371therapy, even in those who have hypertension prior to therapy. This paradox
occurs because after initiation of glucocorticoid therapy, there is inhibition of
ACTH drive for adrenal steroidogenesis, which results in nonavailability of
precursor metabolites required for mineralocorticoid synthesis. Therefore, after
initiation of glucocorticoids, some children may experience fall in blood pres-
sure and require addition of fl udrocortisone.- A 17-year-old tall girl presented with primary amenorrhea, hypertension, and
absent secondary sexual characteristics. What is the likely diagnosis?
The presence of hypertension in an adolescent girl without any sign of pubertal
development should raise the suspicion of CAH due to 17α-hydroxylase defi -
ciency (CYP17A1). Defi ciency of 17α-hydroxylase enzyme results in hyperten-
sion and hypokalemia due to diversion of precursor metabolites to
mineralocorticoid synthetic pathway and accumulation of deoxycorticosterone
(DOCA) and corticosterone. Primary amenorrhea and absent pubertal develop-
ment is due to impaired estradiol synthesis in the ovary, as the enzyme is expressed
both in the adrenal and gonads. Patients with 17α-hydroxylase defi ciency do not
manifest adrenal insuffi ciency, as corticosterone has modest glucocorticoid activ-
ity. The disorder is characterized by hypokalemia, decreased plasma renin activ-
ity and aldosterone, and elevated FSH and LH with low estradiol levels
(hypergonadotropic hypogonadism). The diagnosis is confi rmed by estimation of
pregnenolone, progesterone, deoxycorticosterone, and corticosterone which are
invariably elevated, or by genetic analysis. Boys with CAH due to 17α-hydroxylase
defi ciency present with hypertension and complete female external genitalia or
rarely, with genital ambiguity depending on the residual enzyme activity.- What are the variants of CAH associated with genital ambiguity in a boy?
The variants of CAH associated with genital ambiguity in a boy include
17 α-hydroxylase defi ciency and 3β-hydroxysteroid dehydrogenase type 2 (3β-
HSD2) defi ciency, as these enzymes are expressed in both testes and adrenals.
These disorders can be differentiated by the presence of hypertension and
cryptorchidism (usually intra-abdominal) in 17α-hydroxylase defi ciency and
the presence of salt-wasting crisis with normally located testes in 3β-HSD2
defi ciency. In addition, boys with CAH due to cytochrome P450 oxidoreduc-
tase (POR) defi ciency also have genital ambiguity.- What are the characteristic features of CAH due to cytochrome P450 oxidore-
ductase ( POR ) defi ciency?
The POR protein is essential for electron transport from NADPH for optimal
functioning of various microsomal enzymes like CYP21A2 (21α-hydroxylase),
CYP17A1 (17α-hydroxylase and 17,20-lyase), CYP19A1 (aromatase), and
CYP51A1 (lanosterol 14α-demethylase). CAH due to POR defi ciency is charac-
terized by genital ambiguity, skeletal malformations, and history of maternal
virilization during pregnancy. The genital ambiguity in 46,XY newborns is due10 Congenital Adrenal Hyperplasia