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

Cotreatment of Acromegaly with a Somatostatin Analog and a Growth Hormone Receptor Antagonist
J Clin Endocrinol Metab 2005 90: 5627-5631 ปี 2548

 

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

Jens Otto Lunde Jørgensen, Ulla Feldt-Rasmussen, Jan Frystyk, Jian-Wen Chen, Lars Østergård Kristensen, Claus Hagen and Hans Ørskov

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@dadlnet.dk .

Context: Pegvisomant is a GH receptor antagonist that blocksthe peripheral actions of GH in acromegaly. Pegvisomant, incontrast to somatostatin (SMS) analogs, does not suppress theactivity of the GH-producing adenoma.

Objective: We assessed the effects of cotreatment with pegvisomantand SMS in acromegaly on GH secretion, IGF-I levels, and glucosetolerance.

Design, Patients, and Interventions: Eleven patients with persistentdisease despite previous therapy underwent the following fixedtreatment algorithm: 1) on SMS therapy, 2) off therapy for 2months, 3) 6-wk treatment with 10 mg/d pegvisomant, 4) 6-wktreatment with 15 mg/d pegvisomant, and 5) 3-month treatmentwith 15 mg pegvisomant plus SMS. Blood was sampled in the fastingstate and during an oral glucose tolerance test.

Results: Total serum IGF-I levels (micrograms per liter) decreasedafter pegvisomant, but the lowest levels were obtained withcotreatment [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 similarpattern. Steady-state pegvisomant levels (micrograms per liter)were obtained, but SMS cotreatment increased pegvisomant levelsby 20% (P = 0.02) [2631 ± 616 (10 mg), 6536 ±1413 (15 mg), 8030 ± 1914 (combined)]. Pegvisomant increasedendogenous GH levels (micrograms per liter), which was counteredby 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 glucoselevels (millimoles per liter) were highest during SMS and lowestduring 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 anda SMS analog is feasible in acromegaly.

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