Endocrine Abstracts

Introduction: Daily administration of Pegvisomant normalizes IGF1 levels >71% of acromegalics (1). Few studies have assessed the efficacy of weekly administration. We assessed the efficacy of weekly pegvisomant for 12 months, after withdrawal of long-acting somatostatin analogs (SSA) in acromegalics previously controlled on combination therapy.

Design: Fifteen subjects (8 males), age 58 (35–80) (median (range)) years on combination therapy of high-dose SSA and weekly pegvisomant and IGF1 levels within the normal range for >6 months, were enrolled. IGF1 at baseline was 0.62 (0.3–0.84) times the upper limit of normal (ULN) and the weekly dose of pegvisomant was 60 (30–80) mg. SSA treatment was stopped for 12 months. IGF1, HbA1c, GH and pegvisomant concentrations were assessed at baseline and there after every 6 weeks. When IGF1 levels increased, pegvisomant dose was increased by 20 mg weekly. Dosages were divided into two injections per week when pegvisomant exceeded 80 mg.

Results: Baseline pegvisomant and GH serum levels were 2988 (252–19 440) and 2.99 (0.19–15.95) μg/l respectively. After 12 months, in 73.3% of subjects IGF1 levels remained controlled under monotherapy of pegvisomant. One patient restarted SSA, during the study-period, due to an increase in signs and symptoms of acromegaly. After 12 months, IGF1 was 0.83 (0.30–1.75) ULN, while the cumulative weekly pegvisomant dose increased to 80 (50–120) mg. Pegvisomant and GH levels increased to 4356 (1116–21 276) and 6.36 (0.180–31.45) μg/l. Pegvisomant levels tended to be different between subjects in whom IGF1 remained normal and those who did not: 5544 (1116–21 276) vs 3848 (1296–4392) μg/l, although the weekly pegvisomant dose was the same. HbA1c decreased from 6.0 (5.1–9.2) to 5.9 (5.0–9.1)% (P=0.02).

Conclusion: After cessation of SSA treatment in acromegalic subjects on combination therapy, weekly pegvisomant could control 73.3% of patients. Pegvisomant levels seems to be lower in patients with an elevated IGF1 than in patients with a normal IGF1, with similar subcutaneous administration dosages.