Final height after treatment of early puberty in short adopted girls with gonadotrophin releasing hormone agonist with or without growth hormone.

OBJECTIVE: To compare final height data after treatment with gonadotrophin releasing hormone agonist (GnRHa) alone or in combination with growth hormone (GH) in short adopted girls with early puberty. DESIGN: A randomized controlled trial. PATIENTS AND METHODS: Twenty-six girls with onset of puberty before 10 years of age were treated for 3 years with either GnRHa alone (group A, n = 12) or with GnRHa and GH (group B, n = 14). Mean age at start of treatment was 9.6 years in both groups, bone age was 10.7 (SD 1.1) years in group A and 11.6 (0.8) years in group B. RESULTS: Initial height prediction with average Bayley & Pinneau tables was 149.8 (5.6) and 146.8 (4.8) cm, respectively. Bone age at discontinuation of treatment was 12.3 (0.9) and 13.0 (0.6) years in group A and B, respectively. Height gain defined as the difference between initial height prediction and attained final height, was significantly different between group A and B (5.2 (3.7) and 8.2 (3.4) cm, P < 0.05) using average tables for height prediction. With accelerated tables for prediction the numbers were -1.0 (3.6) and 3.3 (3.5) cm, respectively. At final height, there was no significant difference in height: group A: 155.0 (5.6) cm and group B: 155.0 (5.5) cm. CONCLUSIONS: After 3 years of GnRHa treatment in adopted girls with early puberty, FH is significantly higher than initial height prediction. The addition of GH resulted in a limited further increase in height gain. In the interpretation of the results methodological issues concerning height prediction have to be taken into account.

Evaluation of the usefulness of a quantitative ultrasound device in screening of bone mineral density in children.

BACKGROUND: Osteoporosis is a major public health problem, and its prevention is of great importance. It is known that bone mass later in life is determined by the peak bone mass acquired during adolescence and the subsequent rate of bone loss. Therefore we should give special attention to children that are 'at risk' of low bone mass, and we must seek simple yet reliable methods to measure their bone mineral density (BMD) regularly. AIM: We investigated the value of a quantitative ultrasound device (QUS), the Sahara clinical bone sonometer (Hologic), in screening of low bone mass in children. In contrast to dual energy X-ray absorptiometry (DEXA), the most commonly used technique for measurement of BMD today, the QUS method is free of ionizing radiation, easy to handle and inexpensive. SUBJECTS AND METHODS: Intra- and inter-observer variability of the QUS method was assessed using replicate measurements by two observers in 15 randomly chosen children. QUS parameters were measured in 226 healthy schoolchildren (121 boys, 105 girls) as well as in 41 children at risk for low bone mass (15 boys, 26 girls) between 7 and 18 years old. For comparison we also determined BMD by DEXA in those children at risk. RESULTS: Reproducibility of the QUS device was moderate, as well as the correlation between QUS and DEXA (r = 0.14-0.50). The QUS device was not able to recognize children with low bone mass as determined by DEXA. Although it is well known that BMD increases with age and pubertal stage, we could not find significant differences in QUS parameters between age and pubertal stage groups. CONCLUSION: We conclude that there is enough evidence that the Sahara clinical bone sonometer is not useful in screening of low bone mass in children.

[Bladder control in 1-4 year old children in the the Eindhoven and Kempen region (The Netherlands) in 1996 and 1966]. / Zindelijkheid voor urine bij 1-4-jarige kinderen in de regio Eindhoven en de Kempen, in 1996 en in 1966.

OBJECTIVE: To determine the age at which children gain bladder control and to compare this with the data from 30 years ago. DESIGN: Questionnaires. METHOD: On the basis of the findings of a 1966 study into toilet training in the Eindhoven and de Kempen region, the Netherlands, a questionnaire was drawn up and distributed via 30 child-health clinics in this region to parents of children aged 12-59 months, during the period 1 March-30 June 1996. The results were compared with those of the earlier study. RESULTS: Data from 1176 children could be evaluated (response rate: 65%). In 1996, the median age for bladder control in boys during the day was 32.6 months and 40.5 months for night-time control. In 1996 boys achieved daytime bladder control 6.7 months earlier and night-time control 7.2 months earlier. In 1996, the median age for girls was 29.7 months for daytime control and 35.4 months for night-time bladder control: in 1966 girls achieved daytime and night-time bladder control 8.2 and 4.8 months earlier, respectively. Factors associated with earlier bladder control were: early age at which parents started toilet training, presence of other children in the family, early age at which the child attended a day-care centre, early age at which the child was able to walk. Other factors such as the presence of a complete family set, parental level of education and professional situation did not show a correlation with the age at which the child achieved bladder control. The type of diaper used was an additional factor for bladder control at all ages but was only statistically significant for 3-year-olds, both during the day and during the night. CONCLUSION: Children in the Eindhoven region achieved daytime and night-time bladder control at a significantly later age than 30 years ago. Various factors such as toilet-training age, day-care attendance, family size and type of diaper played a role in this phenomenon.

GH treatment and its effect on bone mineral density, bone maturation and growth in short children born small for gestational age: 3-year results of a randomized, controlled GH trial.

BACKGROUND: To investigate in a group of short children born small for gestational age (SGA), the effects of 3 years of GH treatment vs. no treatment on bone age (BA), height and bone mineral density (BMD). Also, to evaluate the influence of the severity of growth retardation at start and the GH dose on the gain in height. PATIENTS AND METHODS: The study design was an open-labelled, controlled multicentre GH study for 3 years. Non-GH-deficient (GHD) children (n = 87) were randomized to either a GH group (n = 61) or an untreated control group (n = 26). In addition, 12 SGA children had GHD (GHD group) and were treated in parallel. Both the GH and the GHD group were treated with a GH dose of 33 microg/kg/day. BMD was evaluated using dual energy X-ray absorptiometry (DEXA). In addition, data of our first GH trial in which short SGA children were treated with a GH dose of 66 microg/kg/day (n = 24) were used for comparison of height gain. RESULTS: In contrast to the control group, the GH group showed a significant increase in height (P < 0.001), as did the parallel GHD group. Bone maturation [delta bone age (BA)/delta calendar age (CA)] increased significantly during the first 2 years of GH treatment but slowed-down thereafter. The 3-year deltaBA/deltaCA ratio correlated significantly with the gain in height (r = 0.6, P < 0.001). At start, mean BMD SDS and mean BMAD SDS were significantly lower than zero. During GH treatment both increased impressively (P < 0.001). The gain in height of children with severe short stature at start (< or = -3.00 SDS), did not differ between those receiving either a GH dose of 33 or 66 microg/kg/day. CONCLUSION: Three years of GH treatment in short children born SGA results in a normalization of height during childhood. Also, bone maturation increased proportionately to the height gain. At start, mean values of BMD and BMAD were significantly reduced but normalized during GH treatment. We did not find an indication to treat very short SGA children (H SDS < or = -3.00) with a higher GH dose. We rather suggest to start GH treatment at an early age in order to achieve a normal height before puberty starts.

High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature.

BACKGROUND: Long term growth hormone (GH) treatment in children with idiopathic short stature (ISS) results in a relatively small mean gain in final height of 3-9 cm, which may not justify the cost of treatment. As it is unknown whether GH treatment during puberty adds to final height gain, we sought to improve the cost-benefit ratio, employing a study design with high dose GH treatment restricted to the prepubertal period. AIMS: To assess the effect of short term, high dose GH treatment before puberty on growth, bone maturation, and pubertal onset. METHODS: Five year results of a randomised controlled study are reported. Twenty six boys and nine girls were randomly assigned to a GH treatment group (n = 17) or a control group (n = 18). Inclusion criteria were: no signs of puberty, height less than -2 SDS, age 4-8 years for girls or 4-10 years for boys, GH concentration >10 micro g/l after provocation, and normal body proportions. To assess GH responsiveness, children assigned to the GH treatment group received GH treatment for two periods of three months (1.5 IU/m2/day and 3.0 IU/m2/day), separated by three month washout periods, during the first year of study. High dose GH treatment (6.0 IU/m2/day) was then started and continued for at least two full years. When puberty occurred, GH treatment was discontinued at the end of a complete year's treatment (for example, three or four years of GH treatment). RESULTS: In response to at least two years on high dose GH treatment, mean (SD) height SDS for chronological age increased significantly in GH treated children from -2.6 (0.5) to -1.3 (0.5) after two years and -1.4 (0.5) SDS after five years of study. No changes in height SDS were observed in controls. A rapid rate of bone maturation of 3.6 years/2 years in treated children compared to 2 years/2 years in controls was observed in response to two years high dose GH treatment. Height SDS for bone age was not significantly different between groups during the study period. GH treated children entered into puberty at a significantly earlier age compared to controls. CONCLUSIONS: High dose GH treatment before puberty accelerates bone age and induces an earlier onset of puberty. This may limit the potential therapeutic benefit of this regimen in ISS.