title: Conventional and novel biomarkers of treatment outcome in patients with acromegaly: discordant results after somatostatin analog treatment compared with surgery.
abstract: BACKGROUND
  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).
  
  
  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 (μg/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 (μg/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.
authors.affiliation: The Medical Research Laboratories, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. kristinerubeck@dadlnet.dk
authors.forename: Kristine Z
authors.initials: KZ
authors.lastname: Rubeck
authors.forename: Michael
authors.initials: M
authors.lastname: Madsen
authors.forename: Caroline Marie
authors.initials: CM
authors.lastname: Andreasen
authors.forename: Sanne
authors.initials: S
authors.lastname: Fisker
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Jens Otto L
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D019382:Human Growth Hormone / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I