title: Clinical indicators of biochemical remission in acromegaly: does incomplete disease control always mean therapeutic failure?
abstract: OBJECTIVE
  Correction of GH and IGF-I levels are associated with improvements in insulin secretion, cardiac performance and body composition in patients with acromegaly, but whether these parallel post-treatment levels of GH-IGF-I axis activity is undefined. We investigate whether various biochemical outcomes after transsphenoidal pituitary surgery (TSS) in these patients are associated with clinically relevant differences in cardiac performance, insulin resistance and body composition.
  
  
  METHODS
  Cross-sectional study of consecutive patients with acromegaly admitted to the hospital between 2001 and 2002.
  
  
  METHODS
  Forty-one patients after TSS for somatotroph pituitary adenoma and 23 patients with naive acromegaly serving as positive controls were enrolled in the study. Mean daily GH levels (mGH), IGF-I, leptin and lipid levels, glucose, insulin and GH concentrations during oral glucose tolerance test (oGTT) were measured in all study participants. Insulin resistance was measured by homeostatic model index (R(HOMA)). Body composition was assessed by dual-energy X-ray absorptiometry. Left ventricular mass index (LVM(i)) and cardiac index (C(i)) were determined by echocardiography.
  
  
  RESULTS
  We found no difference in cardiac indices, insulin resistance, body composition and leptin levels between patients with complete biochemical remission and those with inadequately controlled disease (P > 0.05 for all) after TSS. Cured patients had lower values (mean +/- SD) of cardiac index (2.2 +/- 0.7 vs. 3.0 +/- 1.0 l/min/m(2); P = 0.04) compared with naive patients. A similar decrease in LVM(i) was observed in controlled (108.4 +/- 30.0 g/m(2); P = 0.015) and inadequately controlled disease (108.8 +/- 30.7 g/m(2); P = 0.03) in comparison with naive disease (160.3 +/- 80.6 g/m(2)). Insulin resistance and leptin changed in opposite ways. In controlled and inadequately controlled disease, R(HOMA) index was lower (2.2 +/- 1.4; P = 0.001 and 3.1 +/- 2.0; P = 0.05 vs. 5.1 +/- 3.1) while leptin concentration was higher (14.9 +/- 8.7 microg/l, P = 0.004 and 12.8 +/- 7.8 microg/l, P = 0.05 vs. 7.4 +/- 3.8 microg/l) than in naive disease. In all patients, leptin correlated negatively with cardiac index (r = -0.46; P = 0.001) and IGF-I levels (r = -0.45; P < 0.001). Independent predictors of biochemical remission, based on normal IGF-I levels only, were cardiac [P = 0.04, odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2-0.9] and R(HOMA) index (P = 0.009, OR 0.6; 95% CI 0.4-0.8). Similar results were obtained if the definition of cure included both normal IGF-I levels and the ability to achieve GH nadir < 1 microg/l during oGTT. Insulin resistance (P = 0.02, OR 0.6; 95% CI 0.4-0.9) and leptin level (P = 0.002, OR 1.3; 95% CI 1.1-1.6) were independent predictors of normalized mGH values.
  
  
  CONCLUSIONS
  This study shows that cardiac indices, insulin resistance and body composition were not different between patients with complete biochemical remission and those with discordant GH and IGF-I levels. It appears that even incomplete disease control after TSS can result in improvement of these clinical markers.
authors.affiliation: Institute of Endocrinology, Diabetes and Diseases of Metabolism, Dr Subotica 13, 11000 Belgrade, Serbia. sova@net.yu
authors.forename: Svetozar S
authors.initials: SS
authors.lastname: Damjanovic
authors.forename: Aleksandar N
authors.initials: AN
authors.lastname: Neskovic
authors.forename: Milan S
authors.initials: MS
authors.lastname: Petakov
authors.forename: Vera
authors.initials: V
authors.lastname: Popovic
authors.forename: Djuro
authors.initials: D
authors.lastname: Macut
authors.forename: Pavle
authors.initials: P
authors.lastname: Vukojevic
authors.forename: Miloje M
authors.initials: MM
authors.lastname: Joksimovic
mesh_terms: D015502:Absorptiometry, Photon; D000172:Acromegaly / Q000097:blood / Q000209:etiology / Q000601:surgery*; D000236:Adenoma / Q000097:blood / Q000150:complications / Q000601:surgery; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D004452:Echocardiography; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000097:blood / Q000150:complications / Q000601:surgery; D012074:Remission Induction; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone