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Updated: Jun 5, 2026

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Brain development and cognitive, psychosocial, and psychiatric functioning in classical 21-hydroxylase deficiency
1NYS Psychiatric Institute/Department of Psychiatry, Columbia University, New York, N.Y., USA.
Abstract:
The disturbance of the hypothalamic-pituitary- adrenal axis characteristic of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is likely to affect brain development, yet neuroanatomic work is only beginning. Fetal hyperandrogenemia in 46, XX 21-OHD leads to masculinized brain organization and, consequently, at later stages of development, to masculinized gender-related behavior and cognitive function, including, although relatively uncommonly, gender identity. Genital masculinization as well as its surgical treatment has implications for social stigmatization and sexual functioning. CAH-associated electrolyte crises in infancy and later may result in severe cognitive impairment. Psychiatric disorders are somewhat increased, especially in patients with severe degrees of CAH.
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