**6. Congenital Adrenal Hyperplasia (CAH)**

It occurs in a family of monogenic inherited enzymatic defects of adrenal steroid biosynthesis, with manifestations secondary to an accumulation of precursors proximal to the enzymatic deficiency. The most common form of CAH is 21-hydroxylase deficiency, seen in more than 90% of the CAH cases in pregnancy (Forest, 2004).

Classic, severe 21-hydroxylase deficiency is associated with ambiguous genitalia, and inadequate vaginal introitis, and progressive postnatal virilization including precocious adrenarche, advanced somatic development, central precocious puberty, menstrual irregularity , a reduced fertility rate, and possible salt wasting (White & Speiser, 2000).

The spontaneous abortion rate is twice that in the normal population, and congenital anomalies are more frecuent. Conception requires adecuate glucocorticoid therapy, which then continues at stables rates during gestation, except at labor and delivery. Nonclassical 21-hydroxilase deficiency patients present with pubertal and postpubertal hirsutism and menstrual irregularity, and may have improved fertility with glucocorticoid therapy ( Krone et al., 2001).

ACTH stimulation testing to measure 17-OH progesterone demonstrates overlap between heterozygotes for CAH and the normal population. Ideally CYP21 genotyping should be performed. Virilization is not seen in the female fetus with non classical 21-hydroxylase deficiency, but occurs in a fetus with classic 21-hydroxylae unless fetal adrenal androgen productions is adequately suppressed.

Dexamethasone most readily crosses the placenta as it is not bound to CBG and is not metabolize at dose of 20 mcg/kg maternal body weight per day to a maximum of 1.5 mg daily in 3 divided doses beginning at recognition of pregnancy before the 9th week of gestation, though lower doses are recommended by some (Coleman MA, Honour, 2004). Maternal plasma and/or urinary estriol levels reflect fetal adrenal synthesis and are monitored to assess efficacy. Maternal cortisol a DHEA-S levels will represent maternal adrenal suppression.

As only 25% of female fetuses are affected in a family with CAH, it is important to discontinue therapy as soon as possible in the male fetus and unaffected female fetus.

 Chorionic villus sampling at 9-11 weeks gestation may be used for gender determination and direct ADN analysis for the 21-hydroxilase gene CYP21.

Side effects of dexamethasone therapy are potentially significant, including excessive weight gain, sever striae with scarring, edema, irritability, gestational diabetes mellitus, hypertension, and gastrointestinal intolerance. In affected pregnancies, dexamethasone may

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