Serum insulin-like growth factor-I, IGF binding protein-3 and IGFBP-3 protease activity after cranial irradiation.
The relationship between peak growth hormone (GH), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3) and IGFBP-3 protease activity was studied in 28 children and adolescents undergoing investigation of pituitary function 0.4-14.2 years after cranial or craniospinal irradiation for the treatment of CNS tumours distant from the hypothalamic-pituitary axis (n = 16) or prophylaxis against CNS leukaemia (n = 12). Seven out of 15 patients with GH deficiency (GHD) (defined as a peak GH concentration <7.5 ng/ml in a stimulation test) had IGF-I <-2 standard deviation score (SDS). None of the 28 patients had serum IGFBP-3 concentrations measured by radioimmunoassay (RIA) <-1.5 SDS with no difference between those with and without GHD. IGFBP-3 concentrations measured by RIA were strongly correlated to IGFBP-3 band density on Western ligand blot (WLB) (r = 0.71; p < 0.0001). IGFBP-3 protease activity was negatively correlated to IGFBP-3 by RIA (r = -0.55; p < 0.01) and to IGFBP-3 by WLB (r = -0.51; p < 0.01). Twenty-two patients had normal IGFBP-3 protease activity (<30% of the activity in pregnancy serum) indicating that serum IGFBP-3 protease activity does not account for the normal levels of IGFBP-3 in RIA. Low serum IGF-I but normal IGFBP-3 concentrations and in the majority normal IGFBP-3 protease activity was found in patients in the years after CNS irradiation. Neither serum IGF-I nor IGFBP-3 can be used as a reliable index of the development of radiation-induced GHD.
Tillmann
V
V
Royal Manchester Children's Hospital, Manchester, UK.
Shalet
S M
SM
Price
D A
DA
Wales
J K
JK
Pennells
L
L
Soden
J
J
Gill
M S
MS
Whatmore
A J
AJ
Clayton
P E
PE
D000293:Adolescent; D000328:Adult; D001827:Body Height; D016543:Central Nervous System Neoplasms / Q000532:radiotherapy; D002648:Child; D010450:Endopeptidases / Q000097:blood*; D005260:Female; D006130:Growth Disorders / Q000209:etiology; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007938:Leukemia / Q000532:radiotherapy; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects*
D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D010450:Endopeptidases; C080473:insulin-like growth factor binding protein-3 protease