An 18-year-old woman comes to the office after fracturing her distal radius when she fell off a chair. The patient had ambiguous external genitalia noted at birth, and laparotomy performed at 17 months of age revealed a normal uterus and fallopian tubes. Ovarian biopsy performed at that time revealed normal-appearing primordial follicles. She has never had a menstrual cycle. Blood pressure is 120/78 mm Hg and height is 160 cm (5 ft 3 in). The patient has nodulocystic acne over the chest and back. No breast development, normal pubic and axillary hair, and marked clitoromegaly are present. Laboratory results show a normal female karyotype and normal glucose and serum electrolytes. Estradiol and estrone are undetectable in the serum. Serum FSH, LH, testosterone, and androstenedione concentrations are high. Pelvic imaging reveals multiple ovarian cysts. Which of the following is the most likely diagnosis in this patient?

Question

An 18-year-old woman comes to the office after fracturing her distal radius when she fell off a chair.  The patient had ambiguous external genitalia noted at birth, and laparotomy performed at 17 months of age revealed a normal uterus and fallopian tubes.  Ovarian biopsy performed at that time revealed normal-appearing primordial follicles.  She has never had a menstrual cycle.  Blood pressure is 120/78 mm Hg and height is 160 cm (5 ft 3 in).  The patient has nodulocystic acne over the chest and back.  No breast development, normal pubic and axillary hair, and marked clitoromegaly are present.  Laboratory results show a normal female karyotype and normal glucose and serum electrolytes.  Estradiol and estrone are undetectable in the serum.  Serum FSH, LH, testosterone, and androstenedione concentrations are high.  Pelvic imaging reveals multiple ovarian cysts.  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

11ec25c8_d9ce_1022_bc81_dbafe5715de1_MD0003_00 Normal internal genitalia, external virilization (eg, clitoromegaly), and undetectable serum estrogen levels in a female patient are consistent with a diagnosis of aromatase deficiency. This rare enzyme deficiency first manifests in utero with the inability of the placenta to convert androgens into estrogens, leading to a transient masculinization of the mother that resolves after delivery. At birth, female infants have normal internal genitalia and ambiguous external genitalia due to high levels of gestational androgens. In adolescence, patients have delayed puberty, osteoporosis, undetectable estrogen levels (eg, no breast development), and high concentrations of gonadotropins that result in polycystic ovaries. (Choice B) Female patients with classic congenital adrenal hyperplasia (ie, 21-hydroxylase deficiency) present at birth with ambiguous external genitalia and normal internal female reproductive organs (eg, uterus, ovaries); however, they also typically have electrolyte abnormalities (eg, hyponatremia). Patients with nonclassic (late-onset) congenital adrenal hyperplasia can present with primary amenorrhea and virilization at puberty; however, they do not have ambiguous genitalia at birth - making these diagnoses unlikely. (Choice C) Kallmann syndrome is an X-linked abnormality characterized by hypogonadotropic hypogonadism with anosmia. Patients have delayed puberty but, unlike in this patient, LH and FSH levels are low or absent. (Choice D) McCune-Albright syndrome is marked by the triad of café au lait spots, polyostotic fibrous dysplasia, and autonomous endocrine hyperfunction. The most common endocrine feature is gonadotropin-independent precocious puberty. Thus, patients have early puberty in contrast to the ambiguous genitalia and delayed menarche in this patient. (Choice E) Ovarian hyperthecosis is a cause of virilization but is typically diagnosed in postmenopausal women. Patients with this condition also typically have signs of insulin resistance (eg, hyperglycemia, acanthosis nigricans) and low/normal LH and FSH levels. Typical ultrasound findings are solid-appearing, enlarged ovaries rather than multiple cysts. Educational objective: Congenital aromatase deficiency is a rare enzyme deficiency that prevents the conversion of androgens to estrogens. It causes virilization of female fetuses, resulting in normal internal genitalia with ambiguous external genitalia. References: Aromatase and estrogen receptor α deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/24485503)

An 18-Year-Old Woman Comes to the Office After Fracturing Her