title: Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing's syndrome.
abstract: OBJECTIVE
  The aim of this work was to clarify the mechanisms underlying growth hormone (GH) hyposecretion in Cushing's syndrome (CS) and in obesity. We studied the GH response to GH-releasing hormone (GHRH) alone and combined with arginine or pyridostigmine, two substances likely to inhibit hypothalamic somatostatin release.
  
  
  METHODS
  Three tests with GHRH alone (1 microgram/kg i.v. at 0 min) and combined with arginine (ARG, 0.5 g/kg infused over 30 min) or pyridostigmine (PD, 120 mg orally at -60 min) were performed 3 days apart and in random order in eight women with CS (five with ACTH-dependent and three with ACTH-independent hypercortisolism, age 18-56, BMI 26.1 +/- 1.5 Kg/m2) and 11 with OB (age 17-54, BMI 42.9 +/- 2.2 Kg/m2). Eleven normal women (age 23-50, BMI 21.9 +/- 0.3 Kg/m2) were studied as controls (C).
  
  
  METHODS
  Serum GH and IGF-I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (micrograms/L) or as areas under the curve (AUC, micrograms/L/h) calculated by trapezoidal integration. IGF-I concentrations were expressed as absolute values (micrograms/L) with reference to a pure recombinant IGF-I preparation.
  
  
  RESULTS
  Basal GH levels in CS were similar to those registered in OB (mean +/- s.e.m. 0.7 +/- 0.1 vs 0.9 +/- 0.2 microgram/L) and lower than in C (3.4 +/- 0.5 microgram/L, P < 0.00001). On the other hand, IGF-I levels were similar in all groups. The GHRH-induced GH rise in CS was lower, though not significantly, to that observed in OB (AUC: 65.6 +/- 13.2 vs 192.5 +/- 61.7 microgram/L/h) and both GH responses were significantly lower than that of C (1029.9 +/- 98.0 micrograms/L/h, P < 0.00001). ARG enhanced the GHRH-induced GH release in CS (331.9 +/- 51.9 micrograms/L/h vs GHRH alone, P < 0.0001), OB (852.4 +/- 162.1 micrograms/L/h, P < 0.0001) and C (3362.6 +/- 386.0 micrograms/L/h, P < 0.0002). However, the GH response to GHRH plus ARG in CS was lower (P < 0.002) than that in OB which, in turn, was lower than that in C (P < 0.00001). Pyridostigmine significantly enhanced the GHRH-induced GH rise in C (2808.5 +/- 221.2 micrograms/L/h, P < 0.00001) and, to a lesser extent, in OB (627.3 +/- 84.7 micrograms/L/h, P < 0.0002) but not in CS (102.9 +/- 25.0 micrograms/L/h).
  
  
  CONCLUSIONS
  Our results indicate that the GH releasable pool is reduced in obesity and, to an even greater extent, in Cushing's syndrome. The inability of pyridostigmine and arginine to restore a normal GH response to GHRH in these conditions makes the existence of a hypothalamic somatostatinergic hyperactivity unlikely.
authors.affiliation: Department of Clinical Pathophysiology, University of Turin, Torino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Procopio
authors.forename: C
authors.initials: C
authors.lastname: Invitti
authors.forename: M
authors.initials: M
authors.lastname: Maccario
authors.forename: S
authors.initials: S
authors.lastname: Grottoli
authors.forename: F
authors.initials: F
authors.lastname: Cavagnini
authors.forename: F
authors.initials: F
authors.lastname: Camanni
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000293:Adolescent; D000328:Adult; D001120:Arginine; D016022:Case-Control Studies; D003480:Cushing Syndrome / Q000097:blood*; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D011729:Pyridostigmine Bromide
chemical_list: D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; D011729:Pyridostigmine Bromide