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

Background: Incidental radiotherapy (RT) to the adrenal gland may have systemic effects. This study aimed to investigate the effects of adrenal RT on fatigue. Methods: BALB/c mice were surgically explored to identify the left adrenal gland and delivered intra-operative RT. The swimming endurance test was used for endurance assessment to represent fatigue. Plasma levels of stress hormones and histopathological features were examined. Three patients with inevitable RT to the adrenal gland were enrolled for the preliminary study. Serum levels of cortisol, aldosterone, and adrenocorticotropic hormone (ACTH) were measured before and after RT. Fatigue score by using the fatigue severity scale and RT dosimetric parameters were collected. Results: In the experimental mouse model, adrenal RT decreased baseline cortisol from 274.6 ± 37.8 to 193.6 ± 29.4 ng/mL (p = 0.007) and swimming endurance time from 3.7 ± 0.3 to 1.7 ± 0.6 min (p = 0.02). In histopathological assessment, the irradiated adrenal glands showed RT injury features in the adrenal cortex. In the enrolled patients, baseline cortisol significantly declined after RT. There were no significant differences in the levels of morning cortisol, aldosterone, and ACTH before and after RT. Conclusions: The RT dose distributed to the adrenal gland may correlate with unwanted adverse effects, including fatigue and adrenal hormone alterations.