An 18-year-old woman arrives in your clinic with
primary amenorrhea, sexual infantilism, and clitoromegaly.
She had ambigous external genitalia at birth. A laparotomy
was performed at 17 months of age and revealed
normal internal female genitalia. An ovarian biopsy revealed
apparently normal primordial follicles. Laboratory
studies revealed a normal female karyotype and high serum testosterone and androstenedione concentrations. Undetectable serum estradiol and estrone concentrations
were also noted. There was a high serum follicle-stimulating
hormone and LH concentration. Pelvic imaging disclosed
multiple ovarian cysts. What is the most likely diagnosis?
(A) Congenital adrenal hyperplasia
(B) Aromatase deficiency
© McCune-Albright syndrome
(D) Kallmann™s syndrome
(E) Galactosemia
safari99
u got it
The answer is BBB. Aromatase deficiency can result in non-adrenal female pseudohermaphroditism, which is characterized by virilized external genitalia at birth and by primary amenorrhea sexual infantilism, eunuchoid proportions, tall stature, high androgen serum levels, low or undetectable estradiol and estrone concentrations, hypergonadotropism, and multicystic ovaries in adolescence. The high androgen serum levels probably result from the disruption in the conversion of androgens to estrogens, which results in hypergonadotropism. The latter causes the multicystic ovaries”a common finding in this disorder. This disorder suggests that the congenital absence of aromatase is compatible with normal ovarian development
and that aromatase deficiency must be considered in the differential diagnosis
of primary amenorrhea. Congenital adrenal hyperplasia is the most frequent cause of adrenal
insufficiency in newborns. 21-Hydroxylase deficiency and 11--hydroxylase deficiency
are most common and affect only adrenal function. 3--Hydroxysteroid dehydrogenase
deficiency affects both adrenal and gonadal function. This is transmitted as an
autosomal recessive trait, and 3--hydroxysteroid dehydrogenase deficiency is characterized
by symptoms of both cortisol and aldosterone deficiency, which may be fatal if not
diagnosed early. Affected females have either normal sexual development or mild viralization, usually detected at puberty. Some patients will present with chronic anovulation,
but primary amenorrhea is a less common presenting symptom. The McCune-Albright
syndrome is characterized by patchy cutaneous hyperpigmentation, polyostotic fibrous
dysplasia, and several endocrine disorders including toxic multinodular goiter. Patients
often have amenorrhea and galactorrhea, Cushing™s syndrome, as well as the development
of precocious puberty. The precocious puberty is gonadotropin-independent, and the defect
lies within a constitutively active G protein. Kallmann™s syndrome is an X-linked disorder
characterized by hypogonadotropic hypogonadism, which is associated with anosmia. This
disorder more commonly affects men than women. Galactosemia results in hepatomegaly,
jaundice, and failure to thrive soon after birth, and is caused by a deficiency of galactose-
1-phosphate uridyltransferase. This enzyme catalyzes the conversion of galactose-1-phosphate to uridyl-dephosphogalactose. Women with galactosemia may have either primary
or secondary ammenorrhea, despite a lifelong galactose-free diet. Ovarian biopsies in
women with galactosemia reveal few primordial follicles, but numerous atretic follicles.
It is unclear whether the ovarian failure is caused by the accumulation of galactose-1-
phosphate or a deficiency of downstream metabolites.