What levels of Dehydroepiandrosterone sulfate (DHEA-S) would be concerning in a young woman?

Concerning DHEA-S Levels in Young Women

DHEA-S levels above 700 μg/dL (7000 ng/mL) are highly concerning and require urgent imaging to exclude adrenal malignancy, while levels above 600 μg/dL (6000 ng/mL) warrant immediate evaluation for adrenocortical carcinoma with adrenal CT imaging. 1

Critical Thresholds

Urgent Evaluation Required

• DHEA-S >600 μg/dL (6000 ng/mL): Immediate adrenal CT with contrast to rule out adrenocortical carcinoma 1
• DHEA-S 300-600 μg/dL (3000-6000 ng/mL): Requires prompt evaluation with imaging and comprehensive hormonal workup, as this range approaches malignancy thresholds 1
• Rapidly progressive virilization (voice deepening, clitoromegaly, male-pattern baldness, increased muscle mass) at any DHEA-S level strongly suggests malignancy and should not be delayed 1

Moderate Elevation

• DHEA-S above age-adjusted upper limit but <300 μg/dL: Most commonly associated with polycystic ovary syndrome (PCOS, affecting 4-6% of women) or non-classical congenital adrenal hyperplasia 2
• DHEA-S has moderate diagnostic accuracy for PCOS with pooled sensitivity of 75% and specificity of 67% 3

Diagnostic Algorithm for Elevated DHEA-S

Immediate Clinical Assessment

Look specifically for:

• Virilization signs: Clitoromegaly, voice deepening, increased muscle mass, male-pattern baldness 2
• Timeline of symptom onset: Rapid progression over weeks to months favors malignancy over benign conditions 1
• Hirsutism pattern: Male escutcheon pattern is particularly significant 1
• Menstrual pattern: Oligomenorrhea or amenorrhea common with androgen-secreting tumors 1

Laboratory Workup (Same Morning Blood Draw)

Order the following tests simultaneously 1:

• Androstenedione: Rule out adrenal/ovarian tumor if >10.0 nmol/L
• Total testosterone: Levels >8.7 nmol/L (250 ng/dL) have 100% sensitivity but only 9% positive predictive value for neoplasm 4
• 17-hydroxyprogesterone: Screen for non-classical congenital adrenal hyperplasia
• LH and FSH: Calculate LH/FSH ratio (>2 suggests PCOS)
• Morning ACTH and cortisol: Distinguish adrenal from pituitary sources
• Sex hormone-binding globulin (SHBG): For calculating free androgen index, which has better diagnostic accuracy (sensitivity 74-89%, specificity 83-86%) than DHEA-S alone 3

Imaging Studies

For DHEA-S >300 μg/dL or any rapid symptom progression 1:

• Adrenal CT with contrast (do not wait for hormone results if clinical virilization present)

  • Look for tumor size >4-5 cm (highly suspicious for malignancy)
  • Irregular margins or heterogeneous appearance
  • Lipid-poor lesions that fail to wash out on contrast-enhanced CT

• Transvaginal ultrasound:

  • Assess for polycystic ovaries (>10 peripheral cysts, 2-8 mm diameter)
  • Evaluate for ovarian masses 1

Differential Diagnosis by DHEA-S Level

Very High (>600 μg/dL)

1. Adrenocortical carcinoma: Approximately 60% present with virilization; peak incidence fourth to fifth decades; female-to-male ratio 1.5:1 1
2. Benign adrenal adenoma: Less likely with this degree of elevation 1

Moderate Elevation (Upper limit to 300 μg/dL)

1. PCOS: Most common cause; characterized by LH/FSH ratio >2, testosterone >2.5 nmol/L, polycystic ovaries on ultrasound 1
2. Non-classical congenital adrenal hyperplasia: Must be ruled out with 17-hydroxyprogesterone 1
3. Adrenal hyperandrogenism in PCOS: More common in non-classic (B and C) phenotypes; elevated DHEA-S found in 33% of PCOS women aged 20-29 years 5

Important Caveats

• Age-dependent values: DHEA-S reduces by 40% from twenties to thirties, so age-adjusted reference ranges are critical 5
• Low positive predictive value: While DHEA-S >600 μg/dL has 98% specificity for neoplasm, only 9% of patients with elevated testosterone actually have tumors 4
• Clinical evaluation is paramount: The presence of rapidly progressive virilization is more predictive of malignancy than absolute hormone levels 1, 4
• Rotterdam criteria: Show better sensitivity (77%) compared to NIH criteria (51%) when using DHEA-S as a diagnostic marker for PCOS 3

Management Based on Etiology

If Malignancy Suspected

• Unilateral adrenalectomy for adrenal masses causing androgen excess 1
• Open adrenalectomy preferred if size >4-5 cm, irregular margins, or heterogeneous appearance (prone to rupture) 1

If PCOS Confirmed

• Weight loss first-line for overweight/obese patients 2
• Hormonal contraceptives to regulate menstrual cycles and reduce androgen effects 3, 2
• Metformin if insulin resistance present (assess fasting glucose/insulin ratio; ratio >4 suggests reduced insulin sensitivity) 1
• Anti-androgen therapy (spironolactone) for persistent hirsutism or acne 2

Monitoring

• Repeat DHEA-S every 3-6 months until normalized or stable 2
• Long-term follow-up for persistent elevations to detect evolving pathology 2