The application of a new highly-sensitive radioimmunoassay for plasma 21-deoxycortisol to the detection of steroid-21-hydroxylase deficiency.
21-deoxycortisol (21-DF) is a steroid of strictly adrenal origin formed by the 11-hydroxylation of 17-hydroxyprogesterone. This metabolic pathway 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 adrenocorticotrophic hormone (ACTH; Synacthène Immédiat, Ciba/Geigy, France). However, this metabolic pathway becomes major in 21-hydroxylase-deficient patients: in those who have the classical form of congenital 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-deoxycortisol-3-carboxymethyloxime (CMO) hapten enabled us to prepare the corresponding E and Z immunogens by coupling them to bovine serum albumin (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 antibody to an iodinated 21-DF histamine-Z isomer (standard curve IC 50 = 8 pg/tube). This plasma 21-DF radioimmunoassay allowed diagnosis of the classical form of CAH in untreated newborn (basal 21-DF levels greater than 144 nmol/L), as well as the late-onset form (post-ACTH 21-DF levels greater than 11.54 nmol/L), and also permitted detection of 21-hydroxylase-deficient heterozygotes of both forms of CAH among the general population (post-ACTH 21-DF levels between 2.02 and 9.52 nmol/L).
Fiet
J
J
Laboratoire de Biologie Hormonale, Hôpital Saint-Louis, Paris, France.
Villette
J M
JM
Galons
H
H
Boudou
P
P
Burthier
J M
JM
Hardy
N
N
Soliman
H
H
Julien
R
R
Vexiau
P
P
Gourmelen
M
M
D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood* / Q000175:diagnosis; D000328:Adult; D000911:Antibodies, Monoclonal; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003350:Cortodoxone / Q000097:blood* / Q000276:immunology; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D011863:Radioimmunoassay; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; C003556:21-deoxycortisol; D003350:Cortodoxone