Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 15 P244

SFEBES2008 Poster Presentations Pituitary (62 abstracts)

Discordant stimulated growth hormone (GH) responses in cranially irradiated adult cancer survivors may occur in the presence of normal GH status: compensated GH deficiency

Ken Darzy 1 , Michael Thorner 2 & Stephen Shalet 1


1Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK; 2Department of Medicine, University of Virginia Health Science Center, Charlottesville, Virginia, USA.


Context: We have previously demonstrated that, in cranially irradiated patients with normal peak GH responses to both the insulin tolerance test (ITT) and the growth hormone-releasing hormone plus arginine stimulation test (GHRH+AST), somatotroph reserve can be substantially reduced, while individual and overall spontaneous GH secretion remain entirely normal due presumably to a compensatory increase in hypothalamic stimulatory input within a partially damaged hypothalamic pituitary (h-p) axis. It is unknown however if such compensatory stimulation can also maintain normality of GH secretion in those who fail the ITT but pass or show only a moderately attenuated GH response to the GHRH+AST.

Study subjects and design: Twenty-four hour spontaneous GH secretion was studied by 20 min sampling both in the fed state (n=11) and the last 24 h of 33-h fast (n=9) in adult cancer survivors with subnormal peak GH responses to the ITT but either relatively less attenuated or normal peak GH responses to the GHRH+AST, 8.3±1.8 (range 2–23) year after cranial irradiation for non-pituitary brain tumours (n=9) or leukaemia/lymphoma (n=2) in comparison with 30 matched normal controls (fasting, 14).

Results: The discordancies in defining GH status using previously published diagnostic thresholds for the ITT, GHRH+AST and spontaneous GH secretion in 4 of the 11 patients with impaired stimulated responses to both tests were of a minor nature. In 5 out of the 7 patients with impaired GH responses to the ITT but normal individual responses to the GHRH+AST, the individual and average spontaneous GH secretion was entirely normal; the remaining 2 had subnormal spontaneous GH secretion.

Conclusions: In isolation severe impairment in the peak GH response to an ITT in cranially irradiated adults may not necessarily signify GH deficiency. It appears that near-maximal compensatory overdrive of the partially damaged somatotroph axis may result in quantitative restoration of spontaneous GH secretion but limit further stimulation with the ITT to the extent that impaired GH responses can be seen even before spontaneous GH secretion starts to decline. A failed GH response to GHRH+AST almost always reflects GHD while a normal response excludes GHD unless IGF-I levels are severely reduced. However, a failed GH response to the ITT may reflect reduced functional reserve rather than current GH status, and the likelihood that a hyperstimulated h-p axis may fail eventually during periods of increased demand such as growth and puberty; thus, making the ITT a more useful indicator of the need for GH replacement in children.

Article tools

My recent searches

No recent searches.