327- Does the presence of gynecomastia help in the differential diagnosis of 46 , XY
DSD with genital ambiguity?
In patients with 46,XY DSD with genital ambiguity, the common differential
diagnosis include partial androgen insensitivity syndrome (PAIS), androgen
biosynthetic defects (ABSD), ovotesticular disorders (OT-DSD), 5α-reductase
type 2 defi ciency, and 46,XY partial gonadal dysgenesis. The presence of gyne-
comastia suggests PAIS, ABSD, and OT-DSD, whereas patients with
5 α-reductase type 2 defi ciency and 46,XY partial gonadal dysgenesis do not
have gynecomastia. Presence of gynecomastia in PAIS and ABSD is due to
defi cient secretion/action of testosterone and induction of aromatase activity by
elevated LH, whereas in OT-DSD, it is due to estrogen secretion from ovotes-
tes/ovary. Patients with 5α-reductase type 2 defi ciency do not have gynecomas-
tia as they have normal to high serum testosterone with normal LH, whereas
patients with 46,XY partial gonadal dysgenesis do not have gynecomastia as
the dysgenetic testes is unable to produce suffi cient quantity of testosterone to
be aromatized, even in the presence of elevated LH.- What are the variants of CAH associated with genital ambiguity in both
genders?
CAH due to 21α-hydroxylase defi ciency and 11β-hydroxylase defi ciency is asso-
ciated with genital ambiguity only in 46,XX individuals, and CAH due to
3 β-HSD2 and 17α-hydroxylase defi ciency is associated with genital ambiguity
only in 46,XY individuals. The only variant of CAH that manifest genital
ambiguity in both genders is CAH due to POR defi ciency. In addition, CAH due
to 3 β-HSD2 defi ciency may also have genital ambiguity in both genders, although
genital ambiguity is rare and less severe (isolated mild clitoromegaly) in females.- What are the DSDs associated with maternal virilization during pregnancy?
CytochromeP450 oxidoreductase defi ciency (POR), placental aromatase
defi ciency, luteoma of pregnancy, and exposure to androgenic progestins/
androgens are the causes of DSDs associated with maternal virilization dur-
ing pregnancy.- What are the characteristic features of aromatase defi ciency?
The acquisition of aromatase activity by placenta is important to prevent viril-
ization of the female fetus by androgens secreted from fetal adrenal gland.
DHEA (and 16α-hydroxy DHEA) synthesized from the fetal adrenal cortex is9 Disorders of Sex Development