title: Differences in serum GH cut-off values for pharmacological tests of GH secretion depend on the serum GH method. Clinical validation from the growth velocity score during the first year of treatment.
abstract: BACKGROUND
  The serum GH cut-off value for pharmacological tests of GH secretion (PhT GH) depends on the type of test and also on the method used for determining serum GH. Cut-off serum GH values as different as 5-10 ng/ml, have been reported, and have been validated biochemically. We have used the growth velocity (GV)-standard deviation score (SDS) during the first year of treatment with rhGH to validate these cut-offs on a biological basis.
  
  
  METHODS
  Fifty pre-pubertal patients with short stature (height < or =-2 SDS and GV < or =-1.2 SDS) were studied. GH deficiency (GHD) was diagnosed in 39 patients, on the basis of clinical and auxological parameters and on the serum concentration of IGF-1, and non-GHD in the other 11 patients. Two PhT GH (arginine and clonidine) were carried out in the 50 patients. Serum GH was determined by two different methods: one detecting most of serum GH isoforms, named Total GH (HGH Bio-Tech, MAIA Clone), and another one, only detecting the 22 kDa GH, named 22K GH (GH-22K IFMA, Wallac).
  
  
  RESULTS
  Basal data: all patients with GHD and with non-GHD had maximal serum GH response (MaxR) values below and above the cut-off, respectively, for the serum Total GH and 22K GH. The mean 22K GH/Total GH ratio was similar to previous publications. Post-rhGH treatment data: the two groups improved their height SDS during the first year of treatment, particularly patients with GHD. A receiver-operator curve was used to define the best threshold for post-treatment GV-SDS that separates GHD from non-GHD patients. This value was 1.91 GV-SDS. A negative correlation between first year treatment GV-SDS and pre-treatment serum GH MaxR was found for the two assays (p < 0.001). Then, the best cut-off GV-SDS, previously calculated with the receiver-operator curve (1.91 SDS) was used to interpolate the corresponding serum GH values, as determined by the two methods. For Total GH, the value was 10.8 ng/ml, and for 22K GH, it was 5.4 ng/ml.
  
  
  CONCLUSIONS
  The cut-off values calculated by biological means to separate GHD from non-GHD were remarkably similar to those calculated biochemically (10.0 and 4.8 ng/ml, respectively) for Total and 22K GH. This is a biological validation for using different cut-off values, appropriate for each assay, to diagnose GHD.
authors.affiliation: Servicio de Endocrinologia, Hospital de Pediatria Garrahan, Buenos Aires, Argentina. echaler@yahoo.com
authors.forename: E A
authors.initials: EA
authors.lastname: Chaler
authors.forename: M A
authors.initials: MA
authors.lastname: Rivarola
authors.forename: B
authors.initials: B
authors.lastname: Guerci
authors.forename: M
authors.initials: M
authors.lastname: Ciaccio
authors.forename: M
authors.initials: M
authors.lastname: Costanzo
authors.forename: P
authors.initials: P
authors.lastname: Travaglino
authors.forename: M
authors.initials: M
authors.lastname: Maceiras
authors.forename: S
authors.initials: S
authors.lastname: Pagani
authors.forename: C
authors.initials: C
authors.lastname: Meazza
authors.forename: E
authors.initials: E
authors.lastname: Bozzola
authors.forename: S
authors.initials: S
authors.lastname: Barberi
authors.forename: M
authors.initials: M
authors.lastname: Bozzola
authors.forename: A
authors.initials: A
authors.lastname: Belgorosky
mesh_terms: D000293:Adolescent; D001681:Biological Assay / Q000379:methods; D001827:Body Height / Q000187:drug effects; D002648:Child; D004393:Dwarfism, Pituitary / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006130:Growth Disorders / Q000097:blood* / Q000188:drug therapy; D019382:Human Growth Hormone / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood* / Q000627:therapeutic use; D012680:Sensitivity and Specificity
chemical_list: D010446:Peptide Fragments; C404802:human growth hormone 22K; D019382:Human Growth Hormone