Endocrine Abstracts

Introduction: Acromegaly (Acro) is characterized by insulin sensitivityreduction, glucose intolerance (IGT) and diabetes mellitus (DM2 in 15%–38% of patients). Studies that investigated action of medical therapies for acro on glucose metabolism, didn’t provide conclusive data. Association between blood glucose (BG) levels and serum IGF-I levels in patients with DM2 and acro has been suggested, however,IGF-I levels and hemoglobin A1c (HbA1c) correlation is still controversial due tomultifactorial influence.

Study aim: Investigate in a large retrospective cross-sectional multicenter study glucose metabolism in patients with acro resistant to 1st gen somatostatin receptor ligands (SRLs) treated with Pegvisomant (Peg) or Pasireotide LAR (Pasi).

Patients and Methods: Consecutive patients enrolled per following inclusion criteria: (1) resistance to 1st gen SRLs (2) treated with Pasi or Peg both for at least 6 consecutive months. Exclusion:patients with treatments influencing glucose, exception being glucocorticoid replacement. Biochemical control of acro was defined as normal IGF-I.

Results: 72 patients with active Acro: mean age 37 yrs (s.d.:15). 47 females (65.3%); 28 (38.9%) treated with Pasi and 44 with Peg (61.1%). Peg was monotherapy in 18 patients (40.9%) and combo with 1st generation SRLs 26 patients (59.1%). The number of patients with IGT and DM2 was superimposable between the 2 groups (Pasi and Peg-V). In Pasi group, 19 patients had acro control (67.9%); glucose metabolism worsened in 16 (57.1%). Worsening of glucose metabolism occurred most frequently in patients with persistently active acro (62.5%) and with higher BG and HbA1c at study start. Likewise, HbA1c was higher in patients with active acro, although HbA1c worsened during Pasi treatment both in euglycemic and IGT at study entry, regardless of normal IGF-I. In Peg group, 31 patients reached normal IGF-I (73%); glucose worsened in 12 (27.3%) but improved in 5 patients (11.4%). All patients who experienced glucose improvement had controlled acro, regardless of the combo use. Among 13 patients with active acro, BG worsened in 5 (38.4%). Patients with worsening BG control had higher HbA1c (P = 0.03) and required higher Peg doses (mean 25 mg/day s.d.: 10; P = 0.04). Patients with higher HbA1c had higher IGF-I, both at entry and study endand were treated with higher Peg dose (mean 25 mg/day).

Conclusion: We suggest that glucose abnormalities in patients treated with Peg (either mono or combo with 1st generation SRLs) or Pasi are dependent on both pre-treatment BG and persistence of active acromegalyand require close monitoring.