ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab. 2020; 105(3): dgaa016. PMID: 31927590.

Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency requires life-long glucocorticoid (GC) replacement therapy. Previous studies on general cognitive ability in patients with CAH have been conflicting, and the majority focused on intelligence in adult patients. Some studies have reported normal intelligence in both women and men with CAH (1), whereas others have noted impaired intelligence (2, 3) and memory deficit (4) in children and adults with CAH. A recent investigation demonstrated that patients with CAH have impaired spatial perception and diminished quantitative abilities, most probably due to altered executive functioning (5-7). On the contrary, others have reported superior performance on spatial tests in women with CAH (8). In addition to the effects of postnatal GC, an excess of prenatal androgens may be associated with permanent changes in brain structures, organization, or function (9). Prenatal treatment with dexamethasone (DEX) may also affect cognitive functions, given that poorer cognitive abilities were shown in DEX-treated women with CAH compared with women with CAH who received no prenatal DEX therapy (7).

This study evaluated the cognitive outcome in children with CAH and the impact of early diagnosis with neonatal screening. The effect of postnatal and prenatal GC treatment on cognitive function was evaluated. Forty-three children with CAH (mean age: 11.5 years; 23 girls, 20 boys; 11 prenatally treated with DEX) and 52 matched control children (mean age 10.7 years) were studied prospectively. All but one patient were identified by neonatal screening and were treated with hydrocortisone (HC). Twelve patients had a null genotype and 30 patients a non-null genotype. Only 2 patients with the salt-wasting phenotype exhibited sodium concentrations <131 mmol/l at diagnosis. In general, all patients had good metabolic control at the time of cognitive function assessment. Their cognitive abilities were assessed with standardized neuropsychological tests (Wechsler scales, Span Board Test, Stroop Interference Test, NEPSY list learning).

The results showed that children with CAH, who were diagnosed early via neonatal screening and treated with HC (mean dose 12.3 mg/m²) to achieve a good metabolic control, had normal general intellectual ability including good executive functions, learning and memory. They performed at the same level as their matched controls from the general population. In addition, children with CAH who were treated with DEX prenatally performed equally well on most measures compared to children not treated with DEX, except that girls treated during the entire gestational period with DEX had lower scores on WISC-III Vocabulary (a proxy for general intellectual ability). However, due to low sample size of DEX treated cases (only 6 girls) the results should be interpreted with caution and need replication in larger studies. These findings confirm that children and adolescents with CAH, who were diagnosed early via neonatal screening and treated with HC, have normal psychometric intelligence and executive functions.

References:

1. Berenbaum SA, Bryk KK, Duck SC. Normal intelligence in female and male patients with congenital adrenal hyperplasia. Int J Pediatr Endocrinol. 2010; 2010:853103.

2. Helleday J, Bartfai A, Ritze?n EM, Forsman M. General intelligence and cognitive profile in women with congenital adrenal hyperplasia (CAH). Psychoneuroendocrinology. 1994; 19(4): 343–356.

3. Johannsen TH, Ripa CP, Reinisch JM, Schwartz M, Mortensen EL, Main KM. Impaired cognitive function in women with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2006; 91(4): 1376–1381.

4. Maheu FS, Merke DP, Schroth EA, et al. Steroid abnormalities and the developing brain: declarative memory for emotionally arousing and neutral material in children with congenital adrenal hyperplasia. Psychoneuroendocrinology. 2008; 33(2):238–245.

5. Browne WV, Hindmarsh PC, Pasterski V, et al. Working memory performance is reduced in children with congenital adrenal hyperplasia. Horm Behav. 2015; 67:83–88.

6. Collaer ML, Hindmarsh PC, Pasterski V, Fane BA, Hines M. Reduced short term memory in congenital adrenal hyperplasia (CAH) and its relationship to spatial and quantitative performance. Psychoneuroendocrinology. 2016; 64:164–173.

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8. Hampson E, Rovet JF, Altmann D. Spatial reasoning in children with congenital adrenal hyperplasia due to 21-hydroxylase de - ciency. Dev Neuropsychol. 1998; 14(2–3):299–320.

9. Hines M, Pasterski V, Spencer D, et al. Prenatal androgen ex- posure alters girls’ responses to information indicating gender-appropriate behaviour. Philos Trans R Soc Lond B Biol Sci. 2016; 371(1688):20150125.