Diagnostic Approach to Elevated DHEAS in Hirsutism

Introduction to Diagnostic Considerations

The American College of Obstetricians and Gynecologists recommends that an elevated DHEAS in a patient with hirsutism primarily indicates increased adrenal androgen production, most commonly from polycystic ovary syndrome (PCOS), but markedly elevated levels (>600 μg/dL or >6000 ng/mL) should prompt urgent evaluation for adrenocortical carcinoma or other androgen-secreting tumors 1, 2

PCOS accounts for approximately 95% of hyperandrogenism cases and affects 10-13% of women globally, making it the overwhelmingly most likely diagnosis in this clinical scenario, according to the Endocrine Society 3, 1
The International PCOS Guidelines recommend DHEAS only as a second-line test when total testosterone and free testosterone are not elevated but clinical suspicion remains high, as stated by the American College of Obstetricians and Gynecologists 1

Adrenocortical carcinoma (ACC) is responsible for more than half of androgen hypersecretion cases and should be suspected with DHEAS >600 μg/dL, tumors >4-5 cm, irregular margins, or heterogeneity on imaging, as recommended by the National Comprehensive Cancer Network 6, 2
The American College of Radiology suggests that immediate imaging with adrenal CT is mandatory if DHEAS >600 μg/dL, or if there are signs of severe virilization, according to the Journal of the National Comprehensive Cancer Network 2, 4

The Endocrine Society recommends total testosterone and free testosterone by LC-MS/MS as first-line hormonal testing, with a sensitivity of 74% and specificity of 86% for total testosterone, and sensitivity of 89% and specificity of 83% for free testosterone 3, 1
The American College of Obstetricians and Gynecologists suggests that 17-hydroxyprogesterone measurement and ACTH stimulation testing should be used to rule out non-classical congenital adrenal hyperplasia, particularly since DHEAS exceeds age-specific threshold 2

If PCOS is confirmed, the American College of Obstetricians and Gynecologists recommends combined oral contraceptives as first-line treatment to regulate cycles and reduce hyperandrogenism, along with lifestyle modifications including diet and exercise for weight management, and screening for and managing metabolic complications 1
If adrenal tumor is suspected, the National Comprehensive Cancer Network recommends unilateral adrenalectomy for confirmed ACC, with minimally invasive surgery when feasible, and open adrenalectomy if malignancy suspected (tumors >5 cm, irregular margins, local invasion) 6, 4