The control on growth hormone release by free fatty acids is maintained inacromegaly

Free fatty acids (FFA) physiologically regulate GH release via a negative f eedback. The aim of this study was to examine whether such feedback is pres erved in acromegaly, a condition in which alterations in other regulatory m echanisms of GPI release occur. Eight acromegalic patients (group 1: five w omen and three men, 43.0 +/- 4.2 yr old, mean +/- SE) received per os on tw o different days, at a 3 day-interval, in a random order, placebo or 250 mg of acipimox, an inhibitor of lipolysis analogous to nicotinic acid, at 070 0 and 1100 h. In both tests GHRH (1-29 NH2), 50 mu g, was administered iv a t 1300 h. Blood samples for GH, FFA,immunoreactive insulin (IRI), and gluco se were taken from 0900 to 1500 h, and the time period considered for stati stical analysis was 1200-1500 h, representative of steady-state condition f or FFA, IRI, and glucose. Mean plasma FFA levels (1200-1500 h) were signifi cantly lower after acipimox than after placebo (0.05 +/- 0.01 vs. 0.17 +/- 0.01 g/L, P < 0.01). In contrast, both mean basal GH levels( 1200-1300 h) a nd the mean GH response to GHRH (GH Delta area, 1300-1500 h) were significa ntly higher after acipimox than after placebo (12.0 +/- 1.9 os. 7.8 +/- 1.2 mu g/L, P < 0.01; 2937 +/- 959 vs. 1154 +/- 432 mu g/L.120 min,P ( 0.01). The increase in bath basal GH levels and GH Delta area occurred in all eigh t patients. Acipimox also reduced mean serum IRI (83 +/- 12 vs. 112 +/- 14 pmol/L) and blood glucose (5.1 +/- 0.1 vs. 5.7 +/- 0.1 mmol/L) levels, as c ompared with placebo (P < 0.03 or less). Eight acromegalic patients (group 2: six women and two men, 46.6 +/- 5.7 yr old) underwent a constant iv 10% lipid infusion (150 mL/h), started at 0900 h and continued until 1500 h. Me an plasma FFA levels (1200-1500 h) were significantly higher during lipid i nfusion than after placebo (0.27 +/- 0.01 vs. 0.16 +/- 0.01 gn, P < 0.02); in contrast, mean basal GH levels (1200-1300 h) were reduced by lipid infus ion, as compared with placebo (9.9 +/- 3.1 vs. 16.6 +/- 4.4 mu g/L, P < 0.0 11) and the same occurred for the GH Delta area after GHRH (2498 +/- 1643 v s. 4512 +/- 1988 mu g/L.120 min, P < 0.01). Serum IRI and blood glucose lev els were similar after placebo and during lipid infusion. These data indicate that, in acromegaly, the acute reduction of circulating FFA levels results in increased GH release, whereas the increase in circul ating FFA levels is accompanied by a reduced GH release. Taken together, th ese findings suggest that, in acromegaly, the control of FFA on GH release is preserved.