Quantitative brain MRI in congenital adrenal hyperplasia: in vivo assessment of the cognitive and structural impact of steroid hormones

Emma Webb, Lucy Elliott, Dominic Carlin, Martin Wilson, Kirsty Hall, Jennifer Netherton, Julie Reed, Timothy Barrett, Vijay Salwani, Jon Clayden, Wiebke Arlt, Nils Krone, Andrew Peet, Amanda Wood

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
243 Downloads (Pure)


Context: Brain white matter hyperintensities are seen on routine clinical imaging in 46% of adults with congenital adrenal hyperplasia (CAH). The extent and functional relevance of these abnormalities have not been studied with quantitative magnetic resonance imaging (MRI) analysis.

Objective: To examine white matter microstructure, neural volumes, and central nervous system (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 women (18 to 50 years) with 21OHD and 19 age-matched healthy women.

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 by 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. Patients with 21OHD exposed to higher glucocorticoid doses had greater abnormalities in white matter microstructure and cognitive performance.

Conclusion: We demonstrate that 21OHD and current glucocorticoid replacement regimens have a profound impact on brain morphology and function. If reversible, these CNS markers are a potential target for treatment.

Original languageEnglish
Pages (from-to)1330-1341
Number of pages12
JournalJournal of Clinical Endocrinology and Metabolism
Issue number4
Early online date20 Nov 2017
Publication statusPublished - Apr 2018


  • Adolescent
  • Adrenal Hyperplasia, Congenital/diagnostic imaging
  • Adult
  • Brain/diagnostic imaging
  • Choline/metabolism
  • Cognition/drug effects
  • Cross-Sectional Studies
  • Dose-Response Relationship, Drug
  • Female
  • Glucocorticoids/administration & dosage
  • Humans
  • Magnetic Resonance Imaging/methods
  • Magnetic Resonance Spectroscopy/methods
  • Middle Aged
  • Neuropsychological Tests
  • Psychometrics
  • Quality of Life
  • Young Adult


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