title: Presence of magnetic resonance imaging abnormalities of the hypothalamic-pituitary axis is a significant determinant of the first 3 years growth response to human growth hormone treatment in prepubertal children with nonacquired growth hormone deficiency.
abstract: OBJECTIVE
  The factors influencing the highly variable growth response to GH treatment in GH-deficient children are not fully understood. Despite a real benefit with GH treatment in term of growth response, most of these patients attain a mean adult height below their target height and the strategy to optimise final height has to be improved. The aim of this study was to investigate whether the presence of congenital abnormalities of the hypothalamic-pituitary axis on magnetic resonance imaging (MRI) could be a determinant of the growth response in nonacquired prepubertal GH-deficient children, and to identify which pretreatment variables most significantly affect the first 3 years growth response to human GH (hGH) therapy.
  
  
  METHODS
  The growth response to hGH treatment (0.55 +/- 0.1 IU/kg/week) was evaluated in 69 prepubertal children with nonacquired GH deficiency, according to the absence (group A: chronological age = 4.8 +/- 2.4 years, n= 37) or the presence (group B: chronological age = 3.4 +/- 2.7 years, n= 32) of developmental abnormalities on cerebral magnetic imaging and, after controlling for GH dose, age, height, height velocity (SDS) and body mass index at start of treatment, maximum stimulated GH peak concentration, GH deficiency type (isolated vs. multiple deficiency), parental height, size at birth and sex.
  
  
  RESULTS
  After 3 years of treatment, the mean height gain was significantly higher in patients of group B vs. group A (2.2 +/- 1.3 vs. 1.6 +/- 1 SDS; P < 0.05). In a multiple regression analysis, age (r2 = 0.19, negatively correlated), pretreatment height velocity (r2 = 0.11, negatively correlated), GH dose (r2 = 0.05, positively correlated) and presence of magnetic resonance imaging developmental abnormalities (r2 = 0.05, positively correlated) were found to significantly explain 40% of the variability in growth response.
  
  
  CONCLUSIONS
  The detection of congenital abnormalities in the hypothalamic-pituitary area on MRI is more important than the level of maximum stimulated GH to predict the growth response to hGH treatment in prepubertal nonacquired GH-deficient children. Although the persistence of GH deficiency remains to be confirmed during follow-up by reassessment of GH secretion in isolated GH-deficient patients with normal MRI findings, further studies are needed to evaluate whether an increased hGH dose in these patients could improve long-term growth response.
authors.affiliation: Paediatric Endocrinology Unit, Radiology Department, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Zenaty
authors.forename: Catherine
authors.initials: C
authors.lastname: Garel
authors.forename: Costanzo
authors.initials: C
authors.lastname: Limoni
authors.forename: Paul
authors.initials: P
authors.lastname: Czernichow
authors.forename: Juliane
authors.initials: J
authors.lastname: Léger
mesh_terms: D000367:Age Factors; D001827:Body Height / Q000502:physiology; D001846:Bone Development / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006128:Growth / Q000187:drug effects* / Q000502:physiology; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000002:abnormalities*; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011627:Puberty / Q000502:physiology
chemical_list: D019382:Human Growth Hormone