Quantitative brain MRI in congenital adrenal hyperplasia: in vivo assessment of the cognitive and structural impact of steroid hormones
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
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.
Date Issued
2018-04-01
Date Acceptance
2017-11-09
Citation
Journal of Clinical Endocrinology and Metabolism (JCEM), 2018, 103 (4), pp.1330-1341
ISSN
0021-972X
Publisher
Oxford University Press
Start Page
1330
End Page
1341
Journal / Book Title
Journal of Clinical Endocrinology and Metabolism (JCEM)
Volume
103
Issue
4
Copyright Statement
This article has been published under the terms of the Creative Commons Attribution License (CCBY;https://creativecommons.org/licenses/by/4.0/), whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29165577
PII: 4642962
Subjects
CHILDREN
CORTICOSTEROIDS
DIFFUSION
DISEASE
Endocrinology & Metabolism
GLUCOCORTICOID MEDICATION
Life Sciences & Biomedicine
MAGNETIC-RESONANCE-SPECTROSCOPY
PREVALENCE
Science & Technology
TERM
TESTOSTERONE
WORKING-MEMORY
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2017-11-20