Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia

Abstract

ContextClassical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain.ObjectiveTo characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compared to age- and sex-matched controls.DesignA cross-sectional study of 27 CAH youth (16 female; 12.6 ± 3.4 year) and 35 typically developing, age- and sex-matched healthy controls (20 female; 13.0 ± 2.8 year) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex, and eight amygdala and six hippocampal subregions. Between-subject effects of group (CAH vs control) and sex, and their interaction (group-by-sex) on brain volumes were studied, while controlling for intracranial volume (ICV) and group differences in body mass index and bone age.ResultsCAH youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral, superior and caudal middle frontal volumes, and smaller left lateral orbito-frontal volumes compared to controls. Medial temporal lobe analyses revealed the left hippocampus was smaller in fully-adjusted models. CAH youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions.ConclusionsThis study replicates previous findings of smaller medial temporal lobe volumes in CAH patients, and suggests that lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus are the most affected regions in CAH youth.PrécisWe collected brain scans of 27 youth with classical CAH and 35 healthy controls. Portions of the prefrontal cortex, amygdala, and hippocampus were smaller in CAH youth compared to controls.Disclosure SummaryMEG receives grant support from Novo Nordisk; consultant fees from Daiichi Sankyo, Ferring, Novo Nordisk, Nutrition & Growth Solutions, Pfizer, Sandoz, and Spruce Biosciences; serves on data safety monitoring boards for Ascendis, Millendo, and Tolmar; and receives royalties from McGraw-Hill and UpToDate.

A Case of Prenatally Diagnosed Congenital Adrenal Hyperplasia With Brain Morphometric Differences

“…Our findings raise the possibility that fetal brain immaturity could underlie neurodevelopmental differences observed in older youth and young adults with CAH such as leukariosis and temporal brain atrophy. 3,9,[16][17][18][19][20][21] However, large-scale, longitudinal studies are required to ascertain the link between our early findings and the various neurodevelopmental differences that have been reported in CAH.…”