title: Anthropometric factors have significant influence on the outcome of the GHRH-arginine test: establishment of normative data for an automated immunoassay specifically measuring 22 kDa human growth hormone.
abstract: BACKGROUND
  Adult growth hormone (GH) deficiency (GHD) is diagnosed by provocative testing of GH secretion.
  
  
  OBJECTIVE
  To improve the diagnostic accuracy of GH-releasing hormone (GHRH) plus arginine (GARG) testing, we evaluated the influence of age, BMI and sex and established normative data for an automatic immunoassay specifically measuring 22 kDa human GH.
  
  
  METHODS
  Prospective multicenter study.
  
  
  METHODS
  Eighty-seven patients with hypothalamic-pituitary disease and 200 healthy controls. Patients were classified according to the number of pituitary hormone deficiencies (PHD). GHD was assumed when ≥2 PHD (in addition to GH) were present (n = 51); 36 patients with <2 PHD were considered GH sufficient (GHS). ROC analysis identified cutoffs with ≥95% specificity for GHD. Controls were prospectively stratified for sex, age and BMI.
  
  
  METHODS
  All participants received GHRH and l-arginine.
  
  
  METHODS
  GH was measured by immunoassay (iSYS, IDS).
  
  
  RESULTS
  In controls, multiple stepwise regression analysis showed that BMI (21%, P < 0.0001), sex (20%, P < 0.0001) and age (5%, P < 0.001), accounted for 46% of GH peak level variability during GARG. Comparison of peak GH during GARG (GHD vs GHS + controls) revealed an overall cutoff of 3.9 ng/mL (sensitivity 86%, specificity 95%). After adjustment for BMI and sex, optimal cutoffs (male vs female) were 6.5 vs 9.7 ng/mL in lean, 3.5 vs 8.5 ng/mL in overweight and 2.2 vs 4.4 ng/mL in obese subjects respectively.
  
  
  CONCLUSIONS
  BMI and sex account for most of the variability of peak GH levels during GARG. Consequently, diagnostic accuracy of the GARG test is significantly improved by use of adjusted cutoffs.
authors.affiliation: Department of Internal Medicine IDivision of Endocrinology and Diabetes, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Deutschbein
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der LMU München, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.affiliation: Medizinische Klinik und Poliklinik IVKlinikum der LMU München, Munich, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schopohl
authors.affiliation: Department of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin, Campus Mitte, Berlin, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Strasburger
authors.affiliation: ENDOC Center for Endocrine TumorsHamburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Petersenn
mesh_terms: D000328:Adult; D001120:Arginine; D015992:Body Mass Index; D005260:Female; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000097:blood* / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000175:diagnosis* / Q000503:physiopathology; D007118:Immunoassay / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood* / Q000172:deficiency*; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D010446:Peptide Fragments; C404802:human growth hormone 22K; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine