Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy.
We studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36 months in six patients with medulloblastoma who underwent surgical removal of the tumor followed by craniospinal irradiation therapy for 6 weeks and then chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation there was a decline in the peak GH secretory response to acute stimulation with arginine/insulin hypoglycemia. Six months after irradiation and during chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP-3), and GH-BP values (respective mean values of 56.1 +/- 9.0 ng/mL, 1.1 +/- 0.2 microgram/mL, and 7.6 +/- 3.3% of radioactivity as compared to time 0 values: 13%%o/- 15 ng/mL, 2.2 +/- 0.2 micrograms/mL, and 20.0 +/- 4.0%, P < 0.001), although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and GH-BP returned to pretreatment ranges by 12-36 months after initiation of the study. There was also a decline in body mass index and serum protein values at 6 months, suggesting suboptimal nutrition during this period. Six months after irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36 months. In one patient we observed a high level of IGFBP-3 proteolysis at this time. This study demonstrates that before the decrease of GH secretion in patients receiving cranial irradiation there is a transient phase of GH insensitivity that may be characteristic of the acute therapeutic phase including the chemotherapy. This partial insensitivity may explain the early growth retardation observed in these patients.
Nivot
S
S
Pediatric Endocrinology Unit, Hôpital des Enfants-Malades, Paris, France.
Benelli
C
C
Clot
J P
JP
Saucet
C
C
Adan
L
L
Souberbielle
J C
JC
Zucker
J M
JM
Rappaport
R
R
Brauner
R
R
D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D015992:Body Mass Index; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D002352:Carrier Proteins / Q000097:blood; D002648:Child; D016371:Cranial Irradiation / Q000009:adverse effects; D005260:Female; D006130:Growth Disorders / Q000209:etiology; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000532:radiotherapy; D011863:Radioimmunoassay; D013002:Somatomedins / Q000032:analysis*; D013116:Spinal Cord / Q000528:radiation effects*
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein