A novel finding of activation of the hypothalamic-pituitary-adrenal axis with increased cortisol production rates and circulating cortisol concentrations in 24-hour profiling study in cranially irradiated adult cancer survivors
KH Darzy & SM Shalet
Cortisol profiling at 20-min intervals over 24 hours during the fed state and in the last 24 hours of a 33-hr fast were undertaken in 34 ACTH-replete adult cancer survivors irradiated for non-pituitary brain tumours and 33 matched normal controls. Compared with normals, patients had significantly higher (mean ± SEM) minimum (nadir) cortisol concentration (37.8 ± 2.5 vs. 29.7 ± 2.9 nmol/L, p = 0.03), maximum cortisol concentration (547 ± 18 vs. 495 ± 14 nmol/L, p = 0.02) and profile mean cortisol concentration (213 ± 6.9 vs. 187 ± 6.7 nmol/L, p = 0.009). Multiparameter deconvolution analysis revealed a 20% increase in cortisol secretion rates (1.8 ± 0.09 vs. 1.5 ± 0.08 nmol.L-1.min-1, p = 0.03) due to selective augmentation of the cortisol mass released per burst with no changes in cortisol secretory burst frequency (12 per 24 hrs) or half-life (82 ± 3.3 vs. 82 ± 2.9 min, p = 0.98). Short-term fasting did not produce a significant shift in cortisol levels or secretion rates but the differences observed between patients and normals in the fed state were amplified by fasting. Cortisol levels and secretion rates were not increased in female patients compared with normal females; thus, the differences between male patients and normal males were amplified, and more so during fasting (mean cortisol concentration and cortisol secretion rate increased by 20% and 29% in the fed state and by 41% and 32% in the fasting state, respectively, p <0.05). This study has demonstrated that activation of the corticotrope-adrenal axis occurs in adults who received irradiation of the h-p axis during treatment of non-pituitary brain tumours, and this is manifested by a parallel increase in circulating cortisol levels and cortisol production rates. The lack of cortisol increase in female patients may be attributed to the adverse effect of their higher BMI on cortisol secretion or may reflect a genuine gender dichotomy.