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3ß-Hydroxysteroid dehydrogenase II deficient congenital adrenal hyperplasia (3ßHSD CAH) is an uncommon form of CAH resulting from a defective gene for one of the key enzymes in cortisol synthesis by the adrenal glands. 3ßHSD CAH can cause salt wasting adrenal crises in infancy. It can also cause mild virilization of genetically female infants and undervirilization of genetically male infants, making it the only form of CAH which can cause ambiguous genitalia in both genetic sexes.
Severe 3ß-HSD II deficient CAH is uncommon, and can cause salt-wasting due to mineralocorticoid deficiency. The most distinctive aspect of sex hormone metabolism in severe deficiency is that the newborn genitalia of both sexes can be affected.
Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive diseases resulting from defects in steps of the synthesis of cortisol from cholesterol by the adrenal glands. All of the forms of CAH involve excessive or defective production of sex steroids and can pervert or impair development of primary or secondary sex characteristics in affected infants, children, and adults. Many also involve excessive or defective production of mineralocorticoids, which can cause hypertension or salt wasting.
The most common type of CAH is due to deficiency of 21-hydroxylase and is covered in detail in the main article on congenital adrenal hyperplasia. 3ßHSD CAH is one of the less common types of CAH due to deficiencies of other proteins and enzymes involved in cortisol synthesis.
3ß-HSD II mediates three parallel dehydrogenase/isomerase reactions in the adrenals that convert ?4 to ?5 steroids: pregnenolone to progesterone, 17-Hydroxypregnenolone to 17-Hydroxyprogesterone, and DHEA to androstenedione. 3ß-HSD II also mediates an alternate route of testosterone synthesis from androstenediol in the testes. 3ß-HSD deficiency results in large elevations of pregnenolone, 17-hydroxypregnenolone, and DHEA.
However, complexity arises from the presence of a second 3ß-HSD (3ß-HSD I) coded by a different gene, expressed in the liver and placenta, and unaffected in 3ß-HSD deficient CAH. The presence of this second enzyme has two clinical consequences. First, 3ß-HSD II can convert enough of the excess 17-hydroxypregnenolone to 17OHP to produce 17OHP levels suggestive of common 21-hydroxylase deficient CAH. Measurement of the other affected steroids distinguishes the two. Second, 3ß-HSD II can convert enough DHEA to testosterone to moderately virilize a genetically female fetus.
The mineralocorticoid aspect of severe 3ß-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 3ß-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.
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