title: Growth hormone therapy with three dosage regimens in children with idiopathic short stature. European Study Group Participating Investigators.
abstract: OBJECTIVE
  In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV).
  
  
  METHODS
  Included were 223 patients who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5 IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard].
  
  
  RESULTS
  During the first year of treatment HV almost doubled and was higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant.
  
  
  CONCLUSIONS
  During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to 4.5 IU/m2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest.
authors.affiliation: Department of Pediatrics of the University Hospital of Leiden, The Netherlands.
authors.forename: L T
authors.initials: LT
authors.lastname: Rekers-Mombarg
authors.forename: G G
authors.initials: GG
authors.lastname: Massa
authors.forename: J M
authors.initials: JM
authors.lastname: Wit
authors.forename: A M
authors.initials: AM
authors.lastname: Matranga
authors.forename: J M
authors.initials: JM
authors.lastname: Buckler
authors.forename: O
authors.initials: O
authors.lastname: Butenandt
authors.forename: J L
authors.initials: JL
authors.lastname: Chaussain
authors.forename: H
authors.initials: H
authors.lastname: Frisch
authors.forename: E
authors.initials: E
authors.lastname: Leiberman
authors.forename: R
authors.initials: R
authors.lastname: Yturriaga
authors.forename: D
authors.initials: D
authors.lastname: Aarskog
authors.forename: P G
authors.initials: PG
authors.lastname: Chatelain
authors.forename: M
authors.initials: M
authors.lastname: Colle
authors.forename: C
authors.initials: C
authors.lastname: Dacou-Voutetakis
authors.forename: H A
authors.initials: HA
authors.lastname: Delemarre-van de Waal
authors.forename: F
authors.initials: F
authors.lastname: Girard
authors.forename: J J
authors.initials: JJ
authors.lastname: Gosen
authors.forename: U
authors.initials: U
authors.lastname: Irle
authors.forename: M
authors.initials: M
authors.lastname: Jansen
authors.forename: R
authors.initials: R
authors.lastname: Jean
authors.forename: J C
authors.initials: JC
authors.lastname: Job
authors.forename: M L
authors.initials: ML
authors.lastname: Kaar
authors.forename: F
authors.initials: F
authors.lastname: Kollemann
authors.forename: H L
authors.initials: HL
authors.lastname: Lenko
authors.forename: J J
authors.initials: JJ
authors.lastname: Waelkens
mesh_terms: D001827:Body Height / Q000187:drug effects; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005317:Fetal Growth Retardation; D006128:Growth / Q000187:drug effects*; D006130:Growth Disorders / Q000188:drug therapy* / Q000503:physiopathology; D013006:Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D012044:Regression Analysis
chemical_list: D013006:Growth Hormone