Increased plasma 21-deoxycorticosterone (21-DB) levels in late-onset adrenal 21-hydroxylase deficiency suggest a mild defect of the mineralocorticoid pathway.
Plasma 21-deoxycorticosterone (21-DB) concentrations were measured before (basal) and 1 h after ACTH stimulation in a population of 34 normal subjects, 18 patients with the late-onset form of congenital adrenal hyperplasia (LO-CAH) due to 21-hydroxylase deficiency, and 19 LOCAH heterozygotes. For comparison, plasma 21-deoxycortisol (21-DOF) and 17-hydroxyprogesterone (17-OHP) were determined simultaneously in the same subjects. Plasma 21-DB concentrations as well as those of 21-DOF did not vary significantly as a function of age, sex, or phase of the menstrual cycle, in contrast to plasma 17-OHP. The mean plasma 21-DB concentrations in normal subjects (adult men, follicular and luteal phase women, and children) were 19.0 +/- 9.5 (+/- SD) pmol/L before and 73.2 +/- 31.0 after ACTH stimulation. In the LOCAH patient group, the mean post-ACTH plasma 21-DB concentration was 1736.0 +/- 1243.0 pmol/L, and all values were above the highest post-ACTH value (148.2 pmol/L) in the normal subjects. Similarly, in the LOCAH patients the post-ACTH plasma 21-DOF concentration was 33.7 +/- 20.3 nmol/L, and the post-ACTH plasma 17-OHP value was 134.0 +/- 70.6 nmol/L; all LOCAH patients had supranormal responses to ACTH. However, 38.9%, 11.2% and 16.7% of the basal plasma 21-DB, 21-DOF, and 17-OHP values in the LOCAH patients overlapped those in the normal subjects. There was a rather large overlap (63.2%) in post-ACTH plasma 21-DB levels between the LOCAH heterozygotes and the normal subjects; it was less than the overlap in plasma 17-OHP (74%) and more than the overlap in plasma 21-DOF values (5.2%) in these same 2 groups. There was moderate overlap (21%) in the post-ACTH plasma 21-DB levels between the LOCAH heterozygotes and LOCAH patients, but no overlap between these 2 groups for either 21-DOF or 17-OHP. The abnormally elevated post-ACTH plasma 21-DB levels found in all the LOCAH patients as well as in some LOCAH heterozygotes suggest the existence of minor 21-hydroxylase deficiency in the mineralocorticoid synthetic pathway in these patients in addition to the well known impairment in the glucocorticoid pathway demonstrated by the elevated post-ACTH 21-DOF and 17-OHP levels.
Fiet
J
J
Laboratoire de Biochimie, Hôpital Saint-Louis, Paris, France.
Gueux
B
B
Raux-DeMay
M C
MC
Kuttenn
F
F
Vexiau
P
P
Brerault
J L
JL
Couillin
P
P
Galons
H
H
Villette
J M
JM
Julien
R
R
D019326:17-alpha-Hydroxyprogesterone; D000311:Adrenal Glands / Q000201:enzymology; D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology / Q000209:etiology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D002648:Child; D003350:Cortodoxone / Q000097:blood; D003900:Desoxycorticosterone / Q000097:blood*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006908:Hydroxyprogesterones / Q000097:blood; D008297:Male; D008875:Middle Aged; D013250:Steroid Hydroxylases / Q000172:deficiency*
D006908:Hydroxyprogesterones; D003900:Desoxycorticosterone; C003556:21-deoxycortisol; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D003350:Cortodoxone