Congenital Adrenal Hyperplasia and Brain Health: A Systematic Review of Structural, Functional, and Diffusion Magnetic Resonance Imaging (MRI) Investigations

J Child Neurol. 2022 Aug;37(8-9):758-783. doi: 10.1177/08830738221100886. Epub 2022 Jun 23.


Background: Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that affects the adrenal glands and is the most common cause of primary adrenal insufficiency in children. In the past few decades, magnetic resonance imaging (MRI) has been implemented to investigate how the brain may be affected by CAH. A systematic review was conducted to evaluate and synthesize the reported evidence of brain findings related to CAH using structural, functional, and diffusion-weighted MRI.

Methods: We searched bibliographical databases through July 2021 for brain MRI studies in individuals with CAH.

Results: Twenty-eight studies were identified, including 13 case reports or series, 10 studies that recruited and studied CAH patients vs unaffected controls, and 5 studies without a matched control group. Eleven studies used structural MRI to identify structural abnormalities or quantify brain volumes, whereas 3 studies implemented functional MRI to investigate brain activity, and 3 reported diffusion MRI findings to assess white matter microstructure. Some commonly reported findings across studies included cortical atrophy and differences in gray matter volumes, as well as white matter hyperintensities, altered white matter microstructure, and distinct patterns of emotion and reward-related brain activity.

Conclusions: These findings suggest differences in brain structure and function in patients with CAH. Limitations of these studies highlight the need for CAH neuroimaging studies to incorporate larger sample sizes and follow best study design and MRI analytic practices, as well as clarify potential neurologic effects seen across the lifespan and in relation to clinical and behavioral CAH phenotypes.

Keywords: 21-hydroxylase deficiency; adrenal insufficiency; brain; congenital adrenal hyperplasia; diffusion MRI; functional MRI; magnetic resonance imaging; neuroimaging.

Publication types

  • Systematic Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital* / diagnostic imaging
  • Adrenal Hyperplasia, Congenital* / pathology
  • Brain / diagnostic imaging
  • Brain / pathology
  • Diffusion Magnetic Resonance Imaging
  • Emotions
  • Humans
  • Magnetic Resonance Imaging / methods