EVOLUTION OF GROWTH-HORMONE NEUROSECRETORY DISTURBANCE AFTER CRANIAL IRRADIATION FOR CHILDHOOD BRAIN-TUMORS - A PROSPECTIVE-STUDY

To determine the aetiopathology of post-irradiation growth hormone (GH ) deficiency, we performed a mixed longitudinal analysis of 56 24 h se rum GH concentration profiles and 45 paired insulin-induced hypoglycae mia 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 leas t 30 Gy. Fourier transforms, occupancy percentage, first-order derivat ives (FOD) and mean concentrations were determined from the GH profile s taken after neurosurgery but before radiotherapy (n = 16) and in thr ee treatment groups: Group 1: neurosurgery only without DXR (n = 9); G roup 2: greater than or equal to 30 Gy DXR only (n = 22); Group 3: gre ater than or equal to 30 Gy DXR with additional chemotherapy (n = 9). Results were compared with those from 26 short normally growing (SN) c hildren. Compared with SN children, children with brain tumours had fa ster GH pulse periodicities (200 min vs 140 min) and attenuated peak G H responses to ITT (24.55 (19.50-30.20) vs 832 (4.57-15.14) mU/l) afte r neurosurgery, before radiotherapy. However, spontaneous GH peaks (19 .05 (15.49-23.44) vs 14.13 (9.12-21.38) mU/1), 24 h mean GH (5.01 (4.3 7-5.62) 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 befor e 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) we re 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 greate r than or equal to 2 years; Group 3: 140 min at 1 year, 280 min at gre ater than or equal to 2 years) and a decrease in 24 h mean GH (Group 2 vs Group 3 at greater than or equal to 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 greater than or equal to 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 (4.27-8.3 2) vs 380 (0.31-46.77) mU/l). After cranial irradiation, a number of c hanges evolved within the GH axis: faster GH pulse periodicities and d iscordance between physiological and pharmacological tests of GH secre tion before irradiation gave way to a slow GH pulse periodicity, decre ased GH pulse amplitude and rate of GH change (FOD) and, with time, ev entual concordance between physiological and pharmacological measures. The evolution of these disturbances may well reflect differential pat hology affecting hypothalamic GH-releasing hormone and somatostatin.