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The Control on Growth Hormone Release by Free Fatty Acids Is Maintained in Acromegaly

Divisione di Medicina Interna (R.L., G.M.), Unitá di Malattie Metaboliche (A.E.P.), Divisione di Neurochirurgia (M.L.), Unitá di Epidemiologia (A.C.), Istituto Scientifico Ospedale San Raffaele and Universitá degli Studi di Milano, 20132 Milano, Italy

Address all correspondence and requests for reprints to: Roberto Lanzi, M.D., Division of Internal Medicine, Istituto Scientifico Ospedale San Raffaele, Via Olgettina 60, 20132 Milano, Italy. E-mail: lanzi.roberto{at}hsr.it

Free fatty acids (FFA) physiologically regulate GH release via a negative feedback. The aim of this study was to examine whether such feedback is preserved in acromegaly, a condition in which alterations in other regulatory mechanisms of GH release occur. Eight acromegalic patients (group 1: five women and three men, 43.0 ± 4.2 yr old, mean ± SE) received per os on two 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 0700 and 1100 h. In both tests GHRH (1–29 NH₂), 50 µg, was administered iv at 1300 h. Blood samples for GH, FFA, immunoreactive insulin (IRI), and glucose were taken from 0900 to 1500 h, and the time period considered for statistical analysis was 1200–1500 h, representative of steady-state condition for FFA, IRI, and glucose. Mean plasma FFA levels (1200–1500 h) were significantly 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) and the mean GH response to GHRH (GH area, 1300–1500 h) were significantly higher after acipimox than after placebo (12.0 ± 1.9 vs. 7.8 ± 1.2 µg/L, P < 0.01; 2937 ± 959 vs. 1154 ± 432 µg/L·120 min, P < 0.01). The increase in both basal GH levels and GH area occurred in all eight 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 compared 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. Mean plasma FFA levels (1200–1500 h) were significantly higher during lipid infusion than after placebo (0.27 ± 0.01 vs. 0.16 ± 0.01 g/L, P < 0.02); in contrast, mean basal GH levels (1200–1300 h) were reduced by lipid infusion, as compared with placebo (9.9 ± 3.1 vs. 16.6 ± 4.4 µg/L, P < 0.01), and the same occurred for the GH area after GHRH (2498 ± 1643 vs. 4512 ± 1988 µg/L·120 min, P < 0.01). Serum IRI and blood glucose levels 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 circulating FFA levels is accompanied by a reduced GH release. Taken together, these findings suggest that, in acromegaly, the control of FFA on GH release is preserved.