Background:The weak androgen oxandrolone (Ox) may increase height but may also affect glucose metabolism in girls with Turner syndrome (TS). Methods: In a randomized, placebo-controlled, double... Show moreBackground:The weak androgen oxandrolone (Ox) may increase height but may also affect glucose metabolism in girls with Turner syndrome (TS). Methods: In a randomized, placebo-controlled, double-blind study, we assessed the effect of Ox at a dosage of either 0.06 or 0.03 mg/kg/day on glucose metabolism in 133 growth hormone (GH)-treated girls with TS. Patients were treated with GH (1.33 mg/m(2)/day) from baseline, combined with placebo (PI) or Ox from the age of 8, and estrogens from the age of 12. Oral glucose tolerance tests (OGTT) were performed, and HbA1c levels were measured before, during, and after discontinuing Ox/PI therapy. Results: Insulin sensitivity, assessed by the whole-body insulin sensitivity index (WBISI) decreased during GH+Ox/PI (p = 0.003) without significant differences between the dosage groups. Values returned to pre-treatment levels after discontinuing GH+Ox/Pl. On GH+Ox, fasting glucose was less frequently impaired (Ox 0.03, p = 0.001; Ox 0.06, p = 0.02) and HbA1c levels decreased more (p = 0.03 and p = 0.001, respectively) than on GH+Pl. Conclusions: We conclude that in GH-treated girls with TS, Ox at a dosage of 0.03 or 0.06 mg/kg/day does not significantly affect insulin sensitivity. Insulin sensitivity decreases during GH therapy, to return to a pretreatment level after discontinuing therapy. Copyright (C) 2010 S. Karger AG, Basel Show less
Background: Renal tubular acidosis (RTA) is a rare cause of growth failure, therefore it is uncertain whether routine screening with blood gas analysis of short infants and children is cost... Show moreBackground: Renal tubular acidosis (RTA) is a rare cause of growth failure, therefore it is uncertain whether routine screening with blood gas analysis of short infants and children is cost-effective. Objective: To investigate the clinical, growth and laboratory parameters in children with RTA to estimate the possible value of laboratory screening for this disorder in infants and children referred for short stature according to a recent guideline. Method: Retrospective chart analysis of 30 children diagnosed between 1978 and 2005 in The Netherlands and 3 centers in Belgium. Results: The current guideline for short stature detected 33% of children with RTA. Assuming a pre-test probability of RTA of 0.6 per 100,000 births, the likelihood ratio of poor growth was 58 and 17 below and above 3 years, respectively. Sensitivity was 17/30 and 12/24 for a -2.0 SDS cutoff for weight and body mass index, respectively. In infants and toddlers diagnosed before 3 years of age, the mean weight loss was 1.5 SD, and 0.8 SDS in older children. In short children >3 years RTA was extremely rare, always associated with clinical symptoms, and rarely detected by blood gas analysis. Conclusion: According to our data a decreasing weight SDS for age is a sufficient indication to perform blood gas analysis in children <3 years of age, particularly in the presence of additional clinical features, whereas it can be omitted in short children >3 years of age. Copyright (C) 2010 S. Karger AG, Basel Show less
Aim: To investigate the effect of 2 growth hormone (GH) doses on adult height (AH) in GH deficiency (GHD). Methods: A multicenter, randomized, controlled dose-response trial compared attained AH... Show moreAim: To investigate the effect of 2 growth hormone (GH) doses on adult height (AH) in GH deficiency (GHD). Methods: A multicenter, randomized, controlled dose-response trial compared attained AH minus target height (TH) between children receiving 0.7 mg/m(2)/day biosynthetic GH (approx. 0.025 mg/kg/day) or 1.4 mg/m(2)/day (approx. 0.050 mg/kg/day). The patients enrolled in the trial were 20 'naive' GHD children (had not received GH before) and 15 'transfer' GHD children (already on GH for at least 1 year). Results: In the naive group, the mean +/- SD AH minus TH was -5.3 +/- 6.1 and -2.2 +/- 6.9 cm in patients on 0.7 and 1.4 mg/m(2)/day, respectively (mean +/- SE difference 3.1 +/- 2.9; p = 0.3). In the transfer group, the mean +/- SD AH minus TH was -4.4 +/- 6.4 and +0.6 +/- 7.0 cm in patients on 0.7 and 1.4 mg/m(2)/day, respectively (mean +/- SE difference 5.0 +/- 3.5; p = 0.17). Spontaneous puberty started 1.1 years earlier in children on 1.4 compared to 0.7 mg/m(2)/day. Induction of puberty was more often delayed in transfer children on 0.7 than on 1.4 mg/m(2)/day. Conclusion: In our GHD patients, AH was 4-5 cm less than TH in patients on 0.7 mg/m(2)/day GH, while it was 0-2 cm less in patients on 1.4 mg/m(2)/day GH, but this difference did not reach statistical significance, probably due to limited numbers of patients, considerable variability in the growth response and earlier spontaneous puberty and pubertal induction in the children on 1.4 mg/m(2)/day. Copyright (C) 2010 S. Karger AG, Basel Show less
P>Objective Untreated girls with Turner syndrome (TS) have short stature, relatively broad shoulders, a broad pelvis, short legs, a high fat mass and low muscle mass. Our objective was to assess... Show moreP>Objective Untreated girls with Turner syndrome (TS) have short stature, relatively broad shoulders, a broad pelvis, short legs, a high fat mass and low muscle mass. Our objective was to assess the effect of the weak androgen oxandrolone (Ox) on body proportions and composition in growth hormone (GH)-treated girls with TS. Design/Patients 133 patients were included in a randomized, placebo-controlled, double-blind study. Methods Patients were treated with GH (1 center dot 33 mg/m2 per day) from baseline, combined with placebo (Pl) or Ox in a low (0 center dot 03 mg/kg per day) or previously conventional (0 center dot 06 mg/kg per day) dose from the age of eight, and oestrogens from the age of twelve. Sitting height, biacromial and biiliacal distances compared with height (i.e. shape values), BMI, waist circumference, sum of 4 skinfolds (sum4skin) and upper arm muscle area (UAMA) SD scores (SDS) were assessed half-yearly. Results Compared with GH + Pl, adult shape values on GH + Ox tended to be higher for sitting height (Ox 0 center dot 03, P = 0 center dot 2; Ox 0 center dot 06, P = 0 center dot 02) and biacromial distance (Ox 0 center dot 03, P = 0 center dot 2; Ox 0 center dot 06, P = 0 center dot 07) and lower for biiliacal distance (Ox 0 center dot 03, P = 0 center dot 004; Ox 0 center dot 06, P = 0 center dot 08). Sum4skin SDS tended to decrease more (Ox 0 center dot 03, P = 0 center dot 2; Ox 0 center dot 06, P = 0 center dot 005) while UAMA SDS increased more (Ox 0 center dot 03, P < 0 center dot 001; Ox 0 center dot 06, P < 0 center dot 001) than on GH + Pl. The increase in BMI and waist circumference SDS was comparable between the dosage groups. Conclusions In GH-treated girls with TS, Ox 0 center dot 06 increases sitting height and tends to increase biacromial distance and decrease biiliacal distance, while Ox 0 center dot 03 significantly decreases biiliacal distance compared with height. Furthermore, Ox 0 center dot 06 reduces subcutaneous fat mass, and both Ox dosages increase muscle mass. Show less
Objective: To assess the long-term effect of prepubertal high-dose GH treatment on growth in children with idiopathic short stature (ISS). Design and methods: Forty children with no signs of... Show moreObjective: To assess the long-term effect of prepubertal high-dose GH treatment on growth in children with idiopathic short stature (ISS). Design and methods: Forty children with no signs of puberty, age at start 4-8 years (girls) or 4-10 years (boys), height SDS < - 2.0 SDS, and birth length > - 2.0 SDS, were randomly allocated to receive GH at a dose of 2 mg/m(2) per day (equivalent to 75 mu g/kg per day at start and 64 mu g/kg per day at stop) until the onset of puberty for at least 2 years (preceded by two 3-month periods of treatment with low or intermediate doses of GH separated by two washout periods of 3 months) or no treatment. In 28 cases, adult height (AH) was assessed at a mean (S.D.) age of 20.4 (2.3) years. Results: GH-treated children (mean treatment period on high-dose GH 2.3 years (range 1.2-5.0 years)) showed an increased mean height SDS at discontinuation of the treatment compared with the controls (-1.3 (0.8) SDS versus -2.6 (0.8) SDS respectively). However, bone maturation was significantly accelerated in the GH-treated group compared with the controls (1.6 (0.4) versus 1.0 (0.2) years per year, respectively), and pubertal onset tended to advance. After an untreated interval of 3-12 years, AH was -2.1 (0.7) and -1.9 (0.6) in the GH-treated and control groups respectively. Age was a positive predictor of adult height gain. Conclusion: High-dose GH treatment restricted to the prepubertal period in young ISS children augments height gain during treatment, but accelerates bone maturation, resulting in a similar adult height compared with the untreated controls. Show less
Context and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and... Show moreContext and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10 centers in The Netherlands. One hundred thirty-three patients with TS were included in age group 1 (2-7.99 yr), 2 (8-11.99 yr), or 3 (12-15.99 yr). Patients were treated with GH (1.33 mg/m(2) . d) from baseline, combined with placebo(Pl) or Oxin low (0.03 mg/kg . d) or conventional (0.06 mg/kg . d) dose from the age of 8 yr and estrogens from the age of 12 yr. Adult height gain (adult height minus predicted adult height) and safety parameters were systematically assessed. Results: Compared with GH + Pl, GH + Ox 0.03 increased adult height gain in the intention-to-treat analysis (mean +/- SD, 9.5 +/- 4.7 vs. 7.2 +/- 4.0 cm, P < 0.02) and per-protocol analysis (9.8 +/- 4.9 vs. 6.8 +/- 4.4 cm, P = 0.02). Partly due to accelerated bone maturation (P < 0.001), adult height gain on GH + Ox 0.06 was not significantly different from that on GH + Pl (8.3 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.3). Breast development was slower on GH + Ox (GH + Ox 0.03, P = 0.02; GH + Ox 0.06, P = 0.05), and more girls reported virilization on GH + Ox 0.06 than on GH + Pl (P < 0.001). Conclusions: In GH-treated girls with TS, we discourage the use of the conventional Ox dosage (0.06 mg/kg . d) because of its low benefit to risk ratio. The addition of Ox 0.03 mg/kg . d modestly increases adult height gain and has a fairly good safety profile, except for some deceleration of breast development. (J Clin Endocrinol Metab 95: 1151-1160, 2010) Show less
The weak androgen oxandrolone (Ox) increases height gain in growth-hormone (OH) treated girls with Turner syndrome (TS), but may also give rise to virilizing side effects. To assess the effect of... Show moreThe weak androgen oxandrolone (Ox) increases height gain in growth-hormone (OH) treated girls with Turner syndrome (TS), but may also give rise to virilizing side effects. To assess the effect of Ox, at a conventional and low dosage, on behavior, aggression, romantic and sexual interest, mood, and gentler role in OH-treated girls with TS, a randomized, placebo-controlled, double-blind study was conducted. 133 patients were treated with OH (1.33 mg/m(2)/d) from baseline, combined with placebo (Pl). Ox 0.03 mg/kg/d. or Ox 0.06 mg/kg/d from the age of eight, and with estrogens from the age of 12. The child behavior checklist (CBCL), Junior Dutch Personality Questionnaire (DPQ-J), State-subscale of the Spielberger's State-Trait Anger Scale, Romantic and Sexual Interest Questionnaire, Mood Questionnaire, and Gender Role Questionnaire were filled out before, during, and after discontinuing Ox/Pl. The changes during Ox/Pl therapy were not significantly different between the dosage groups. In untreated patients, the mean CBCL total (P = 0.002) and internalizing (P = 0.003) T scores, as well as the mean DPQ-J social inadequacy SD score (SDS) (P = 0.004) were higher than in reference girls, but decreased during OH + Ox/Pl therapy (P<0.001, P = 0.05, P<0.001, respectively). Whereas the mean total (P = 0.01) and internalizing (P<0.001) T score remained relatively high, the mean social inadequacy SDS became comparable with reference values. We conclude that in OH-treated girls with TS, Ox 0.03 mg/kg/d or 0.06 mg/kg/d does not cause evident psychological virilizing side effects. Problem behavior, frequently present in untreated girls with TS, decreases during therapy, but total and internalizing problem behavior remain increased. (C) 2010 Elsevier Inc. All rights reserved. Show less
