Objective: To examine white matter microstructure, neural volumes and CNS metabolites in CAH due to 21-hydroxylase deficiency (21OHD) and to determine whether identified abnormalities are associated with cognition, glucocorticoid and androgen exposure.
Design, setting and participants: A cross-sectional study at a tertiary hospital including 19 females (18-50 years) with 21OHD and 19 age-matched healthy females.
Main outcome measure: Recruits underwent cognitive assessment and brain imaging including; diffusion weighted imaging of white matter, T1-weighted volumetry and magnetic resonance spectroscopy for neural metabolites. We evaluated white matter microstructure using tract-based spatial statistics. We compared cognitive scores, neural volumes and metabolites between groups and relationships between glucocorticoid exposure, MRI and neurologic outcomes.
Results: Patients with 21OHD had widespread reductions in white matter structural integrity, reduced volumes of right hippocampus, bilateral thalami, cerebellum and brainstem, and reduced mesial temporal lobe total choline content. Working memory, processing speed, and digit span and matrix reasoning scores were reduced in patients with 21OHD, despite similar education and intelligence to controls. 21OHD individuals exposed to higher glucocorticoid doses had greater abnormalities in white matter microstructure and cognitive performance.
Conclusion: For the first time we demonstrate that 21OHD and current glucocorticoid replacement regimens have a profound impact on brain morphology and function. If reversible, these CNS markers represent a potential target for treatment.