Norms for Clinical Use of CXM, a Real-Time Marker of Height Velocity.

CONTEXT: Height velocity (HV) is difficult to assess because growth is very slow. The current practice of calculating it from measurements taken at several-month intervals is insufficient for managing children with growth disorders. We identified a bone growth by-product (collagen X biomarker, CXM) in blood that in preliminary analysis in healthy children correlated strongly with conventionally determined HV and displayed a pattern resembling published norms for HV vs age. OBJECTIVE: The goal was to confirm our initial observations supporting the utility of CXM as an HV biomarker in a larger number of individuals and establish working reference ranges for future studies. DESIGN, SETTINGS, AND PARTICIPANTS: CXM was assessed in archived blood samples from 302 healthy children and 10 healthy adults yielding 961 CXM measurements. A total of 432 measurements were plotted by age, and sex-specific reference ranges were calculated. Serial values from 116 participants were plotted against observed HV. Matched plasma, serum, and dried blood spot readings were compared. RESULTS: A correlation of blood CXM with conventional HV was confirmed. Scatter plots of CXM vs age showed a similar pattern to current HV norms, and CXM levels demarcated the pubertal growth spurt both in girls and boys. CXM levels differed little in matched serum, plasma, and dried blood spot samples. CONCLUSIONS: Blood CXM offers a potential means to estimate HV in real time. Our results establish sex-specific, working reference ranges for assessing skeletal growth, especially over time. CXM stability in stored samples makes it well suited for retrospective studies.

Use of Telehealth Videoconferencing in Pediatric Type 1 Diabetes in Oregon.

INTRODUCTION: We reviewed the impact of telehealth videoconferencing clinics on outcomes of care in pediatric patients with type 1 diabetes in rural Oregon. METHODS: We performed a chart review as well as the review of patient satisfaction questionnaires from 27 patients seen in the first year of the program. RESULTS: The number of yearly visits to diabetes clinic increased from average 1.5 to 2.7, which was statistically significant (p < 0.0001). Glycemic control remained stable, and there was no difference in the amount of emergency department visits or hospitalizations related to diabetes. Patients expressed high satisfaction with the service and majority considered it equal to in-person visits. CONCLUSION: We conclude that telehealth videoconferencing visits have the potential to improve care in pediatric diabetes patients, particularly the patients living in areas distant from subspecialty centers.

A degradation fragment of type X collagen is a real-time marker for bone growth velocity.

Despite its importance as a key parameter of child health and development, growth velocity is difficult to determine in real time because skeletal growth is slow and clinical tools to accurately detect very small increments of growth do not exist. We report discovery of a marker for skeletal growth in infants and children. The intact trimeric noncollagenous 1 (NC1) domain of type X collagen, the marker we designated as CXM for Collagen X Marker, is a degradation by-product of endochondral ossification that is released into the circulation in proportion to overall growth plate activity. This marker corresponds to the rate of linear bone growth at time of measurement. Serum concentrations of CXM plotted against age show a pattern similar to well-established height growth velocity curves and correlate with height growth velocity calculated from incremental height measurements in this study. The CXM marker is stable once collected and can be accurately assayed in serum, plasma, and dried blood spots. CXM testing may be useful for monitoring growth in the pediatric population, especially responses of infants and children with genetic and acquired growth disorders to interventions that target the underlying growth disturbances. The utility of CXM may potentially extend to managing other conditions such as fracture healing, scoliosis, arthritis, or cancer.

Cardiac function in congenital adrenal hyperplasia: a pattern of reversible cardiomyopathy.

OBJECTIVE: To evaluate cardiac function in infants with congenital adrenal hyperplasia (CAH) before and after corticosteroid replacement therapy. STUDY DESIGN: This prospective, case-control study included 9 infants with CAH. Cardiac function was assessed by echocardiography at presentation and after corticosteroid replacement therapy. Six term infants underwent 2 echocardiograms each and served as the control group. Data on fractional shortening (FS), rate-corrected velocity of circumferential fiber shortening (Vcf), wall stress, tissue Doppler indices, myocardial performance index, left ventricular mass, and Vcf/wall stress were obtained. RESULTS: The infants with CAH exhibited myocardial dysfunction at baseline and lower systolic blood pressure (SBP) compared with the control group. FS, a measure of systolic contractility, differed significantly from before to after corticosteroid treatment (mean, 32.3%±4.7% pretreatment, 39.9%±5.0% posttreatment). Vcf, a preload-independent measure of cardiac contractility, also differed significantly before and after treatment (mean, 1.23±0.16 circumferences/second pretreatment, 1.45±0.22 circumferences/second posttreatment). SBP was also lower (mean, 84±9.3 mmHg) and improved with treatment (mean, 95±4.8 mmHg). The control group demonstrated no statistically significant changes in FS, Vcf, or SBP. There was a change in left ventricular mass in the control group between the 2 studies. CONCLUSION: Newborns with CAH have evidence for cardiac dysfunction at baseline that reverses with corticosteroid replacement therapy. These data suggest that corticosteroids play a direct role in modulating cardiac function in the newborn.

Congenital hypothyroidism caused by excess prenatal maternal iodine ingestion.

We report the cases of 3 infants with congenital hypothyroidism detected with the use of our newborn screening program, with evidence supporting excess maternal iodine ingestion (12.5 mg/d) as the etiology. Levels of whole blood iodine extracted from their newborn screening specimens were 10 times above mean control levels. Excess iodine ingestion from nutritional supplements is often unrecognized.

Imatinib mesylate causes growth deceleration in pediatric patients with chronic myelogenous leukemia.

BACKGROUND: Imatinib mesylate, a tyrosine kinase inhibitor, is used in the treatment of chronic myelogeneous leukemia (CML). Given its ease of administration and manageable side effects in adults, imatinib mesylate was introduced as therapy for pediatric CML. Recently published case reports describe growth deceleration in children treated with imatinib. This study details the growth phenotype of seven pediatric patients maintained in remission on imatnib mesylate over an extended period of time. PROCEDURE: This study is a retrospective chart review of pediatric patients with CML at Oregon Health & Science University treated with imatinib. Height, weight, and body mass index (BMI) measurements were collected before and during treatment. Median standard deviation scores (SDS) were analyzed by Wilcoxon Rank-Sum test and Wilcoxon signed rank cohort analysis. RESULTS: Individual patient analysis demonstrated five of seven subjects with a statistically significant decrease in height SDS pre versus during treatment. The whole group analysis showed a trend to significance for difference in median height SDS pre and during treatment (P = 0.078). Bone age was delayed in all four patients in whom bone ages were obtained. IGF-1, IGFBP-3, and thyroid levels during treatment were normal. Four patients experienced an improvement in height SDS during puberty. However, three patients approaching near final adult height failed to achieve genetic height potential determined by mid-parental target height. CONCLUSION: Growth in children with CML appears to be adversely impacted by imatinib therapy. BMI and IGF-1/IGFBP-3 are maintained during treatment, suggesting a direct effect of imatinib on the growth plate.

Natural history of idiopathic diabetes insipidus.

OBJECTIVE: To determine what percentage of diabetes insipidus (DI) in childhood is idiopathic and to assess the natural history of idiopathic DI. STUDY DESIGN: We conducted a retrospective chart review of 105 patients with DI who were born or had DI diagnosed between 1980-1989 at 3 medical centers. A second cohort of 30 patients from 6 medical centers in whom idiopathic DI was diagnosed after 1990 was evaluated retrospectively for subsequent etiologic diagnoses and additional hypothalamic/pituitary deficiencies and prospectively for quality of life. RESULTS: In the first cohort, 11% of patients had idiopathic DI. In the second cohort, additional hypothalamic/pituitary hormone deficiencies developed in 33%, and 37% received an etiologic diagnosis for DI. Health-related quality of life for all the patients with idiopathic DI was comparable with the healthy reference population. CONCLUSIONS: Only a small percentage of patients with DI will remain idiopathic after first examination. Other hormone deficiencies will develop later in one-third of those patients, and slightly more than one-third of those patients will have an etiology for the DI diagnosed. Long-term surveillance is important because tumors have been diagnosed as long as 21 years after the onset of DI. Quality of life for these patients is as good as the reference population.

Prevalence and trends of metabolic syndrome among Korean adolescents: from the Korean NHANES survey, 1998-2005.

OBJECTIVES: To evaluate the prevalence and trend of metabolic syndrome (MetS) among Korean adolescents. STUDY DESIGN: Data from 1998, 2001, and 2005 Korean National Health and Nutrition Examination Surveys were analyzed (N = 4164; age, 10 to 19 years) for MetS prevalence using the modified International Diabetes Federation criteria. RESULTS: The combined prevalence of MetS in Korean adolescents was 2.2% in 1998, 3.6% in 2001, and 1.8% in 2005. MetS in Korean boys increased from 1.4% in 1998 to 5.3% in 2001 but decreased to 2.0% in 2005. The prevalence of MetS in girls decreased over the study periods (3.0% in 1998, 1.9% in 2001, and 1.6% in 2005). MetS prevalence declined from 1998 to 2005 despite an increase in overweight or obese individuals among both sexes (1998: boys, 15.1%; girls, 17.8%; 2005: boys, 26.8%; girls, 21.7%). Among individual MetS components, hyperglycemia decreased dramatically in 2005 in both sexes and accounted for the majority of the decline in the prevalence of the MetS in Korean adolescents. CONCLUSIONS: The prevalence of MetS has declined despite an increase in obesity in Korean youth. Recent changes in physical activity in addition to national health care initiatives in Korea may have had a positive impact on the prevalence of MetS.

Childhood obesity and the metabolic syndrome.

The current epidemic of obesity reflects environmental changes that have an impact on a genetically susceptible population. The scope of obesity and its associated comorbidities warrants its position among the most crucial global public health problems faced today. Society has gained better appreciation for the significance of this problem yet still has much to learn regarding how best to address the obesity crisis. Although strategies for treating individuals who have weight problems successfully continue to evolve, the most profound impacts ultimately will arise from societal changes dictating that all individuals strive to adopt a healthy lifestyle.

The hypothalamic path to obesity.

Obesity is a growing public health concern, affecting an estimated 11% of children in Western society. The impact of obesity-related morbidity and mortality on society is significant, with both genetic and environmental factors contributing to its development. In most individuals, food intake and energy expenditure are tightly regulated by a feedback system comprising a number of hormonal and central nervous system pathways. Leptin released from adipocytes acts on hypothalamic neurons to release proopiomelanocortin (POMC), leading to a cascade of neuronal and hormonal events that inhibit feeding behavior. Specific gene mutations in the leptin/POMC pathways account for only 5% of all cases of obesity, and most cases of familial or idiopathic obesity are polygenic in origin. Although further research to identify specific genetic causes of obesity may lead to more tailored therapies, significant changes in societal and individual behavior are needed to stop the obesity epidemic from progressing.