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. AIM & DESIGN: 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). CONCLUSION: 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.