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43. A woman with non-classical CAH is planning pregnancy. What is the probabil-
    ity of having a child with non-classical CAH?

If a woman has non-classical CAH, the likelihood of having a child with non-

classical CAH depends on the genotype of the woman (whether she has severe

and mild mutant alleles or two mild mutant alleles of 21α-hydroxylase gene)

and partner (whether he is a carrier for gene for classical or non-classical CAH).

The various possibilities in this scenario are given in the table below.

Female genotype Male genotype Risk of NCCAH

Severe and mild

mutation

Severe and normal (carrier for classical

CAH)

(1:60) × (1:4) = 1 in 240

Mild and normal (carrier for NCCAH) (1:16) × (1:2) = 1 in 32

Mild and mild mutation Severe and normal (carrier for classical

CAH)

(1:60) × (1:2) = 1 in 120

Mild and normal (carrier for NCCAH) (1:16) × (1:2) = 1 in 32

44. When does cortisol biosynthesis start in intrauterine life?

Although the fetal hypothalamic–pituitary–adrenocortical (HPA) axis is func-

tional only by 15 weeks of intrauterine life, it has been shown that embryonic

adrenal gland can synthesize cortisol as early as 8–9 weeks of intrauterine life.

This is due to the expression of the enzyme 3β-HSD2, which is obligatory for

cortisol biosynthesis. This early synthesis of cortisol is important because it

suppresses ACTH production from the pituitary and, consequently, inhibits the

production of adrenal androgens, thereby preventing virilization of external

genitalia in a normal female fetus. The cortisol biosynthesis during this period

is independent of CRH-ACTH axis; however, fetal adrenal androgen production

during this period is ACTH dependent as evidenced by the presence of genital

virilization in affected female fetuses with CAH. The expression of enzyme

3 β-HSD2 in adrenal gland (and hence cortisol synthesis) declines after 12 weeks

till about 24 weeks of intrauterine period. Therefore, cortisol levels in fetus dur-

ing mid-gestation are approximately ten times lower than that found in maternal

serum.

10 Congenital Adrenal Hyperplasia