Endogenous GH levels after growth hormone receptor antagonist treatment with and without additional Octreotide

Pegvisomant is a peripheral GH receptor antagonist and normalizes IGF-I while endogenous GH values increase. We performed this preliminary study to investigate whether additional octreotide may decrease endogenous GH-levels during therapy with Pegvisomant. Analyses were performed using special immuno-assays measuring only endogenous GH with no cross reactivity with Pegvisomant.

We studied 5 active acromegalic patients: 2f, 3m, median age 50y (42–55); 5/5 pat. underwent adenomectomy, 4/5 were irradiated; prior to pegvisomant, 5/5 patients were active despite somatostatin analogue treatment. Median duration of Pegvisomant treatment was 9 months (4–16m).

In each pat. we performed two 6-h-GH profiles: the first one after sc Pegvisomant (15mg (10–20mg)) alone (PGV); the second one after sc injection of both, Pegvisomant and Octreotide 100µg (PGV/OCT). After fasting baseline serum test, medication was applicated. All pat. had a standard mixed meal after 180 minutes.

In the two profiles (PGV vs. PGV/OCT), basal GH values did not differ significantly. 4/5 were normalized (xULN of IGF-I 0.71 (0.55–1.54)). In PGV profiles we found no variance in endogenous GH values. In PGV/OCT profiles, endogenous GH decreased significantly (p<0.05) from a median basal value of 15.6ng/ml (3.3–19.7) to a nadir of 4.9ng/ml (2.3–12.2) after 120 minutes in all the 5 patients. Afterwards GH levels remained on this stable low level (120min-360min) with a median AUC of GH of 1184 (540–2754). The corresponding AUC of endogeneous GH in PGV profiles was significantly higher (3734 (698–4353), p<0.05).

In conclusion we could demonstrate that in Pegvisomant treated acromegalic patients endogenous GH levels can be lowered significantly by additional administration of Octreotide. The acute application of sc Octreotide with measurement of endogenous GH is useful to discover responders for additional Octreotide. A combined therapy of Pegvisomant and somatostatin analogues should be discussed in patients with risk of tumour growth or those needing very high doses of Pegvisomant.