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Pituitary-independent effect of octreotide on IGF1 generation

Department of Endocrinology, Christie Hospital, Manchester, M20 4BX, UK¹ Medical Research Laboratories, Clinical Institute and Medical Department M, Diabetes and Endocrinology, Aarhus University Hospital, Aarhus, DK 8200, Denmark

(Correspondence should be addressed to A Pokrajac; Email: anapokrajac{at}yahoo.co.uk)

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/m²; peak-stimulated GH <3 µg/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 µg 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 µg/l, P=0.04), free IGF1 (by 13%, 0.83±0.36 vs 0.70±0.33 µg/l, P=0.01) and IGFBP3 (6%, 4475±745 vs 4209±912 µg/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 µg/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.

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