Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

To determine the aetiopathology of post-irradiation growth hormone (GH) deficiency, we performed a mixed longitudinal analysis of 56 24 h serum GH concentration profiles and 45 paired insulin-induced hypoglycaemia tests (ITT) in 35 prepubertal children, aged 1.5-11.8 years, with brain tumours in the posterior fossa (n = 25) or cerebral hemispheres (n = 10). Assessments were made before (n = 16), 1 year (n = 25) and 2 to 5 years (n = 15) after a cranial irradiation (DXR) dose of at least 30 Gy. Fourier transforms, occupancy percentage, first-order derivatives (FOD) and mean concentrations were determined from the GH profiles taken after neurosurgery but before radiotherapy (n = 16) and in three treatment groups: Group 1: neurosurgery only without DXR (n = 9); Group 2: > or = 30 Gy DXR only (n = 22); Group 3: > or = 30 Gy DXR with additional chemotherapy (n = 9). Results were compared with those from 26 short normally growing (SN) children. Compared with SN children, children with brain tumours had faster GH pulse periodicities (200 min vs 140 min) and attenuated peak GH responses to ITT (24.55 (19.50-30.20) vs 8.32 (4.57-15.14) mU/l) after neurosurgery, before radiotherapy. However, spontaneous GH peaks (19.05 (15.49-23.44) vs 14.13 (9.12-21.38) mU/l), 24 h mean GH (5.01 (4.37-5.62) vs 3.98 (2.63-5.89) mU/l) and FODs (1.43 (1.17-1.69) vs 1.22 (0.88-1.56) mU/l per min) were similar. The abnormalities present before radiotherapy persisted in group 1 children at 1 year when 24 h mean GH (2.45 (1.17-5.01) mU/l) and FODs (0.73 (0.26-1.20) mU/l per min) were additionally suppressed, although partial recovery was evident by 2 years. With time from radiotherapy, there was a progressive increase in GH pulse periodicity (Group 2: 200 min at 1 year, 240 min at > or = 2 years; Group 3: 140 min at 1 year, 280 min at > or = 2 years) and a decrease in 24 h mean GH (Group 2 vs Group 3 at > or = 2 years: 2.45 (1.70-3.47) vs 1.86 (1.32-2.69) mU/l) and FODs (Group 2 vs Group 3 at > or = 2 years; 0.56 (0.44-0.69) vs 0.44 (0.27-0.61) mU/l per min). Initial discrepancies between measures of spontaneous and stimulated (ITT) GH peaks were lost by 2 or more years (spontaneous vs ITT; Group 2: 7.76 (5.89-9.77) vs 3.80 (0.91-15.84) mU/l; Group 3: 6.03 (4.27-8.32) vs 3.80 (0.31-46.77) mU/l). After cranial irradiation, a number of changes evolved within the GH axis: faster GH pulse periodicities and discordance between physiological and pharmacological tests of GH secretion before irradiation gave way to a slow GH pulse periodicity, decreased GH pulse amplitude and rate of GH change (FOD) and, with time, eventual concordance between physiological and pharmacological measures. The evolution of these disturbances may well reflect differential pathology affecting hypothalamic GH-releasing hormone and somatostatin.

Original publication




Journal article


J Endocrinol

Publication Date





329 - 342


Brain Neoplasms, Child, Child, Preschool, Combined Modality Therapy, Cranial Irradiation, Female, Follow-Up Studies, Fourier Analysis, Growth Hormone, Humans, Hydrocortisone, Infant, Insulin, Insulin-Like Growth Factor I, Male, Prospective Studies, Secretory Rate