Rikke Beck Jensen1, Ajay Thankamony2, Susan M O'Connell2, Jeremy Kirk2, Malcolm Donaldson2, Sten-A Ivarsson2, Olle Söder2, Edna Roche2, Hilary Hoey2, David B Dunger2, Anders Juul2. 1. Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden rikke.beck@dadlnet.dk. 2. Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of PediatricsAddenbrooke's Hospital, University of Cambridge, Hills Road, CB2 0QQ Cambridge, UKDepartment of PediatricsThe National Children's Hospital, Trinity College, University of Dublin, Dublin, IrelandDepartment of EndocrinologyBirmingham Children's Hospital, Birmingham, UKDepartment of EndocrinologyRoyal Hospital for Sick Children, Glasgow, UKDepartment of Clinical SciencesEndocrine and Diabetes Unit, University of Lund, Malmø, SwedenPediatric Endocrinology UnitDepartment of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Abstract
BACKGROUND: Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies. METHODS: In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration. RESULTS: The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, s.d. 0.019) and the low-dose group (35 μg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups. CONCLUSION:IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children.
RCT Entities:
BACKGROUND: Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies. METHODS: In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration. RESULTS: The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, s.d. 0.019) and the low-dose group (35 μg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups. CONCLUSION:IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children.
Authors: Emma L Wakeling; Frédéric Brioude; Oluwakemi Lokulo-Sodipe; Susan M O'Connell; Jennifer Salem; Jet Bliek; Ana P M Canton; Krystyna H Chrzanowska; Justin H Davies; Renuka P Dias; Béatrice Dubern; Miriam Elbracht; Eloise Giabicani; Adda Grimberg; Karen Grønskov; Anita C S Hokken-Koelega; Alexander A Jorge; Masayo Kagami; Agnes Linglart; Mohamad Maghnie; Klaus Mohnike; David Monk; Gudrun E Moore; Philip G Murray; Tsutomu Ogata; Isabelle Oliver Petit; Silvia Russo; Edith Said; Meropi Toumba; Zeynep Tümer; Gerhard Binder; Thomas Eggermann; Madeleine D Harbison; I Karen Temple; Deborah J G Mackay; Irène Netchine Journal: Nat Rev Endocrinol Date: 2016-09-02 Impact factor: 43.330