THE APPLICATION OF A NEW HIGHLY-SENSITIVE RADIOIMMUNOASSAY FOR PLASMA21-DEOXYCORTISOL TO THE DETECTION OF STEROID-21-HYDROXYLASE DEFICIENCY

21-deoxycortisol (21-DF) is a steroid of strictly adrenal origin forme d by the ll-hydroxylation of 17-hydroxyprogesterone. This metabolic pa thway is minor in normal subjects, in whom basal plasma concentrations range from 0.03 to 0.63 nmol/L and from 0.865 to 1.50 nmol/L. after a drenocorticotrophic hormone (ACTH; Synacthene Immediat, Ciba/Geigy, Fr ance). However, this metabolic pathway becomes major in 21-hydroxylase -deficient patients: in those who have the classical form of congenita l adrenal hyperplasia (CAH) basal plasma 21-DF levels can attain more than 144 nmol/L. The synthesis of two isomers, E and Z, of the 21-deox ycortisol-3-carboxymethyloxime (CMO) hapten enabled us to prepare the corresponding E and Z immunogens by coupling them to bovine serum albu min (BSA), as well as the corresponding iodinated E and Z 21-DF-3-CMO- histamine tracers. We developed a very sensitive radioimmunoassay for 21-DF in plasma by associating an anti-21-DF-3-CMO-BSA-E isomer antibo dy to an iodinated 21-DF histamine-Z isomer (standard curve IC 50=8 pg /tube). This plasma 21-DF radioimmunoassay allowed diagnosis of the cl assical form of CAH in untreated newborn (basal 21-DF levels greater t han 144 nmol/L), as well as the late-onset form (post-ACTH 21-DF level s greater than 11.54 nmol/L), and also permitted detection of 21-hydro xylase-deficient heterozygotes of both forms of CAH among the general population (post-ACTH 21-DF levels between 2.02 and 9.52 nmol/L).