A 28-year-old woman comes to the office due to increasing facial hair. The patient discontinued a combined estrogen/progestin oral contraceptive 6 months ago because she is trying to conceive. She has since noticed increasing hair on her upper lip and chin that she has tried removing, but it continues to grow back. The patient had regular menses while taking combined oral contraceptives but has not had a menstrual cycle since discontinuing them. She has no chronic medical conditions and has had no surgeries. The patient's only medication is a prenatal vitamin. Temperature is 36.7 C (98.1 F), blood pressure is 107/89 mm Hg, and pulse is 78/min. BMI is 21 kg/m². Physical examination shows multiple inflamed pustules and scars in various stages of healing on the cheeks and forehead. There is dense, pigmented hair growth over the upper lip and chin. Pelvic examination shows normal-appearing external genitalia with no clitoromegaly. The uterus is small and mobile and the ovaries are not enlarged. Pelvic ultrasound is normal. Which of the following is the most likely diagnosis in this patient?

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11ec25c8_d30b_4269_bc81_9d341c734625_MD0003_00 The most common cause of hyperandrogenism (eg, hirsutism) and abnormal uterine bleeding (eg, amenorrhea) in reproductive-aged women is polycystic ovary syndrome (PCOS). However, PCOS is a relative diagnosis of exclusion, and evaluation is required for other causes, particularly in this patient who has more significant signs of hyperandrogenism (eg, scar-forming, nodulocystic acne, dense hirsutism). In this patient, the most likely cause of hyperandrogenism is nonclassic (late-onset) congenital adrenal hyperplasia (NCCAH), a disorder most commonly caused by partial 21-hydroxylase deficiency. In this condition, there is impaired conversion of 17-hydroxyprogesterone in the adrenal glands, resulting in increased 17-hydroxyprogesterone levels and, consequently, increased androgen synthesis. Because NCCAH is a partial defect, patients typically do not develop symptoms until adolescence or early adulthood and rarely have virilization (eg, clitoromegaly, voice deepening). Often, the initial presentation is abnormal uterine bleeding (eg, irregular menses, amenorrhea), which may be masked by combined oral contraceptives, as in this patient. Diagnosis is with an elevated 17-hydroxyprogesterone level and an ACTH stimulation test. partial 21-hydroxylase deficiency (Choice A) 5-α reductase deficiency causes defective conversion of testosterone to dihydrotestosterone and classically presents in genotypically male newborns (46,XY) with male internal genitalia and female external genitalia. At puberty, elevated testosterone causes virilization (eg, clitoromegaly), which is not seen in this patient. In addition (and in contrast to this patient), those with 5-alpha reductase deficiency cannot menstruate (ie, no uterus). 5-α reductase deficiency (Choice B) Anorexia nervosa can cause abnormal uterine bleeding, acne (due to starvation), and increasing body hair (to maintain body temperature). However, rather than terminal hair, patients typically have fine, dark hair (lanugo-like) primarily on the back, abdomen, and arms; in addition, diagnosis requires a BMI <18.5 kg/m², making anorexia unlikely in this patient. ² (Choice C) Granulosa cell tumors are estrogen-producing ovarian tumors. Because of the excess estrogen, patients typically have breast tenderness and abnormal uterine bleeding due to concomitant endometrial hyperplasia/cancer. (Choice E) A Sertoli-Leydig cell tumor is an androgen-producing ovarian tumor that can cause rapid-onset hirsutism. However, patients typically have profound virilization (eg, clitoromegaly) and an adnexal mass on ultrasound, making this diagnosis unlikely in this patient. Educational objective: Nonclassic congenital adrenal hyperplasia occurs due to partial 21-hydroxylase deficiency and typically presents in reproductive-aged women with signs of hyperandrogenism (eg, hirsutism, acne) and abnormal uterine bleeding. References: Endocrinology update: hirsutism. (http://www.ncbi.nlm.nih.gov/pubmed/27936531) Hirsutism in women. (http://www.ncbi.nlm.nih.gov/pubmed/22335316) Non polycystic ovary syndrome-related endocrine disorders associated with hirsutism. (http://www.ncbi.nlm.nih.gov/pubmed/21623779) Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline. (http://www.ncbi.nlm.nih.gov/pubmed/29522147) Diagnosis and management of hirsutism. (http://www.ncbi.nlm.nih.gov/pubmed/20840269)

A 28-Year-Old Woman Comes to the Office Due to Increasing