Endocrine Abstracts

The GH-receptor antagonist PEG, used as monotherapy or in combination to SA, has been demonstrated to normalize IGF1 levels in up to 90% of acromegalic patients after unsuccessful surgery and/or radiotherapy and resistant to conventional SA treatment. The aim of this study is to evaluate the efficacy and safety of combined treatment with SA plus PEG in a cohort of acromegalic patients resistant to conventional SA therapy. Thirty-two acromegalic patients (17 M, 15 F, age 39.6±12.6 years) were recruited; GH and IGF1 levels, maximum tumoral diameter, systolic (SBP) and diastolic (DBP) blood pressure, glucose and lipid profile and liver function enzymes were evaluated at diagnosis, after long-term high-dose SA therapy and after 12–24 months of combined therapy with SA plus PEG. Compared to baseline, SA induced a significant reduction, but not normalization, in GH and IGF1 levels (P<0.001), as well as in maximum tumoral diameter (P=0.003) and insulin levels (INS, P<0.01). The addiction of PEG to SA induced a further decrease, until normalization, of GH and IGF1 levels (P<0.001), glycated haemoglobin (HbA1c, P<0.001) and INS (P<0.001), as well as the significant increase of gamma glutamyltransferase (γGT, P=0.03), although they were still normal. Eleven out of 32 patients were treated also with PEG as monotherapy, inducing the significant reduction in IGF1 levels (P<0.001), SBP (P=0.02), INS (P<0.001) and triglycerides levels (TRIG, P<0.05) when compare to SA treatment. In those patients, combined therapy with SA plus PEG induced a further decrease in GH and IGF1 levels (P<0.001), without any further change in metabolic parameters and blood pressure. None of the patients experienced a significant increase in liver function enzymes or in tumor diameter during PEG monotherapy or SA plus PEG combined treatment. At diagnosis, six patients were afflicted with type 2 diabetes mellitus and were treated with insulin-sensitizers; after SA plus PEG therapy, only five patients needed treatment with insulin-sensitizers, but at lower dose, and one patient discontinued therapy. In conclusion, the results of the present study demonstrated that combined treatment with SA plus PEG is safe and effective in controlling GH and IGF1 levels excess as well as metabolic and cardiovascular complications of acromegaly.