Endocrine Abstracts (2005) 9 P116

The dynamics of GH secretion in adult cancer survivors with severe radiation-induced GH deficiency

KH Darzy1, SS Pezzoli2, MO Thorner2 & SM Shalet1

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

We have used a sensitive chemiluminescence GH assay to analyse 24-hour GH profiles (20 minute sampling) from 11 adult cancer survivors with severe GH deficiency acquired following brain irradiation in childhood for non-pituitary brain tumours and 30 matched healthy normal volunteers. Cluster analysis revealed that the area under the curve for GH (AUCGH), absolute (maximum) GH peak height, mean peak height, maximum pulse area, mean pulse area, absolute (minimum) nadir, and mean valley nadir levels were significantly reduced (P<0.05) in the patients. Complete separation between GH deficiency and normality was achieved by the absolute GH peak (less than 2 microgram per litre in the patients) and almost completely by the AUCGH. No difference was observed in the pulse duration, interpulse interval, or pulse frequency. Cosinor analysis showed no difference in the acrophase of the diurnal variation (mean ± SEM, 0224 h ± 26 min in the patients vs. 0216 h ± 33 min in normals) or the relative amplitude. Pulsatile secretion was relatively more attenuated than basal secretion in the patients who had significantly (P<0.0001) lower pulsatile AUCGH / total AUCGH ratio (45%) compared with that seen in normals (76%). Approximate entropy (ApEn) scores (mean ± SEM) were significantly (P<0.05) raised in the patients (0.705 ± 0.095) compared with all normals (0.458 ± 0.042).

Radiation inflicts quantitative damage to the h-p axis that leads to amplitude-dependent dampening of GH secretion with relative preservation of non-pulsatile (tonic) secretion. Qualitative perturbation in hypothalamic control of GH release, however, is evident by the increase in ApEn values reflecting more disordered GH secretion. The integrity of the h-p axis and, hence, GH neuroregulation is fundamentally preserved in the irradiated GH-deficient patients with a GH secretory pattern similar to that observed in normals and those with GH deficiency due to other etiologies.

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