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


METHODS
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 microg/kg/day) or a standard dose (43 microg/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.


OBJECTIVE
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 (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 (FM) 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 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.
Decker
Ralph
R
Department of Pediatrics, Gothenburg Pediatric Growth Research Center, University of Gothenburg, Institute of Clinical Sciences, The Queen Silvia Children's Hospital, Gothenburg, Sweden. Ralph.Decker@vgregion.se
Albertsson-Wikland
Kerstin
K
Kriström
Berit
B
Nierop
Andreas F M
AF
Gustafsson
Jan
J
Bosaeus
Ingvar
I
Fors
Hans
H
Hochberg
Ze'ev
Z
Dahlgren
Jovanna
J
D052242:Adiponectin / Q000378:metabolism; D000704:Analysis of Variance; D001823:Body Composition / Q000187:drug effects*; D001827:Body Height / Q000187:drug effects; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004393:Dwarfism, Pituitary / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D025341:Principal Component Analysis; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D052242:Adiponectin; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D020738:Leptin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone