title: The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index.
abstract: OBJECTIVE
  The diagnosis of growth hormone (GH) deficiency (GHD) in adults is based on a reduced peak GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone-arginine (GHRH-ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. Aim of this study was to evaluate the diagnostic cut-off limits of peak GH response to the GHRH-ARG test in overweight and obese as well as in lean population.
  
  
  METHODS
  The GH responses to the GHRH-ARG test were studied in 322 patients with organic hypothalamic-pituitary disease and in 318 control subjects. Patients were subdivided into two groups on the basis of the number of pituitary hormone deficits, except for GH deficiency: (a) patients with total pituitary hormone deficit (TPHD) and (b) patients without or with no more than two pituitary hormone deficits (PHD). Both patients and control subjects were divided into three subgroups according to body mass index (BMI): lean (BMI <25 kg/m(2)), overweight (BMI > or = 25 and <30 kg/m(2)) and obese (BMI > or =30 kg/m(2)). TPHD patients were assumed to be GH deficient, whereas PHD patients may include subjects with either normal or impaired GH secretion. The statistical analysis was carried out by the Receiver-Operating Characteristic curve analysis (Medcalc 7.2). The diagnostic cut-off points were calculated for lean, overweight and obese subjects to provide optimal separation of GH-deficient patients and control subjects according to two criteria: (1) a balance between high sensitivity and high specificity; (2) to provide the highest pair of sensitivity/specificity values for GH deficiency.
  
  
  RESULTS
  In the lean population the best pair of values, with highest sensitivity as 98.7% and highest specificity as 83.7%, was found using a peak GH cut-off point of 11.5 mug/l. In the overweight population the best pair of values, 96.7 and 75.5%, respectively, was found using a peak GH cut-off point of 8.0 mug/l. In the obese population the best pair of values, 93.5 and 78.3%, respectively, was found using a peak GH cut-off point of 4.2 mug/l. Applying the above mentioned cut-off points, among PHD patients we found that 80 subjects (72%) were GHD whereas 31 (28%) had normal GH secretion.
  
  
  CONCLUSIONS
  In conclusion the GHRH-ARG test is a reliable tool for the diagnosis of adult GH deficiency in lean, overweight and obese patients, provided that specific BMI-related cut-off limits are assumed.
authors.affiliation: Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, University of Turin, Italy.
authors.forename: Ginevra
authors.initials: G
authors.lastname: Corneli
authors.forename: Carolina
authors.initials: C
authors.lastname: Di Somma
authors.forename: Roberto
authors.initials: R
authors.lastname: Baldelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Rovere
authors.forename: Valentina
authors.initials: V
authors.lastname: Gasco
authors.forename: Chiara Giulia
authors.initials: CG
authors.lastname: Croce
authors.forename: Silvia
authors.initials: S
authors.lastname: Grottoli
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccario
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lombardi
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Franco
authors.initials: F
authors.lastname: Camanni
authors.forename: Gianluca
authors.initials: G
authors.lastname: Aimaretti
mesh_terms: D000328:Adult; D001120:Arginine; D015992:Body Mass Index; D003940:Diagnostic Techniques, Endocrine / Q000592:standards; D005260:Female; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000175:diagnosis*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine