Endocrine sequelae of irradiation in childhood
Endocrine sequelae of irradiation in childhood
Growth hormone (GH) deficiency is a common sequel to irradiation to the hypothalmic-pituitary (h-p) axis. GH secretion is regulated by GH-releasing hormone (GHRH) and somatostatin (SRIH) which are in turn regulated by neurotransmitters. The effect of cranial irradiation (CI) on neuroregulatory control of GH secretion is unknown. This was examined by manipulating cholinergic tone in 8 male adults with radiation (DXT)-induced GH deficiency, after childhood cranial irradiation + 10 male volunteers. Each individual underwent 3 separate studies: the GH response to 100μg GHRH-(1-29)-NH_2 (GHRHa) was assessed alone + after pretreatment with pyridostigmine (Py) or pirenzepine (Pz). Py significantly enhanced + Pz significantly attenuated the GH response to GHRHa cf GHRHa alone within groups (p< 0.0005). Between groups there was no significant difference in GH area under the curve after GHRHa alone, but a significantly greater increment (p = 0.0014), of GH secretion after Py + GHRHa compared with GHRHa alone. These data suggest that CI reduces but does not abolish SRIH tone + reduces endogenous GHRH secretion. Although SRIH tone is reduced, it can be increased by cholinergic manipulation + is thus not irreversibly fixed. This has implications if GHRH analogues were to be used to treat DXT-induced GH deficiency.
Low doses of CI (18-24 Gy) used in the management of acute lymphoblastic leukaemia (ALL) may cause early puberty in girls. To determine if this sexual dichotomy exists at higher DXT doses (25-47 Gy) the onset of puberty was identified in 46 GH deficient children (30 male), irradiated for a brain tumour not involving the h-p axis + compared with normal standards. There was a significant linear association between age at DXT + age at onset of puberty which occurred at an early age in both sexes. At high doses of DXT, early puberty is not restricted to girls. The clinical consequence of early puberty in the management of poor growth associated with DXT-induced GH deficiency is to foreshorten the time available for treatment with GH.
University of Southampton
Ogilvy-Stuart, Amanda Lesley
1993
Ogilvy-Stuart, Amanda Lesley
Ogilvy-Stuart, Amanda Lesley
(1993)
Endocrine sequelae of irradiation in childhood.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Growth hormone (GH) deficiency is a common sequel to irradiation to the hypothalmic-pituitary (h-p) axis. GH secretion is regulated by GH-releasing hormone (GHRH) and somatostatin (SRIH) which are in turn regulated by neurotransmitters. The effect of cranial irradiation (CI) on neuroregulatory control of GH secretion is unknown. This was examined by manipulating cholinergic tone in 8 male adults with radiation (DXT)-induced GH deficiency, after childhood cranial irradiation + 10 male volunteers. Each individual underwent 3 separate studies: the GH response to 100μg GHRH-(1-29)-NH_2 (GHRHa) was assessed alone + after pretreatment with pyridostigmine (Py) or pirenzepine (Pz). Py significantly enhanced + Pz significantly attenuated the GH response to GHRHa cf GHRHa alone within groups (p< 0.0005). Between groups there was no significant difference in GH area under the curve after GHRHa alone, but a significantly greater increment (p = 0.0014), of GH secretion after Py + GHRHa compared with GHRHa alone. These data suggest that CI reduces but does not abolish SRIH tone + reduces endogenous GHRH secretion. Although SRIH tone is reduced, it can be increased by cholinergic manipulation + is thus not irreversibly fixed. This has implications if GHRH analogues were to be used to treat DXT-induced GH deficiency.
Low doses of CI (18-24 Gy) used in the management of acute lymphoblastic leukaemia (ALL) may cause early puberty in girls. To determine if this sexual dichotomy exists at higher DXT doses (25-47 Gy) the onset of puberty was identified in 46 GH deficient children (30 male), irradiated for a brain tumour not involving the h-p axis + compared with normal standards. There was a significant linear association between age at DXT + age at onset of puberty which occurred at an early age in both sexes. At high doses of DXT, early puberty is not restricted to girls. The clinical consequence of early puberty in the management of poor growth associated with DXT-induced GH deficiency is to foreshorten the time available for treatment with GH.
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Published date: 1993
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Local EPrints ID: 462771
URI: http://eprints.soton.ac.uk/id/eprint/462771
PURE UUID: f8ab5afb-d31d-4ab5-9911-d8fd43d69957
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Date deposited: 04 Jul 2022 19:58
Last modified: 04 Jul 2022 19:58
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Author:
Amanda Lesley Ogilvy-Stuart
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