Effect of growth hormone (GH) during puberty in GH‐deficient children: preliminary results from an ongoing randomized trial with different dose regimens

Wikland, Kerstin Albertsson; Alm, Fredrik; Aronsson, S; Gustafsson, Jan Åke; Hagenäs, Lars; Häger, A; Ivarsson, Sten-Anders; Kriström, Berit; Marcus, Claude; Maaser, Christian; Nilsson, K. O.; Ritzén, Martin; Tuvemo, Torsten; Westgren, U; Westphal, Otto; Åman, Jan

doi:10.1111/j.1651-2227.1999.tb14358.x

Cited by 24 publications

(15 citation statements)

References 19 publications

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“…This suggests that the chosen modalities of the induction and maintenance of puberty with sex steroid had no negative effects on TPG. Likewise, in other studies applying ‘prepubertal’ replacement doses to adolescents with GHD an adequate, almost normal TPG was observed in GHD [30,31,32,33]. Along these lines is the observation by Mauras et al [3 ]that doubling the GH dose from 0.3 to 0.7 mg/kg/week during 3 pubertal years only resulted in a mean total gain of 4.6 cm.…”

Section: Discussionsupporting

confidence: 54%

Observed and Predicted Total Pubertal Growth during Treatment with Growth Hormone in Adolescents with Idiopathic Growth Hormone Deficiency, Turner Syndrome, Short Stature, Born Small for Gestational Age and Idiopathic Short Stature: KIGS Analysis and Review

Ranke

Lindberg²

2011

Horm Res Paediatr

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Background/Aims: The aim was to describe the factors determining total pubertal growth (TPG) in adolescents with growth hormone deficiency (GHD), Turner syndrome (TS), who were small for gestational age (SGA) or had idiopathic short stature (ISS). Methods: The patients were documented within KIGS (Pfizer International Growth Database). TPG was defined as growth from puberty onset – spontaneous (>B1 or testes >3 ml) or induced with sex steroids to adult height in idiopathic GHD (n = 639; males 399), TS (n = 463), SGA (n = 59; males 35), and ISS (n = 130; males 87). Algorithms to predict TPG at puberty onset were developed by multiple linear regression analysis. Results: In GHD (males, females) and TS TPG could be explained with the same four predictors: (1) age (years) at puberty onset (neg.), (2) age – bone age at puberty onset (pos.), (3) height – midparental height (SDS) at puberty onset (neg.), and (4) mean dose of growth hormone (GH) during puberty (pos.). The algorithms explained 66, 65 and 68%, respectively, of the variability with total errors of 4.5, 3.8 and 2.9 cm, in spontaneous and induced TPG. Conclusions: TPG is determined by the same factors at puberty onset in adolescents with GHD, TS, SGA or ISS treated with GH. Thus, TPG depends mostly on the outcomes achieved at the end of prepubertal growth and less so on the dose of GH.

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Section: Discussionsupporting

confidence: 54%

Observed and Predicted Total Pubertal Growth during Treatment with Growth Hormone in Adolescents with Idiopathic Growth Hormone Deficiency, Turner Syndrome, Short Stature, Born Small for Gestational Age and Idiopathic Short Stature: KIGS Analysis and Review

Ranke

Lindberg²

2011

Horm Res Paediatr

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“…Interestingly, during the pubertal period we did not find a dose effect in growth response. This is in line with a randomized trial in GHD children (32), and the results of the limited impact of GH dose in prediction models of pubertal growth (33).…”

Section: Final Height In Short Sga On Ghsupporting

confidence: 55%

Final Height in Short Children Born Small for Gestational Age Treated with Growth Hormone

2005

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The aim of this observational study was to assess the longterm growth responses to GH treatment of children born small for gestational age (SGA). GH treatment was begun before puberty and continued to final height (FH). Seventy-seven short (height SD score below Ϫ2) prepubertal children born SGA (below Ϫ2 SD for birth weight and/or birth length), with a broad range of GH secretory capacity, were treated with GH in a daily dose of 33 g/kg (0.1 U/kg), beginning before the onset of puberty. We observed a difference between adult and pretreatment projected height of 1.3 SD (9 cm) for the entire group. Among the children treated for Ͼ2 y before puberty, this mean gain (i.e. difference) in final height was 1.7 SD, whereas the mean gain was 0.9 SD among those in whom treatment was begun Ͻ2 y before puberty. Better catch-up growth was observed in the younger (r ϭ Ϫ0.56, p Ͻ 0.0001), shorter (r ϭ Ϫ0.49, p Ͻ 0.0001), and lighter (r ϭ Ϫ0.46, p Ͻ 0.0001) subjects. We conclude that GH treatment improves the final height of short children born SGA. The height gain attained before the onset of puberty is maintained to final height. The younger, shorter, and lighter the child at the start of GH treatment, the better the response. Moreover, most of these SGA individuals treated with GH reach their target height. There is a 5-to 7-fold higher risk of short stature among adults who were born SGA, compared with those born AGA (1,2). Children born SGA comprise one-third of children who are short during childhood (1). As short stature is present in 10 -15% of children born SGA (1-3), efforts have been made to understand the etiology of their growth restriction and to increase their FH.Birth length has been shown in population-based studies to be the single most important predictor of adult height (1,2). Short children born SGA keep their prepubertal height SDS to FH, whereas short children born AGA gain further 0.6 -0.7 SDS in height during puberty (4). French data show that adult men who were born SGA are, on average 7.5 cm, and women are 9.6 cm below their mid-parent target height (5). This is at the lower end of the range compared with other studies (1,6,7), which find a growth deficit of 0.7-0.9 SDS below the MPH.Either low GH secretion or reduced sensitivity to GH may account for some of the growth retardation of children born SGA (8 -10). Boguszewski et al. (11,12) reported that short children born SGA have both lower mean GH secretion rates and lower serum IGF-I (IGF-I) values than children born AGA. In children born SGA, there is a correlation between the GH dose and the growth response, mainly during prepubertal years (13-16). The majority of short children born SGA show improvement in growth rate during GH treatment, particularly if treatment is begun early (14,16). With the exception of one large study (17), however, no information is available on the FH achieved by short children born SGA and treated with GH from a young age to FH. We report here the observational data on the effect of GH therapy on final height of childr...

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“…+2.8 cm in the study of Mauras et al [22] in 97 pubertal GHD patients on 0.1 compared to 0.050 mg/kg/day GH (approx. 3.0 and 1.5 mg/m 2 /day) and no differences between GH dosages in the studies of Albertsson Wikland et al [26] and Coelho et al [27]. Studies on the KIGS database reported a significant positive relation between dose and pubertal growth spurt [28], but not for total height increment from childhood to adulthood in a multivariate analysis [29].…”

Section: Discussionmentioning

confidence: 99%

Adult Height in Children with Growth Hormone Deficiency: A Randomized, Controlled, Growth Hormone Dose-Response Trial

et al. 2010

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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 minus target height (TH) between children receiving 0.7 mg/m²/day biosynthetic GH (approx. 0.025 mg/kg/day) or 1.4 mg/m²/day (approx. 0.050 mg/kg/day). The patients enrolled in the trial were 20 ‘naïve’ GHD children (had not received GH before) and 15 ‘transfer’ GHD children (already on GH for at least 1 year). Results: In the naïve 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/m²/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/m²/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/m²/day. Induction of puberty was more often delayed in transfer children on 0.7 than on 1.4 mg/m²/day. Conclusion: In our GHD patients, AH was 4–5 cm less than TH in patients on 0.7 mg/m²/day GH, while it was 0–2 cm less in patients on 1.4 mg/m²/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/m²/day.

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Effect of growth hormone (GH) during puberty in GH‐deficient children: preliminary results from an ongoing randomized trial with different dose regimens

Abstract: Aman J. Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens. Acta Pxdiatr 1999; Suppl 428:80-4. Stockholm.

Cited by 24 publications

References 19 publications

Observed and Predicted Total Pubertal Growth during Treatment with Growth Hormone in Adolescents with Idiopathic Growth Hormone Deficiency, Turner Syndrome, Short Stature, Born Small for Gestational Age and Idiopathic Short Stature: KIGS Analysis and Review

Observed and Predicted Total Pubertal Growth during Treatment with Growth Hormone in Adolescents with Idiopathic Growth Hormone Deficiency, Turner Syndrome, Short Stature, Born Small for Gestational Age and Idiopathic Short Stature: KIGS Analysis and Review

Final Height in Short Children Born Small for Gestational Age Treated with Growth Hormone

Adult Height in Children with Growth Hormone Deficiency: A Randomized, Controlled, Growth Hormone Dose-Response Trial

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