Review Question - QID 221279

Aromatase Deficiency ETIOLOGY Pathophysiology QID: 221279 (M2.OMB.2)

QID 221279 (Type "221279" in App Search)

A 29-year-old G1P0 woman presents to her obstetrician at 20 weeks of gestation for routine follow-up. She has noticed increased body hair and acne that has worsened since her last visit. Her temperature is 98.6°F (37°C), blood pressure is 128/82 mmHg, pulse is 90/min, and respirations are 14/min. Fetal heart tones on Doppler are normal. Examination of the mother reveals hair growing on her chest and face, moderate acne of the face and back, and an enlarged clitoris. Bimanual examination reveals a uterus of appropriate gestational size with no adnexal masses. Fetal ultrasound reveals a fetus with a size appropriate for gestational age and ambiguous external genitalia. Prior genetic testing revealed that the fetus karyotype is 46 XX. The remainder of the exam is within normal limits. Which of the sets of laboratory results shown in Figure A would be seen in the fetus?

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This patient who presents with increased body hair, acne, voice changes, and clitoromegaly as well as virilization of the fetus most likely has a fetus with aromatase deficiency. This would result in elevated testosterone levels, decreased estrogen levels, and decreased luteinizing hormone levels.

Aromatase is responsible for converting androgens into estrogens. In aromatase deficiency, the fetus and placenta cannot make estrogens from androgens, leading to the virilization of both the female fetus and her mother. For the fetus, high levels of androgens in the absence of estrogens will result in ambiguous genitalia, including labioscrotal fusion and clitoromegaly at birth. For the mother, androgens pass from the placenta into her bloodstream, leading to hirsutism and virilization. Labs taken from a child born with aromatase deficiency will show high androgen levels, low/undetectable estrogen levels, and high follicle-stimulating hormone/luteinizing hormone levels. Male children born with aromatase deficiency have normal genitalia at birth, but their mothers experience the same hirsutism and virilization during pregnancy.

Fan et al. studied the role of cytochrome P450 family 19 subfamily A polypeptide 1 (CYP19A1) variants in aromatase deficiency. They identified 2 new variants of CYP19A1 that caused this pathological condition. They recommend consideration of aromatase deficiency as a diagnosis in patients with a putative diagnosis of congenital adrenocortical hyperplasia.

Incorrect Answers:
Answer 1: Low levels of all hormones would be seen in patients who have an inability to produce both pituitary and peripheral hormones. This would be very rare and is not generally seen in clinical practice.

Answer 2: Decreased testosterone levels and an elevation in both estrogen and LH would be seen in patients with an androgen production pathway deficit. Male patients with this disorder would present with abnormal development of the genitalia and infertility.

Answer 4: Increased testosterone levels and suppression of LH would be seen in patients who are taking exogenous androgens. These patients can present with aggression as well as virilization of female children.

Answer 5: Increased production of all hormones could be seen in patients who have a pituitary adenoma that results in excessive release of gonadotropins.

Bullet Summary:
Aromatase deficiency presents during pregnancy with maternal hirsutism and ambiguous female fetal genitalia due to the accumulation of androgens in the absence of estrogen.