ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Cereb Cortex. 2020; 30(5): 2777–2788. PMID: 31819952.

Congenital adrenal hyperplasia (CAH), most commonly caused by 21-hydroxylase deficiency, is an autosomal recessively inherited life-threatening impairment in cortisol and, in the severe salt wasting form, aldosterone synthesis. The implementation of neonatal screening programs for CAH and the continuous improvement in its clinical care has led to CAH being now a lifelong chronic disease. However, over time patients with CAH are at risk of metabolic and cognitive sequelae.

Here, the authors performed an observational study using structural magnetic resonance imaging in adolescents and young adults with CAH in order to investigate possible alterations in brain morphology and their associations with genotype/phenotype, cognition and behaviour, as well as DNA methylation. Patients with CAH (n =37, mean age 22 years) were compared with sex- and age-matched population controls (n =43). They also included a small group of patients prenatally treated with dexamethasone (n =8). The major findings were that CAH patients have smaller whole brain volume, as well as altered structures of the prefrontal, parietal, and superior occipital cortex, areas that are hubs of the visuospatial working memory and default mode networks. Interestingly, these structural alterations correlated with visuospatial working memory performance, and CAH patients performed worse on this task. Finally, prenatal dexamethasone treatment was associated with smaller surface area and volume in parietal regions.

This study provides evidence that patients with CAH show alterations in brain structure, specifically in regions important for working memory performance, and these alterations might underlie the observed cognitive deficits. Early diagnosis and optimal lifelong treatment with glucocorticoids are important factors that may ameliorate cognitive deficits and alterations in brain structure.