Pituitary-independent effect of octreotide on IGF1 generation
A Pokrajac, J Frystyk, A Flyvbjerg… - European Journal of …, 2009 - academic.oup.com
A Pokrajac, J Frystyk, A Flyvbjerg, PJ Trainer
European Journal of Endocrinology, 2009•academic.oup.comBackground 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 …
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 …
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.
Oxford University Press