<unk> -HSD II mediates three parallel dehydrogenase/isomerase reactions in the adrenals that convert Δ4 to Δ5 steroids: pregnenolone to progesterone, 17α-hydroxypregnenolone to 17α-hydroxyprogesterone, and dehydroepiandrosterone (DHEA) to androstenedione.<unk> -HSD II also mediates an alternate route of testosterone synthesis from androstenediol in the testes.<unk> -HSD deficiency results in large elevations of pregnenolone, 17α-hydroxypregnenolone, and DHEA. However, complexity arises from the presence of a second<unk> -HSD isoform (HSD3B1) coded by a different gene, expressed in the liver and placenta, and unaffected in<unk> -HSD-deficient CAH. The presence of this second enzyme has two clinical consequences. First,<unk> -HSD II can convert enough of the excess 17α-hydroxypregnenolone to 17α-hydroxyprogesterone to produce 17α-hydroxyprogesterone levels suggestive of common 21-hydroxylase deficient CAH. Measurement of the other affected steroids distinguishes the two. Second,<unk> -HSD I can convert enough DHEA to testosterone to moderately virilize a genetically female fetus. Mineralocorticoids The mineralocorticoid aspect of severe<unk> -HSD CAH is similar to those of 21-hydroxylase deficiency. Like other enzymes involved in early stages of both aldosterone and cortisol synthesis, the severe form of<unk> -HSD deficiency can result in life-threatening salt-wasting in early infancy. Salt-wasting is managed acutely with saline and high-dose hydrocortisone, and long-term fludrocortisone. Sex steroid The sex steroid consequences of severe<unk> -HSD CAH are unique among the<unk>  adrenal hyperplasias: it is the only form of CAH that can produce ambiguity in both sexes. As with 21-hydroxylase-deficient CAH, the degree of severity can determine the magnitude of over- or undervirilization. In an XX (genetically female) fetus, elevated amounts of DHEA can produce moderate virilization by conversion in the liver to testosterone. Virilization of genetic females is partial, often mild, and rarely raises assignment questions. The issues surrounding corrective surgery of the virilized female genitalia are the same as for moderate 21-hydroxylase deficiency but surgery is rarely considered desirable. The extent to which mild<unk> -HSD CAH can cause early appearance of pubic hair and other aspects of hyperandrogenism in later childhood or adolescence is unsettled. Early reports about 20 years ago suggesting that mild forms of<unk> -HSD CAH comprised significant proportions of girls with premature pubic hair or older women with hirsutism have not been confirmed and it now appears that premature pubarche in childhood and hirsutism after adolescence are not common manifestations of<unk> -HSD CAH. Undervirilization of genetic males with<unk> -HSD CAH occurs because synthesis of testosterone is impaired in both adrenals and testes. Although DHEA is elevated, it is a weak androgen and too little testosterone is produced in the liver to offset the deficiency of testicular testosterone. The degree of undervirilization is more variable, from mild to severe. Management issues are those of an undervirilized male with normal sensitivity to testosterone. If the infant boy is only mildly undervirilized, the hypospadias can be surgically repaired, testes brought into the scrotum, and testosterone supplied at puberty. Management decisions are more difficult for a moderately or severely undervirilized genetic male whose testes are in the abdomen and whose genitalia look at least as much female as male. Male sex can assigned and major reconstructive surgery done to close the midline of the perineum and move the testes into a constructed scrotum. Female sex can be assigned and the testes removed and vagina enlarged surgically. A recently advocated third choice would be to assign either sex and defer surgery to adolescence. Each approach carries its own disadvantages and risks. Children and their families are different enough that none of the courses is appropriate for all.
Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency
Lipoid congenital adrenal hyperplasia
Pituitary ACTH hypersecretion
Cortisone reductase deficiency
17β-Hydroxysteroid dehydrogenase III deficiency