Pituitary-independent effect of octreotide on IGF1 generation.
BACKGROUND
Somatostatin analogues are frequently used for medical treatment of acromegaly. The rationale for their use is based on the inhibition of pituitary GH secretion; however, there is in vitro evidence that octreotide also acts to inhibit hepatic IGF1 generation.


OBJECTIVE
We studied the pituitary-independent effects of octreotide on IGF1 generation in 11 severely GH-deficient (GHD) humans (age 38, range 23-52; seven males; body mass index 24.7+/-3 kg/m(2); peak-stimulated GH <3 microg/l; 3+/-1 pituitary hormone deficiencies) on a stable dose of GH replacement (0.4+/-0.1 mg) for at least 6 months. Patients were studied before and after 50 microg of s.c. octreotide three times a day for 7 days.


RESULTS
At study entry, all patients had total IGF1 within age- and gender-related reference range (SDS 0.4+/-1.0). Octreotide treatment resulted in a significant decrease in total IGF1 (by 18%, 208+/-89 vs 173+/-62 microg/l, P=0.04), free IGF1 (by 13%, 0.83+/-0.36 vs 0.70+/-0.33 microg/l, P=0.01) and IGFBP3 (6%, 4475+/-745 vs 4209+/-912 microg/l, P=0.02). Octreotide suppressed fasting insulin from 8.1+/-3.4 to 6.3+/-4.1 mU/l (P=0.01) and was associated with an increase in fasting glucose from 5.2+/-0.9 to 5.8+/-0.9 mmol/l (P<0.01). IGFBP1 increased by 84% from 42+/-26 to 95+/-52 microg/l (P=0.04).


CONCLUSIONS
Our study demonstrates that octreotide induces a significant decrease in IGF1 in severely GHD adults on a fixed dose of GH replacement. This is the evidence for a non-pituitary action of octreotide on the GH/IGF1 axis, most likely by antagonising the action of GH on hepatic IGF1 generation and indirectly, by suppressing insulin secretion.
Pokrajac
Ana
A
Department of Endocrinology, Christie Hospital, Manchester, UK. anapokrajac@yahoo.co.uk
Frystyk
Jan
J
Flyvbjerg
Allan
A
Trainer
Peter J
PJ
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology*; D010902:Pituitary Gland / Q000502:physiology*; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D015282:Octreotide