A 45-year-old woman comes to the office due to 3 months of excessive hair growth over her face and body. Her last menstrual period was 4 months ago. The patient's menstrual cycle had previously been regular, and she has had 2 successful pregnancies. Medical history includes hypothyroidism, for which she takes a stable dose of levothyroxine; a recent TSH level was normal. The patient has smoked half a pack of cigarettes daily for 25 years. Blood pressure is 124/82 mm Hg and pulse is 72/min. BMI is 24 kg/m². The patient is muscular and has an enlarged clitoris. There is temporal balding, and a large amount of coarse terminal hair is present on the face, back, chest, and lower abdomen. The remainder of the physical examination is normal. Urine pregnancy test is negative. Which of the following is the best next step in evaluation of this patient?

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Explanation: 11ec25c8_d3ae_fc6a_bc81_073e0110c099_MD0003_00 Although most women with hirsutism (excessive terminal hair growth) have polycystic ovary syndrome (PCOS), rapid-onset hirsutism (eg, <1 year), particularly with virilization (eg, temporal balding, excessive muscular development, enlarged clitoris), suggests very high androgen levels due to an androgen-secreting neoplasm of the ovaries or adrenal glands. The primary ovarian androgens are testosterone, androstenedione, and dehydroepiandrosterone (DHEA). The adrenals also produce these androgens as well as DHEA sulfate (DHEAS). Therefore, women with a suspected androgen-producing tumor should be evaluated with serum testosterone and DHEAS levels: Elevated testosterone levels with normal DHEAS levels suggest an ovarian source (more common). Elevated DHEAS levels suggest an adrenal tumor (far less common). DHEAS and DHEA have negligible intrinsic androgenic action but are converted to androstenedione and subsequently to testosterone in peripheral tissues. (Choice A) Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency causes elevated androgen precursors (eg, 17-hydroxyprogesterone). Female infants with classic CAH present at birth with ambiguous genitalia. In contrast, women with nonclassic CAH due to partial 21-hydroxylase deficiency develop hyperandrogenism from late childhood to early adulthood. However, symptoms are typically slowly progressive over years. Initial testing is with a basal 17-hydroxyprogesterone level; an ACTH stimulation test may be performed in patients with a moderately elevated basal screening for diagnosis. (Choice B) Imaging studies prior to biochemical confirmation of hyperandrogenism can be misleading because many patients have nonfunctioning adrenal and ovarian masses that have no disease manifestations. If DHEAS levels are elevated, an abdominal CT scan is performed to evaluate the adrenal glands. (Choice C) Excessive body hair is common in women with acromegaly (elevated growth hormone increases insulin-like growth factor 1 levels). However, hair growth is usually not rapidly progressive, and other clinical features of acromegaly (eg, enlarging facial features, macroglossia) are typically seen. (Choice D) An increased LH to FSH ratio is sometimes seen in PCOS; however, it is not diagnostic as results are inconsistent. Hirsutism is common in patients with PCOS but is typically chronic and slowly progressive, beginning around puberty. Educational objective: Rapid-onset hyperandrogenism, particularly with virilization, suggests an androgen-secreting ovarian or adrenal neoplasm. Serum testosterone and DHEAS levels are used to delineate the site of androgen production. Elevated testosterone with normal DHEAS suggests an ovarian source, whereas elevated DHEAS suggests an adrenal source. References: Causes, patterns, and severity of androgen excess in 1205 consecutively recruited women. (http://www.ncbi.nlm.nih.gov/pubmed/29342266) Endocrinology update: hirsutism. (http://www.ncbi.nlm.nih.gov/pubmed/27936531) Hyperandrogenism in post-menopausal women: a diagnosis challenge. (http://www.ncbi.nlm.nih.gov/pubmed/24188447)

A 45-Year-Old Woman Comes to the Office Due to 3