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  • Title: Variable degree of growth hormone (GH) and insulin-like growth factor (IGF) sensitivity in children with idiopathic short stature compared with GH-deficient patients: evidence from an IGF-based dosing study of short children.
    Author: Cohen P, Germak J, Rogol AD, Weng W, Kappelgaard AM, Rosenfeld RG, American Norditropin Study Group.
    Journal: J Clin Endocrinol Metab; 2010 May; 95(5):2089-98. PubMed ID: 20207829.
    Abstract:
    CONTEXT: We recently showed that, in IGF-based GH therapy, the IGF-I target chosen affects GH dose requirements, and higher IGF-I targets are associated with more robust growth parameters. OBJECTIVE: The objective of the study was to compare the response of GH-deficient (GHD) vs. idiopathic short-stature (ISS) children to IGF-based GH therapy. DESIGN: This was a 2-yr, open-label, randomized trial. SETTING: The setting was multicenter and outpatient. PATIENTS: Prepubertal short children [height sd score (SDS) < -2] with low IGF-I levels (<or=-1 SDS), subclassified based on the peak stimulated serum GH concentration at baseline, into two subgroups: GHD (n = 63, GH < 7 ng/ml) and ISS (n = 102, GH >or= 7 ng/ml). INTERVENTIONS: Patients were randomized 2:2:1 to three treatment groups: IGF-I target of 0 SDS (IGF0T), 2 SDS (IGF2T), or a conventional weight-based GH dosing of 40 microg/kg x d (Conv). MAIN OUTCOME MEASURES: Change in (Delta) height SDS, IGF-I SDS, and GH dose was measured. RESULTS: ISS subjects required higher GH doses than GHD patients in the IGF2T (but not IGF0T) arm (medians 119 and 65 microg/kg x d, respectively), indicating that ISS represents a partial GH-insensitive state that manifests during treatment with higher doses of GH. GHD children grew more than those with ISS in both IGF-targeted dosage groups despite similar IGF-I levels (suggesting a degree of IGF insensitivity in ISS subjects): Delta height SDS of 2.04 +/- 0.17 for GHD and 1.33 +/- 0.09 for ISS groups in IGF2T, 1.41 +/- 0.13 for children with GHD, and 0.84 +/- 0.07 for those with ISS in IGF0T. CONCLUSION: IGF-based GH dosing is clinically feasible in both GHD and ISS patients, although GH dose requirements and auxological outcomes are distinct between these groups. This suggests a degree of both GH and IGF insensitivity in subjects with ISS that requires specific management strategies to optimize growth during GH therapy.
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