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Submitted on October 12, 2004
Accepted on February 10, 2005
Department of Endocrinology, Christie hospital (K.H.D. and S.M.S.), Manchester, United Kingdom, M20 4BX; and the Department of Medicine, University of Virginia Health Science Center (S.S.P and M.O.T.), Charlottesville, Virginia 22908, USA
* To whom correspondence should be addressed. E-mail: stephen.m.shalet{at}man.ac.uk.
Dynamics of GH secretion in patients with GH deficiency due to radiation damage of the hypothalamic-pituitary (h-p) axis acquired in childhood has rarely been studied. Thus, we have used a sensitive chemiluminescence GH assay to analyze 24-hour GH profiles (20 min sampling) from 10 adult cancer survivors with severe GH deficiency acquired following brain irradiation in childhood for non-pituitary brain tumors. An age and sex-matched control group of 30 normal healthy volunteers, 8 of whom were BMI matched with the patients, were also studied. Cluster analysis with gender-specific comparisons revealed a significant reduction (P < 0.05) in all amplitude-related measurements (profile mean GH levels or area under curve for GH (AUCGH), absolute (maximum) GH peak height, mean peak height and mean pulse area) in patients. No differences were observed in frequency-related measurements (pulse frequency, pulse duration and interpulse interval). Pulsatile secretion was relatively more attenuated than basal secretion in patients and approximate entropy (ApEn) scores were significantly (P < 0.05) raised suggesting more disordered GH secretion.
Radiation inflicts quantitative damage to the h-p axis leading to amplitude-dependent dampening of GH secretion with relative preservation of non-pulsatile secretion. Qualitative perturbation in hypothalamic control of GH release is evident by the increase in ApEn values reflecting more disordered GH secretion. Integrity of the h-p axis and GH neuroregulation is fundamentally preserved in 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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