Fracture risk among children and adolescents with celiac disease: a nationwide cohort study.

BACKGROUND: Metabolic bone disease is a common manifestation of celiac disease (CD). We aimed to assess fracture risk among children and adolescents with CD compared with a matched group. METHODS: This registry-based cohort study included 2372 children with CD who were matched 1:5 to 11,860 children without CD. Demographic and clinical data were obtained from the electronic database of Meuhedet, a health maintenance organization. Fracture events at ages 1-18 years were identified by coded diagnoses. RESULTS: The overall fracture incidence rate was 256 per 10,000 patient-years (PY) in the CD group and 165 per 10,000 PY in the comparison group (p < 0.001). The hazard ratio (HR) to have a fracture was 1.57 (95% CI 1.43-1.73, p < 0.001) for the CD group compared to the matched group. The HR for multiple fractures was 1.67 (95% CI 1.38-2.01, p < 0.001). Analysis of the pre- and post-diagnosis periods separately showed that the HR for fractures in the pre-diagnosis period was 1.64 (95% CI 1.42-1.88, p < 0.001) for the CD group compared to the matched group, and 1.52 (95% CI 1.26-1.71, p < 0.001) in the period from diagnosis to the end of the follow-up period. CONCLUSIONS: Children with CD had increased fracture risk both preceding and following the diagnosis of CD. IMPACT: One manifestation of celiac disease (CD) is metabolic bone disease, including osteoporosis and impaired bone mineralization. We found increased fracture risk among children with CD, both preceding the CD diagnosis and during the years following the diagnosis. Recognition of the high risk of fractures in this population may help promote prevention. Further studies are needed to evaluate changes in bone quantity and quality after initiation of a gluten-free diet, and to identify those at risk for persistent metabolic bone disease.

The contribution of medical burden to 22q11.2 deletion syndrome quality of life and functioning.

PURPOSE: To date, there is no systematic method to quantify the medical burden of individuals with 22q11.2 deletion syndrome (22q11.2DS). This study aimed to design a Medical Burden Scale for 22q11.2DS to evaluate the effect of medical symptoms severity on quality of life (QoL) and functioning in individuals with this syndrome. METHODS: Individuals with 22q11.2DS (n = 76) were included in the study. A multidisciplinary group of physicians determined the severity of symptoms (on a scale of 0 to 4) of 8 major medical systems affected in 22q11.2DS, as well as the level of cognitive deficits and psychiatric morbidity. Regression models were used to evaluate the impact of medical, cognitive, and psychiatric symptoms' severity on global assessment of functioning (GAF) and QoL. RESULTS: The total Medical Burden Scale score was significantly associated with both QoL and GAF scores, beyond the effect of the psychiatric and cognitive deficits. We also found that QoL and GAF scores were associated with the severity scores of specific medical systems, particularly neurological symptoms, but also cardiovascular, ear-nose-throat, endocrinology, and orthopedics. CONCLUSION: Quantifying the medical burden of 22q11.2DS individuals is feasible and indicates the overall and specific contribution of medical symptoms to QoL and functioning of 22q11.2DS individuals.

Increased fracture risk among children diagnosed with attention- deficit/hyperactivity disorder: a large matched cohort study.

To analyse the risk of fractures among children with attention-deficit/hyperactivity disorder (ADHD) compared with matched children without ADHD; and to evaluate the impact of pharmacological treatment. This registry-based cohort study included 31,330 children diagnosed with ADHD and a comparison group of 62,660 children matched by age, sex, population sector and socioeconomic status. Demographic and clinical information was extracted from the electronic database of Meuhedet, a health maintenance organization. Fracture events between 2-18 years of age were identified by coded diagnoses. The overall fracture incidence rate was 334 per 10,000 patient-years (PY) in the ADHD group and 284 per 10,000 PY in the comparison group (p < 0.001). Among boys, the fracture incidence rates were 388 per 10,000 PY and 327 per 10,000 PY (p < 0.001), for the respective groups. Among girls, the rates were lower in both groups compared to boys, but higher in the ADHD compared to the matched group (246 vs 203 per 10,000 PY, p < 0.001). Among the children with ADHD, the hazard ratios (HR) to have a fracture were similar in boys (1.18, 95%CI 1.15-1.22, p < 0.001) and girls (1.22, 95%CI 1.16-1.28, p < 0.001). Children with ADHD were also at increased risk for two and three fractures; the hazard ratios (HRs) were 1.32 (95%CI 1.26-1.38, p < 0.001) and 1.35 (95%CI 1.24-1.46, p < 0.001), respectively. In a multivariable model of the children with ADHD, pharmacological treatment was associated with reduced fracture risk (HR 0.90, 95%CI 0.82-0.98, p < 0.001) after adjustment for sex, resident socioeconomic status and population sector.   Conclusion: Children with ADHD had greater fracture risk than a matched group without ADHD. Pharmacological treatment for ADHD may decrease this risk. What is Known: • Children with attention-deficit/hyperactivity disorder (ADHD) may be more prone to injuries and fractures than children without ADHD. What is New: • Children with ADHD were 1.2 times more likely to have a fracture than children with similar characteristics, without ADHD. The increased risk for fractures was even greater for two and three fractures (hazard ratios 1.32 and 1.35, respectively). • Our study suggests a positive effect of pharmacological treatment for ADHD in reducing fracture risk.

Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study.

To assess the long-term efficacy of burosumab for pediatric patients with X-linked hypophosphatemia, focusing on linear growth. This multi-center retrospective study included 35 pediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results, and Rickets Severity Score (RSS), from 2 years prior to treatment initiation and up to 4 years after. Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6-15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1-4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after 3 months and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8 to 90.1 ± 5.3% after 12 months of treatment (p = 0.041). The RSS improved from 1.7 ± 1.0 at burosumab initiation to 0.5 ± 0.6 and 0.3 ± 0.6 after 12 and 24 months, respectively (p < 0.001). Both height z-score and weight z-score improved from burosumab initiation to the end of the study: from - 2.07 ± 1.05 to - 1.72 ± 1.04 (p < 0.001) and from - 0.51 ± 1.12 to - 0.11 ± 1.29 (p < 0.001), respectively. Eight children received growth hormone combined with burosumab treatment. Height z-score improved among those who received growth hormone (from - 2.33 ± 1.12 to - 1.94 ± 1.24, p = 0.042) and among those who did not (from - 2.01 ± 1.01 to - 1.66 ± 1.01, p = 0.001). CONCLUSION:  Burosumab treatment in a real-life setting improved phosphate homeostasis and rickets severity and enhanced linear growth. WHAT IS KNOWN: • Compared to conventional therapy, burosumab treatment has been shown to increase serum phosphate levels and reduce the severity of rickets. • The effect of burosumab on growth is still being study. WHAT IS NEW: • Height z-score improved between the start of burosumab treatment and the end of the study (-2.07 ± 1.05 vs. -1.72 ± 1.04, p < 0.001). • Eight children received burosumab combined with growth hormone treatment without side effects during the concomitant treatments.

Growth hormone treatment and the risk of adolescent scoliosis: A large matched cohort study.

AIM: We aimed to evaluate the risk of developing adolescent scoliosis among recipients of recombinant human growth hormone (rhGH). METHODS: This registry-based cohort study included 1314 individuals who initiated rhGH treatment since 2013, treated during 10-18 years of age for at least 6 months. This group was matched to a comparison group of 6570 individuals not treated with rhGH. Demographic and clinical information was extracted from the electronic database. The results are presented using hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: During a median follow-up of 4.2 years, 59 (4.5%) rhGH recipients and 141 individuals (2.1%) from the comparison group were diagnosed with adolescent scoliosis. The age at diagnosis did not differ between the groups (14.7 versus 14.3 years, p = 0.095). Patients treated with rhGH were more likely diagnosed with scoliosis (HR 2.12, 95% CI 1.55-2.88, p < 0.001). Among males, the risk was about three times greater in the treated versus the comparison group (HR 3.15, 95% CI 2.12-4.68, p < 0.001), while in females the risk was not increased (HR 1.12, 95% CI 0.72-2.04, p = 0.469). CONCLUSIONS: Recombinant human growth hormone treatment was associated with an increased risk to be diagnosed with adolescent scoliosis in males. Scoliosis development should be monitored appropriately in rhGH recipients.

Trabecular Bone Score Change Is Not Predicted by Bone Turnover: Short-term Sequential Follow-up.

BACKGROUND: Trabecular bone score (TBS) reflects vertebrae microarchitecture and assists in fracture risk assessment. The International Society of Clinical Densitometry postulates that the role of TBS in monitoring antiresorptive therapy is unclear. Whether changes in TBS correlate with bone resorption measured by bone turnover markers is not known. OBJECTIVES: To determine whether longitudinal changes in TBS correlate with C-terminal telopeptide (CTX) of type I collagen. METHODS: Examinees with two bone mineral density (BMD) measurements were detected via the institutional database. Over 5.8% change in TBS was considered least significant and patients were grouped accordingly (increment, decrement, or unchanged). CTX, BMD, co-morbidities, incident fractures, and medication exposure were compared between the groups by Kruskal-Wallis. The correlation between TBS and BMD change and CTX in a continuous model was analyzed by Pearson's correlation coefficient. RESULTS: In total, 110 patients had detailed medical records. In 74.5%, TBS change was below least significant change. Two other TBS categories, fracture incidence or medication exposure, did not differ by CTX. In the continuous model, BMD and TBS change was positively correlated (r = 0.225, P = 0.018). A negative correlation was observed between BMD change and CTX. The decrease in BMD level was associated with higher CTX (r = -0.335, P = 0.004). No correlation was observed between CTX and TBS. CONCLUSIONS: No correlation between TBS dynamics and bone resorption marker was found. Clinical interpretation and implication of longitudinal TBS changes should be further explored.

Decreases in pediatric fractures during the COVID-19 pandemic - a nationwide epidemiological cohort study.

The COVID-19 pandemic led to fundamental changes in daily routines of children. Our aim was to evaluate the incidence and characteristics of fractures among Israeli children during 2020 compared with 2015-2019. Demographic, clinical data, and incidence rates of fractures in individuals aged < 18 years were derived from the electronic database of Meuhedet Health Services, which provides healthcare services to 1.2 million people in Israel. We further subdivided the year to five periods according to government regulations of lockdown and isolation at each period. Fracture sites were determined according to ICD9 definitions. During 2020, 10,701 fractures occurred compared with 12,574 ± 599 fractures per year during 2015-2019 (p-value < 0.001). Fracture rates were lower during all periods in 2020. The largest decline was observed during the first lockdown for both boys (56% decline, 95% confidence interval [CI] 52-60%) and girls (47% decline CI 41-53%). While the fracture rate declined for most age groups, the largest decline was recorded for the age group 11-14 years, with significant reduction rates of 66% (CI 59-71%) for boys and 65% (CI 54-73%) for girls. The most prominent declines were of fractures of the hand bones of both boys and girls (64% and 59%, respectively). Conclusions: Our data showed a significant decrease in fracture rate in 2020 compared to the previous 5 years, as well as differences between periods within that year. What is New: •The COVID-19 pandemic led to fundamental change in daily routines of children with significant decrease in school attendance and sport activities. •Consequent to these public health measures, the incidence rate of pediatric fractures decreased significantly. What is New: •This study demonstrates declines in fracture rates during lockdown periods, with only partial reversing of the trends between the lockdown periods. •The most pronounced decline was observed during the first lockdown period. •The decline was most prominent in children aged 11-14 years; there was no significant change in fracture incidence of children aged <3 years.

Changes in trabecular bone score and bone density in female adolescents with anorexia nervosa: a longitudinal study.

Impaired bone health is a common complication of anorexia nervosa (AN). We aimed to assess longitudinal changes in bone mineral density (BMD) and trabecular bone score (TBS), a measure of bone quality, in female adolescents with anorexia nervosa (AN). We conducted a retrospective longitudinal study of 41 female adolescents with AN who underwent two dual-energy X-ray absorptiometry (DXA) scans. Clinical data, including age, weight, height, body mass index (BMI), and DXA measurements were retrieved from the medical charts. Lumbar bone mineral apparent density (BMAD) was calculated to correct for size. Changes (Δ) in BMD, BMAD, and TBS were examined for correlations with clinical characteristics. Mean ages at the time of DXA scans were 14.8±1.9 and 16.8±2.0 years. There was a significant improvement in anthropometric parameters and DXA measurements at the second DXA scan. However, these values were still significantly lower than expected in the general population. The Δlumbar BMD Z-score was 0.3±0.7, the Δlumbar BMAD Z-score was 0.2±0.7 and the ΔTBS Z-score was 0.5±0.7. ΔTBS Z-score was positively correlated with Δheight Z-score, Δweight Z-score and ΔBMI Z-scores, and negatively correlated height Z-score, weight Z-score and TBS Z-scores at the first DXA scan (p<0.05). Δheight Z-score, ΔBMI Z-score and the progression from early to late puberty were identified as significant independent predictors of Δlumbar BMAD Z-score (p<0.05). During two years of treatment, both BMD and TBS increased significantly. Improvement in height and in weight status, and progression in puberty are predictors of improvement in BMD and TBS.

Clinical Features in a Large Cohort of Patients With 22q11.2 Deletion Syndrome.

OBJECTIVES: To evaluate various clinical aspects, specifically regarding immune status, in a large cohort of patients with DiGeorge syndrome. STUDY DESIGN: Data were collected for 98 patients with DiGeorge syndrome treated at a tertiary medical center. This included general information, laboratory results, and clinical features. RESULTS: The median age at diagnosis was 2.0 years (range, 0.0-36.5 years). The most common symptoms that led to diagnosis were congenital heart defect, speech delay, palate anomalies, and developmental delay. Common clinical features included recurrent infections (76 patients), congenital heart diseases (61 patients), and otorhinolaryngology disorders (61 patients). Twenty patients had anemia; the incidence was relatively high among patients aged 6-59 months. Thrombocytopenia was present in 20 patients. Recurrent chest infections were significantly higher in patients with T cell and T cell subset deficiencies. Decreased T cell receptor excision circles were more common with increasing age (P < .001). Of the 27 patients hospitalized due to infection, pneumonia was a leading cause in 13. CONCLUSIONS: Awareness of DiGeorge syndrome's typical and uncommon characteristics is important to improve diagnosis, treatment, surveillance, and follow-up.

Dual diagnosis of type 1 diabetes mellitus and attention deficit hyperactivity disorder.

BACKGROUND: Data regarding glycemic control in children and adolescents with a dual diagnosis of type 1 diabetes mellitus (T1DM) and attention-deficit/hyperactivity disorder (ADHD) are limited. OBJECTIVE: To compare various aspects of diabetes control among youth with T1DM, between those with and without ADHD. METHODS: In this cross-sectional study of youth with T1DM, 39 had ADHD (mean age 14.1 ± 2.8 years) and 82 did not (control group, mean age 12.6 ± 3.3 years). Health-related quality of life was assessed by a Diabetes Quality of Life (DQOL) questionnaire submitted to their parents. Glycemic data were downloaded from glucometers, pumps, and continuous glucose monitoring systems. HbA1c levels, hospitalizations, and severe hypoglycemic and diabetes ketoacidosis events were retrieved from the medical files. RESULTS: Compared to the control group mean HbA1c level of the ADHD group was higher: 8.3 ± 1.1% versus 7.7 ± 1.0% (p = 0.005) and the percent of time that glucose level was in the target range (70-180 mg/dl) was lower: 48 ± 17% versus 59 ± 14% (p = 0.006). Mean glucose and glucose variability were higher in the ADHD group. Youth with ADHD who were not pharmacologically treated had worse HbA1c and more hospitalizations than those who were treated. DQOL did not differ between the control group, the treated ADHD group, and the untreated ADHD-Group. CONCLUSIONS: Dual diagnosis of T1DM and ADHD during childhood leads to worse diabetes control, which is more pronounced in the context of untreated ADHD. Healthcare providers should be aware of the difficulties facing youth with T1DM and ADHD in coping with the current intensive treatment of diabetes.

Trabecular Bone Score in Children and Adolescents With Inflammatory Bowel Diseases.

INTRODUCTION: Trabecular bone score (TBS) is a textural index that evaluates bone microarchitecture of the lumbar spine. Our aim was to assess TBS in children with inflammatory bowel diseases and to evaluate correlations with clinical, laboratory and densitometric variables. METHODS: A retrospective study of TBS and areal bone mineral density measurements by dual-energy X-ray absorptiometry (DXA) of children with either Crohn's disease (CD) or ulcerative colitis (UC). Bone mineral apparent density was calculated for size adjustment. TBS Z-score for each child were calculated based on data from a healthy population of similar age and gender distribution. Variables significantly associated with TBS were included in stepwise linear regression models to examine independent predictors of TBS. RESULTS: Fifty patients (age at DXA scan 13.8 ± 3.0 years, 29 males) were included. No significant differences were observed between the patients with CD and UC, in age at diagnosis, age at DXA scan and disease duration. The mean TBS of patients with CD (n = 35) was lower than of patients with UC (n = 15): 1.340 ± 0.080 vs 1.395 ± 0.092, p = 0.040. The mean TBS Z-score of patients with CD, -0.443 ± 0.788, was significantly lower than expected in healthy children (p = 0.002), while the mean TBS Z-score of patients with UC, 0.231 ± 0.685, was similar to that of healthy children (p = 0.212). In the stepwise linear regression analysis, BMI Z-score at diagnosis, phosphorus level at diagnosis and age at the time of the DXA scan were significant independent predictors of TBS (r²â€¯= 0.604; ß = 0.037, 95% confidence interval (CI) for ß 0.022-0.051, p < 0.001; ß = 0.045, 95% CI: 0.017-0.073, p = 0.002; and ß = 0.031, 95% CI: 0.005-0.021, p < 0.002, respectively). CONCLUSIONS: TBS is significantly reduced in pediatric patients with CD but not in patients with UC. This finding likely reflects the effect of CD on bone microarchitecture.

Longitudinal changes in bone mineral density in children with inflammatory bowel diseases.

AIM: Children with inflammatory bowel disease (IBD) are prone to low bone mineral density (BMD). Our aim was to assess longitudinal changes in BMD in this population. METHODS: A retrospective longitudinal study of children with IBD, treated at two tertiary centres in Israel, who underwent two BMD measurements by dual-energy X-ray absorptiometry (DXA). Changes in lumbar spine BMD (∆L1-4 z-scores) were examined for correlations with clinical characteristics. RESULTS: The cohort included 41 patients (age at diagnosis 12.1 ± 3.5 years, 23 females).The mean interval between the scans was 3.4 ± 2.0 years. There was a trend towards improvement in L1-4 z-scores (-1.64 ± 1.02 vs -1.45 ± 0.83, P = .12). ∆L1-4 z-scores correlated positively with ∆weight-standard deviation scores (SDS), ∆height-SDS and ∆BMI-SDS, and with age at the second scan (R = .55, P < .01; R = .42, P < .01; R = .42, P = .01; R = .35, P = .02, respectively); and negatively with L1-4 z-scores at the first scan (R = -.63, P < .01). Stepwise linear regression analysis identified the first scan L1-4 z-scores and ∆weight-SDS as independent predictors of ∆L1-4 z-scores. An L1-4 z-score ≤-2 at the first DXA scan was associated with significant improvement at the second scan. CONCLUSION: Improvement in BMD was more pronounced in children who gained weight or whose BMD was low at the first scan.

Neonatal osteoma cutis due to a mutation in GNAS.

We describe a 4-week-old baby boy who presented with white firm cutaneous nodules and failure to thrive. He did not have dysmorphic features, and laboratory tests including serum calcium, phosphorous, thyroid function, and parathyroid hormone level were within normal ranges. Whole exome sequencing revealed an inactivating mutation in GNAS that was previously described as causing pseudohypoparathyroidism.

Endocrine manifestations in children with Williams-Beuren syndrome.

AIM: Endocrine abnormalities in Williams-Beuren syndrome (WBS) include growth retardation, precocious puberty, hypercalcaemia and thyroid disorders. We aimed to characterise these abnormalities in a national cohort of children with WBS. METHODS: A retrospective study comprising a national cohort of individuals with WBS in Israel (16 males, 18 females) followed between 2010 and 2016. RESULTS: The age at diagnosis of WBS was 1.4 ± 1.0 years. Height standard deviation score (SDS) at last visit was correlated with the midparental height SDS (r = 0.46 p = 0.007). Yet, participants did not reach their midparental height, with a difference of 1.40 ± 0.85SD (p < 0.001). Short stature below the 3rd percentile was found in 14 participants (41%). Mean insulin-like growth factor 1 SDS was low (-0.61 ± 1.64) and was correlated with the mean height SDS (r = 0.63 p = 0.038). Two participants were diagnosed with growth hormone deficiency, and initiation of growth hormone treatment improved their height velocity. A total of eight participants (23.5%) had mild hypercalcaemia, five girls (14.7%) had precocious puberty and five participants (14.7%) had thyroid abnormalities. CONCLUSION: Individuals with WBS had a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Precocious puberty, hypercalcaemia and thyroid abnormalities should be screened for and treated as needed.

Elevated Baseline Cortisol Levels Are Predictive of Bad Outcomes in Critically Ill Children.

OBJECTIVE: The definition of an adequate adrenal response in critically ill children continues to be controversial. We aimed to evaluate the cortisol levels at baseline and after adrenocorticotropin (ACTH) stimulation and determine their association to clinical outcome of critically ill children. METHODS: All children who underwent an ACTH test in the pediatric intensive care unit (PICU) in a tertiary medical center between 2006 and 2013 were included in the study. Data on age, sex, diagnosis, vasoactive-inotropic score, length of pediatric intensive care unit stay, and mortality were obtained. Laboratory variables included hematologic and chemistry data, arterial lactate, and total plasma cortisol levels at baseline and after ACTH stimulation. RESULTS: Ninety-nine patients (61 males; median [range] age, 2 [0-204] months) were enrolled. The mortality rate of children with a baseline cortisol level of 600 nmol/L or greater was 36% (12/33 patients) versus 18% (12/66 patients) for children with a baseline cortisol level of less than 600 nmol/L (odds ratio, 2.6 [95% confidence interval, 1-6.6]; P = 0.05). There was a positive correlation between baseline cortisol and lactate levels (r = 0.40, P < 0.0001), vasoactive-inotropic scores (r = 0.24, P = 0.02), and mortality (P = 0.05). There was no correlation between peak cortisol measured at the ACTH test or the delta increment of cortisol from baseline and mortality. CONCLUSIONS: A high baseline cortisol level in critically ill children was associated with more severe illness, higher lactate level, and a higher mortality rate. Routine baseline cortisol assessment is recommended to identify patients at high mortality risk.

Growth characteristics and endocrine abnormalities in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) has a wide range of clinical features including endocrine abnormalities. We aimed to characterize growth patterns, hypoparathyroidism, and thyroid dysfunction of individuals with 22q11.2DS. Anthropometric and laboratory measurements were obtained from the charts of 48 individuals (males=28, 8.0±6.8 visits/participant) followed at a national 22q11.2DS clinic between 2009 and 2016. Age at diagnosis was 4.3±4.9 years and age at last evaluation 11.2±7.2 years. Median height-SDS was negative at all ages. Height-SDS at last visit was correlated to the midparental height-SDS (r=0.52 P=0.002). Yet, participants did not reach their target height, with a difference of 1.06±1.07 SD (P <0.0001). Height-SDS at last visit of participants with a heart defect was lower compared to participants with a normal heart (-1.5±1.4 vs. -0.6±0.8, P=0.036), with lower height-SDS in the subgroup of participants with severe heart defects (-2.1±1.6, P=0.009). Mean IGF1-SDS was low (-0.99±1.68) but was not correlated with height-SDS. Thirteen patients (27%) had hypoparathyroidism: 10 presented during infancy and 3 during adolescence. Five patients (10.4%, female=4) had thyroid abnormalities. In conclusions, individuals with 22q11.2 DS have a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Hypoparathyroidism is common and may present during the neonatal period as well as later in life. Thyroid abnormalities may present during childhood, adolescence, or adulthood.

Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort.

BACKGROUND: Ataxia telangiectasia (AT) is a genetic multisystem disorder, presenting with progressive ataxia, immune deficiency, and propensity toward malignancy. Endocrine abnormalities (growth retardation, reproductive dysfunction, and diabetes) have been described, however detailed information regarding this aspect is lacking. We aimed to characterize endocrine anomalies and growth patterns in a large cohort of AT patients. METHODS: Retrospective study comprising all 52 patients (aged 2-26.2 y) followed at a national AT Clinic. Anthropometric and laboratory measurements were extracted from the charts. RESULTS: Median height-SDS was already subnormal during infancy, remaining negative throughout follow up to adulthood. Height-SDS was more impaired than weight-SDS up to age 4 y, thereafter weight-SDS steadily decreased, resulting in progressively lower BMI-SDS. IGF-I-SDS was low (-1.53 ± 1.54), but did not correlate with height-SDS. Gonadal failure was present in all 13 females older than 10 y but only in one male. Two patients had diabetes and 10 had dyslipidemia. Vitamin D deficiency was observed in 52.2% of the evaluated patients. CONCLUSION: Our results suggest a primary growth abnormality in AT, rather than secondary to nutritional impairment or disease severity. Sex hormone replacement should be considered for female patients. Vitamin D levels should be followed and supplementation given if needed.

High prevalence of vitamin D deficiency and insufficiency in adolescent inpatients diagnosed with eating disorders.

OBJECTIVE: Previous studies assessing vitamin D status in adolescents with eating disorders showed inconsistent results. The aim of the current study was to assess vitamin D status in a large cohort of adolescent inpatients with eating disorders and its relation to bone mineral density (BMD) and depression. METHOD: 25-Hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline phosphatase levels as well as BMD and depression were assessed on admission in 87 inpatients (aged 16 ± 2 years, females = 81) with eating disorders [anorexia nervosa (AN) = 64; bulimia nervosa (BN) = 5; eating disorders not otherwise specified-binge/purge type (EDNOS-B/P) = 18]. RESULTS: Mean 25OHD levels were 24.1 ± 7.5 ng/ml (25.0 ± 7.6, 25.4 ± 9.9, and 22.0 ± 9.9 ng/ml in patients with AB, BN, and EDNOS-B/P, respectively). Vitamin D deficiency (<15 ng/ml) was found in 7.8% of the patients, and insufficiency (15-20 ng/ml) in 22.2%. Only 16.7% had levels >32 ng/ml, considered optimal by some experts. No associations were found between 25OHD levels and BMD or comorbid depression. 25OHD levels during winter were significantly lower than summer levels (p < .001). Mean lumbar spine BMD z-score in patients with AN and EDNOS-B/P type was low (-1.5 ± 1.1) and correlated with body mass index standard deviation score (p = .03). DISCUSSION: Adolescents with eating disorders show a high prevalence of vitamin D deficiency and insufficiency. Given the risk of osteoporosis in this population, 25OHD levels found in this group may not offer optimal bone protection. Vitamin D levels should be routinely checked and supplementation should be administered as required.

The many etiologies of neonatal hypocalcemic seizures.

Seizures during the neonatal period have a broad differential diagnosis. Unlike in developing countries where hypovitaminosis D and hypocalcemia constitutes a major cause of infantile seizures, the number of neonatal seizures attributed to hypocalcemia in developed countries has decreased dramatically due to the improvement of infant formulas and vitamin D supplementation. In these countries, most infants that present with hypocalcemic seizures have underlying endocrinological etiologies rather than dietary insufficiencies. Here, we describe 3 cases of neonatal seizures due to hypocalcemia. Although the symptoms and calcium concentrations at presentation were similar in all 3 cases, the course of the disease and the final diagnosis for each were distinct. The cases are presented along with a brief review of the pathophysiology, differential diagnosis, and treatment of neonatal hypocalcemia.

Pituitary function in children following infectious diseases of the central nervous system.

Recent studies in adults suggest that pituitary deficiencies develop in a considerable proportion of patients who recover from infectious meningitis. The aim of this study was to evaluate pituitary function of children with a history of meningitis. Seventy-nine children were admitted to the Safra Children's Hospital due to meningitis between 2007 and 2010. Twenty-four families were lost for follow-up, 55 were interviewed by phone and 14 (9 males) participated in the study. Evaluation included medical history, physical examination, auxological measurements and basal levels of TSH, fT4, cortisol and IGF1. Children with abnormal results were followed for a year and dynamic testing was performed when indicated. Mean age at time of infectious meningitis was 3.8 ± 5.4 years (range 0.03-15.8), and at clinical evaluation 6.4 ± 6.4 (range 1.2-20). The interval between the acute event and evaluation was 2.7 ± 1.2 years. Thyroid function tests and basal cortisol levels were normal for all children. Three children had low IGF1 levels; however over a year of follow-up two of them had normal height and growth velocity, making growth hormone deficiency unlikely. One child had low height SDS, but exhibited a normal response to a growth hormone stimulation test. Pituitary dysfunction with overt clinical symptoms is not a frequent consequence of acute meningitis in children. Follow-up of growth and puberty of children post-meningitis by the primary care physician is probably sufficient. Invasive assessments should be reserved for selected cases where there is slow growth or other clinical suspicion of hypopituitarism.