Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing's syndrome.
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.
Procopio
M
M
Department of Clinical Pathophysiology, University of Turin, Torino, Italy.
Invitti
C
C
Maccario
M
M
Grottoli
S
S
Cavagnini
F
F
Camanni
F
F
Ghigo
E
E
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
D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; D011729:Pyridostigmine Bromide