglobin A1c (HbA1c) levels were lower in second affected family members in both parent-offspring (p = 0.05 and p0.001) and sib-pair subgroups (p0.001, for both parameters). Consanguinity and T1D were more frequent in the extended family of familial than sporadic cases (p0.001 and p = 0.012, respectively) with no difference between the two subgroups.The genetic background for T1D would appear to differ not only between familial and sporadic cases but also between parent-offspring and sib-pair subgroups. Whereas differences in age of onset are attributable to both genetic and environmental factors, the less severe clinical manifestations in second affected family members may result from increased awareness or a less aggressive disease process.

To determine whether age at premature thelarche (PT) onset affects the clinical characteristics, course, and risk of progression to precocious puberty (PP).Data regarding course of growth and puberty were retrieved from the medical files of 139 girls with PT followed up from 1995 to 2005. Analysis was based on age at PT appearance (birth, 1-24 months, and 2-8 years); course was categorized as regressive, persistent, progressive, or cyclic.At diagnosis, height standard deviation score, bone age-chronological age ratio, and hormonal values were comparable in the 3 age groups. PT regressed in 50.8%, persisted in 36.3%, progressed in 3.2% and had a cyclic course in 9.7%. A progressive or cyclic course was significantly more prevalent among girls presenting after 2 years (52.6%) compared with girls presenting at birth (13.0%) or at 1 to 24 months (3.8%) (P.001). PP occurred in 13% irrespective of age at PT presentation or clinical course.Clinical and anthropometric characteristics at admission and risk of PP were similar in all girls with PT, regardless of age at onset. There are currently no clinical or laboratory tests that can predict the risk of progression to PP at presentation.

Low growth hormone (GH) secretion during puberty may stem from either a permanent GH axis abnormality or from transient GH deficiency secondary to lack of sex hormones. Although well known to enhance stimulated GH secretion in pre- or early puberty, sex hormone priming for the evaluation of the function of the GH-IGF-I axis remains controversial. Many pediatric endocrinologists consider that omission of such priming during the preadolescent period decreases the specificity of GH stimulation tests and increases the percentage of false-positive diagnosis results. Others believe that it leads only to a temporary augmentation of GH secretion followed by a decrease in spontaneous secretion to levels which may be insufficient for normal pubertal growth; thus priming with sex hormones may lead to underdiagnosis of peripubertal children that could have benefited from GH treatment. The increased availability of biosynthetic GH has enabled expanding the indications for GH therapy and judging and renewing the criteria for the diagnosis of GH deficiency, including the practice of sex hormone priming which was and still is executed in clinical use in many centers in the world. We would like to recommend that priming should not be routinely performed in every peripubertal child undergoing GH evaluation but may be considered in adolescents with pubertal delay – girls aged >11.5–12 years and boys aged >13–13.5 years exhibiting no evidence of puberty or only initial signs.

Pseudohypoparathyroidism (PHP) is a rare inherited syndrome characterized by parathyroid hormone (PTH) resistance and is frequently associated with Albright’s hereditary osteodystrophy and resistance to other cAMP-mediated hormones. The usual neonatal presentation is mild primary hypothyroidism secondary to resistance to thyroid-stimulating hormone; hypocalcemia usually develops after age 3–5 years. This work describes the diversity in the clinical expression and course of PHP, with emphasis on calcium levels by age and treatment, in 8 children under long-term follow-up at our pediatric tertiary center. The calcium levels at presentation ranged from transient neonatal hypocalcemia to infantile hypercalcemia to childhood/adolescence hypocalcemia. Interestingly, relative hypocalciuria at diagnosis and during therapy, in the presence of renal PTH resistance, was the rule. These findings indicate that transient neonatal hypocalcemia associated with other clinical features or a family history of PHP may be a flag for clinicians to screen for PTH resistance later in life. In addition, PTH resistance may be missed by surveying calcium levels only; thus the PTH levels have to be checked as well. In addition, the recommendation for patients with hypoparathyroidism that strict low-normal calcium levels be maintained during therapy in order to prevent hypercalciuria is probably not applicable in PHP.

The objective of the study was to determine whether height gain after discontinuation of gonadotropin-suppressive (GnRHa) therapy differs in girls with sexual precocity diagnosed at various ages and assess its influence on final height (FHt) outcome.We compared data on post-GnRHa treatment course and FHt of 115 girls [22 diagnosed before chronological age of 6 yr; 38 between ages 6 and 8 yr; and 55 early fast puberty (EFP) between ages 8 and 9 yr] treated with GnRHa from Tanner stage 2-3 to chronological age 11-12 yr and bone age 12-12.5 yr.Despite comparable bone age at cessation of treatment, similar time to resumption of puberty (0.6 +/- 0.7, 0.5 +/- 0.7, and 0.5 +/- 0.7 yr), and age at menarche (12.6 +/- 0.5, 12.6 +/- 0.6, and 12.7 +/- 0.9 yr), height gain from cessation of therapy to FHt was greater and time to epiphyseal fusion was longer in the younger central precocious puberty (CPP) than in the older CPP (P0.05) and EFP (P0.001) groups. The percentage of residual growth predicted at discontinuation of treatment was achieved only by the younger CPP (6.6 +/- 1.6% vs. 6.7 +/- 1.6%), whereas in older CPP and EFP, it was significantly lower (6.2 +/- 1.6% vs. 4.6 +/- 2.7% and 6.3 +/- 1.5% vs. 3.6 +/- 1.5%, respectively). FHt of these two groups was compromised, compared with FHt predicted at discontinuation of treatment (P0.01 and P0.001, respectively).Girls with sexual precocity diagnosed after the age of 6 yr exhibit earlier epiphyseal fusion with diminished posttreatment height gain and compromised FHt. Because recovery of gonadal axis was similar in all girls, differences were probably due to pretreatment intrinsic changes in the growth plate. Prediction of residual growth at discontinuation of treatment is unreliable in these girls.

Background Type 1 diabetes mellitus (T1DM) is a T-cell-mediated autoimmune disease that leads to the destruction of insulin-producing beta cells. Treatment with DiaPep277, a peptide derived from heat-shock protein 60 (hsp60), has been found to slow the deterioration of beta-cell function after clinical onset of diabetes in NOD mice and human adults. Our aim was to evaluate the efficacy and safety of DiaPep277 treatment in attenuating beta-cell destruction in children with recent-onset T1DM. Methods A prospective, randomized, double-blind, phase II design was used. The sample included 30 children (19 males) aged 7–14 years who had been diagnosed with T1DM from 53 to 116 days previously, and had basal C-peptide concentrations above 0.1 nmol/L. The children were randomized to receive subcutaneous injections of 1 mg DiaPep277 (15 patients) or 40 mg mannitol (placebo) at entry and at 1, 6, and 12 months. The duration of follow-up was 18 months. The groups were compared for stimulated C-peptide level, exogenous insulin dose, and HbA1c concentration. Results C-peptide levels similarly decreased over time in the DiaPep277- and placebo-treated patients. There was no significant difference in insulin dose or HbA1c concentration between the groups at any time point. No serious drug-related adverse effects were recorded throughout the study period. Conclusions One-year treatment with DiaPep277 at a dosage of 1 mg is safe for use and well tolerated in children with recent-onset T1DM. However, it appears to have no beneficial effect in preserving beta-cell function or improving metabolic control. Copyright © 2007 John Wiley & Sons, Ltd.

Objective To study the pattern of thyroid function testing in healthy newborns during the first year of life. Study design We used the computerized database of a health management organization. Among the 18 507 infants insured by the Clalit Health Services born in the Sheba Medical Center between 2002 and 2007, 652 full-term healthy newborns with birth weight >2 kg and no significant perinatal morbidity underwent thyrotropin (TSH) determination as outpatients in their first year of life. The Clalit Health Services database provided demographic data, laboratory results, and dispensed medications for the newborns and their mothers. Results Initial serum TSH levels were within normal range (0.35-5.5 mIU/L) in 91.1%, elevated (>5.5-≤10 mIU/L) in 8.3%, and highly elevated (>10 mIU/L) in 0.6% of the studied cohort. The 97.5 and 2.5 percentile values were 7.4 and 0.74 mIU/L, respectively. TSH measurements were repeated in 34.2%, 72.2%, and 100% of children with normal, elevated, and highly elevated initial levels, respectively; results were normal in 96%, 74%, and 50% of patients with initial normal, elevated, and highly elevated TSH, respectively; repeated TSH levels were >97.5 percentile in 35% of patients with initial TSH >97.5 percentile compared with 1% with first results P = .005). Only 4 (0.6%) of the 652 newborns included in the study received thyroxin treatment. Conclusion The normal TSH levels found in most healthy infants with normal thyroid screening and the spontaneous normalization of TSH values below 7.4 mIU/liter, substantiate the reliability of the screening, reduce unnecessary work-up and unnecessary thyroxin treatment of neonates meeting these criteria.

Growth hormone (GH) registries indicate that boys receive preferential GH treatment for idiopathic short stature (ISS). The aim was to determine whether age, auxological parameters, pubertal status, and target height differ between genders at GH initiation.Review of the computerized files of the endocrine department of a tertiary pediatric medical center identified 184 patients who started GH therapy for ISS between 2003–2011. Data on auxologic parameters, predicted height, parental height, and pubertal status were collected and compared between boys and girls.Boys accounted for a significantly higher percentage of the study group (65.8%, pThe similar age, height deficit, and pubertal status at onset of GH treatment in boys and girls suggests that gender differences do not exist. Male predominance may stem from family preferences to treat boys. Future studies are warranted to assess the psychosocial aspects in the decision to initiate therapy.

The precise neuroendocrine mechanisms underlying activation of hypothalamic-pituitary-gonadal (HPG) axis maturation are elusive. The wide age range of pubertal onset among normal individuals throughout the world may suggest that both genetic and environmental factors modulate the timing of puberty. Early activation of the HPG axis, termed central precocious puberty (CPP), causes psychosocial difficulties and may lead to compromised final height, especially if medical intervention is delayed. Although CPP is considered to be idiopathic in the majority of patients, we have recently reported a 27.5% prevalence of familial cases among 147 patients with idiopathic CPP. Segregation analysis of this cohort suggested an autosomal dominant transmission with incomplete sex-dependent penetrance. Allelic variants of candidate genes that regulate the timing of puberty may cause familial CPP. Detection of these genes will provide a tool for identification of children at risk of developing CPP, enabling early intervention with the aim of preventing its distressing outcomes.

BACKGROUND Growth without GH has been reported in patients with organic combined pituitary hormone deficiency (CPHD) after resection of craniopharyngiomas and hypothalamic tumours or in septo-optic dysplasia. METHODS This study describes the growth pattern and final height of five children (four boys, one girl) with idiopathic CPHD (GH, TSH, ACTH, LH and FSH) who maintained normal growth despite persistent GH deficiency throughout the growth period. RESULTS Presenting findings were borderline small penis in two children diagnosed at ages 3 and 9 years, and absence of pubertal signs in three adolescents diagnosed at age 12.8-13.7 years. The latter three patients also exhibited acromegaloid features. The height of all patients was within the 10-25th percentiles, and weight at the 25-50th percentiles. Although they were moderately overweight, accelerated weight gain was not observed. Prepubertal growth rate was 4-5 cm/year. The pubertal growth period, starting after initiation of sex hormone therapy (chronological age 15.9-16.3 years and bone age 12.5-14.5 years) continued for 4-5.5 years. Total pubertal growth was 6-11.7 cm with reduced growth spurt. Final height, which was attained at an advanced age (19-22 years), was 170-179 cm in the boys and 164 cm in the girl, equal to or exceeding the target height range. Repeated hormonal evaluations revealed undetectable GH and IGF-I levels, and no evidence of hyperprolactinaemia or hyperinsulinism. CONCLUSIONS Final height attainment within or above target height range may occur in patients with idiopathic CPHD despite persistent GHD. As this was not mediated by GH, IGF-I, insulin or prolactin, some other growth factors probably played a growth-promoting role.

Early and fast puberty (EFP) in girls, defined as pubertal onset at age 8-9 yr, with an accelerated course, may cause compromised final height (FHt) and psychosocial distress. Treatment with a gonadotropin-suppressive agent is controversial, because the improvement in FHt is equivocal and there may be risk of obesity. We analyzed the data of 126 girls with EFP: 63 treated with GnRH analog (GnRHA) since Tanner stage 3, for 2-4 yr; and 63 untreated. Age at onset of puberty; accelerated time of transition from Tanner stage 2 to 3 (1.3 yr); and clinical, hormonal and sonographic findings were similar in the 2 groups. The girls given GnRHA treatment had a significantly prolonged pubertal course, compared with the accelerated course in the untreated girls (4.7 +/- 0.4 vs. 2.45 +/- 0.4 yr, P0.001). After therapy, they reached Tanner stages 4 and 5 and FHt at a significantly older age than the untreated group (P0.001), and their menarche was delayed (12.8 +/- 0.6 vs. 10.8 +/- 0.5 yr, P0.001). However, the different pace of puberty in the 2 groups did not change the total pubertal growth and the bone maturation rate. The Ht gain from Tanner stage 3 to 4 (10.4 +/- 2.7 vs. 11.2 +/- 3.1 cm) and from Tanner stage 4 to FHt (8.2 +/- 2.7 vs. 8.8 +/- 3.6 cm) was similar in the treated and untreated girls, as were absolute Ht and bone age at each pubertal stage. The weight gain of the treated girls was more pronounced during treatment (P = 0.0016), but it was arrested after discontinuation of therapy; and by the time FHt was reached, the body mass index was similar in the 2 groups. The treated and untreated girls achieved a similar mean FHt, which was not significantly different from their respective mean target Ht (THt). Individual analysis revealed that 70% of the treated girls and 67% of the untreated girls attained their THt range (THt +/- 0.5 SD) or surpassed it. In conclusion, treatment with GnRHA affected only the pace of EFP. The similar Ht gain and bone maturation rate at each pubertal stage in the treated and untreated girls may suggest that the total pubertal growth is not dependent on pubertal duration and pace and is probably determined already at the onset of the normal pubertal development. The treatment did not compromise the FHt and did not cause long-lasting obesity. Therefore, GnRHA therapy may be suggested for use in girls who have psychosocial difficulties in coping with EFP.

Objective To determine the effect of nutritional supplementation on height, weight, and body mass index (BMI) in short and lean prepubertal children. Study design A prospective, randomized, double-blinded, placebo-controlled trial of nutritional supplementation at the endocrinology department of a tertiary pediatric medical center of healthy, lean, short, prepubertal children 3-9-years-old. Anthropometry measurements were measured at 6 months. Results Two hundred participants (149 boys) entered the study and 171 (85.5%) completed the intervention period. Baseline characteristics including age, sex, height-SDS, weight-SDS, BMI-SDS, and dietary caloric and protein intakes were similar in the formula and placebo groups. ‘Good' consumers (intake of ≥50% of the recommended dose) in the formula group significantly improved height-SDS ( P P = .005) with no change in BMI-SDS compared with ‘poor' consumers and the placebo group. In the formula-treated group a positive correlation was found between the amount of formula consumed per body weight and the gain in height-SDS (r = 0.44, P P = .002); no significant correlations were found in the placebo group. No serious adverse events were reported during the study. Conclusions Nutritional intervention with the formula was found to be a feasible, effective, and safe approach for promoting the physical growth of short and lean prepubertal children.

Data on adolescent precursors of thyroid cancer in adulthood are scant.In order to evaluate potential risk factors for thyroid cancer, we linked two national data sources: the military recruitment health examinations and the Israel National Cancer Register. The study population (1,624,310 participants) included 1,145,865 Jewish males aged 16-19 years when examined between 1967 and 2005, and 478,445 Jewish females aged 16-19 years when examined between 1989 and 2005. The cancer follow-up extended up to 2006. Multivariable Cox proportional hazards modeling was used.During 24,389,502 person years of follow-up, 760 incidence cases of thyroid cancer were identified. The mean age at diagnosis was 25.2±4.2 years for women and 37.2±10.0 years for men. Women had a substantially higher incidence (birth cohort-adjusted hazard ratio (HR)=5.70 [95% CI 4.45-7.31]; p0.001). Height predicted incidence in both sexes, with birth cohort-adjusted HRs of 1.03 (p0.001) in males and 1.04 (p0.001) in females, per 1 cm increment in height. In males, but not in females, there was a graded association between education, as measured by years of schooling, and incidence of thyroid cancer. Body mass index was not associated with incidence. In a multivariable analysis of 617,613 males and 469,185 females examined from 1989 onwards, which included sex, birth year, height, and education, the excess risk in females persisted strongly (HR=5.67 [CI 4.30-7.13]), as did the association with height.Female sex, measured height in adolescence, and later birth cohorts were independent predictors of thyroid cancer in young and middle-aged adults in Israel. Further study is needed to unravel the mechanisms whereby height is associated with thyroid cancer.

The indication for GnRH analog treatment in boys with central sexual precocity is based mainly on the age of onset of puberty. Our aim was to determine whether the rate of pubertal progression should also be taken into consideration. Included in the study were 81 boys with central sexual precocity: 27 with true precocious puberty (onset at