RADIATION AND NEUROREGULATORY CONTROL OF GROWTH-HORMONE SECRETION

OBJECTIVE Cranial irradiation frequently results in growth hormone (GH ) deficiency. Patients with radiation-induced GH deficiency usually re main responsive to exogenous growth hormone releasing hormone, implyin g radiation damages the hypothalamus rather than the pituitary. Little is known about the effect of cranial irradiation on the neuroendocrin e control of GH secretion. This study was to determine the effect of c ranial irradiation on somatostatin tone. DESIGN Somatostatin tone was examined by manipulating cholinergic tone in young adults with radiati on-induced GH deficiency and a control population. Each individual und erwent three separate studies: the GH response to 100 mu g GHRH-(1-29) -NH2 was assessed alone, and 60 minutes after pyridostigmine or pirenz epine. PATIENTS Eight young male adults with radiation induced GH defi ciency following treatment in childhood for a brain tumour or acute ly mphoblastic leukaemia, and ten healthy adult men were studied. MEASURE MENTS Serum growth hormone was measured at 15-minute intervals through out each of the three study periods. RESULTS One of 10 controls and fo ur of eight irradiated subjects had a peak GH level to GHRH analogue o f less than 20 mU/l. After pretreatment with pyridostigmine, all subje cts except one irradiated subject had a peak GH level of greater than 20 mU/l. Pretreatment with pyridostigmine and pirenzepine significantl y modified the GH response to GHRH analogue within both groups (P<0.00 05). Pretreatment with pyridostigmine significantly enhanced the GH re sponse to GHRH analogue (median (range) area under the curve, 9029 (19 56-20940) mU/l/min in controls vs 1970 (628-3608) mU/l/min in the irra diated group) compared with GHRH analogue alone (1953 (512-16140) mU/l /min in control group vs 997 (266-3488) mU/l/min in the irradiated gro up). Pretreatment with pirenzepine significantly attenuated tile GH re sponse to GHRH analogue (552 (64-1274) mU/l/min in controls vs 305 (13 4-2726) mU/l/min in irradiated group). Between the groups there was no significant difference in GH area under the curve (AUC) after GHRH an alogue alone. There was a significantly (P=0.0014) greater increment o f GH secretion after pyridostigmine and GHRH analogue compared with GH RH analogue alone (difference in AUC of pyridostigmine + GHRH analogue and GHRH analogue alone 6348 (696-12856) mU/l controls vs 542 (120-13 40) mU/l in the irradiated group) and significantly (P=0.033) greater suppression of GH secretion after pirenzepine and GHRH analogue compar ed with GHRH analogue alone (difference in AUC of GHRH analogue alone and pirenzepine + GHRH analogue 1644 (222-15205) mU/l in controls vs 4 79 (469-1623) mU/l in the irradiated group) in the control population compared with those who had received cranial irradiation in childhood. CONCLUSIONS These data suggest that cranial irradiation reduces but d oes not abolish somatostatin (SRIH) tone and also reduces endogenous G HRH secretion. Although SRIH tone is reduced, it can be increased by c holinergic manipulation and is therefore not irreversibly fixed. This has possible implications if GHRH analogues were used to treat childre n with radiation induced GH deficiency.