Adrenal Gland Irradiation Causes Fatigue Accompanied by Reactive Changes in Cortisol Levels

Abstract Background: Fatigue is a complicated syndrome associated with multiple factors. The development of fatigue after incidental radiotherapy (RT) to the adrenal gland has been observed in clinical practice. This study aimed to investigate the effect of adrenal RT on fatigue and related physiological impacts.Methods: Three patients with inevitable RT to the adrenal gland were enrolled. Serum levels of cortisol, aldosterone, and adrenocorticotropic hormone (ACTH) were measured before, during, and after RT. Fatigue was scored according to the validated fatigue severity scale, and dosimetric parameters were collected. BALB/c mice were surgically explored for the identification of the left adrenal gland. Intra-operative RT was delivered with an electron beam. The swimming endurance test was applied for endurance assessment to represent fatigue. Plasma levels of stress hormones and histopathological features were examined.Results: In the enrolled patients, serum baseline cortisol levels declined after RT. Alterations in levels of morning cortisol and aldosterone showed a similar trend to baseline cortisol, whereas ACTH levels increased, indicating possible compensatory feedback from the hypothalamic-pituitary-adrenal axis. In an experimental mouse model, RT to a unilateral adrenal gland decreased baseline cortisol levels and swimming endurance time. In the histopathological assessment, the irradiated adrenal glands showed characteristic RT injury features in the adrenal cortex.Conclusions: The preliminary clinical observation of fatigue development and characteristic hormone alterations indicated that the adrenal glands could be regarded as an organ at risk from RT adverse effects. This observation was supported by functional and histopathological evidence from an experimental animal model.