Endocrine Abstracts

Introduction: The treatment of choice in acromegaly is a transsphenoidal surgery of a growth hormone (GH) - producing pituitary adenoma. In patients with persistent acromegaly after surgery medical treatment is recommended. First generation somatostatin analogs: lanreotide autogel and octreotide LAR are effective in 25% to 45% of patients depending on population and study protocol. Second-generation somatostatin analog – pasireotide LAR seems to be more effective. The possibility to indicate clinical predictive factors of pasireotide LAR response could help in selecting patients who would benefit the most from the treatment.

Aim: The aim of the study was to check if the response to short-acting pasireotide can predict the efficacy of treatment with pasireotide LAR in patients with active acromegaly resistant to first-generation somatostatin analogs.

Patients and methods: Twenty four patients with active acromegaly after surgical debulking treated with first-generation somatostatin analogs were enrolled in the prospective study. After two-month wash-out period all patients had a test with short-acting pasireotide performed (GH measurements 0, 60, 120 and 180 minutes after s.c. administration of 600 μg of short-acting pasireotide) and were then switched to pasireotide LAR 60 mg administered i.m. every 28 days for 3 months. The effects of pasireotide LAR on GH, IGF-1, insulin, glucose and HgbA1c concentrations and the predictive value of the test were analysed after 3-month treatment.

Results: After 3 months of treatment with pasireotide LAR eight patients (33%) reached GH<1 μg/l, fifteen patients (62.5%) reached GH<2.5 μg/l. Four patients (16.7%) reached IGF-1<1×upper limits of normal (ULN), eleven patients (45.8%) IGF-1 <1.5×ULN. There was a significant decrease in median GH and the mean IGF-1 after pasireotide LAR treatment vs first-generation somatostatin analogs: 1.66 μg/l (IQR:0.24–12.1) vs 2.88 μg/l (IQR:0.75–9.3), P<0.001 and 1.49±0.582×ULN vs 2.31±0.696×ULN, P<0.001, respectively. Pasireotide LAR was well tolerated, but hyperglycemia was the most frequent adverse event. Insulin decreased: 10 (IQR:2.4–46.8) vs 7.1 μIU/ml (IQR:1.3–25) P=0.001 and fasting glucose increased: 104 (IQR:84–191) vs 119 (IQR:96–453) mg/dl, P<0.001) within 3 months of pasireotide treatment. We found a statistical significant correlation between a maximal GH decrease during the short-acting pasireotide test and GH and IGF-1 after 3-month treatment (R=0.57, P<005 and R=0.56, P<0,05 respectively).

Conclusions: Pasireotide LAR is more effective in decreasing GH and IGF-1 levels than first-generation somatostatin analogs in acromegalic patients after surgical debulking. Better efficacy of pasireotide LAR is correlated with higher GH decrease after administration of 600 ug short-acting pasireotide.