ESPE Abstracts

Background: Patients with autoimmune Addison’s disease (AAD) lack production of glucocorticoids (GCs), mineralocorticoids (MCs) and androgens from the adrenal gland, due to autoimmune destruction of its cortex. Patients require replacement of GCs and MCs for the rest of their lives. In some cases, testosterone is supplemented in females. Brain function is sensitive to fluctuations in cortisol and may therefore be affected in AAD due to long-term disturbances in cortisol levels and rhythmicity. Such alterations in brain function may contribute to mood disturbances and reduced quality of life in this patient group. Currently, no brain research exists in AAD. The current study therefore sought to investigate resting-state functional connectivity in patients with AAD compared to controls.

Methods: Resting-state fMRI data was collected from 57 (33 females) patients with AAD and 69 (39 females) control participants, aged 19-43 years. Independent component analysis was used to identify resting-state brain networks in the entire cohort, using FSL MELODIC software. Next, dual-regression analysis was applied to test for group differences in resting-state functional connectivity (rs-fc) in the identified networks, using sex and age as covariates. We also tested the interaction between group and sex on rs-fc in the networks. Significant clusters were identified with threshold free cluster enhancement (TFCE), and clusters were considered to be significant at P<0.001.

Results: Patients with AAD had increased functional connectivity in the bilateral medial orbitofrontal cortex. There were no interactions with sex.

Conclusion: AAD seems to be associated with stronger functional connectivity at rest in the medial orbitofrontal cortex. This area is known to contain a high density of GC receptors. It has previously been implicated in reward-related processing, decision making and has often been linked with mood disorders, in particular depression. Further research is needed to investigate if this increased activity is part of an adaptive mechanism to having long-term cortisol disturbances, or if it contributes to disturbances in mood and/or executive functioning.