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Prenatal diagnosis of 11beta-hydroxylase deficiency congenital adrenal hyperplasia
Insights
Prenatal diagnosis of 11beta-hydroxylase deficiency congenital adrenal hyperplasia is feasible using urinary tetrahydro-11-deoxycortisol (THS) levels. Elevated THS in urine and amniotic fluid, along with an increased THS to THF plus THE ratio, indicate the condition antenatally.
Area of Science:
- Endocrinology
- Medical Genetics
- Reproductive Medicine
Background:
- Congenital adrenal hyperplasia (CAH) encompasses genetic disorders affecting adrenal steroidogenesis.
- 11beta-hydroxylase deficiency is a form of CAH that can be diagnosed antenatally.
- Accurate prenatal diagnosis is crucial for timely intervention and management.
Purpose of the Study:
- To evaluate the feasibility of antenatal prediction for 11beta-hydroxylase deficiency congenital adrenal hyperplasia.
- To identify reliable hormonal markers in maternal urine and amniotic fluid for prenatal diagnosis.
Main Methods:
- Analysis of urinary tetrahydro-11-deoxycortisol (THS) in mothers with affected infants.
- Measurement of THS, tetrahydrocortisol (THF), and tetrahydrocortisone (THE) in amniotic fluid using radioimmunoassay (RIA).
- Comparison of metabolite levels and ratios between affected pregnancies, normal pregnancies, and heterozygote parents.
Main Results:
- Urinary THS was significantly elevated during pregnancy in affected mothers, normalizing post-delivery.
- Amniotic fluid showed markedly increased THS levels with normal THF and THE in affected pregnancies.
- The ratio of THS to THF plus THE was significantly elevated in affected pregnancies compared to normal controls.
Conclusions:
- Hormonal measurements in maternal urine and amniotic fluid can facilitate prenatal diagnosis of 11beta-hydroxylase deficiency CAH.
- Elevated THS and an increased THS/THF+THE ratio are key indicators for antenatal detection.
- This diagnostic approach enables early identification and management of affected infants.
Abstract:
To predict 11beta-hydroxylase deficiency congenital adrenal hyperplasia antenatally, studies were performed in urines and amniotic fluids from 2 pregnant women who had previously given birth to affected infants and whose present pregnancies also resulted in infants with the disease. Urinary tetrahydro-11-deoxycortisol [pregnane-3alpha, 17alpha, 21-triol-20-one (THS)] was abnormally elevated in the first, second, and third trimesters (maximal values, 3.5 and 0.9 mg/24 h, respectively) but was undetectable after delivery in these mothers, in 15 normal pregnancies (10--40 weeks of gestation), and in 6 heterozygote parents. Amniotic fluid levels of THS, tetrahydrocortisol [pregnane-3alpha, 11beta, 17alpha, 21-tetra-o1-20-one (THF)], tetrahydrocortisone [pregnane-3alpha, 17alpha, 21-triol-11, 20-dione (THE)] measured by RIA at 18 weeks of gestation in the first mother and at 40 weeks in the second revealed 12.5- and 8.4-fold increases in THS, respectively, but normal THF and THE levels compared to mean levels in normal pregnancies. The THS to THF plus THE ratio, which was constant throughout pregnancy in 125 normal women (mean +/- SD, 0.63 +/- 0.34) despite the variable levels of these metabolites, was significantly elevated in both patients (4.4 and 3.8, respectively). These studies indicate that prenatal diagnosis of 11beta-hydroxylase deficiency congenital adrenal hyperplasia based on hormonal measurements is feasible.