Insulin-like growth factor-I raises serum procollagen levels in children and adults with Laron syndrome.
OBJECTIVE
Recombinant IGF-I is now available for the treatment of GH insensitivity (Laron syndrome). We have determined the effects of IGF-I on soft connective tissue and bone metabolism in a group of patients with this disorder.


METHODS
Thirteen patients with Laron syndrome (LS) (8 children and 5 adults) were included in the study. The children with LS were treated with IGF-I for 3 years with daily doses of 150-200 micrograms/kg. The adult LS patients were treated for 9 months with daily doses of 50-120 micrograms/kg. Blood samples for procollagens were collected before, during and at the end of IGF-I treatment.


METHODS
Serum levels of the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) and of the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were determined before and during IGF-I administration.


RESULTS
Untreated patients with LS had lower than normal serum levels of PICP and PIIINP for age. IGF-I treatment increased significantly the PIIINP levels in children from 7.2 +/- 2.8 (SD) to 12.5 +/- 2.2 micrograms/l (P < 0.001), and in adults from 2.7 +/- 1.0 to 8.4 +/- 3.6 micrograms/l (P < 0.001); serum PICP increased from 243 +/- 123 to 384 +/- 190 micrograms/l (P < 0.087) in children, and in adults from 43.4 +/- 8.1 to 135.8 +/- 41.9 micrograms/l (P < 0.001). ICTP levels in children increased from 9.7 +/- 3.7 to 14.3 +/- 5.9 micrograms/l (P < 0.001) and in adult patients levels increased from 3.6 +/- 0.9 to 5.5 +/- 2.2 micrograms/l (P < 0.001) during treatment and returned to basal values after stopping IGF-I administration.


CONCLUSIONS
Low procollagen levels in untreated Laron syndrome patients and their rise during replacement therapy with IGF-I provide evidence that IGF-I plays an important role in bone and soft connective tissue metabolism and that serum procollagen may serve as a marker to reflect some of the biochemical changes induced by IGF-I in connective tissue in the initial periods of treatment.
Klinger
B
B
Pediatric Endocrinology and Diabetes Research Unit, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Jensen
L T
LT
Silbergeld
A
A
Laron
Z
Z
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001823:Body Composition / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D003238:Connective Tissue / Q000378:metabolism; D004392:Dwarfism / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000627:therapeutic use; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013577:Syndrome
D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D011994:Recombinant Proteins; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003094:Collagen