Endocrine Abstracts

Pasireotide is a second-line therapy for acromegaly, that allows to obtain disease control in patients previously uncontrolled. However, pasireotide-induced hyperglycemia is of major concern. Currently, few data concerning prolonged use of pasireotide are available. The current retrospective study aimed at investigating the efficacy and safety of long-term pasireotide therapy. Sixteen consecutive patients (5 males, 11 females, age 47 ± 11 years) undergoing pasireotide for a minimal period of 36 months, were considered for the current study. In these patients, hormonal (GH, IGF-I), biochemical (fasting glucose and HbA1c), and radiological parameters (tumour maximal diameter and volume) have been considered at baseline and at 6, 12, 36 months, and last follow-up (LFU), during pasireotide therapy. At baseline, GH levels were 4.56 ± 3.82 ng/ml, IGF-I levels were 1.74 ± 0.72 x ULN, resulting 13 patients (81.25%) uncontrolled. Diabetes mellitus (DM) was present in 7 (43.75%), and 4 patients (25%) showed an impaired fasting glucose (IFG). After 6 months of pasireotide, GH and IGF-I levels were significantly reduced compared to baseline (P=0.017 andP=0.001, respectively). At 12 months, all patients achieved disease control (P<0.0001), tumour maximal diameter and volume were significantly reduced (P=0.003 andP=0.019, respectively). Disease control was maintained at 36 months evaluation, being tumour volume significantly further reduced compared to 12 months (P=0.010). Twelve patients (75%) were treated with pasireotide for a longer period (range 42-66 months); all these patients were controlled with a stable size adenoma at LFU. At 6 months, an increase in dose was recorded in 4 patients (25%, P=0.046), no further dose variation have been required. Pasireotide starting dose was significantly inversely correlated to IGF-I at 36 months (r=-0.614, P=0.011). Fasting glucose (FG) significantly increased in the first year of pasireotide therapy, particularly in the first 6 months (P=0.005); without a consistent increase in HbA1c (P=0.303) and DM (P=0.285). FG at 6 months was significantly correlated to age (r=0.692, P=0.003), rather than pasireotide dose (r=0.417, P=0.108). After 6 months, 75% IFG patients developed DM. At 36 months, 80% euglycemic patients at baseline were diabetic, and 20% showed IFG. As consequence, a significant increase in DM (P=0.023), and in the number of antidiabetic drugs used (P=0.005) were observed. Pasireotide therapy is effective in determining disease control, and tumour shrinkage, even after a long period of treatment. Change in FG mainly occur in the first period, depending on age and glycemic status before pasireotide starting.