21-hydroxylase deficiency transiently mimicking combined 21- and 11beta-hydroxylase deficiency.
21-Hydroxylase deficiency (21OHD) is the commonest form of congenital adrenal hyperplasia, while 11betaOHD represents 5% of cases. Although both result from mutations in distinct genes, cases of 'apparent' combined 21OHD and 11betaOHD (AC21,11OHD) have been occasionally reported. A 6 year-old girl, born with ambiguous genitalia and salt-loss, had serum elevations (ng/dl) of androstenedione (>1,000), 17-hydroxyprogesterone (17OHP; 38,483), 21-deoxycortisol (21DF; 23,338), and 11-deoxycortisol (S; 4,928), suggesting AC21,11OHD. CYP21A and CYP11B1 genotyping identified mutations only in the former. On follow-up, serum S became normal but 17OHP and 21DF were still elevated. ACTH stimulation disclosed elevated levels of 17OHP and 21DF, but unresponsive S and undetectable deoxycorticosterone. The hormonal pattern initially suggested AC21,11OHD, but subsequent normalization of S showed transient 11-hydroxylase inhibition. This may have occurred by enzyme or co-enzyme immaturity or functional discrepancy, but also by selective inhibition of 11betaOH by excess intra-adrenal concentration of androgens, acting as pseudo-substrates for this enzyme.
Tonetto-Fernandes
Vânia
V
Division of Endocrinology, Department of Medicine, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, SP, Brazil.
Lemos-Marini
Sofia H V
SH
De Mello
Maricilda P
MP
Ribeiro-Neto
Luciane M
LM
Kater
Claudio E
CE
D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000235:genetics*; D000735:Androstenedione / Q000097:blood; D002648:Child; D003350:Cortodoxone / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics*; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
D000735:Androstenedione; C003556:21-deoxycortisol; D013255:Steroid 21-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase; D003350:Cortodoxone