Endocrine Abstracts

Pegvisomant is a novel medical therapy for acromegaly that functions as a GH receptor antagonist. Insulin resistance is an important factor in the increased cardiovascular morbidity and mortality associated with acromegaly. The aim of this study was to compare insulin sensitivity (IS) in a group of 7 patients with acromegaly (3 male, mean age 59+/-13 years, SD), treated first with a stable dose of depot octreotide (OT) (median dose 20mg four weekly, range 10-20) for at least three months; and who were then treated with pegvisomant (median dose 15mg daily, range 10-20) for a median of 8 months (range 7-9). Ethical Committee approval was obtained. IS was assessed by short insulin tolerance test (sITT). In this test, which has been validated against the hyperinsulinaemic euglycaemic clamp, the rate of fall of plasma glucose following intravenous soluble insulin (0.1IU/kg body weight) provides a reproducible measure of peripheral insulin sensitivity. Body composition was assessed by dual energy X-ray absorptiometry (DXA) at the same time as the sITTs. No statistically significant change in mean serum IGF-I was observed (283+/-119 ng/ml (SD) vs on OT; 191+/-39 ng/ml on pegvisomant, (p=0.4). Mean fasting plasma glucose fell from 6.2+/-1.0 mmol/l (SD) on OT to 5.2+/-0.6 mmol/l on pegvisomant and was lower on pegvisomant in all 7 patients. In four patients, fasting plasma glucose fell from values diagnostic of diabetes mellitus or impaired fasting glucose on OT to within the normal range on pegvisomant. Mean IS increased from 139+/-39 mcmol/l/min on OT to 169+/-59 mcmol/l/min on pegvisomant (p=0.037). No statistically significant change in total fat (p=0.3) or %fat (p=0.28) was observed during the study. IS improves in patients converted from OT therapy to pegvisomant, without a change in body composition. This may be an important factor in the choice of medical therapy for patients with acromegaly.