Growth hormone releasing hormone plus arginine stimulation testing in young adults treated in childhood with cranio-spinal radiation therapy.
OBJECTIVE
Growth hormone deficiency (GHD) secondary to cranio-spinal radiation therapy (CSRT) is a complication seen in medulloblastoma survivors. The standard for diagnosis of adult GHD is a peak GH < 3 microg/l by the insulin tolerance test (ITT). However, insulin tolerance testing exposes patients to the risks of hypoglycaemia. Recent studies suggest that the GH releasing hormone + arginine (GHRH + ARG) test can identify GHD in cranially irradiated patients at longer time intervals after radiation. We evaluated the GHRH + ARG stimulation test compared to the ITT in young adults diagnosed with medulloblastoma during childhood.


METHODS
We evaluated 10 young adult patients (age range 17-26 years) who were treated with CSRT during childhood for medulloblastoma, and who had resultant childhood-onset GHD.


METHODS
Subjects underwent GH provocative testing with the ITT and the GHRH + ARG test. IGF-I and IGFBP3 levels were also measured at baseline.


RESULTS
Insulin tolerance testing and GHRH + arginine stimulation were performed at a mean +/- SD 14 +/- 4.4 years after cranial radiation. All patients failed the ITT with median peak GH 0.40 microg/l (range < 0.05-2.2). GHRH + arginine gave higher peak GH levels with a mean of 7.9 +/- 5.7 microg/l (P = 0.003). Four patients had peak GH > 9 microg/l and were between 7.8 and 19.6 years from cranial radiation. There was no correlation of peak GH levels with time interval since CSRT. Thirty-three per cent of subjects had normal IGF-I; neither IGF-I nor IGFBP3 standard deviation scores (SDS) correlated with ITT results.


CONCLUSIONS
Using a GHRH + arginine cut-off for GHD of 9 microg/l, four patients would have been misclassified as GH sufficient, despite being > 7 years (with two patients being nearly 20 years) out from CSRT. These findings suggest that the pituitary GH-producing cells of young adults continue to maintain responsiveness to GHRH + arginine more than 5-10 years after cranial irradiation.
Ham
J Nina
JN
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Ginsberg
Jill P
JP
Hendell
Christine D
CD
Moshang
Thomas
T
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001120:Arginine; D002528:Cerebellar Neoplasms / Q000532:radiotherapy; D016371:Cranial Irradiation / Q000009:adverse effects; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D007004:Hypoglycemic Agents; D007018:Hypopituitarism / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008527:Medulloblastoma / Q000532:radiotherapy; D013131:Spine / Q000528:radiation effects; D013268:Stimulation, Chemical
D007004:Hypoglycemic Agents; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine