title: Changes in circulating IGF1 receptor stimulating activity do not parallel changes in total IGF1 during GH treatment of GH-deficient adults.
abstract: BACKGROUND
  Previously we demonstrated that IGF1 receptor stimulating activity (IGF1RSA) offers advantages in diagnostic evaluation of adult GH deficiency (GHD). It is unknown whether IGF1RSA can be used to monitor GH therapy.
  
  
  OBJECTIVE
  To investigate the value of circulating IGF1RSA for monitoring GH therapy.
  
  
  METHODS
  106 patients (54 m; 52 f) diagnosed with GHD were included; 22 were GH-naïve, 84 were already on GH treatment and discontinued therapy 4 weeks before baseline values were established. IGF1RSA was determined by the IGF1R kinase receptor activating assay, total IGF1 by immunoassay (Immulite). GH doses were titrated to achieve total IGF1 levels within the normal range.
  
  
  RESULTS
  After 12 months, total IGF1 and IGF1RSA increased significantly (total IGF1 from 8.1 (95% CI 7.3-8.9) to 14.9 (95% CI 13.5-16.4) nmol/l and IGF1RSA from 115 (95% CI 104-127) to 181 (95% CI 162-202) pmol/l). After 12 months, total IGF1 normalized in 81% of patients, IGF1RSA in 51% and remained below normal in more than 40% of patients in whom total IGF1 had normalized.
  
  
  CONCLUSIONS
  During 12 months of GH treatment, changes in IGF1RSA did not parallel changes in total IGF1. Despite normalization of total IGF1, IGF1RSA remained subnormal in a considerable proportion of patients. At present our results have no short-term consequences for GH therapy of GHD patients. However, based on our findings we propose future studies to examine whether titrating GH dose against IGF1RSA results in a better clinical outcome than titrating against total IGF1.
authors.affiliation: Division of EndocrinologyDepartment of Internal Medicine, Room D-443, Erasmus MC, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Aimee J
authors.initials: AJ
authors.lastname: Varewijck
authors.affiliation: Division of EndocrinologyDepartment of Internal Medicine, Room D-443, Erasmus MC, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
authors.affiliation: Division of EndocrinologyDepartment of Internal Medicine, Room D-443, Erasmus MC, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.affiliation: Division of EndocrinologyDepartment of Internal Medicine, Room D-443, Erasmus MC, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Sebastian J C M M
authors.initials: SJ
authors.lastname: Neggers
authors.affiliation: Division of EndocrinologyDepartment of Internal Medicine, Room D-443, Erasmus MC, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.affiliation: Division of EndocrinologyDepartment of Internal Medicine, Room D-443, Erasmus MC, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands j.a.m.j.l.janssen@erasmusmc.nl.
authors.forename: Joseph A M J L
authors.initials: JA
authors.lastname: Janssen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004393:Dwarfism, Pituitary / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D017526:Receptor, IGF Type 1