Background: The default-mode network (DMN) has been increasingly recognized as relevant to cognitive status.

Objective: We aimed to investigate the efficacy of pegvisomant in patients with acromegaly resistant to long-term (≧ 24-month), high-dose treatment with octreotide-LAR (40 mg/month) or lanreotide (120 mg/month). Design: This was an open, prospective study. Subjects and Methods: We studied 16 patients with acromegaly (nine women; aged 28–61 years). The main outcome measures were IGF-I levels, blood pressure, glucose tolerance and safety (liver function and tumor size). Pegvisomant was given at doses of 10–40 mg s.c. daily. Dose titration was performed every month by IGF-I assay. Results: Three patients spontaneously stopped pegvisomant treatment after 6–9 months because of poor compliance; from the measurement of serum pegvisomant, another patient was found not to inject herself properly. After 6 months, IGF-I levels decreased by 63 ± 19% (767.8 ± 152.9 vs 299.8 ± 162.9 μg/l, P < 0.0001, t-test); serum IGF-I levels normalized in 57%. After 12 months, IGF-I levels normalized in nine (75%) patients and were reduced by over 50% in another three (25%). The mean tumor volume remained stable during the study (1198 ± 1234 vs 1196 ± 1351 mm³, P = 0.37): it did not change ( ± 25% vs basal) in nine patients, increased by 39.4% and 40.8% in two and decreased by 30.8–46.5% in four. The total/high-density lipoprotein (HDL):cholesterol ratio (from 4.4 ± 1.0 to 3.7 ± 0.6, P= 0.0012), glucose levels (from 5.6 ± 1.2 to 4.4 ± 1.4 mmol/l, P = 0.026), insulin levels (from 12.4 ± 6.7 to 8.1 ± 3.0 mUl/l, P = 0.0023) and homeostasis model assessment (HOMA) index (from 3.4 ± 2.1 to 1.9 ± 1.0, P = 0.0017) decreased. Conclusions: Treatment for 12 months with pegvisomant normalized IGF-I levels, and improved cardiovascular risk parameters and insulin sensitivity in patients with acromegaly resistant to long-term, high-dose treatment with somatostatin analogs. The tolerance of treatment was good.

Context: Primary treatment with depot octreotide and lanreotide induces tumor shrinkage in newly diagnosed patients with acromegaly. Objective: The objective of the study was to evaluate clinical predictors of tumor shrinkage. Design: This was an analytical, observational, open, prospective study. Subjects: The study included 99 patients: 13 with microadenoma and 86 with macroadenoma (25 enclosed, 32 extrasellar, 29 invasive). Main Outcome Measures: Age, gender, estimated disease duration, body mass index, GH and IGF-I levels, and tumor volume at diagnosis and after 12 months of treatment were measured. Percentage of GH, IGF-I, and tumor size changes from baseline were also analyzed. Tumor changes were scored as absent (± 0–25%), mild (± 25.1–50%), moderate (± 50.1–75%), or notable (75%). Interventions: Sixty patients (60.6%) received depot octreotide im (20–30 mg every 28 d), and 39 patients (39.4%) received lanreotide im (60–90 mg every 28 d). Results: Basal tumor volume and maximal tumor diameter correlated with age, disease duration, and GH levels. After 12 months, GH levels were controlled (≤2.5 μg/liter) in 57.6%, IGF-I levels in 45.5%, and both in 42.4%. Shrinkage was absent in 22 patients (22.2%), mild in 31 (31.1%), moderate in 30 (30.3%), and notable in 14 patients (14.1%). Two patients (not responding to treatment) had a mild tumor increase (by 34 and 31.2%, respectively). Basal and posttreatment tumor volumes were highly correlated (r = 0.79, P < 0.0001). At the multistep regression analysis, the percent IGF-I decrease (t = 2.6; P = 0.011) was the best predictor of posttreatment tumor volume, followed by patients’ age (t = 2.1; P = 0.042) and percent GH decrease (t = 2.0; P = 0.044). Conclusions: Most patients with acromegaly (75.5%) had 25% or greater tumor shrinkage after 12 months of primary somatostatin analog therapy: significant increase of tumor mass occurred in only 2.1% of patients (uncontrolled during treatment). Best predictor of tumor shrinkage was posttreatment IGF-I.