ESPE Abstracts (2015) 84 P-2-406

ESPE2015 Poster Category 2 GH & IGF (40 abstracts)

Metabolic Health in Short Children Born Small for Gestational Age Treated with GH and GnRHa: Results of a Randomised, Dose-response Trial

M van der Steen a, , A J Lem a , D C M van der Kaay a , W M Bakker-van Waarde c , F J P C M van der Hulst d , F S Neijens e , C Noordam f , R J Odink g , W Oostdijk h , E J Schroor i , E J Sulkers j , C Westerlaken k & A C S Hokken-Koelega a,

aDutch Growth Research Foundation, Rotterdam, The Netherlands; bChildren’s Hospital Erasmus MC-Sophia, Rotterdam, The Netherlands; cUniversity Medical Center Groningen, Groningen, The Netherlands; dZaans Medisch Centrum, Zaandam, The Netherlands; eRijnstate Hospital, Arnhem, The Netherlands; fRadboud University Medical Center, Nijmegen, The Netherlands; gCatharina Hospital, Eindhoven, The Netherlands; hLeiden University Medical Center, Leiden, The Netherlands; iIsala Clinics, Zwolle, The Netherlands; jAdmiraal de Ruyter Hospital, Vlissingen, The Netherlands; kCanisius Hospital, Nijmegen, The Netherlands

Background: Previously we showed that pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment with GH 1 mg/m2 per day (~0.033 mg/kg per day) in combination with 2 years of GnRH analogue (GnRHa) and even more so with a double GH dose. GnRHa treatment is thought to have negative effects on body composition and blood pressure. Long-term effects and GH-dose effects on metabolic health in children treated with combined GH/GnRHa treatment are unknown.

Objective and hypotheses: To investigate body composition, blood pressure and lipid profile during GH treatment, either with or without 2 years of additional GnRHa. To assess whether GH 2 mg/m2 per day (~0.067 mg/kg per day) results in a similar or even more favorable metabolic health at AH than GH 1 mg/m2 per day.

Method: Longitudinal, randomized, dose-response GH trial involving 107 short SGA children (58 girls) treated with GH until AH (GH randomized 1 or 2 mg/m2 per day during puberty). 64 children received additional GnRHa. At AH, metabolic parameters were compared between children treated with combined GH/GnRHa and those with only GH. The GH-dose effect on metabolic health was evaluated in a subgroup of 47 children who started GH treatment in early puberty (randomized 1 or 2 mg/m2 per day) with 2 years of GnRHa.

Results: At AH, fat mass percentage (FM%) SDS, lean body mass (LBM) SDS, blood pressure SDS and lipid profile were similar between children treated with combined GH/GnRHa and those with only GH. In the pubertal subgroup, FM% SDS was lower during treatment with 2 mg GH/m2 per day. There was no GH dose-dependent effect on LBM SDS, blood pressure and lipid profile.

Conclusion: Combined GH/GnRHa treatment has no long-term negative effects on metabolic health compared to only GH. Started in early puberty, a GH dose of 2 mg/m2 per day results in a similar metabolic health at AH and a more favorable FM% than the standard 1 mg/m2 per day.

Funding: This study was an investigator initiated study, supported by an independent research grant from Pfizer B.V. the Netherlands.

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