Amino-terminal propeptide of C-type natriuretic peptide and linear growth in children: Effects of puberty, testosterone, and growth hormone

Context: C-type natriuretic peptide (CNP), a paracrine factor of the growth plate, plays a key role in stimulating bone growth. The amino-terminal propeptide of CNP (NTproCNP) is produced in equimolar amounts with CNP and is measurable in plasma, providing a potential biomarker for growth plate activity and, hence, linear growth. Objective: We explored the effects of puberty, testosterone, and GH treatment on NTproCNP levels in normal and short-statured children. Design: This was a retrospective analysis of samples obtained during previous studies. Setting: The study was conducted at a pediatric clinical research center. Subjects: Children with short stature due to GH deficiency, idiopathic short stature (ISS), or constitutional delay of growth and maturation (CDGM) were studied (n = 37). A cohort of normal-statured adolescent boys was also studied (n = 23). Interventions: Children with GH deficiency and ISS were studied before and during testosterone and/or GH treatment. Boys with CDGM and healthy controls were studied once. Main Outcome Measures: The main outcomes were NTproCNP levels before and during growth-promoting therapy and during pubertal growth. Results: Children with short stature due to GH deficiency, ISS, or CDGM had comparable baseline levels of NTproCNP, and levels increased markedly in response to GH or testosterone treatment. In boys with CDGM, levels were comparable with height-matched controls but were less than those from age-matched controls. In healthy boys, NTproCNP appears to peak with the pubertal growth spurt. Conclusions: NTproCNP levels increase during growth-promoting therapy and are increased during puberty in boys. This novel biomarker of growth may have clinical utility in the evaluation of children with short stature and for monitoring growth-promoting therapy.