ESPE Abstracts

Background: Patients with congenital adrenal hyperplasia (CAH) are treated with life-long glucocorticoid (GC) replacement therapy. Negative effects on cognition, brain structure and function during working memory tasks have been identified. To date, no studies on functional connectivity during rest have been performed in patients with CAH. One study conducted on patients with Cushing’s syndrome, another disorder of cortisol imbalance, suggests that long-term cortisol excess results in increased connectivity within the default-mode network (DMN), in particular medial temporal lobe and prefrontal cortex. Interestingly, the precuneus, which was reduced in volume in our study in CAH patients (Van’t Westeinde et al. 2019) is functionally connected to both the fronto-parietal and the default mode network. Thus, altered structure, as a result of prolonged cortisol imbalance, might result in altered connectivity of both working memory and default mode network.

Objective: To investigate resting-state functional connectivity in patients with CAH compared with healthy untreated controls and the association between functional connectivity in our region of interest (ROI) and disease severity, dose of GC and visuo-spatial working memory.

Design, Setting and Participants: Thirty-one patients with CAH (18 females) and 38 healthy controls (24 females), aged 16-33 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. Two patients in the CAH group had non-classic (NC) CAH, 13 had simple-virilising (SV) CAH and 16 had salt-wasting (SW) CAH.

Results: Patients with CAH showed increased functional connectivity in the precuneus compared with controls. However, activity was not associated with executive functions. Analyses in this ROI indicated a significant quadratic association between genotype, phenotype and functional connectivity. Patients with the null genotype showed reduced functional connectivity, whereas patients with non-null and simple virilising genotypes exhibited increased functional connectivity in the precuneus.

Conclusion: Patients with CAH demonstrated altered functional connectivity during rest in the precuneus. Such a change may reflect a functional reorganisation in response to the CAH disease. The change in functional connectivity may depend on the severity of CAH.