Randomized Trial of Aromatase Inhibitors, Growth Hormone, or Combination in Pubertal Boys with Idiopathic, Short Stature.

CONTEXT: Growth of short children in puberty is limited by the effect of estrogen on epiphyseal fusion. OBJECTIVES: To compare: 1) the efficacy and safety of aromatase inhibitors (AIs) vs GH vs AI/GH on increasing adult height potential in pubertal boys with severe idiopathic short stature (ISS); and 2) differences in body composition among groups. DESIGN: Randomized three-arm open-label comparator. SETTING: Outpatient clinical research. PATIENTS: Seventy-six pubertal boys [mean (SE) age, 14.1 (0.1) years] with ISS [height SD score (SDS), -2.3 (0.0)]. INTERVENTION: Daily AIs (anastrozole or letrozole), GH, or AI/GH for 24-36 months. OUTCOMES: Anthropometry, bone ages, dual x-ray absorptiometry, spine x-rays, hormones, safety labs. RESULTS: Height gain [mean (SE)] at 24 months was: AI, +14.0 (0.8) cm; GH, +17.1 (0.9) cm; AI/GH, +18.9 (0.8) cm (P < .0006, analysis of covariance). Height SDS was: AI, -1.73 (0.12); GH, -1.43 (0.14); AI/GH, -1.25 (0.12) (P < .0012). Those treated through 36 months grew more. Regardless of treatment duration, height SDS at near-final height [n = 71; age, 17.4 (0.2) years; bone age, 15.3 (0.1) years; height achieved, ∼97.6%] was: AI, -1.4 (0.1); GH, -1.4 (0.2); AI/GH, -1.0 (0.1) (P = .06). Absolute height change was: AI, +18.2 (1.6) cm; GH, +20.6 (1.5) cm; AI/GH, +22.5 (1.4) cm (P = .01) (expected height gain at -2.0 height SDS, +13.0 cm). AI/GH had higher fat free mass accrual. Measures of bone health, safety labs, and adverse events were similar in all groups. Letrozole caused higher T and lower estradiol than anastrozole. CONCLUSIONS: Combination therapy with AI/GH increases height potential in pubertal boys with ISS more than GH and AI alone treated for 24-36 months with a strong safety profile.

Benefits of integration of radiology services across a pediatric health care system with locations in multiple states.

BACKGROUND: Integration was implemented of previously independently practicing pediatric radiology services across a pediatric health care system with sites 1,000 miles apart. OBJECTIVE: The purpose of this manuscript is to describe the process utilized to integrate imaging services across our enterprise and to study the direct effects on report turnaround time and other parameters. MATERIALS AND METHODS: Parameters were evaluated both the year before integration as well as the 2 years following integration and compared for improvement. Parameters studied included report turnaround time, academic productivity (as measured by peer review publications per year), and degree of sub-subspecialization within pediatric radiology (as measured by the percentage of neuroimaging CT and MRI studies read by pediatric neuroradiologists). RESULTS: Comparing pre- to post-integration measures, the median report turnaround time decreased from 2.3 h to 1.1 h (52.1% improvement), the percentage of neuroimaging studies read by neuroimaging faculty increased from 15.0% to 86.6% (477% improvement), and peer review publication by calendar year increased from 3 to 30 (1,000% improvement). Other benefits included increased hours of in-house coverage and execution on multiple quality improvement efforts. CONCLUSION: A pediatric health care system successfully integrated radiology services across multiple previously non-integrated locations into one functional group. This integration was associated with a positive effect on multiple parameters.

Metformin use in children with obesity and normal glucose tolerance--effects on cardiovascular markers and intrahepatic fat.

OBJECTIVE: To determine if metformin improves markers of inflammation, thrombosis, and intrahepatic fat contents in children with uncomplicated obesity. METHODS: Obese children with normal glucose tolerance but elevated highly sensitive C-reactive protein (hsCRP) and/or fibrinogen concentrations (>2 standard deviations) were randomized to structured diet/exercise or diet/exercise and metformin for 6 months. Blood samples, dual energy X-ray absorptiometry data, and liver magnetic resonance images were obtained. RESULTS: Forty-two of 66 recruited children (7-18 years) completed 6 months. Weight loss was modest but more pronounced in the metformin group (-4.9 +/- 1.0 kg) than in the diet/exercise group (-1.7 +/- 1.1 kg, p<0.03), whereas hsCRP and fibrinogen decreased more in the diet/exercise pubertal group. Baseline intrahepatic fat was high but decreased only in the diet/exercise (not metformin) pubertal group. CONCLUSIONS: Six months of metformin therapy improved weight loss and reduced abdominal adiposity, but did not enhance the beneficial effect of diet and exercise on markers related to inflammation, thrombosis, or hepatic fat in obese children with normal glucose tolerance.

Pharmacokinetics and pharmacodynamics of anastrozole in pubertal boys with recent-onset gynecomastia.

CONTEXT: Use of aromatase inhibitors to suppress estrogen production is being actively investigated in a variety of experimental conditions in both females and males. Anastrozole (Arimidex) is a potent and selective reversible inhibitor of the aromatase enzyme in females. OBJECTIVE: Our objective was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of anastrozole in adolescent males with gynecomastia of less than 1 yr duration. The effect of anastrozole on breast size was also assessed as an exploratory aim. DESIGN: We conducted a PK/PD open-label study. SETTING: This clinical research center study was undertaken at pediatric academic centers. PATIENTS: Forty-two boys with gynecomastia (mean age 13 +/- 1.8 yr; duration of gynecomastia 7.0 +/- 2.5 months; body mass index 28.3 +/- 5.9 kg/m(2)) were recruited. INTERVENTIONS: Anastrozole, 1 mg, was given daily for 6 months. MAIN OUTCOMES: We assessed PK/PD of anastrozole after 14 d daily dosing and changes in breast size (exploratory aim) by manual tape measurements (area) and ultrasound (volume) after 6 months. RESULTS: Anastrozole was rapidly absorbed orally (time to reach maximum concentration, 1 h) with a slow apparent clearance of 1.54 liters/h and a terminal half-life of 46.8 h. Testosterone/estradiol ratios increased significantly with concomitant increase in LH/FSH concentrations indicating aromatase blockade. There was a reduction in breast area (approximately 63%) and breast volume (approximately 57%) in the study group as compared with baseline (P = 0.004). The drug was well tolerated. CONCLUSIONS: Anastrozole is a potent aromatase inhibitor in adolescent males, with rapid absorption and slow elimination kinetics after oral dosing. Exploratory analysis of changes in breast size showed breast reduction in the cohort; this deserves further study.

Hip ultrasound.

Sonography has been widely utilized for several decades in the diagnosis and follow-up of developmental dysplasia of the hip due to its ability to visualize the nonossified femoral head and portions of the acetabulum in neonates, dynamic capabilities, accuracy, and lack of nonionizing radiation. Furthermore, hip sonography is also used throughout parts of the world to diagnose and guide intervention for both children and adults. The hip joint, tendons, and periarticular structures can be delineated with sonography in a variety of congenital, developmental, infectious, inflammatory, arthritic, traumatic, and neoplastic disorders. The following discussion focuses on the sonographic technique and imaging characteristics of congenital and developmental anomalies of the hip in children, as well as the sonographic evaluation of the hip joint and tendons.