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

Abstract

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 (nZ36) or SA (nZ27) 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 (mg/l) levels were similar (total: 185G10 (SA) versus 171G8 (surgery) (PZ0.28); bioactive: 1.9G0.2 vs 1.9G0.1 (PZ0.70)). Suppression of total and free GH (mg/l) during OGTT was blunted in the SA group (total GH nadir : 0.59G0.08 (SA) versus 0.34G0.06 (surgery) (PZ0.01); free GH nadir : 0.43G0.06 vs 0.19G0.04 (P!0.01)). The insulin response to OGTT was delayed, and the 2-h glucose level was elevated during SA treatment (PZ0.02). Disease-specific health status was better in patients after surgery (PZ0.02). 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.

Hypothesis: Extra-hepatic acromegaly: a new paradigm?

“…1a). This is further supported by a recent report by Rubeck et al (43). They compared traditional and novel biomarkers and health status in patients with acromegaly treated with either surgery alone or SMSA.…”

“…They reported that despite similar and normalized IGF1 levels, SMSA treatment compared with surgery alone was associated with less suppressed GH levels and less symptom relief. They concluded that this discordance may be due to specific suppression of hepatic IGF1 production by SMSA (43).…”

Quality of life is impaired in association with the need for prolonged postoperative therapy by somatostatin analogs in patients with acromegaly

“…It is postulated by Neggers et al (37) that long-acting SSTA normalize serum IGF1 levels in certain patients in the presence of elevated GH actions in extrahepatic tissues. Also, Rubeck et al (38) compared traditional and novel biomarkers and health status in patients with acromegaly treated with either surgery alone or SSTA. These authors concluded that despite similar and normalized IGF1 levels, SSTA treatment compared with surgery alone was associated with less suppressed GH levels and less symptom relief.…”

Acromegalia: una nuova prospettiva fisiopatologica dai tessuti periferici?

“…Rubeck et al hanno valutato, in acromegalici trattati soltanto chirurgicamente o con LA-SMSA, differenti biomarcatori e lo stato di salute globale [11]. Le IGF-I totali e biologicamente attive erano simili; nel gruppo trattato con LA-SMSA i livelli di GH in risposta al carico di glucosio risultavano più elevati rispetto ai pazienti sottoposti a chirurgia mentre lo stato di salute specifico della malattia risultava migliore nei pazienti operati [11].…”