Diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
- Deborah P Merke, MD, MS
Deborah P Merke, MD, MS
- Pediatric Endocrinologist
- Bethesda, MD
Defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol accounts for more than 95 percent of cases of congenital adrenal hyperplasia (CAH) [1,2]. This conversion is mediated by 21-hydroxylase due to mutations in the CYP21A2 gene. Based upon neonatal screening studies that detect classic CAH, 21-hydroxylase deficiency is one of the more common inherited disorders.
The laboratory findings and diagnosis of classic CAH due to 21-hydroxylase deficiency in neonates and adults are reviewed here. The genetics, clinical presentation, and treatment of classic 21-hydroxylase deficiency in children and adults and an overview of nonclassic CAH (NCCAH) are discussed separately. (See "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults" and "Diagnosis and treatment of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency".)
A very high serum concentration of 17-hydroxyprogesterone, the normal substrate for 21-hydroxylase, is diagnostic of classic 21-hydroxylase deficiency (figure 1). Most affected neonates have concentrations greater than 3500 ng/dL (105 nmol/L).
Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency results in one of two clinical syndromes: a salt-losing form or a non-salt-losing (simple virilizing) form. (See "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency", section on 'Infants/children'.)
●Girls with either form present as neonates with ambiguous genitalia, with clitoral enlargement and a common urethral-vaginal orifice (urogenital sinus). Partial or complete fusion of the labial folds and rostral migration of the urogenital orifice may also occur. Internal female reproductive organs (uterus and ovaries) are normal. (See "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency", section on 'Ambiguous genitalia'.)
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