Endocrine Abstracts

Introduction: The treatment of choice in persistent acromegaly after transsphenoidal adenomectomy is pharmacological treatment with first generation somatostatin analogs. They are effective in 25% to 45% of patients. Second generation somatostatin analog – pasireotide seems to be more effective.

Aim: The aim of the study was to assess the efficacy and safety of pasireotide LAR in acromegaly patients resistant to first generation somatostatin analogs.

Material and Methods: Twenty eight patients (males n = 15, 53.6%, mean age 43.59 ± 13.48 years) with acromegaly after surgical debulking resistant to first generation somatostatin analogs were involved in the study. Four patients had radiotherapy performed 59, 23, 18 and 24 months before study beginning. Poor diabetes management was an exclusion criterion. All patients started with pasireotide LAR 40 mg every 28 days and had GH, IGF-1, glucose and HgbA1c measured every three months. Patients who did not achieved biochemical control of acromegaly after three-month treatment had the dose escalated to 60 mg if pasireotide tolerability and adverse events allowed. Dose reduction to 20 mg was performed in one patient with full biochemical control and difficulties with diabetes management. Within the study period 16 patients completed twelve-month treatment.

Results: After twelve-month treatment a significant decrease in GH (4.06 IQR: 1.86–6.37 µg/l vs 1.3 IQR: 0.9–2.92 µg/l, P = 0.0005) and IGF-1 concentration (605.63 ± 203.05 ng/ml vs 381.46 ± 201.82 ng/ml, P <0.0001, i.e. 2.39 ± 0.8 × ULN vs 1.51 ± 0.82 × ULN, P < 0.0001) was observed. The increase in fasting glucose concentration (106, 95 ± 13.85 mg/dl vs 120.46 ± 17.76 mg/dl) and glycated hemoglobin (5.91 ± 0.44% vs 6.39 ± 0.63%) were also significant (P = 0.002 and P < 0.0001 respectively). In five patients 5/16 = 31.3% GH concentration fell below 1 µg/l and in twelve GH concentration was below 2.5 µg/l (12/16 = 75%). In five patients (5/16 = 31.3%) IGF-1 concentration was within normal limits after twelve-month treatment and in ten patients IGF-1 concentration was below 1.5 × UNL (10/16 = 62.5%). Three patients (3/16 = 18.8%) achieved full biochemical normalization after one-year treatment with pasireotide LAR.

Conclusions: Pasireotide LAR is more effective than first generation somatostatin analogs in patients with persistent acromegaly after surgical debulking. Carbohydrate metabolism should be regularly monitored on pasireotide treatment.