Conventional and novel biomarkers of treatment outcome in patients with acromegaly: discordant results after somatostatin analog treatment compared with surgery

Context: Control of disease activity in acromegaly is critical, but the biochemical definitions remain controversial. Objective: To compare traditional and novel biomarkers and health status in patients with acromegaly treated with either surgery alone or somatostatin analog (SA). Design and methods: Sixty-three patients in long-term remission based on normalized total IGF1 levels after surgery alone (n = 36) or SA (n = 27) were studied in a cross-sectional manner. The groups were comparable at diagnosis regarding demographic and biochemical variables. Each subject underwent 3 h of serum sampling including a 2-h oral glucose tolerance test (OGTT). Health status was measured by two questionnaires: EuroQoL and Acrostudy (Patient-assessed-Acromegaly symptom questionnaire (PASQ)). Results: Total and bioactive IGF1 (mu g/l) levels were similar (total: 185 +/- 10 (SA) versus 171 +/- 8 (surgery) (P=0.28); bioactive: 1.9 +/- 0.2 vs 1.9 +/- 0.1 (P=0.70)). Suppression of total and free GH (mu g/l) during OGTT was blunted in the SA group (total GH(nadir): 0.59 +/- 0.08 (SA) versus 0.34 +/- 0.06 (surgery) (P=0.01); free GH(nadir): 0.43 +/- 0.06 vs 0.19 +/- 0.04 (P<0.01)). The insulin response to OGTT was delayed, and the 2-h glucose level was elevated during SA treatment (P=0.02). Disease-specific health status was better in patients after surgery (P=0.02). Conclusions: i) Despite similar and normalized IGF1 levels, SA treatment compared with surgery alone was associated with less suppressed GH levels and less symptom relief; ii) this discordance may be due to specific suppression of hepatic IGF1 production by SA; iii) we suggest that biochemical assessment during SA treatment should include both GH and IGF1.