Endocrine Abstracts

JOINT105

Background: Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is the most common cause of primary adrenal insufficiency in youth resulting in impaired cortisol synthesis and excess androgen exposures starting in utero. Children with CAH exhibit increased risk for developmental delay compared to unaffected children. As well, adolescents and adults exhibit differences in cognitive function including decreased reward-based inhibitory control and working memory. However, more needs to be understood about how clinical factors (e.g., treatments and disease severity) in CAH affect cognitive function from early childhood through adulthood. Thus, we aimed to investigate the connection between cognitive function, age, glucocorticoid dose, and genotype-based severity in patients with CAH.

Methods: A cross-sectional study through various stages of development was performed in 56 patients (4–23 years; 11.7±5.4 years, 55% female) with classical CAH due to 21OHD. All patients completed iPad-based testing of cognitive function (NIH ToolBox Cognition Battery) including: inhibitory control (Flanker), cognitive flexibility (Dimensional Change Card Sort), and working memory (List Sort). Patients were compared to a normative population mean of 100 utilizing Welch’s t test. Within the CAH group, Pearson’s correlations between cognition scores and age or glucocorticoid dose (mg/m² per day) were analyzed. Disease severity was categorized by CYP21A2 genotype (n=38): Null (0% enzyme activity including deletions, large gene conversions; n=18) and Non-Null (category A: <1% enzyme activity, n=15; category B: 1–2% enzyme activity, n=5). Data are presented as mean ± S.D..

Results: Overall, inhibitory control (90.9±16.3), cognitive flexibility (95.0±18.5), and working memory scores (94.6±11.6) were lower in patients with CAH compared to normative mean (P’s<0.05). Within the CAH group, inhibitory control (R=−0.7) and cognitive flexibility (R=−0.4) scores were inversely correlated to age (P’s<0.01). In addition, inhibitory control (R=−0.6) and cognitive flexibility (R=−0.5) scores were inversely correlated to glucocorticoid dose (P’s<0.01). Finally, inhibitory control was lower in Null (87.3±14.0) vs Non-Null (103.6±21.2, P<0.01) patients.

Conclusion: Our findings suggest that patients with CAH have worse inhibitory control and cognitive flexibility scores compared to unaffected individuals, that is also seen with increasing age and glucocorticoid dose. In addition, inhibitory control scores are lowest in those most severely-affected (Null genotype). Thus, it is important to consider the effects of clinical factors inherent to CAH on cognitive function throughout the lifespan.