Circulating levels of pegvisomant and endogenous growth hormone during prolonged pegvisomant therapy in patients with acromegaly

Objective To investigate whether pegvisomant treatment in acromegaly induces gradual elevations in endogenous serum growth hormone (GH) levels and whether serum pegvisomant levels predict the therapeutic outcome. Patients and Methods Seventeen patients (6 women), mean age 46.3 years (range: 23.2-76.2), were studied. For each patient, four hospital visits were identified including 'active disease' (no treatment) and last follow-up. At each visit, 12 blood samples were drawn during 3h including an oral glucose tolerance test (OGTT). Eight patients received a somatostatin analogue in addition to pegvisomant on the last visit. Results Median (range) pegvisomant doses (mg/day) were 10 (10-10), 15 (10-15) and 15 (10-15) at visits 2, 3 and 4, respectively, and the mean duration of pegvisomant treatment was 17.5 +/- 3.2 (SEM) months. Serum IGF-I changed significantly during the treatment period with the highest level at baseline and lowest levels at visits 3 and 4. GH levels increased in a dose-dependent manner during pegvisomant treatment and decreased at visit 4. Changes in IGF-I levels correlated negatively with changes in serum pegvisomant levels between visits. Serum pegvisomant at each visit correlated with baseline growth hormone levels, whereas no associations between serum pegvisomant and either dose, gender, age or body weight were found. Conclusions (1) Serum GH levels increased initially, but remained stable during prolonged pegvisomant treatment in patients with acromegaly, (2) serum pegvisomant levels predicted the reduction in serum IGF-I during treatment and (3) the interindividual variation in serum pegvisomant levels seems not predicted by either age, gender or body composition.