Pegvisomant increases intra-abdominal fat in patients with acromegaly:: a pilot study

Objective: Acromegalic patients have increased lipolysis and decreased fat mass as well as reduced insulin sensitivity and glucose intolerance. During somatostatin analog therapy, these changes persist despite GH suppression, but they are now due to drug-induced suppression of insulin secretion. By contrast, during pegvisomant (PEG) therapy, GH no longer stimulates lipolysis due to the blockade of its receptor, while insulin action is unabated. Hence, both insulin sensitivity and fat mass, including intra-abdominal fat, should increase. We therefore studied intra-abdominal fat and insulin resistance in acromegalic patients after a 3-month octreotide-washout period, i.e., during untreated acromegaly, and during PEG treatment. Methods: Five acromegalic patients, not controlled on octreotide (OCT) therapy, were studied after 3-month OCT washout and 6-month PEG therapy, Insulin sensitivity was determined by homeostatic model assessment value and hyperinsulinemic, normoglycemic clamp. Subcutaneous and intra-abdominal fat were measured by electron beam computed tomography Results: During PEG therapy, all the patients had normal, age-adjusted IGF-I concentrations. Compared with washout, insulin sensitivity (HOMA and M value) was not significantly different. However, intraabdominal fat mass increased significantly during therapy (median (range) cm(2): 112 (84-480) and 172 (112-524) respectively, P < 0.05), while subcutaneous fat was not significantly different. Low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides remained unchanged. Conclusions: During PEG therapy of acromegalic patients, intra-abdominal fat increases. Visceral obesity is a risk factor for cardiovascular disease. Hence, confirmation and further studies in a larger cohort of acromegalic patients on PEG treatment are warranted.