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

Ralph Decker (1) , Kerstin Albertson-Wikland (1) , Berit Kriström (2, 1) , Andreas F. M. Nierop (3) , Jan Gustafsson (4) , Ingvar Bosaeus (5) , Hans Fors (1) , Ze'Ev Hochberg (6) , Jovanna Dahlgren (1)

1 Department of Pediatrics, The Queen Silvia Children's Hospital
2 Department of Pediatrics
3 Multivariate Analysis of Research Data
4 Department of Women and Children's Health
5 Department of Clinical Nutrition
6 Department of Pediatrics

Context: Few studies have evaluated the metabolic outcomes of growth hormone (GH) treatment in idiopathic growth 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 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 (∆) height SDS correlated with ∆insulin-like growth factor I (IGF-I), ∆leptin and ∆body composition. Principal component analysis identified an anabolic and a lipolytic component. Anabolic variables [∆lean body mass (LBM) SDS and ∆IGF-I SDS] clustered together and correlated strongly with ∆height SDS and GH dose, whereas lipolytic variables [∆fat mass SDS and ∆leptin] were clustered separate from the anabolic. Regression analysis showed GH dose-dependency in ISS, and to a lesser degree in GHD, for ∆LBM SDS and ∆height 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.

Mots clés: Medicine

Ralph Decker, Kerstin Albertson-Wikland, Berit Kriström, Andreas F. M. Nierop, Jan Gustafsson, et al.. Metabolic outcome of GH treatment in prepubertal short children with and without classical GH-deficiency. Clinical Endocrinology, 2010, 73 (3), pp.346. ⟨10.1111/j.1365-2265.2010.03812.x⟩. ⟨hal-00552606⟩