Brain and behavior in primary adrenal insufficiency - with emphasis on the precuneus & orbitofrontal cortex

Diana Kancsar; Westeinde Annelies van; Svetlana Lajic

doi:10.1530/endoabs.110.P38

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Endocrine Abstracts (2025) 110 P38 | DOI: 10.1530/endoabs.110.P38

ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)

Brain and behavior in primary adrenal insufficiency – with emphasis on the precuneus & orbitofrontal cortex

Diana Kancsar ¹ , Annelies van’t Westeinde ¹ & Svetlana Lajic ¹

Author affiliations

¹Karolinska Institute, Women’s and Children’s health, Paediatric Endocrinology Unit, Stockholm, Sweden

JOINT3615

Context: Primary adrenal insufficiency (PAI), including congenital adrenal hyperplasia (CAH) and autoimmune Addison’s disease (AAD), result in low cortisol levels and abnormal sex hormone levels due to adrenal cortex dysfunction. Previous studies on PAI found that the hormonal imbalance can alter brain structure and connectivity, affecting multiple brain areas including the left precuneus and the orbitofrontal cortex. These brain areas are major hubs in the brain, and alterations may lead to changes in structural and functional connectivity between the hub and other networks, which in turn could contribute to cognitive impairments and mental health issues. Objective: This study analyzed changes in structural and functional connectivity of the left precuneus and orbitofrontal cortex between patients with PAI and control subjects.

Design, setting, and participants: A total of 150 participants were included in the analysis: 29 individuals with CAH (18 females), 55 patients with AAD (33 females), and 66 healthy controls (37 females), aged 16 to 43 years, from a single research institute. All subjects underwent functional and structural magnetic resonance imaging (MRI).

Results: In patients with AAD, the resting-state functional connectivity analyses showed a decreased connectivity between the left precuneus and the left insula compared with the healthy controls. The analyses also showed a decreased connectivity between the orbitofrontal cortex and the left insula compared with the healthy controls. No such differences in functional connectivity were found in patients with CAH compared to controls. In contrast, CAH patients had impaired white matter microstructure in the left precuneus and orbitofrontal cortex, while patients with AAD did not.

Conclusions: The results suggest that long-term cortisol imbalances in primary adrenal insufficiency led to altered functional connectivity of the precuneus and orbitofrontal cortex in AAD, but not CAH. The underlying effects of these differences remain unexplained. Further research is needed to investigate the influence of the changes in functional connectivity and white matter and their relevance to cognitive functioning and mental health.

Keywords: PAI, precuneus, orbitofrontal cortex, brain health, dwi, rs-fc