title: GH response to GHRH combined with pyridostigmine or arginine in different conditions of low somatotrope secretion in adulthood: obesity and Cushing's syndrome in comparison with hypopituitarism.
abstract: BACKGROUND
  Diagnosing GH deficiency in adults is difficult due to the age-related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH replacement is allowed for patients with GH peak to provocative stimuli < 3 micrograms/L. Somatotrope insufficiency is present in hypopituitarism but also in obesity and hypercortisolism. However, to evaluate GH insufficiency in adults is difficult due to variations of GH and IGF-I levels as function of age and nutrition status.
  
  
  METHODS
  We aimed to verify the GH response to GHRH (1 microgram/kg i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine (ARG, 0.5 g/kg i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS).
  
  
  RESULTS
  IGF-l levels in GHD were lower than those in OB (p < 0.01) and in CS (p < 0.01) which, in turn, were lower to those in NS (p < 0.02). In NS, the GH peak responses to GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak was 16.5 micrograms/L. GHD had GH responses similar, lower than those in NS (p < 0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks < 3 micrograms/L; conventionally, below this limit severe GH deficiency is shown and rhGH replacement is allowed. In OB, the GH responses to GHRH + PD and GHRH + ARG were similar, lower (p < 0.01) and higher (p < 0.01) than those in NS and GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but nobody < 3 micrograms/L. In CS the GH response to GHRH + PD was lower than that to GHRH + ARG (p < 0.01); both these responses were lower than those in NS (p < 0.01) and even in OB (p < 0.01) but higher than those in GHD (p < 0.01). All and 7/8 CS had GH peaks lower than normal limits after PD + GHRH and ARG + GHRH, respectively while 6/8 showed GH peak < 3 micrograms/L after PD + GHRH but only 1 after ARG + GHRH.
  
  
  CONCLUSIONS
  Present data demonstrate that the maximal somatotrope secretory capacity is reduced in OB and even more in CS. From a diagnostic point of view, PD + GHRH and ARG + GHRH tests distinguish OB from severe GHD. As hypercortisolism impairs the activity of cholinesterase inhibitors, only ARG + GHRH, but not PD + GHRH is a reliable test to explore the maximal somatotrope secretory capacity in CS. Notably, even with the ARG + GHRH test, in CS the maximal somatotrope secretory capacity is sometimes so reduced as to overlap with that of severe GHD.
authors.affiliation: Department of Internal Medicine, University of Turin, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Procopio
authors.forename: M
authors.initials: M
authors.lastname: Maccario
authors.forename: P
authors.initials: P
authors.lastname: Savio
authors.forename: M R
authors.initials: MR
authors.lastname: Valetto
authors.forename: G
authors.initials: G
authors.lastname: Aimaretti
authors.forename: S
authors.initials: S
authors.lastname: Grottoli
authors.forename: S E
authors.initials: SE
authors.lastname: Oleandri
authors.forename: C
authors.initials: C
authors.lastname: Baffoni
authors.forename: F
authors.initials: F
authors.lastname: Tassone
authors.forename: E
authors.initials: E
authors.lastname: Arvat
authors.forename: F
authors.initials: F
authors.lastname: Camanni
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000328:Adult; D001120:Arginine; D016022:Case-Control Studies; D003480:Cushing Syndrome / Q000175:diagnosis / Q000503:physiopathology; D005260:Female; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000172:deficiency* / Q000378:metabolism*; D006801:Humans; D007018:Hypopituitarism / Q000175:diagnosis / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology; D011729:Pyridostigmine Bromide
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; D011729:Pyridostigmine Bromide