11β-Hydroxylase Deficiency Congenital Adrenal Hyperplasia: Update of Prenatal Diagnosis*

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Abstract
Hormonal measurements in maternal urine and amniotic fluid (AF) during pregnancy and/or at delivery correctly predicted the postnatal diagnosis of 11β-hydroxylase deficiency congenital adrenal hyperplasia (11β-OH deficiency CAH) in 7 fetuses at risk. In the 4 affected ones, maternal urinary tetrahydro-11-deoxycortisol (THS) excretion was high during the first trimester [0.3–2.2 mg/day (1.1–7.7 μmol/day)] and rose further during the third trimester [0.5–3.5 mg/day (1.8–12.3 μmol/day)] compared to urinary THS excretion in 20 normal pregnancies of the same gestational age (P < 0.01). In 1 mother, dexamethasone administration (2 mg/day for 72 h) greatly reduced urinary THS excretion (and plasma steroid levels). Urinary THS excretion was low after delivery in these mothers, in normal pregnancies, and in parents of affected individuals [μmol/day); P = NS]. However, 2 of the 3 heterozygous mothers who carried nonaffected fetuses excreted moderately increased amounts of THS during pregnancy, ranging from 0.15–0.26 mg/day (0.53–0.91 μmol/day), significantly higher than normal (P < 0.01). Although urinary THS excretion in these mothers was similar to that in 2 mothers with affected fetuses early in pregnancy, urinary THS excretion was higher in mothers with affected compared to those with nonaffected fetuses after the first trimester (P < 0.01). AF THS and 11-deoxycortisol concentrations were markedly elevated in pregnancies with affected fetuses (P < 0.01), but normal in nonaffected ones. AF Δ4-androstenedione levels were high in 2 pregnancies and borderline elevated in a third. Although the AF tetrahydrocortisol and tetrahydrocortisone levels were always within the normal range, the AF THS to tetrahydrocortisol plus tetrahydrocortisone ratio was significantly elevated in all pregnancies with affected fetuses (2.8–5.5; P < 0.01) and normal in nonaffected ones (0.48–1.2; P = NS) compared to that in 160 normal pregnancies [0.64 ± 0.34 (±SD)]. AF 17-hydroxyprogesterone, testosterone, and 11-deoxycorticosterone levels were normal in all pregnancies. Maternal plasma 11-deoxycortisol and Δ4-androstenedione concentrations, determined sequentially throughout gestation, were variable and did not contribute to prenatal diagnosis. All affected infants were born hyperpigmented, 2 were large for gestational age, and the female was severely virilized. In the first week of life 2 males developed severe hypertension with seizures and adrenal insufficiency, respectively. In the affected newborns plasma 11-deoxycortisol, Δ4-androstenedione, and 11-deoxycorticosterone levels were increased during the neonatal period, but urinary THS excretion was initially low. Prenatal diagnosis of lljS-hydroxylase deficiency congenital adrenal hyperplasia based on hormonal parameters is reliable when sequential maternal urine and AF determinations are performed in parallel.

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