ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab. 2020; 105(4):1098-111. PMID: 31950148.

Classical congenital adrenal hyperplasia (CAH) is characterized by impaired glucocorticoid, and often also mineralocorticoid, secretion and increased adrenal androgen production (1). Given the widespread expression of androgen and glucocorticoid receptors throughout the brain (2, 3), there has been a growing interest in understanding how hormonal imbalances related to CAH may impact distinct subregions of the developing brain (4).

Here, the authors characterized brain gray matter morphology in the prefrontal cortex and subregions of the amygdala and hippocampus using structural magnetic resonance imaging in young patients with CAH (n =27, mean age 12.6 years) compared with unaffected controls (n =35, 13 years). Patients with CAH had smaller intracranial volumes and larger cerebrospinal fluid volumes compared with controls. Patients with CAH showed smaller volumes of the bilateral superior frontal cortex, bilateral caudal middle frontal cortex, and left rostral middle frontal cortex, as well as smaller left hippocampus and several subregions of the amygdala. The results cannot be inferred to be directly associated with differences in cognition or behaviour, however, they highlight areas for possible future research.

While the clinical care of patients with CAH has improved over the years, long-term negative effects from their life-long treatment with glucocorticoids remain a concern. Identifying long-term sequelae and their contributing factors is important to optimize treatment. This study demonstrates that young CAH patients have reduced intracranial volume as well as regional volumes of the prefrontal cortex, amygdala and hippocampus. It significantly adds to the evidence for long-term effects on brain morphology in patients with CAH, and raises the question whether differences in clinical care might possibly contribute to these differences.

References:

1. Clayton PE, Miller WL, Ober eld SE, Ritze?n EM, Sippell WG, Speiser PW; ESPE/ LWPES CAH Working Group. Consensus statement on 21-hydroxylase deficiency from the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society. Horm Res. 2002; 58(4): 188–195.

2. Nun?ez JL, Huppenbauer CB, McAbee MD, Juraska JM, DonCarlos LL. Androgen receptor expression in the developing male and female rat visual and prefrontal cortex. J Neurobiol. 2003; 56(3): 293–302.

3. Gray JD, Kogan JF, Marrocco J, McEwen BS. Genomic and epigenomic mechanisms of glucocorticoids in the brain. Nat Rev Endocrinol. 2017; 13(11): 661–673.

4. Mueller SC. Magnetic resonance imaging in paediatric psychoneuroendocrinology: a new frontier for under- standing the impact of hormones on emotion and cognition. J Neuroendocrinol. 2013; 25(8): 762–770.