SAT-224 Polycystic Ovary Syndrome with Adrenal Hyperandrogenemia and Refractory Hirsutism

Background. Hirsutism affects 5 to 10 percent of premenopausal women and is usually an indication of an underlying endocrine disorder. Polycystic ovary syndrome (PCOS) is the most common etiology of hirsutism and is diagnosed in approximately 70% of cases. We present a case of PCOS with adrenal hyperandrogenism (AH) in which elevated adrenal androgens may have limited the effects of conventional PCOS treatment on a patient’s hirsutism. Case. A 26-year-old Asian Indian female reported onset of hirsutism at age 13 years. She subsequently experienced weight gain and noted occurrence of irregular menses and thinning scalp hair. Hirsutism did not respond to treatment with an oral contraceptive (drosperinone-ethinyl estradiol), spironolactone, and metformin. Examination was notable for obesity, Tanner stage 5 breast development, a Ferriman -Gallwey score of 23 (normal < 9), dorsal cervical acanthosis nigricans, and thinning scalp hair in an androgenetic pattern. Laboratories on treatment were notable for a testosterone level of 44 ng/dL (8-60), dehydroepiandrosterone (DHEA) level 1,907 μg/dL (102-1,185) and DHEA-sulfate (DHEAS) 562 μg/dL (18-391). Hormonal evaluation off medications yielded a total testosterone of 90 ng/dL, DHEAS 608 μg/dL, basal 17-hydroxyprogesterone 45 ng/mL (< 200), 17-hydroxypregnenolone 99 ng/dL (< 905), morning ACTH 20 pg/mL (6-50), prolactin 7.2 ng/mL (2.7-26.7), and IGF-1 297 ng/mL (63-373). Cortisol suppressed appropriately on an overnight 1 mg dexamethasone suppression test (DST). Normal size adrenal glands without mass lesions were demonstrated on computed tomography of the abdomen. During a two-day low dose DST, DHEAS, DHEA, and testosterone fell by 70, 88, and 85 percent, respectively, from baseline at the end of testing (fall of DHEAS by > 60% and testosterone by > 40% indicative of an adrenal source of androgen). Conclusion. AH occurs in approximately 25-50% of PCOS cases. Exaggerated responsiveness of the zona reticularis to ACTH appears to be the primary cause of AH in PCOS (AH-PCOS), though the cause of increased sensitivity to ACTH remains unclear. Potential etiologies of hirsutism that can mimic AH-PCOS such as Cushing syndrome, nonclassical CAH, 3β-hydroxysteroid dehydrogenase deficiency, 11-hydroxylase deficiency, and androgen producing adrenal masses were excluded on the patient’s metabolic and imaging work up. Women with AH-PCOS have reduced insulin sensitivity compared to PCOS patients without AH, and occurrence of AH-PCOS in obese women increases the risk of hypertension. Despite significant improvements in adrenal androgens and testosterone levels, treatment of AH-PCOS women with glucocorticoids does not significantly improve ovulatory function or hirsutism and is associated with significant weight gain.