Serum 21-Deoxycortisol, 17-Hydroxyprogesterone, and 11-deoxycortisol in classic congenital adrenal hyperplasia: clinical and hormonal correlations and identification of patients with 11beta-hydroxylase deficiency among a large group with alleged 21-hydroxylase deficiency.
BACKGROUND
21-Hydroxylase deficiency (21OHD) is the most common cause of congenital adrenal hyperplasia, followed in frequency by 11beta-hydroxylase deficiency (11betaOHD). Although the relative frequency of 11betaOHD is reported as between 3 and 5% of the cases, these numbers may have been somewhat underestimated.


METHODS
In 133 patients (89 females/44 males; 10 d-20.9 yr) with alleged classic 21OHD and five (three females/two males; 7.3-21 yr) with documented 11betaOHD, we measured serum 21-deoxycortisol (21DF), 17-hydroxyprogesterone (17OHP), and 11-deoxycortisol (S), 48 h after glucocorticoid withdrawal. We also studied 20 sex- and age-matched control subjects. Serum steroid levels were determined by RIA after HPLC purification.


OBJECTIVE
The objectives of this study were to: 1) quantify 21DF in patients with congenital adrenal hyperplasia, 2) correlate hormonal with clinical data, and 3) identify possible misdiagnosed patients with 11betaOHD among those with 21OHD.


RESULTS
In 21OHD, 17OHP (217-100,472 ng/dl) and 21DF (<39-14,105 ng/dl) were mostly elevated and positively correlated (r = 0.7202; P < 0.001). Except for higher 17OHP in pubertal patients, 17OHP and 21DF values were similar according to sex, disease severity, or prevailing glucocorticoid dose. One additional patient with 11betaOHD was detected (1%) and also one with apparent combined 11beta- and 21OHD. S levels were elevated in 11betaOHD and normal but significantly higher in 21OHD than in controls.


CONCLUSIONS
To recognize patients with 21- and/or 11betaOHD, we recommend evaluation of 17OHP or 21DF and S. Also, 21DF may be useful to follow up pubertal patients with 21OHD. Because 1% of patients with alleged 21OHD may have 11betaOHD, its frequency seems underestimated, as per our experience in a Brazilian population.
Steroids Laboratory, Division of Endocrinology, Universidade Federal de Sao Paulo, Rua Pedro de Toledo, 781-13 andar, SP 04039-032 Sao Paulo, Brazil.
Vania
V
Tonetto-Fernandes
Sofia H V
SH
Lemos-Marini
Hilton
H
Kuperman
Luciane M
LM
Ribeiro-Neto
Ieda T N
IT
Verreschi
Claudio E
CE
Kater
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood*; D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood* / Q000201:enzymology; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003350:Cortodoxone / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D013252:Steroid 11-beta-Hydroxylase / Q000032:analysis*; D013255:Steroid 21-Hydroxylase / Q000032:analysis*
C003556:21-deoxycortisol; D019326:17-alpha-Hydroxyprogesterone; D013255:Steroid 21-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase; D003350:Cortodoxone