Effects of a 7-day continuous infusion of octreotide on circulating levelsof growth factors and binding proteins in growth hormone (GH)-treated GH-deficient patients

In patients with acromegaly, clinical improvement has been reported after o ctreotide (OCT) treatment, even in cases of only a moderate suppression of growth hormone (GH) levels. In rats, OCT suppresses IGF-I mRNA expression a nd generation of serum and tissue IGF-I levels. A direct effect of OCT on t he IGF system could have therapeutical implications in diabetes mellitus, c ardiovascular disease, and certain malignancies in which IGF-I might be inv olved. The aim of this study was to examine possible GH-independent effects of OCT on IGF components in humans. Six GH-deficient (GHD) patients were s tudied for 24 h after each of the following treatment regimens (each of 1 w eeks duration): (a) daily s.c. GH injection (2 IU/m(2)); (b) as (a) + conti nuous s.c. infusion of OCT (200 mu g/24 h) by means of a portable pump (Nor dic Infuser); (c) no treatment. Serum GH binding protein (GHBP) levels tend ed to be lower after GH and OCT than after GH alone (P = 0.10). OCT reduced the GH induced increase in serum IGF-I levels (P<0.05, ANOVA). Mean integr ated levels (mu g/l) were 359.1+/-49.6 (GH), and 301.6+/-58.9 (GH+OCT). OCT did not significantly reduce serum IGFBP-3 levels (mu g/l) [3460+/-270 (GH ), and 3112+/-435 (GH+/-OCT); P=0.14]. Serum levels of free IGF-I (P=0.39), IGF-II (P=0.54), and of the acid-labile subunit (ALS) of the ternary compl ex (P=0.50) were similar during GH+/-OCT as compared with GH alone. After 1 week off GH treatment, significantly lower levels of IGF-I, IGF-II, IGFBP- 3, and ALS were recorded (P<0.001), Serum IGFBP-1 levels were significantly higher after GH+OCT than after GH alone (P<0.0001), and levels were even h igher without GH, Serum insulin levels (pmol/l) were significantly higher a fter GH alone as compared with no GH (P<0.05, ANOVA), whereas OCT partly su ppressed the insulinotropic effect of GH (P<0.05) [mean: 114.5+/-33.0 (GH), 91.3+/-29.6 (GH+OCT), 65.9+/-22.5 (no GH)]. This was also reflected in hig her blood glucose levels during GH+OCT. Finally, GH+OCT reduced glucagon le vels significantly as compared with GH alone (P=0,02). In conclusion, 7 day s' administration of OCT to GH-treated GHD patients slightly attenuated ser um IGF-I generation, and tended to decrease levels of the other components of the 150 kDa ternary complex. Whether these effects are mediated directly by OCT or indirectly via the accompanying changes in insulin levels remain s to be investigated. (C) 1999 Harcourt Publishers Ltd.