Amniotic Fluid Concentrations of Δ5 and Δ4 Steroids in Fetuses with Congenital Adrenal Hyperplasia due to 21 Hydroxylase Deficiency and in Anencephalic Fetuses*

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Abstract
Amniotic fluid concentrations of the Δ5 steroids [17-hydroxypregnenolone (Δ5-17P) and dehydroepiandrosterone] and the Δ4 steroids [17-hydroxyprogesterone (17-OHP), androstenedione (Δ4-A), and testosterone (T)] of 77 normal pregnancies with gestational ages of 12 weeks to term were compared with those of 8 pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) and 5 pregnancies with anencephalic fetuses. At midgestation (14, 14.5, and 17 weeks) in 3 fetuses at risk for CAH (1 male and 2 females), all of whom were later proven to be affected with CAH, the amniotic fluid hormonal concentrations compared to controls of the same sex showed elevated 17-OHP and Δ4-A in all fetuses, elevated Δ5-17P in the 2 females and upper normal level in the 1 male fetus, and elevated T in both females and upper normal level in the male. At term, concentrations of 17-OHP, Δ4-A, Δ5-17P, and T in a follow-up amniotic fluid sample in 1 female fetus with CAH were clearly elevated. In 5 other pregnancies at risk for CAH, all amniotic fluid steroids were completely within the normal range for their sex at both midgestation and term, and these fetuses were proven to be normal at birth (3 males and 2 females). In the four midgestational anencephalic fetuses (14.5, 16, 17, and 18 weeks), amniotic fluid concentrations of 17-OHP, and Δ5-17P in both male and female fetuses and Δ4-A in one female were below or in the lowest range of normal, while Δ4-A and T in the male anencephalic fetuses did not clearly differ from normal. At term, the steroid concentrations in one female anencephalic amniotic fluid sample were all undetectable. However, these could not be distinguished from normal levels. The concentrations of dehydroepiandrosterone in midgestational or term amniotic fluid samples of CAH and anencephalic fetuses did not differ from normal values for the same sex. In conclusion, the decreased Δ5 and Δ4 17-hydroxylated steroids (Δ5-17P and 17-OHP) in the amniotic fluid of anencephalic fetuses whose ACTH secretion is presumably decreased suggests that adrenal steroidogenesis is under ACTH regulation during midgestation. Further, the increased Δ5 and Δ4 17-hydroxylated steroid concentrations (Δ5-17P, 17-OHP, and Δ4-A) in the amniotic fluid of CAH fetuses suggests that ACTH secretion may be increased due to decreased cortisol synthesis in these fetuses and supports the concept that there is a functional feedback in the hypothalamic-pituitary-adrenocortical axis in the midgestational human fetus.