title: Long-term auxological and pubertal outcome of patients with hereditary insulin-like growth factor-I deficiency (Laron and growth hormone-gene deletion syndrome) treated with recombinant human insulin-like growth factor-I.
abstract: BACKGROUND
  GH-IGF-I axis is mainly involved in the complex process of somatic growth but emerging evidence suggests that it also influences hypothalamic-pituitary-gonadal (HPG) function.
  
  
  METHODS
  We report some data regarding long-term auxological and pubertal outcome of five female patients with hereditary forms of GH-IGF-I deficiency (Laron and GH-gene deletion syndrome) and a mean age of 23.4±5.3 yr (range 19-32).
  
  
  METHODS
  All the patients received recombinant human IGF-I (rhIGF-I, Pharmacia and Upjohn, Stockholm, Sweden, and rhIGF-I, Genentech, San Francisco, CA, USA) from a mean age of 8.6 yr (range 3.2-14.2) up to the final height.
  
  
  RESULTS
  Final height was very disappointing (≤ -5.0 SD scores) and lower than target height in all the patients. Pubertal onset was delayed in most of them but menarche occurred spontaneously in all the patients. Median age at menarche was 15.1 yr. Menstrual cycles were regular for several years. Median duration of gynecological follow- up was 8.3 yr with the longest span of 17.2 yr.
  
  
  CONCLUSIONS
  We can assert that GH-IGF-I axis has an essential role in promoting linear growth in humans and its physiological action cannot be replaced by pharmacological treatment in most patients with hereditary forms of IGF-I insufficiency as demonstrated by their subnormal final height. Our clinical observations can also support an essential role of IGF-I in genitalia growth but not in the function of HPG axis as demonstrated by the maintenance of regular menstrual cycles in the presence of subnormal levels of IGF-I after treatment discontinuation.
authors.affiliation: Department of Pediatrics, University of Messina, Viale Gazzi, 98124 Messina, Italy. francesca.messina@unime.it
authors.forename: M F
authors.initials: MF
authors.lastname: Messina
authors.forename: T
authors.initials: T
authors.lastname: Arrigo
authors.forename: M
authors.initials: M
authors.lastname: Valenzise
authors.forename: L
authors.initials: L
authors.lastname: Ghizzoni
authors.forename: M
authors.initials: M
authors.lastname: Caruso-Nicoletti
authors.forename: S
authors.initials: S
authors.lastname: Zucchini
authors.forename: P
authors.initials: P
authors.lastname: Chiabotto
authors.forename: G
authors.initials: G
authors.lastname: Crisafulli
authors.forename: G
authors.initials: G
authors.lastname: Zirilli
authors.forename: F
authors.initials: F
authors.lastname: De Luca
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency / Q000235:genetics* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000627:therapeutic use*; D046150:Laron Syndrome / Q000235:genetics / Q000503:physiopathology*; D008597:Menstrual Cycle / Q000502:physiology; D011627:Puberty / Q000502:physiology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I