title: Confirmation of severe GH deficiency after final height in patients diagnosed as GH deficient during childhood.
abstract: OBJECTIVE
  Human GH treatment of patients with childhood-onset (CO) growth hormone deficiency (GHD) ceases when they reach final height; this provides an opportunity to retest GH status in all patients before determining whether GH therapy will be required in adult life. At present, the diagnostic approach to these patients is not fully standardized. This study aimed to characterize a large group of previously GH-treated CO GHD patients and establish their GH status.
  
  
  METHODS
  The multinational study included 167 patients diagnosed as GH deficient and treated with hGH to final height during childhood. Mean age was 19.2 years and mean height standard deviation score (SDS) was -1.08. Peak serum GH concentrations were determined in standard GH stimulation tests. IGF-I and IGFBP-3 concentrations were determined at a central laboratory and converted to SDS values by reference to a normal population.
  
  
  RESULTS
  Using only a peak GH value of less than 3 microg/l (1 mg = 3 U) in stimulation tests as the cut-off, 133 (79.6%) patients would be classed as GH deficient. Using only an IGF-I value less than -2 SDS as the cut-off, 134 (80.2%) patients would be classed as GH deficient. However, by using both criteria there were 120 (71.9%) patients who were definitely severely GH deficient (group 1) and 20 (12.0%) who were not GH deficient (group 2), leaving 14 (8.4%) classed as GH deficient from IGF-I SDS only (group 3) and 13 (7.8%) classed as GH deficient from stimulation test only (group 4). There was no difference between the groups in height SDS or body mass index (BMI), but the GH-deficient patients tended to have been diagnosed at a younger age (group 1, 8.2 +/- 3.9; group 2, 10.0 +/- 4.0; P = 0.052). For patients classed as GH deficient compared with those not GH deficient, the percentage of males was lower (group 1, 64.2%; group 2, 90.0%; P = 0.022) and the percentage with multiple pituitary hormone deficiencies was higher (group 1, 81.7%; group 2, 20.0%; P < 0 .001), with the other two groups being intermediate in each case. Only the group classed as GH deficient by both criteria had a mean IGFBP-3 less than -2 SDS and both IGF-I SDS and IGFBP-3 SDS increased steadily across the four groups.
  
  
  CONCLUSIONS
  A high percentage (71.9%) of these childhood-onset GH-deficient patients were still GH deficient in adult life and are likely to require further hGH treatment. While 12.0% could be classed as definitely no longer GH deficient, there are some patients who are intermediate (16.2%) and may be classed as GH deficient by one criterion but not the other. When GH stimulation test results and IGF-I concentration are discordant, the IGFBP-3 level does not establish diagnosis and the hGH treatment requirement of such patients remains a dilemma.
authors.affiliation: Eli Lilly Italia SPA, Via Gramsci 731-733, 50019 Sesto Fiorentino, Florence, Italy. attanasio_andrea@lilly.com
authors.forename: Andrea F
authors.initials: AF
authors.lastname: Attanasio
authors.forename: Simon
authors.initials: S
authors.lastname: Howell
authors.forename: Peter C
authors.initials: PC
authors.lastname: Bates
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.forename: Paul
authors.initials: P
authors.lastname: Frewer
authors.forename: Charmian
authors.initials: C
authors.lastname: Quigley
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Shalet
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001827:Body Height; D015992:Body Mass Index; D002648:Child; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I