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

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    Authors
    Darzy, Ken H
    Pezzoli, Suzan S
    Thorner, Michael O
    Shalet, Stephen M
    Affiliation
    Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, United Kingdom. stephen.m.shalet@man.ac.uk.
    Issue Date
    2007-05
    
    Metadata
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    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.
    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
    URI
    http://hdl.handle.net/10541/70040
    DOI
    10.1210/jc.2006-2599
    PubMed ID
    17284618
    Type
    Article
    Language
    en
    ISSN
    0021-972X
    ae974a485f413a2113503eed53cd6c53
    10.1210/jc.2006-2599
    Scopus Count
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    All Christie Publications

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