Session: SUN 624-646-Growth: Clinical Trials & Observational Studies
Poster Board SUN-631
Objective: To describe the pharmacodynamic response of CNP and NTproCNP to rhGH in previously untreated short children.
Methods: Twenty prepubertal subjects with either idiopathic short stature (ISS) or GH deficiency (GHD) were recruited for a prospective, longitudinal pharmacodynamic study. Subjects were started on rhGH (Norditropin, Novo Nordisk, Princeton NJ) at 0.05 mg/kg/day and followed for one year. Subjects were seen 12 times during the study for determination of height and plasma levels of CNP and NTproCNP. Data are presented as medians with intra-quartile ranges (25th–75thpercentile).
Results: Preliminary analyses showed no differences in CNP and NTproCNP levels between the ISS and GHD groups (Mann-Whitney U tests), so the groups were combined. For both CNP and NTproCNP, plasma levels increased after two days of treatment and remained above baseline for six months (P<0.0005 for both, ANOVA with repeated measures and Holm’s post-hoc pairwise analysis). CNP levels peaked at 14 days (7-28 days) at a concentration of 2.0 pM (1.7-2.3 pM), increasing 77.8% (43.1-107%) over baseline. Levels of NTproCNP also peaked at 14 days (12-28 days) at 43.7 pM (39.7-50.0 pM), increasing 47.9% (31.4-65.4%) over baseline. There was a positive correlation between day 14 NTproCNP levels and six-month height velocity (R2=0.22, P<0.05, n=18).
Conclusion: In children with either ISS or GHD, levels of CNP and NTproCNP increase rapidly following initiation of rhGH treatment. Levels peak between 7 and 28 days, indicating that this is the optimal interval in which to measure these peptides.While there was a correlation between 14-day NTproCNP levels and height velocity at six months, a larger study is needed to determine the clinical value of measuring this biomarker in predicting responsiveness to rhGH treatment.
Disclosure: MEG: Coinvestigator, Research contract, Coinvestigator, Genentech, Inc., Advisory Group Member, EMD Serono, , Ipsen, Coinvestigator, Consulting fee, Coinvestigator, Eli Lilly & Company. Nothing to Disclose: PS, JL, EAE, TCP, KS, RCO
*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm
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