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Difficulty: HardMenstrual Cycle Abnormalities and Contraception

A 28-year-old woman, nulligravida, comes to the clinic reporting an absence of menstruation for the past 6 months. Prior to this, her menstrual cycles were regular, occurring every 28 to 30 days. Over the same 6-month period, she has noticed rapid growth of coarse, dark hair on her upper lip, chin, and lower abdomen. She also reports that her voice has deepened, and she has experienced thinning of the hair on her scalp. She has no significant past medical history and takes no medications. Her body mass index (BMI) is 22 kg/m². Vital signs are within normal limits. Physical examination reveals temporal balding and significant facial hirsutism. Pelvic examination demonstrates a normal-sized, mobile uterus and distinct clitoromegaly. A urine pregnancy test is negative. Which of the following is the most appropriate next step in diagnosis?

  1. Measurement of serum testosterone and dehydroepiandrosterone sulfate levelsAnswer
  2. B
    Prescription of combined oral contraceptive pills
  3. C
    Endometrial biopsy
  4. D
    Measurement of serum thyroid-stimulating hormone and prolactin levels
  5. E
    Measurement of early morning serum 17-hydroxyprogesterone level

Answer

The correct answer is the measurement of serum testosterone and dehydroepiandrosterone sulfate (DHEA-S) levels.
The patient's presentation of secondary amenorrhea accompanied by rapid-onset clitoromegaly, voice deepening, and temporal balding indicates frank virilization. Unlike simple hirsutism, which is often seen in benign conditions like Polycystic Ovary Syndrome (PCOS), rapid-onset virilization is a major red flag for an androgen-secreting tumor. To localize the tumor, the first step is biochemical testing with serum testosterone (produced primarily by the ovaries) and dehydroepiandrosterone sulfate (DHEA-S, produced exclusively by the adrenal glands). Elevated testosterone points to an ovarian source, while elevated DHEA-S points to an adrenal source.

Step-by-Step Solution

1
Analyze the clinical presentation.
The patient has secondary amenorrhea combined with rapid-onset signs of severe hyperandrogenism, specifically virilization (deepening voice, temporal balding, clitoromegaly).
Differentiating between simple hirsutism (gradual onset, mild androgen excess) and virilization (rapid onset, severe androgen excess) is critical for determining the etiology.
2
Formulate a differential diagnosis for virilization.
Rapid-onset virilization is highly suspicious for an androgen-secreting neoplasm of either ovarian or adrenal origin.
Unlike PCOS or NCCAH which cause gradual, mild-to-moderate hyperandrogenism, tumors secrete massive amounts of androgens rapidly.
3
Select the appropriate diagnostic workup.
Serum testosterone and DHEA-S levels must be measured to localize the source of the androgens.
Markedly elevated testosterone (>150 ng/dL) points to an ovarian tumor, prompting a pelvic ultrasound. Markedly elevated DHEA-S (>700 mcg/dL) points to an adrenal tumor, prompting an adrenal CT scan.

Key Concept

Evaluation of rapid-onset virilization and androgen-secreting tumors
Estimated Time:1m 30s
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Topics

Menstrual Cycle Abnormalities and Contraception

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