Defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol accounts for more than 90 percent of cases of congenital adrenal hyperplasia [1-3]. This conversion is mediated by 21-hydroxylase, or in current terminology, CYP21A2.
The most severely affected individuals with classic congenital adrenal hyperplasia due to CYP21A2 deficiency present during the neonatal period and early infancy with adrenal insufficiency with or without salt wasting, or later, with virilization. Females have genital ambiguity.
"Nonclassic," or late-onset CYP21A2 deficiency, does not manifest with neonatal genital ambiguity; rather, it presents later in life with signs of androgen excess. Clinical features in late childhood include premature pubarche, acne, and accelerated bone age; adolescent and adult females present with acne, hirsutism, and menstrual irregularity [4-10].
The diagnosis and treatment of late-onset congenital adrenal hyperplasia due to CYP21A2 deficiency are reviewed here. The genetics and clinical manifestations of the nonclassic form of CYP21A2 deficiency, and the classic form of CYP21A2 deficiency are reviewed separately. (See "Genetics and clinical presentation of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults".)
Classic CYP21A2 deficiency — The characteristic biochemical abnormality in patients with CYP21A2 deficiency is a high serum concentration of 17-hydroxyprogesterone, the normal substrate for CYP21A2. Most affected neonates (with the classic form) have concentrations greater than 3500 ng/dL (105 nmol/L) , with most exceeding 10,000 ng/dL (300 nmol/L), whereas the levels in normal newborns are below 100 ng/dL (3 nmol/L) . Patients with this disorder also have an exaggerated serum 17-hydroxyprogesterone response to ACTH stimulation with values more than 10,000 ng/dL (300 nmol/L), providing good diagnostic separation from patients with nonclassic CYP21A2 deficiency [3,4].