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 mu g/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 mu g 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 mu g/l, P = 0.04), free IGF1 (by 13%, 0.83 +/- 0.36 vs 0.70 +/- 0.33 mu g/l, P = 0.01) and IGFBP3 (6%, 4475 +/- 745 vs 4209 +/- 912 mu g/l, P = 0.02). Octreotide suppressed fasting insulin from 5.2 +/- 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 mu g/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.