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The GH response to low-dose bolus growth hormone-releasing hormone ( GHRH ( 1-29 ) NH2 ) is attenuated in patients with longstanding post-irradiation GH insufficiency . OBJECTIVE Previous studies have suggested that post-irradiation GH insufficiency results from a loss of GHRH secretion , since many patients were able to release GH following exogenous GHRH stimulation . However , supramaximal doses of GHRH were used and the response may decline with time after radiotherapy . We re-evaluated the GHRH dose-response curve in patients post cranial irradiation and in controls . DESIGN Randomized controlled study . METHODS Five adult male long-term survivors of childhood brain tumours ( median age 21.8 years ( 18.4-26.7 ) ; 13.7 years ( 11.4-15.7 ) post-radiotherapy , > 30Gy ) and five matched controls were studied . An intravenous bolus of GHRH ( 1-29 ) NH ( 2 ) was administered in doses at the lower ( 0.05 microg/kg ) and upper ( 0.15 microg/kg ) range of the dose-response curves for young males , as well as the standard supramaximal dose ( 1 . 0 microg/kg ) . GH was measured before stimulation , every 2min for the first hour and every 5min for the second hour . All studies were conducted in a random fashion . RESULTS Significantly lower peak and area under the curve ( AUC ) GH concentrations occurred in the irradiated group using 0.15 microg/kg ( median peak Irradiated , 4 . 5mU/l vs median Controls , 37.4mU/l ; P < 0.01 ) and 1.0 microg/kg ( median peak Irradiated , 4.8mU/l vs median Controls , 15.2mU/l ; P < 0 . 05 ) GHRH ( 1-29 ) NH ( 2 ) . In irradiated subjects there was an incremental rise in GH output with increasing doses of GHRH ( 1-29 ) NH ( 2 ) ( median AUC : 122mU/l.min vs 179mU/l.min vs 268mU/l.min ; P=0.007 ) reflecting altered pituitary sensitivity and reduced responsiveness . CONCLUSION The GH response to bolus GHRH ( 1-29 ) NH ( 2 ) is attenuated in adult long-term survivors of childhood brain tumours . This may reflect direct pituitary damage and/or the loss of the tropic effects of chronic GHRH deficiency .
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Intervention_Pharmacological
low-dose bolus growth hormone-releasing hormone ( GHRH ( 1-29 ) NH2 )
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Intervention_Pharmacological
supramaximal doses of GHRH
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Intervention_Physical
radiotherapy
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Intervention_Pharmacological
GHRH
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Intervention_Pharmacological
GHRH ( 1-29 ) NH ( 2 )
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Intervention_Pharmacological
GHRH ( 1-29 ) NH ( 2 )
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Intervention_Pharmacological
GHRH ( 1-29 ) NH ( 2 )
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Outcome_Physical
GH
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Outcome_Other
Significantly lower peak and area under the curve ( AUC ) GH concentrations
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Outcome_Physical
rise in GH output
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Outcome_Physical
pituitary sensitivity and reduced responsiveness .
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Participant_Condition
patients with longstanding post-irradiation GH insufficiency
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Participant_Condition
patients post cranial irradiation
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Participant_Condition
controls
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Participant_Sample-size
Five
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Participant_Age
adult
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Participant_Sex
male
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Participant_Sample-size
childhood brain tumours
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Participant_Sample-size
five
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Participant_Age
young
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Participant_Age
adult
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Participant_Condition
childhood brain tumours