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Submitted on March 11, 2005
Accepted on July 19, 2005
stergård Kristensen, rskov
Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus (J.O.L.J, J.F, J.-W.J, H..), and Rigshospitalet, Copenhagen, (U. F.-R.), and Herlev Sygehus, Copenhagen, (L..K.), and Odense University Hospital, Odense, (C. H.), Denmark
* To whom correspondence should be addressed. E-mail: jolj{at}dadlnet.dk.
Context: Pegvisomant is a GH receptor antagonist, which blocks the peripheral actions of GH in acromegaly. Pegvisomant, in contrast to somatostatin analogs (SMS), does not suppress the activity of the GH producing adenoma.
Objective: We assessed the effects of cotreatment with pegvisomant and SMS in acromegaly on GH secretion, IGF-I levels and glucose tolerance.
Design, patients, and interventions: 11 patients with persistent disease despite previous therapy underwent the following fixed treatment algorithm: 1) on SMS therapy, 2) off therapy for 2 months, 3) 6 weeks treatment with 10 mg pegvisomant/d, 4) six weeks treatment with 15 mg pegvisomant/d, 5) 3 months treatment with 15 mg pegvisomant plus SMS. Blood was sampled in the fasting state and during an OGTT.
Results: Total serum IGF-I levels (µg/l) decreased following pegvisomant, but the lowest levels were obtained with cotreatment [458 ± 67 (SMS), 562 ± 78 (active), 376 ± 51 (10 mg), 269 (15 mg), 195 ± 24 (combined) (P < 0.0001)]. Free and bioactive IGF-I changed in a similar pattern. Steady-state pegvisomant levels (µg/l) were obtained, but SMS cotreatment increased pegvisomant levels by 20% (P = 0.02) [2631 ± 616 (10 mg), 6536 ± 1413 (15 mg), 8030 ± 1914 (combined)]. Pegvisomant increased endogenous GH levels (µg/l), which was countered by SMS cotreatment [5.1 ± 1.3 (SMS), 8.9 ± 2.9 (active), 14.6 ± 4.9 (10 mg), 19.7 ± 6.5 (15 mg), 11.8 ± 2.8 (combined) (P < 0.01)]. Plasma glucose levels (mmol/l) were highest during SMS and lowest during pegvisomant 15 mg [2-h OGTT: 10.3 ± 0.7 (SMS), 8.9 ± 0.7 (active), 7.2 ± 0.7 (10 mg), 6.5 ± 0.5 (15 mg), 8.0 ± 0.8 (combined) (P = 0.02)].
Conclusions: dual blockade of the GH axis with pegvisomant and a somatostatin analog is feasible in acromegaly.
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