Objectives: The treatment of brain tumors in childhood is frequently complicated by growth retardation with a high proportion of irradiation (Irr)-induced GH deficiency (GHD) resulting in reduced adult final height (AFH) even after GH therapy (GHT). In order to optimize future GHT protocols, more information on the factors influencing the growth response to GH in these children is needed. This retrospective study evaluated AFH and influencing auxological and treatment factors of a standardized daily biosynthetic GHT in childhood survivors of brain tumors with documented GHD after brain Irr.Design and methods: From the Belgian GH Registry, 57 children survivors of a brain tumor outside the hypothalamo-pituitary area with available AFH were stratified into two groups depending on cranial (C-Irr; n=25) or craniospinal (CS-Irr; n=32) Irr.Results: In the C-Irr patients, results showed an AFH of -0.8 (-2.5, 1.4) SDS (median (range)) and in the CS-Irr patients, results showed a significantly (P < 0.001) lower AFH of -1.8 (-4.2, 0.0) SDS. AFH SDS corrected for mid-parental height (MPH) in the C-Irr group was -0.5 (-2.2, 0.9) and -1.5 (-3.6, 0.0) SDS in the CS-Irr group. AFH was positively correlated with age at end of tumor therapy, height SDS at start GHT, height gain SDS first year GHT, and negatively correlated with CS-Irr.Conclusions: GHT failed to restore adult height to MPH in nearly half of Irr-induced GHD patients for brain tumor, especially those receiving CS-Irr, irradiated at a younger age or shorter at start GHT.

Background/Aims: Few data are available about parental concerns and psychosocial functioning of young children born small for gestational age (SGA) treated with growth hormone (GH). The present study focused on the perception of short stature and the concerns and expectations of the parents regarding GH treatment. Methods: Forty prepubertal short SGA children, randomized into a GH-treated and a GH-untreated group, and their parents were evaluated by a questionnaire and a semi-structured interview at start and after 2 years of follow-up. Results: Before start, 85% of the parents were concerned about short stature, 76% expected an increase in adult height of ≧10 cm and 81% expected a positive impact on well-being. Half of the parents expressed fears regarding GH treatment. After 2 years, more parents of treated children reported obvious growth and physical changes, and fewer parents reported teasing because of short stature. An improvement of well-being was reported by half of the parents of treated and untreated children. Fears about GH treatment disappeared almost completely. Conclusion: The perspective of GH treatment induced major adult height expectations. In treated children, the physical effects of GH treatment became obvious, teasing because of short stature decreased and initial concerns about short stature and GH therapy decreased.

OBJECTIVE AND DESIGN Children born small for gestational age (SGA) are not only at risk for short stature, but also for neurodevelopmental and behavioral problems. In this study, we analyzed the effects of high-dose GH therapy on cognitive development and psychosocial functioning in 34 prepubertal (3-8 years) short SGA children, equally randomized into a GH-treated group (TRG) and an untreated group (UTRG). METHODS At start and after 2 years, children underwent standardized tests measuring the intellectual abilities (Wechsler Preschool and Primary Scale of Intelligence-Revised, or Wechsler Intelligence Scale for Children-Revised); their parents completed a standardized questionnaire evaluating psychosocial functioning (Child Behavior Checklist; CBCL). RESULTS At start, total IQ scores were significantly (P < 0.05) lower in the SGA group than in the general population: 32% of the SGA patients had scores below 85. After 2 years, IQ scores remained unchanged in the TRG, but increased significantly (P < 0.05) in the UTRG. After exclusion of children with developmental problems, however, no significant changes in IQ scores occurred in the UTRG as well as the TRG. At baseline, 24% (8/34) children had problematic CBCL total problems scores, equally distributed among the two groups; no significant changes in the different subscale scores occurred after 2 years. CONCLUSION No beneficial effect of 2 years of GH therapy on cognitive and behavioral profile could be observed in a cohort of rather young short SGA children presenting a variable degree of developmental delay and behavioral problems. Subsequent follow-up could reveal potential long-term effects of GH therapy on development and behavior.

The age at diagnosis of 242 girls with Turner syndrome (TS) treated in Belgium with growth hormone between 1991 and 2002 was evaluated. The median (range) age at diagnosis was 6.6 (0–18.3) years. Patients with 45,X karyotype were diagnosed earlier than patients with other karyotypes. Compared to a previous survey, performed on 100 patients 12 years earlier, more patients were diagnosed during infancy and childhood, and less during adolescence. However, in 22% of the girls the diagnosis was made after the age of 12 years; these girls showed the largest height deficit. As early diagnosis has several potential advantages we recommend that a cytogenetic analysis should be considered in all girls with unexplained short stature with height below –2 SD of the mean for age or below the parent specific lower limit of height.

Objective: Since the availability of recombinant human growth hormone (rhGH) all children with growth hormone deficiency (GHD) living in Belgium are offered rhGH treatment after approval by a peer-review board. In this study, we evaluated the prevalence and demographic features of childhood GHD in Belgium during the period 1986-2001 and we compared them with the data from other countries.Methods: Diagnostic, demographic and baseline auxological data of 714 children diagnosed as having GHD between 1986 and 2001 were retrieved from the database of the Belgian Study Group for Paediatric Endocrinology.Results: The prevalence of GHD in Belgium was estimated to be 1/5600. The origin of GHD was idiopathic (idGHD) in 41% of the patients, congenital (congGHD) in 20% and acquired (acqGHD) in 35%. During the first 4 years (1986-1989) more patients were classified as idGHD; thereafter the distribution between the three aetiology groups did not change. In all groups, boys outnumbered girls but this preponderance was especially pronounced in congGHD patients (male:female = 4:1) with a central malformation that associates an anterior pituitary hypoplasia, a missing, fine or normal pituitary stalk and an ectopic posterior pituitary. Thirteen percent of the patients with idGHD, 50% with congGHD and 52% with acqGHD had multiple pituitary deficiencies. Patients with congGHD were the youngest (mean+/-S.D. age: 6.5+/-4.7 years) and were the shortest (-3.0+/-1.3 standard deviation score (SDS)) at the start of rhGH treatment. There was no time trend over the studied period for age and height at onset of GH therapy.Conclusion: In Belgium, the prevalence of childhood GHD can be estimated as 1/5600 which is comparable to other recent surveys. The yearly number of new patients for the different aetiologies and the auxological parameters have remained relatively constant over the last 16 years.

Although it has been well established that GH treatment increases final height (FH) in girls with Turner syndrome (TS), the optimal ages to start GH therapy and introduce estrogens for pubertal induction have not been defined. We evaluated retrospectively the influence of the age at onset of GH treatment and age at onset of puberty on FH of 186 adult TS women treated during childhood with GH. Puberty started spontaneously in 38 patients, and it was induced in 148 girls with ethinyl estradiol (mean +/- SD starting dose, 66 +/- 32 ng/kg.d). Patients with spontaneous or induced puberty were divided into quartiles on the basis of age at initiation of GH treatment (3-10, 10-12, 12-14, and 14-19 yr). FH was 151.7 +/- 6.0 cm; there were no FH differences between patients with induced or spontaneous puberty, nor were there differences between the age quartiles. Puberty started earlier in the girls with spontaneous puberty than in those with induced puberty (12.4 +/- 1.3 yr vs. 14.5 +/- 1.9 yr; P < 0.0001). The age at onset of puberty was not related to FH. Pubertal growth was 15.4 +/- 4.6 cm in the girls with spontaneous puberty and 8.6 +/- 4.3 cm in the girls with induced puberty (P < 0.0001). We conclude that GH treatment results in a significant increase in FH in most TS girls. Under the conditions of GH treatment and induction of puberty that we have used, the age at start of GH treatment was not related to FH; in addition, late or delayed induced or spontaneous puberty did not affect FH.

Background: Recent studies have shown that many patients treated with growth hormone (GH) during childhood because of idiopathic GH deficiency (GHD) are no longer GH deficient when retested after cessation of GH therapy when final height is achieved. These patients are labelled as transient GHD. We hypothesized that normalization of GH secretion in transient GHD could occur earlier during the course of GH treatment, which could allow earlier cessation of GH treatment. Methods: In a retrospective study, GH secretion was re-evaluated after cessation of GH treatment at final height in 43 patients diagnosed during childhood as idiopathic GHD (10 with multiple pituitary hormonal deficiencies (MPHD) and 33 with isolated GHD (IsGHD)). In a prospective study, GH secretion was re-assessed after interruption of GH treatment given for 1 year in 18 children with idiopathic GHD (2 MPHD, 16 IsGHD). GH secretion was evaluated by glucagon or insulin stimulation tests. Results: In the retrospective study, all the 10 patients with MPHD and 64% of the 33 patients with IsGHD were still deficient at re-evaluation using the paediatric criteria to define GHD (GH peak <10 ng/ml at provocative test). The proportion of persisting deficiency was greater in patients with complete IsGHD (86%, 12/14 patients) than in patients with partial IsGHD (47%, 9/19 patients). With the criteria proposed in adulthood (GH peak <3 ng/ml), all the 10 patients with MPHD were still considered to be deficient. In contrast, only 15% (5/33 patients) with IsGHD had a maximal GH value <3 ng/ml (36% of the 14 patients with complete IsGHD and none of the 19 patients with partial IsGHD). In the prospective study, after interruption of GH therapy given for 1 year, the 2 patients with MPHD were still GHD at re-evaluation and they resumed GH treatment. Among the 16 patients with IsGHD, 13 (81%) were still deficient (peak response <10 ng/ml) after 1 year. Two of the 3 patients in whom GHD was not confirmed at retesting after 1 year GH showed again a deficient response at second retesting. Conclusions: Although many patients diagnosed with IsGHD during childhood have a normalized GH secretory capacity when retested during adulthood, early retesting after interruption of GH treatment given for 1 year during childhood does not enable to determine if GH therapy has to be discontinued before cessation of growth.

Background: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. Patients/Methods: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5–0.7 IU/kg/week (0.17–0.23 mg/kg/week) from the mean ± SD age of 11.9 ± 3.1 years during 5.1 ± 2.1 years. Results: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was –0.7 ± 1.1 SDS, being 170.4 ± 7.2 cm in boys and 158.0 ± 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 ± 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 ± 7.0 cm vs. 27.5 ± 6.6 cm (p < 0.005); girls: 9.6 ± 7.4 cm vs. 22.2 ± 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. Conclusions: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5–0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.