Part of “CHAPTER 77 – CONGENITAL ADRENAL HYPERPLASIA“

Several other disorders involve adrenal steroid-synthesizing enzymes. Strictly speaking, the CMO deficiencies and other enzyme defects discussed below are not included among the adrenal hyperplasias, because they do not affect cortisol synthesis and cause no disturbance of the hypothalamic–pituitary–adrenal axis. A distal block in aldosterone synthesis results from defects in the CYP11B2 gene encoding 18-hydroxylase (CMO I) and 18-oxidase (CMO II) and causes rare forms of recessively inherited salt wasting with hypotension and failure to thrive in infancy. The biochemical profile in cases of CMO II deficiency is notable for low levels of aldosterone, with high PRA, and high serum corticosterone and 18-hydroxycorticosterone. The latter steroid is found in low levels in cases of CMO I deficiency.110 Affected individuals are often clinically asymptomatic in later life.

Defects in the CYP19 gene encoding cytochrome P450 aromatase (P450arom) prevent the normal synthesis of estrogens and create a relative abundance of androgens. Such defects have been identified as a novel cause of ambiguous genitalia in 46,XX neonates, of primary amenorrhea with hypergonadotropic hypogonadism in adolescent girls, or of virilism in the setting of polycystic ovaries in young women.111,112 In men the defect results in continued linear bone growth beyond puberty, delayed bone age, and failure of epiphyseal closure, findings which prove that estrogens are critical for epiphyseal fusion. These symptoms are alleviated by estrogen administration.113