Endocrine Abstracts (2006) 11 P583

Spontaneous GH secretion in the fed and fasting states in cranially irradiated adult cancer survivors with normal peak GH responses to two provocative tests: does GH neurosecretory dysfunction exist?

KH Darzy1, RD Murray1, HK Gleeson1, SS Pezzoli2, MO Thorner2 & SM Shalet1


1Department of Endocrinology, Christie Hospital NHS Trust, Manchester, United Kingdom; 2Department of Medicine, University of Virginia Health Science Center, Charlottesville, Virginia 22908, United States.


A few studies have suggested that radiation-induced growth hormone neurosecretory dysfunction (GHNSD) exists in children irradiated for leukemia (18–24 Gy). The presence or absence of GHNSD in adult cancer survivors has not been studied before. Thus, 24-hour spontaneous GH secretion was studied by 20 min sampling both in the fed state (n=16; 6 women) and the last 24 hours of 33-hour fast (n=10; 3 women) in adult cancer survivors, of normal GH status defined by two provocative tests. The patients had been irradiated for non-pituitary brain tumours (n=12) or leukemia (n=4), aged 16–53.7 (median, 20.25) yr, and studied 13.1±1.6 (mean±S.E.M.) yr after irradiation. Gender-specific comparisons with age and BMI-matched 21 normal men (11 fasting) and 9 normal women (3 fasting) were conducted. Using, previously published diagnostic thresholds, all patients had stimulated peak GH responses in the normal range (>5 mcg/l and >16.5 mcg/l to the insulin tolerance test (ITT) and the combined GHRH plus arginine stimulation test (AST), respectively) as well as normal physiological GH secretion (mean profile GH levels >0.35 mcg/l and 1.25 mcg/l during the fed and fasting states, respectively). However, patients’ peak GH responses were significantly reduced compared with normal controls (women responses: ITT, 9±1.2 vs. 19.9±4.3 mcg/l, P=0.04; GHRH+AST, 33±6.4 vs. 77±18 mcg/l, P=0.05; men responses: ITT, 20±3 vs. 34±4 mcg/l, P=0.03; GHRH+AST, 37±7 vs. 64±7 mcg/l, P=0.02), while no differences were seen in the profile mean GH levels. In the women: fed 1.03±0.18 vs. 1.17±0.17 mcg/l, P=0.6; fasting: 2.14±0.9 vs. 2.33±0.8 mcg/l, P=0.9. In the men: fed: 0.92 (0.25–3.1) vs. 0.64 (0.22–2.1) mcg/l, P=0.5; fasting: 2.2±0.4 vs. 2.5±0.3 mcg/l, P=0.5. One leukemia patient had subnormal fed profile mean GH level of 0.25 mcg/l but achieved normal fasting mean GH level of 2.4 mcg/l. We conclude that radiation-induced GHNSD does not exist in adult cancer survivors. Despite ‘normal’ peak GH responses, radiation-induced damage to the h-p axis is evidenced by the attenuation of the maximum somatotrophic reserve during pharmacological stimulation.

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