The dynamics of growth hormone (GH) secretion in adult cancer survivors with severe GH deficiency acquired after brain irradiation in childhood for nonpituitary brain tumors: evidence for preserved pulsatility and diurnal variation with increased secretory disorderliness.

Abstract

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 used a sensitive chemiluminescence GH assay to analyze 24-h GH profiles (20-min sampling) from 10 adult cancer survivors with severe GH deficiency acquired after brain irradiation in childhood for nonpituitary brain tumors. An age- and sex-matched control group of 30 normal healthy volunteers, eight of whom were matched for body mass index 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, 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) elevated, 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 nonpulsatile secretion. Qualitative perturbation in hypothalamic control of GH release is evident by the increase in ApEn values reflecting more disordered GH secretion. The 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 normal subjects and those with GH deficiency due to other etiologies.