OGTT GH profile is predictive of a higher risk of glucose metabolism alterations in acromegaly treated with pasireotide

Context: A paradoxical GH increase after oral glucose load (GH-Par) characterizes about one-third of acromegaly patients and is associated with a better response to first-generation somatostatin receptor ligands (fg-SRLs). Pasireotide (PAS) is usually considered as a second-/third-line treatment.
Objective and outcome: To test the predictive role of GH-Par (GH increase ≥120% over basal levels) in PAS response and in the development of adverse events.
Design, setting and patients: Multi-center Italian retrospective cohort of 78 patients treated for at least 3 months with PAS.
Results: IGF-1 levels were 1.64 times the upper limit of normality (ULN) in patients with large (mean 21mm) and invasive (77%) adenomas after fg-SRL treatment failure. PAS was effective in 66 patients after mean 37 months: ≥20% or ≥50% IGF-1 ULN reduction was observed in 86% and 59% of cases, respectively. Of 59 patients with available OGTTs, 13 exhibited GH-Par (22%): IGF-1 levels before PAS were lower (326 vs 440 µg/L, p=0.008) and ULN reduction before PAS was higher (-54% vs -37%, p=0.036) in GH-Par than those without. PAS duration (27.6 vs 39.3 months), dose (48 vs 49 mg/monthly), and efficacy in reducing IGF-1 (-32% vs -42% IGF-1 ULN) were similar in both GH-Par and GH-NPar groups (P= NS). PAS was discontinued in 11 patients due to new-onset or worsening of glucose metabolism alterations, whose incidence was higher in GH-Par vs GH-NPar groups (77% vs 37%, p=0.011).
Conclusions: The GH-Par does not predict the response to PAS in acromegaly but can predict new-onset PAS-induced glucose metabolism alterations.