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Cotreatment of Acromegaly with a Somatostatin Analog and a Growth Hormone Receptor Antagonist

Medical Department M (Endocrinology and Diabetes) (J.O.L.J., J.F., J.-W.C., H.Ø.), Aarhus University Hospital, DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet (U.F.-R.), DK-2200 Copenhagen, Denmark; Department of Medicine and Endocrinology, Herlev Sygehus (L.Ø.K.), DK-2730 Copenhagen, Denmark; and Department of Endocrinology (C.H.), Odense University Hospital, DK-5000 Odense, Denmark

Address all correspondence and requests for reprints to: J. O. L. Jørgensen, Medical Department M, Aarhus University Hospital, Norrebrogade 44, DK-8000 C Aarhus, Denmark. E-mail: jolj{at}dadlnet.dk.

Context: Pegvisomant is a GH receptor antagonist that blocks the peripheral actions of GH in acromegaly. Pegvisomant, in contrast to somatostatin (SMS) analogs, 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: Eleven 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-wk treatment with 10 mg/d pegvisomant, 4) 6-wk treatment with 15 mg/d pegvisomant, and 5) 3-month treatment with 15 mg pegvisomant plus SMS. Blood was sampled in the fasting state and during an oral glucose tolerance test.

Results: Total serum IGF-I levels (micrograms per liter) decreased after 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 (micrograms per liter) 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 (micrograms per liter), 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 (millimoles per liter) were highest during SMS and lowest during pegvisomant 15 mg [2-h oral glucose tolerance test: 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 SMS analog is feasible in acromegaly.

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