Endocrine Abstracts

JOINT2954

Background: Both Congenital Adrenal Hyperplasia (CAH) and autoimmune Addison’s Disease (AAD) are characterized by impaired cortisol and aldosterone production, along with increased adrenal androgens in CAH, but reduced adrenal androgens in AAD. Current oral replacement medication for cortisol is sub-optimal and leads to imbalances in adrenal hormone levels that might negatively affect the brain and cognitive functioning. The hippocampus plays a vital role in memory and emotional regulation, and it is particularly sensitive to changes in corticosteroid levels as well as sex hormones and might therefore be especially vulnerable to cortisol and androgen imbalances in both CAH and AAD. This study investigates the relationship between hippocampal subfield volumes, white matter microstructure, and cognitive performance in patients with CAH and AAD.

Methods: Hippocampal subfield volumes and white matter microstructure (mean diffusivity, MD) were measured in CAH, AAD, and healthy control groups based on T1 and DWI MRI scans (3T). Participants completed a battery of memory tasks, including assessments of verbal and visuo-spatial working memory, as well as immediate and long-term recall. ANCOVA and regression analyses were performed to examine group differences and the relationship between hippocampal measures and memory performance, controlling for age, sex, education, and intracranial volume.

Results: No significant differences in hippocampal subfield volumes were found between the groups (CAH, Addisons and controls). However, CAH patients exhibited significantly higher MD values in the left subiculum body compared to controls. In CAH, higher volumes in the left CA1-body were associated with better immediate recall, while higher MD values, reflecting more impaired white matter, in the same region were linked to worse performance in immediate recall. In AAD, hippocampal volume interactions with memory performance were found in the right CA1-head for immediate recall, where larger volumes predicted better recall in controls but not in AAD patients. No significant interactions between hippocampal measures and long-term memory were found.

Discussion: Since no group differences between CAH, Addisons and controls in hippocampal subfield volumes were observed, our findings suggest that the hippocampus is relatively unaffected in this patient group, possibly due to their young age and early detection through neonatal screening. However, subtle alterations in white matter microstructure were linked to memory performance. Future studies should investigate whether hippocampal changes might emerge over time and contribute to memory difficulties in the long term, helping to refine interventions for cognitive challenges in these populations.