Pituitary-independent effect of octreotide on IGF-I generation.

Abstract

Background: Somatostatin analogues (SSTAs) are frequently used for medical treatment of acromegaly. The rationale for their use is based on inhibition of pituitary GH secretion; however, there is in vitro evidence that octreotide also acts to inhibit hepatic IGF-I generation. Aim&Design: We studied the pituitary-independent effects of octreotide on IGF-I generation in 11 severely GH deficient humans (age 38, range 23-52; 7 male; BMI 24.7+/-3 kg/m2; peak stimulated GH <3mug/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 mug of subcutaneous octreotide three times a day for 7 days. Results: At study entry, all patients had total IGF-I within age- and gender-related reference range (SDS 0.4+/-1.0). Octreotide treatment resulted in a significant fall in total IGF-I (by 18%, 208+/-89 vs. 173+/-62 mug/L, P=0.04), free IGF-I (by 13%, 0.83+/-0.36 vs. 0.70+/-0.33 mug/L, P=0.01) and IGFBP-3 (6%, 4475+/-745 vs. 4209+/-912 mug/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 a rise in fasting glucose from 5.2+/-0.9 to 5.8+/-0.9 mmol/L (P<0.01). IGFBP-1 increased by 84% from 42+/-26 to 95+/-52 mug/L (P=0.04). Conclusion: Our study demonstrates that octreotide induces a significant fall in IGF-I in severely GH deficient adults on fixed-dose of GH replacement. This is the evidence for a non-pituitary action of octreotide on the GH/IGF-I axis, most likely by antagonizing the action of GH on hepatic IGF-I generation and indirectly, by suppressing insulin secretion.