White matter variations in congenital adrenal hyperplasia: possible implications for glucocorticoid treatment

Abstract

Congenital Adrenal Hyperplasia (CAH) has been reported to manifest with white matter aberrations. However, many previous studies included only small samples, restricted their analyses to females, lacked a control group, and/or did not correct for brain size. Here we examined the largest sample to date, comprising 53 male and female participants with CAH, who were matched with 53 male and female controls in terms of sex, age, education, and verbal intelligence. The four groups were compared with respect to their total white matter as well as white matter hyperintensities while applying brain size corrections. For both measures, total white matter and white matter hyperintensities, there were no significant sex differences or group-by-sex interactions. However, individuals with CAH had significantly smaller total white matter volumes compared to controls. Our findings align with previous reports of white matter variations in CAH. The absence of a group-by-sex interaction suggests that white matter variations in CAH may not be attributable to prenatal androgens. Instead, they may be a result of the condition itself and/or its treatment with glucocorticoids. The latter aspect warrants follow-up, particularly given that glucocorticoids are employed not only in CAH but also in other medical conditions.