title: The growth and cardiovascular effects of high dose growth hormone therapy in idiopathic short stature.
abstract: OBJECTIVE
  It is possible that high dose GH treatment may have beneficial effects on growth but important adverse effects on cardiac function. We have therefore investigated the efficacy and cardiovascular effects of high dose biosynthetic human GH (r-hGH) treatment in children with idiopathic short stature and a normal pretreatment height velocity.
  
  
  METHODS
  Randomized controlled study.
  
  
  METHODS
  Twenty-nine short (height SDS < 1.5), normally growing (height velocity SDS > -1.5), prepubertal children referred to two specialist growth clinics.
  
  
  METHODS
  Children were randomly assigned to an observation group or to receive 'standard' (20 IU/m2/week) or 'high' (40 IU/m2/week) dose r-hGH by daily subcutaneous injection. At the end of 1 year the observation group were randomly assigned to 'standard' or 'high' dose r-hGH therapy for the second year of the study. Regular growth, biochemical and echocardiographic monitoring were performed throughout the study period.
  
  
  METHODS
  Changes in height velocity, HtSDS for bone age (HtSDSBA), left ventricular mass index (LVMI) and left ventricular function (fractional shortening) during 2 years treatment.
  
  
  RESULTS
  Twenty-seven children completed the study. Ht velocity SDS increased with r-hGH therapy in a dose dependent fashion. First-year height velocity SDS was +5.7 in the high dose r-hGH group compared with +2.7 in the standard dose r-hGH group and -0.5 in the observation group (P < 0.001). In those children treated for 2 years HtSDSBA was -0.5 in the high dose group but had not changed significantly in the standard dose group (-1.7) (P = 0.01). After one year r-hGH treatment LVMI was 71 g/m2 (observation group), 73 g/m2 (20 IU/m2/week group) and 74 g/m2 (40 IU/m2/week group) (P = 0.77). LVMI increased significantly from baseline to 76 g/m2 after 2 years therapy with 40 IU/m2/week r-hGH (P = 0.04) but nevertheless remained within the normal range. Fractional shortening did not change significantly over 2 years of r-hGH therapy.
  
  
  CONCLUSIONS
  High dose (40 IU/m2/week) r-hGH treatment of children with idiopathic short stature resulted in a greater short-term acceleration in growth rate than 'standard' dose therapy without an excessive advance in skeletal maturity and probably represents the optimal growth promoting dose for short, normally growing children. Whether continued high dose r-hGH therapy increases final height requires further study. Left ventricular morphology and function remained within the normal range during r-hGH therapy but regular monitoring of cardiovascular status should continue in non-GHD children receiving r-hGH in high doses over a longer time period.
authors.affiliation: Growth Research Centre, Medical Unit, Institute of Child Health, London, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Barton
authors.forename: H M
authors.initials: HM
authors.lastname: Gardineri
authors.forename: S
authors.initials: S
authors.lastname: Cullen
authors.forename: P C
authors.initials: PC
authors.lastname: Hindmarsh
authors.forename: C G
authors.initials: CG
authors.lastname: Brook
authors.forename: M A
authors.initials: MA
authors.lastname: Preece
mesh_terms: D001827:Body Height; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy*; D013006:Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008297:Male; D011446:Prospective Studies; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D013006:Growth Hormone