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

Journal article
Authors Ralph Decker
Kerstin Albertsson-Wikland
Berit Kriström
Andreas F M Nierop
Jan Gustafsson
Ingvar Bosaeus
Hans Fors
Ze'ev Hochberg
Jovanna Dahlgren
Published in Clinical Endocrinology
Volume 73
Issue 3
Pages 346–354
ISSN 1365-2265
Publication year 2010
Published at Institute of Medicine, Department of Clinical Nutrition
Institute of Clinical Sciences, Department of Pediatrics
Pages 346–354
Language en
Keywords DEXA, Growth hormone, Insulin, Leptin, metabolism, principal component analysis
Subject categories Pharmacology, Clinical physiology


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 mug/kg/day) or a standard dose (43 mug/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 HOMA (-38.9%) after two years of individualized GH treatment in comparison to standard GH dose treatment. Similar metabolic changes were seen in ISS and GHD. Delta (Delta) height SDS correlated with Deltainsulin-like growth factor I (IGF-I), Deltaleptin and Deltabody composition. Principal component analysis identified an anabolic and a lipolytic component. Anabolic variables [Deltalean body mass (LBM) SDS and DeltaIGF-I SDS] clustered together and correlated strongly with Deltaheight SDS and GH dose, whereas lipolytic variables [Deltafat mass SDS and Deltaleptin] were clustered separately from anabolic variables. Regression analysis showed GH dose-dependency in ISS, and to a lesser degree in GHD, for DeltaLBM SDS and Deltaheight SDS, but not for changes in fat mass. 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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