Context: In patients with severe radiation-induced GH deficiency, we have previously demonstrated that pulsatile GH secretion and diurnal rhythm are maintained in the fed state, albeit with great attenuation of the pulse amplitude. However, it remained unclear whether or not stressing the h-p axis could unmask neurosecretory dysregulation that is not seen under basal conditions. In addition, the impact of fasting on GH pulsatility and diurnal variation in GH deficient patients has not been studied in detail before.

Study Subjects and Design: 24-hour GH profiles at 20-minute intervals were undertaken in the fed state and in the last 24 of a 33-hour fast in 8 young adult cancer survivors (2 women) with severe GH deficiency following cranial irradiation for non-pituitary brain tumors in childhood and 14 matched normal controls (3 women). A sensitive chemiluminescence GH assay was used with cluster analysis.

Results: Fasting induced a significant (P < 0.05) rise in all amplitude-dependent measures (absolute GH peak and nadir, profile mean GH and mean pulse amplitude and area) in both groups. Pulse frequency was non-significantly increased (by 10%) in normals but significantly increased (by 20%) in the patients. The average increase in the individual fasting profile mean GH concentration was 3.7 fold (range, 1.5-8.3) in normals compared with 2.7 fold (range, 1-4.7) in the patients (P > 0.05). Fasting amplified amplitude related differences between patients and controls and thus, unlike in the fed state, the day (0900-2040 h) mean GH completely demarcated patients from normals. An absolute GH peak level of 2 µg/L and 4 µg/L and a profile mean GH level of 0.25 µg/L and 0.65 µg/L completely separated patients from normals in the fed and the fasting states, respectively. Overall, fasting seems to induce a feminized pattern of GH secretion with relatively higher inter-peak levels, preserved but diminished diurnal variation and increased secretory disorderliness (increased approximate entropy scores).

Conclusion: The overall pulsatile pattern of GH secretion during fasting in patients with radiation-induced GH deficiency and the relative augmentation in GH release are similar to that seen in normals emphasizing that GH neuroregulation is preserved in these patients even when the h-p axis is under physiological stress.