This issue highlights Endocrine Board Review Online. Test your clinical knowledge and prepare for your exam with access to live course session recordings and case questions. Available on the online store.
A 50-year-old woman presents to your office with concerns of hirsutism and male-pattern balding. She had normal menarche at age 12 years and regular menses with 2 uncomplicated pregnancies. Her periods stopped 1 year ago, and she has noticed increased facial hair in a beard-like distribution over the past 18 months, some male-pattern balding, and increased hair on her breasts.
On physical examination, her BMI is 27 kg/m2, and blood pressure is 150/90 mm Hg. She is very muscular. She has terminal hairs on her chin in a full-beard distribution, 15 hairs on her areolae, and hair above and below the umbilicus. Her clitoris measures 2.8 × 1.7 cm.
Laboratory test results:
- LDL cholesterol = 151 mg/dL (3.91 mmol/L)
- Testosterone = 350 ng/dL (12.1 nmol/L)
- DHEA-S = 120 μg/dL (3.3 μmol/L) (reference range, 15-200 μg/dL [0.41-5.42 μmol/L])
- Prolactin = 15 ng/mL (0.65 nmol/L)
- FSH = 19 mIU/mL (19 IU/L)
- LH = 18 mIU/mL (18 IU/L)
- Hemoglobin A1c = 5.8% (40 mmol/mol)
Which of the following is the best next test to evaluate this patient?
- Transvaginal ultrasonography
- Dexamethasone suppression test
- Pituitary MRI with and without contrast
- Ovarian vein sampling
Postmenopausal hirsutism or virilization is most commonly associated with obesity or hyperthecosis. However, the rapid onset and severity of the symptoms and signs in this patient raise the concern of an ovarian tumor (usually Sertoli-Leydig–cell tumor, arrhenoblastoma, or hilus-cell tumor) that is secreting testosterone and causing virilization. Because these tumors are rare, more common causes of postmenopausal hirsutism and virilization should be considered. Transvaginal ultrasonography (Answer A) is the first test to look for a tumor or asymmetry of the ovaries since the tumors are usually small. If only testosterone is elevated and the ultrasound is negative, performing ultrasonography again in 3 months may be helpful. In addition, there have been reports of rare testosterone-secreting tumors of the adrenal gland, so CT of the abdomen and pelvis might be considered (but this was not given as a choice). CT is not optimal imaging for evaluating ovarian morphology and transvaginal ultrasonography is preferred.
A dexamethasone suppression test (Answer B) is used in the workup of Cushing syndrome and might be indicated if an adrenal mass is detected. With adrenal Cushing syndrome, the presentation would be different from this patient’s and the testosterone level would not be as high as it is in this vignette. Pituitary MRI (Answer C) is appropriate in the workup for a pituitary tumor and is not indicated in this case. Ovarian vein sampling (Answer D) was in vogue in the 1980s, but multiple studies have shown that it cannot distinguish between an ovarian tumor and an adrenal tumor. Hyperthecosis is a more common cause of postmenopausal hirsutism in which high gonadotropin levels drive androgen production from the ovarian theca cells. Whether women who present with hyperthecosis in menopausal years had polycystic ovary syndrome before menopause has not been clarified. Obesity can cause hirsutism—adipose tissue can have increased 5α-reductase activity, as well as local aromatase activity, which can cause androgenic and estrogenic effects. However, obesity alone does not usually result in virilization. Exposure to exogenous androgens might also be in the differential diagnosis because many men now use testosterone gel. Testosterone therapy for women is not approved for hypoactive sexual desire disorder in the United States. If it were administered, a physiologic, not pharmacologic, level would be the goal. In addition, with exogenous supraphysiologic testosterone administration, FSH and LH levels are usually suppressed.
Evaluate postmenopausal hyperandrogenism.
Alpañés M, González-Casbas JM, Sánchez J, Pián H, Escobar-Morreale HF. Management of postmenopausal virilization. J Clin Endocrinol Metab. 2012;97(8):2584-2588.
Vollaard ES1, van Beek AP, Verburg FA, Roos A, Land JA. Gonadotropin-releasing hormone agonist treatment in postmenopausal women with hyperandrogenism of ovarian origin. J Clin Endocrinol Metab. 2011;96(5):1197-1201.
Rothman MS, Wierman ME. How should postmenopausal androgen excess be evaluated? Clin Endocrinol (Oxf). 2011;75(2):160-164.
Pugeat M, Déchaud H, Raverot V, Denuzière A, Cohen R, Boudou P; French Endocrine Society. Recommendations for investigation of hyperandrogenism. Ann Endocrinol (Paris). 2010;71(1):2-7.