Characterization and prevalence of severe primary IGF1 deficiency in a large cohort of French children with short stature.

OBJECTIVE: The prevalence of severe primary IGF1 deficiency (IGFD) is unclear. IGFD must be identified promptly as treatment with recombinant human IGF1 (rhIGF1) is now available. Our objective was to characterize and assess the prevalence of severe primary IGFD in a large cohort of patients evaluated for short stature at a pediatric endocrinology unit in France. DESIGN: Observational study in a prospective cohort. METHODS: Consecutive patients referred to our unit between 2004 and 2009 for suspected slow statural growth were included. Patients were classified into eight etiological categories. IGFD was defined by height ≤-3 SDS, serum IGF1 levels <2.5th percentile, GH sufficiency, and absence of causes of secondary IGFD. RESULTS: Out of 2546 patients included, 337 (13.5%) were born small for gestational age and 424 (16.9%) had idiopathic short stature. In these two categories, we identified 30 patients who met our criterion for IGFD (30/2546, 1.2%). In these 30 patients, we assessed the response to IGF1 generation test, time course of IGF1 levels, and efficiency of GH replacement therapy. The results indicated that only four of the 30 children were definite or possible candidates for rhIGF1 replacement therapy. CONCLUSION: The prevalence of severe primary IGFD defined using the standard criterion for rhIGF1 treatment was 1.2%, and only 0.2% of patients were eligible for rhIGF1 therapy.

Unexpected high frequency of skeletal dysplasia in idiopathic short stature and small for gestational age patients.

OBJECTIVE: To assess the prevalence of skeletal dysplasias (SDs) in patients with idiopathic short stature (ISS) or small for gestational age (SGA) status. SETTING: Rare Endocrine/Growth Diseases Center in Paris, France. DESIGN: A prospective study on consecutive patients with ISS and SGA enrolled from 2004 to 2009. METHOD: We used a standardized workup to classify patients into well-established diagnostic categories. Of 713 patients with ISS (n=417) or SGA status (n=296), 50.9% underwent a skeletal survey. We chose patients labeled normal or with a prepubertal slowdown of growth as a comparison group. RESULTS: Diagnoses were ISS (16.9%), SGA (13.5%), normal growth (24.5%), transient growth rate slowing (17.3%), endocrine dysfunction (12%), genetic syndrome (8.9%), chronic disease (5.1%), and known SD (1.8%). SD was found in 20.9% of SGA and 21.8% ISS patients and in only 13.2% in our comparison group. SD prevalence was significantly higher in the ISS group than in the comparison group, especially (50%) for patients having at least one parent whose height was <-2 SDS. Dyschondrosteosis and hypochondroplasia were the most frequently identified SD, and genetic anomaly was found in 61.5 and 30% respectively. Subtle SD was found equally in the three groups and require long-term growth follow-up to evaluate the impact on final height. CONCLUSION: SD may explain more than 20% of cases of growth retardation ascribed to ISS or SGA, and this proportion is higher when parental height is <-2 SDS. A skeletal survey should be obtained in patients with delayed growth in a context of ISS or SGA.

Childhood craniopharyngioma: hypothalamus-sparing surgery decreases the risk of obesity.

CONTEXT: Craniopharyngioma is a brain tumor whose high local recurrence rate has for a long time led to a preference for extensive surgery. Limited surgery minimizing hypothalamic damage may decrease the severe obesity rate at the expense of the need for radiotherapy to complete the treatment. OBJECTIVE: We compared weight gain and local recurrence rates after extensive resection surgery (ERS) and hypothalamus-sparing surgery (HSS). DESIGN: Our observational study compared a historical cohort managed with ERS between 1985 and 2002 to a prospective cohort managed with HSS between 2002 and 2010. SETTING: The patients were treated in a pediatric teaching hospital in Paris, France. PATIENTS: Thirty-seven boys and 23 girls were managed with ERS (median age, 8 years); 38 boys and 27 girls were managed with HSS (median age, 9.3 years). MAIN OUTCOME MEASURES: Data were collected before and 6 months to 7 years after surgery. Body mass index (BMI) Z-score was used to assess obesity and the number of surgical procedures to assess local recurrence rate. RESULTS: Mean BMI Z-score before surgery was comparable in the 2 cohorts (0.756 after ERS vs 0.747 after HSS; P = .528). At any time after surgery, mean BMI Z-score was significantly lower after HSS (eg, 1.889 SD vs 2.915 SD, P = .004 at 1 year). At last follow-up, the HSS cohort had a significantly lower prevalence of severe obesity (28% vs 54%, P < .05) and higher prevalence of normal BMI (38% vs 17%, P < .01). Mean number of surgical procedures was not significantly different in the 2 cohorts. CONCLUSIONS: Hypothalamus-sparing surgery decreases the occurrence of severe obesity without increasing the local recurrence rate.

Effects of growth reduction therapy using high-dose 17beta-estradiol in 26 constitutionally tall girls.

OBJECTIVE: The efficacy and safety of height-limiting therapy with high-dose 17beta-oestradiol in girls with constitutionally tall stature (CTS) are controversial. We evaluated the effectiveness of high-dose 17beta-oestradiol in premenarchal girls with CTS treated until their bone age reached 14 years. DESIGN: We retrospectively reviewed the medical records of the girls managed between 1989 and 2000 with high-dose 17beta-estradiol for CTS with a predicted final height greater than +3SDs. PATIENTS: Twenty-six girls met our inclusion criteria. At baseline, mean chronological age was 12.06 +/- 1.51 years and mean height was 171.1 +/- 6.5 cm with a height standard deviation score of 4.5 +/- 0.24, and mean predicted final height was 183.0 +/- 4.2 cm. Treatment was stopped when bone age reached 14 years; mean treatment duration was 1.62 +/- 0.76 years. MEASUREMENTS: The following were obtained at 6-month intervals: height, body weight, Tanner stage, bone age, plasma cholesterol and triglycerides, plasma glucose and side effects. A mailed questionnaire on final height and satisfaction was sent 2 years after treatment discontinuation (response rate, 24/26). Results Final height was significantly (P < 0.001) reduced, by 2.4 +/- 3.2 cm, as compared to predictions. High-dose 17beta-estradiol therapy decreased growth velocity and significantly increased skeletal maturation (P < 0.001). Linear growth after treatment discontinuation was 3.3 +/- 1.9 cm. No serious side effects were recorded. Most of the patients were satisfied with the treatment. CONCLUSION: High-dose 17beta-estradiol was moderately effective in reducing final height and should probably be reserved for selected patients, particularly as knowledge on potential long-term side effects is lacking.