The Causes of Low Oestrogen Excretion in Pregnancy: The Development of Diagnostic Methods for the Antenatal Detection of Familial Congenital Adrenocortical Hypoplasia

Abstract

A pregnancy producing a boy with congeital adrenocortical hypoplasia is described. Consistently low oestrogen excretion, less than 10 umol/24 h, was not associated with any anatomical abnormality or diminished growth of the fetus as judged by ultrasound examination. Fetoplacental steroid sulphatase definciency was excluded by finding normal maternal excretion of oestrogen precursors, the 3Beta-hydroxy-5-ene steroid sulphates. Generalized adrenocortical hypoplasia was proven in the baby boy by analysis of steroid netabolites excreted in his urine. He suffered from salt loss and progressive jaundice. Both were responsive to gluco- and mineralo-corticoid replacement therapy. It is suggested that amniocentesis may be required for the antenatal diagnosis of congenital adrenocortical hypoplasia.

Review: Placental sulphatase deficiency

“…Using anencephalic pregnancies as a model for fetal adrenal hypoplasia, Oakey (1978) found subnormal maternal 17-oxogenic steroid excretion, while it was normal in PSD. Only the patients with PSD excreted <ll.5gmol oestrogen and >26gmol 17oxogenic steroids/24 h. However, Harkness et al (1980) found normal levels of 17-oxogenic steroids in one patient carrying a fetus later confirmed as having congenital adrenal hypoplasia and two of our patients with PSD excreted 18gmol/24h (patient 14) and 26 gmol/24 h (patient 30), levels within the 'hypoplasia' range. There is thus incomplete discrimination, but this assay has the advantage of being readily available.…”

“…Adrenal hypoplasia is comparatively rare: four infants excreted markedly subnormal levels of steroids post partum. One had severe salt loss and pigmentation consistent with adrenal hypoplasia (reported by Harkness et al, 1980) and three others showed less overt signs of adrenal failure, possibly consequent on ACTH insufficiency (see Grimsberg et at., 1978;Zachman et al, 1979). Congenital adrenal hypoplasia in pregnancy is not necessarily associated with oestrogen excretion as low as that in PSD.…”

“…This approach should detect deficiencies of enzymes 17~-hydroxylase and 20, 22 desmolase, disorders which would also be expected to cause abolition of the oestrogen increase during pregnancy, but no examples have so far been recognized. In two pregnancies with fetal congenital adrenal hypoplasia, maternal urinary steroid sulphates were not different from normal (Taylor and Shackleton, 1979;Harkness et al, 1980).…”

Prenatal diagnosis for placental steroid salfatase deficiency with fluorescence in situ hybridization: A case of X‐linked ichthyosis

“…Beside fetal death, an undetectable uE3 level in the second‐trimester maternal serum screening might be caused by fetal congenital adrenocortical hypoplasia. However, the incidence of primary adrenal hypoplasia is extremely rare 11 …”

Current clinical problems in placental steroid or aryl sulphatase C deficiency and the related ‘cervical dystocia’ and X‐linked ichthyosis

“…There are also the alternative methods of diagnosis discussed in that review. If the cause of the low oestrogen excretion is not the common PSD or drugs then adrenocortical hypoplasia should be suspected; amniotic fluid steroid analyses may be a practicable means of diagnosis for this defect (Harkness et al, 1980), which is usually fatal in the newborn period if untreated. If the diagnosis is PSD, delivery of a preterm infant on the basis of a low oestrogen excretion is unjustified.…”