title: Dynamic response of C-type natriuretic peptide and its aminoterminal propeptide (NTproCNP) to growth hormone treatment in children with short stature.
abstract: OBJECTIVE
  C-type natriuretic peptide (CNP) and its aminoterminal propeptide (NTproCNP) are potential biomarkers of recombinant human growth hormone (rhGH) efficacy. The objective of this study was to describe the pharmacodynamics of plasma CNP and NTproCNP levels in response to rhGH treatment and to identify the optimal time of sampling after starting rhGH.
  
  
  METHODS
  This was a prospective, observational study. Subjects were treated with rhGH for 1 year, with blood sampled at regular intervals.
  
  
  METHODS
  Eighteen prepubertal children, eight with low levels of GH on biochemical testing and ten with idiopathic short stature, completed the study.
  
  
  METHODS
  Blood levels of CNP, NTproCNP, GH, insulin-like growth factor-I, leptin and bone-specific alkaline phosphatase were measured. Anthropometrics were obtained.
  
  
  RESULTS
  Plasma levels of both CNP and NTproCNP reached peak levels 7-28 days after starting rhGH treatment and then declined to intermediate levels through the first year. Plasma NTproCNP levels after 14 days trended towards a correlation with height velocity after 6 and 12 months of treatment. Unexpectedly, serum GH levels measured 2 and 28 days after starting rhGH correlated strongly with height velocity after 6 and 12 months of treatment.
  
  
  CONCLUSIONS
  This study identified 14 days after starting rhGH treatment as the optimal time for assessing CNP and NTproCNP levels as biomarkers of rhGH efficacy. Additionally, we identified GH levels as a potential biomarker. Larger, prospective studies are now needed to test the clinical utility of these biomarkers.
authors.affiliation: Nemours Children's Health System, Jacksonville, FL, USA. rolney@nemours.org.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Olney
authors.affiliation: Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, CA, USA.
authors.forename: Parisa
authors.initials: P
authors.lastname: Salehi
authors.affiliation: University of Otago, Christchurch, New Zealand.
authors.forename: Timothy C R
authors.initials: TC
authors.lastname: Prickett
authors.affiliation: Nemours Children's Health System, Jacksonville, FL, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Lima
authors.affiliation: University of Otago, Christchurch, New Zealand.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Espiner
authors.affiliation: Nemours Children's Health System, Jacksonville, FL, USA.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Sikes
authors.affiliation: Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, CA, USA.
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Geffner
mesh_terms: D015415:Biomarkers / Q000097:blood; D001837:Body Weights and Measures; D002648:Child; D004392:Dwarfism / Q000188:drug therapy*; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000097:blood* / Q000493:pharmacokinetics; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D015415:Biomarkers; C000623155:NTproCNP; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D020098:Natriuretic Peptide, C-Type