5-androstene-3-16-17-triol and 16-hydroxydehydroepiandrosterone

A method for determining whether a pregnant woman with an extremely low serum oestriol (ELSE) measurement of mid-trimester is carrying a fetus with steroid sulphatase deficiency or another more serious disorder is described. We undertook GC/MS analysis of steroids in random maternal urine samples and quantified oestriol, oestriol precursors (dehydroepiandrosterone (DHEA), 5-androstene-3 beta, 17 beta-diol, 16 alpha-hydroxy-dehydroepiandrosterone and 5-androstene-3 beta, 16 alpha, 17 beta-triol), pregnanediol, and five other steroids largely unaffected by pregnancy (androsterone, etiocholanolone, tetrahydrocortisol, 5 alpha-tetrahydrocortisol and tetrahydrocortisone). Thirty-two samples collected from seven normal pregnant women between the 7th and 27th week of pregnancy and 22 from individuals with ELSE were analysed. Diagnostic ratios of excreted products were developed. These included ratios of oestriol and oestriol precursors to the cumulative value for the five non-pregnancy-related steroids and ratios of oestriol and oestriol precursors to pregnanediol and to each other. Our data demonstrated high 3 beta-hydroxy-5-ene steroid excretion in all ELSE patients together with low urinary oestriol excretion, a situation only consistent with deficiency of steroid sulphatase. The normal individuals had high oestriol and low excretion of oestriol precursors. No patient in our series showed the low oestriol levels and low oestriol precursor values that would indicate a fetal adrenal abnormality as the underlying defect.

Topics: Androstenediol; Androstenols; Arylsulfatases; Dehydroepiandrosterone; Estriol; Female; Fetus; Gas Chromatography-Mass Spectrometry; Gestational Age; Humans; Pregnancy; Pregnancy Trimester, Second; Pregnanediol; Prenatal Diagnosis; Protein Precursors; Steroids; Steryl-Sulfatase

Twenty-three cases of placental steroid sulfatase deficiency are reported. All children were boys who later acquired ichthyosis of the recessive X-linked type. The steroid sulfatase deficiency was present in placental tissue, umbilical cord leucocytes, and cultured skin fibroblasts of affected boys. An antepartum diagnosis can be obtained either by detecting the enzyme deficiency in cultured amniotic fluid cells or by finding an elevated total excretion of androstenetriol , 16 alpha-hydroxy-dehydroepiandrosterone, and 16 alpha-hydroxy-pregnenolone in maternal third-trimester urine. Vaginal delivery was accomplished in 16 patients (70%). No conspicuous pregnancy complications or neonatal problems were noted. However, birth weights tended to be relatively low. Intervention is unnecessary unless other obstetric indications require it. The incidence of this disorder appears to be approximately one per 2000 male births.

Topics: 17-alpha-Hydroxypregnenolone; Amniocentesis; Androstenols; Birth Weight; Dehydroepiandrosterone; Female; Humans; Ichthyosis; Infant, Newborn; Male; Placenta; Pregnancy; Pregnancy Trimester, Third; Prenatal Diagnosis; Steryl-Sulfatase; Sulfatases

A gas chromatographic procedure for the quantitation of neutral steroid sulphates in maternal urine and its application to a suspected case of placental sulphatase deficiency is described. Low levels of oestriol coincident with elevated 16-hydroxylated metabolites of dehydroepiandrosterone in the maternal urine are shown to occur in this particular condition, and thus provide a convenient differentiation from fetal adrenal hypoplasia before birth.

Topics: Androstenediols; Androstenols; Arylsulfatases; Chromatography, Gas; Dehydroepiandrosterone; Female; Glucuronates; Humans; Hydrolysis; Infant, Newborn; Male; Nitrophenols; Placenta Diseases; Pregnancy; Prenatal Diagnosis; Sulfatases