Acute effect of the growth hormone antagonist pegvisomant injection alone and in combination with a somatostatin analogue on endogenous GH and pegvisomant levels

Introduction: Cotreatment of somatostatin analogues and growth hormone receptor antagonists in acromegaly might be a new treatment option abolishing the negative effects of monotherapy as rising endogenous GH levels, deterioration of glucose tolerance and lack of tumor growth control. Nevertheless, little is known about the acute effect of the combined treatment on endogenous GH and pegvisomant levels. Methods: 10 acromegalic patients on constant pegvisomant therapy were included. Two 6 hour integrated GH secretion profiles were performed once after pegvisomant alone (P), the other after an additional 100µg octreotide sc injection (PO). After 180min all patients received a standardized light mixed meal. Endogenous serum GH and pegvisomant levels were measured by special in-house assays. Results: In the combined profile PO a significant decrease of endogenous GH from 14.8µg/l (3.3–45.4) to 4.5µg/l (0.6–12.2, p<0.01) was seen with a nadir at 180min (median percentage decline 75.2%, range 23.7–88.2), which was not seen in profile P (13.8µg/l (3.2–36.6) to 14.3µg/l (0.4–27.1), p>0.05). After meal endogenous GH significantly decreased with a nadir at 300min only in profile P (14.3µg/l (0.4–27.1) to 9µg/l (0.2–24.7), p<0.01). Pegvisomant levels did not differ significantly between profiles and did not change significantly during the tests (median baseline pegvisomant in P: 7507µg/l (2950–14900), in PO 6491µg/l (3550–24600), p>0.05). After meal glucose levels rose higher and later in profile PO than in profile P. Accordingly, during profile PO insulin levels rose later and maximum insulin levels were lower than during profile P. Conclusion: During pegvisomant treatment, endogenous GH can be reduced significantly by acute application of a somatostatin analogue. The acute test with the combination of octreotide and pegvisomant may help to assess the effectiveness of long term treatment with both drugs. Additional acute octreotide injection seems to have no influence on pegvisomant levels.