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Metabolic outcome of GH treatment in prepubertal short children with and without classical GH deficiency

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Summary Context 

Few studies have evaluated the metabolic outcomes of growth hormone (GH) treatment in idiopathic short stature (ISS). Moreover, children with ISS appear to need higher GH doses than children with GH deficiency (GHD) to achieve the same amount of growth and may therefore be at increased risk of adverse events during treatment. The individualized approach using prediction models for estimation of GH responsiveness, on the other hand, has the advantage of narrowing the range of growth response, avoiding too low or high GH doses. Design 

Short prepubertal children with either isolated GHD (39) or ISS (89) participated in a 2-year randomized trial of either individualized GH treatment with six different GH doses (range, 17–100 μg/kg/day) or a standard dose (43 μg/kg/day). Objective 

To evaluate if individualized GH treatment reduced the variance of the metabolic measures as shown for growth response and to compare changes in metabolic variables in children with ISS and GHD. Hypothesis 

Individualized GH dose reduces the range of metabolic outcomes, and metabolic outcomes are similar in children with ISS and GHD. Results 

We observed a narrower variation for fasting insulin (−34·2%) and for homoeostasis model assessment (HOMA) (−38·9%) after 2 years of individualized GH treatment in comparison with standard GH dose treatment. Similar metabolic changes were seen in ISS and GHD. Delta (Δ) height SDS correlated with Δinsulin-like growth factor I (IGF-I), Δleptin and Δbody composition. Principal component analysis identified an anabolic and a lipolytic component. Anabolic variables [Δlean body mass (LBM) SDS and ΔIGF-I SDS] clustered together and correlated strongly with Δheight SDS and GH dose, whereas lipolytic variables [Δfat mass (FM) SDS and Δleptin] were clustered separately from anabolic variables. Regression analysis showed GH dose dependency in ISS, and to a lesser degree in GHD, for ΔLBM SDS and Δheight SDS, but not for changes in FM. Conclusions 

Individualized GH dosing during catch-up growth reduces the variance in insulin and HOMA and results in equal metabolic responses irrespective of the diagnosis of GHD or ISS.
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Document Type: Research Article

Affiliations: 1: Department of Pediatrics, Gothenburg Pediatric Growth Research Center (GP-GRC), University of Gothenburg, Institute of Clinical Sciences, The Queen Silvia Children’s Hospital, Gothenburg 2: Muvara bv, Multivariate Analysis of Research Data, Leiderdorp, Netherlands 3: Department of Women’s and Children’s Health, Uppsala University, Uppsala 4: Department of Clinical Nutrition, Research Centre for Endocrinology and Metabolism, Sahlgrenska, University Hospital, Gothenburg, Sweden 5: Division of Pediatric Endocrinology, Rambam Medical Centre, Haifa, Israel

Publication date: September 1, 2010

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