Cranial irradiation and growth hormone neurosecretory dysfunction: a critical appraisal.

2.50
Hdl Handle:
http://hdl.handle.net/10541/70040
Title:
Cranial irradiation and growth hormone neurosecretory dysfunction: a critical appraisal.
Authors:
Darzy, Ken H; Pezzoli, Suzan S; Thorner, Michael O; Shalet, Stephen M
Abstract:
CONTEXT: It has been suggested that radiation-induced GH neurosecretory dysfunction exists in children; however, the pathophysiology is poorly understood, and it is unknown if such a phenomenon exists in adult life. STUDY SUBJECTS: Twenty-four-hour spontaneous GH secretion was studied by 20-min sampling both in the fed state (n = 16; six women) and the last 24 h of 33-h fast (n = 10; three women) in adult cancer survivors of normal GH status defined by two GH provocative tests, 13.1 +/- 1.6 (range, 3-28) yr after cranial irradiation (18-40 Gy) for nonpituitary brain tumors (n = 12) or leukemia (n = 4) in comparison with 30 (nine women) age- and body mass index-matched normal controls (fasting, 11 men and three women). RESULTS: Using previously published diagnostic thresholds, all patients had stimulated peak GH responses in the normal range to both the insulin tolerance test and the combined GHRH plus arginine stimulation test, as well as normal individual mean profile GH levels during the fed and fasting states. However, gender-specific comparisons revealed marked reduction (by 40%) in the overall peak GH responses to both provocative tests but similar GH secretory profiles; no differences were seen in the pulsatile attributes of GH secretion (cluster analysis) or the profile absolute and mean GH levels in the fed state or when the hypothalamic-pituitary axis was stimulated by fasting. CONCLUSIONS: Radiation-induced GH neurosecretory dysfunction either does not exist or is a very rare phenomenon in irradiated adult cancer survivors. The normality of physiological GH secretion in the context of reduced maximum somatotroph reserve suggests compensatory overdrive of the partially damaged somatotroph axis and constitutes a relative argument against somatotroph dysfunction being explained purely by hypothalamic damage with secondary atrophy due to GHRH deficiency. It is therefore possible that radiation in doses less than 40 Gy causes dual damage to both the pituitary and the hypothalamus.
Affiliation:
Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, United Kingdom. stephen.m.shalet@man.ac.uk.
Citation:
Cranial irradiation and growth hormone neurosecretory dysfunction: a critical appraisal. 2007, 92 (5):1666-72 J. Clin. Endocrinol. Metab.
Journal:
The Journal of Clinical Endocrinology and Metabolism
Issue Date:
May-2007
URI:
http://hdl.handle.net/10541/70040
DOI:
10.1210/jc.2006-2599
PubMed ID:
17284618
Type:
Article
Language:
en
ISSN:
0021-972X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorDarzy, Ken H-
dc.contributor.authorPezzoli, Suzan S-
dc.contributor.authorThorner, Michael O-
dc.contributor.authorShalet, Stephen M-
dc.date.accessioned2009-06-09T16:42:57Z-
dc.date.available2009-06-09T16:42:57Z-
dc.date.issued2007-05-
dc.identifier.citationCranial irradiation and growth hormone neurosecretory dysfunction: a critical appraisal. 2007, 92 (5):1666-72 J. Clin. Endocrinol. Metab.en
dc.identifier.issn0021-972X-
dc.identifier.pmid17284618-
dc.identifier.doi10.1210/jc.2006-2599-
dc.identifier.urihttp://hdl.handle.net/10541/70040-
dc.description.abstractCONTEXT: It has been suggested that radiation-induced GH neurosecretory dysfunction exists in children; however, the pathophysiology is poorly understood, and it is unknown if such a phenomenon exists in adult life. STUDY SUBJECTS: Twenty-four-hour spontaneous GH secretion was studied by 20-min sampling both in the fed state (n = 16; six women) and the last 24 h of 33-h fast (n = 10; three women) in adult cancer survivors of normal GH status defined by two GH provocative tests, 13.1 +/- 1.6 (range, 3-28) yr after cranial irradiation (18-40 Gy) for nonpituitary brain tumors (n = 12) or leukemia (n = 4) in comparison with 30 (nine women) age- and body mass index-matched normal controls (fasting, 11 men and three women). RESULTS: Using previously published diagnostic thresholds, all patients had stimulated peak GH responses in the normal range to both the insulin tolerance test and the combined GHRH plus arginine stimulation test, as well as normal individual mean profile GH levels during the fed and fasting states. However, gender-specific comparisons revealed marked reduction (by 40%) in the overall peak GH responses to both provocative tests but similar GH secretory profiles; no differences were seen in the pulsatile attributes of GH secretion (cluster analysis) or the profile absolute and mean GH levels in the fed state or when the hypothalamic-pituitary axis was stimulated by fasting. CONCLUSIONS: Radiation-induced GH neurosecretory dysfunction either does not exist or is a very rare phenomenon in irradiated adult cancer survivors. The normality of physiological GH secretion in the context of reduced maximum somatotroph reserve suggests compensatory overdrive of the partially damaged somatotroph axis and constitutes a relative argument against somatotroph dysfunction being explained purely by hypothalamic damage with secondary atrophy due to GHRH deficiency. It is therefore possible that radiation in doses less than 40 Gy causes dual damage to both the pituitary and the hypothalamus.en
dc.language.isoenen
dc.subjectBrain Canceren
dc.subjectLeukaemiaen
dc.subject.meshAdolescent-
dc.subject.meshAdrenal Cortex Function Tests-
dc.subject.meshAdrenocorticotropic Hormone-
dc.subject.meshAdult-
dc.subject.meshArginine-
dc.subject.meshBrain Neoplasms-
dc.subject.meshCluster Analysis-
dc.subject.meshFasting-
dc.subject.meshFemale-
dc.subject.meshGlucose Tolerance Test-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshHypothalamo-Hypophyseal System-
dc.subject.meshLeukemia-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPituitary Diseases-
dc.subject.meshRadiotherapy-
dc.subject.meshSex Characteristics-
dc.subject.meshSurvivors-
dc.titleCranial irradiation and growth hormone neurosecretory dysfunction: a critical appraisal.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, United Kingdom. stephen.m.shalet@man.ac.uk.en
dc.identifier.journalThe Journal of Clinical Endocrinology and Metabolismen
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.