Reduced cortical thickness in individuals with congenital adrenal hyperplasia (CAH)

TL;DR

This study finds that individuals with congenital adrenal hyperplasia have thinner brain cortices, regardless of sex, possibly due to hormonal and treatment-related factors.

Contribution

The study reveals widespread cortical thinning in CAH patients, independent of sex, offering new insights into brain structure changes in this endocrine disorder.

Findings

Individuals with CAH showed thinner cortices in multiple brain regions compared to controls.

Cortical thinning was observed in both lateral and medial surfaces of the left and right hemispheres.

The effect was consistent regardless of biological sex.

Abstract

Congenital adrenal hyperplasia (CAH), a genetic condition that disrupts cortisol synthesis, is associated with elevated androgen levels in females with CAH. Altered hormonal milieus have been linked to changes in brain structure, yet little is known about how CAH affects the cerebral cortex. Here, we investigated vertex-wise cortical thickness in 53 individuals with CAH (33 women and 20 men) and 53 sex- and age-matched controls (33 women and 20 men) using surface-based morphometry. There were no significant effects of biological sex and no significant diagnosis-by-sex interaction. However, there was a significant effect of diagnosis, with thinner cortices in various regions across the left and right lateral and medial surfaces in individuals with CAH compared to controls. These findings point to widespread cortical alterations in CAH, independent of sex, and extend prior evidence of structural brain variations in this endocrine disorder. The observed cortical thinning may result from multiple factors, including prenatally reduced cortisol levels, potential long-term consequences of postnatal glucocorticoid treatment, and ongoing physiological and psychosocial stressors.

The online version contains supplementary material available at 10.1038/s41598-026-45407-2.

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