What is the appropriate diagnosis and management for a female patient with elevated DHEA (Dehydroepiandrosterone) sulfate, free testosterone, and testosterone bioavailability levels?

Elevated Androgens in a Female Patient: Diagnosis and Management

These laboratory values indicate biochemical hyperandrogenism requiring systematic evaluation to exclude serious causes, particularly androgen-secreting tumors, followed by targeted treatment based on the underlying etiology.

Interpretation of Laboratory Values

Your patient's results show:

• DHEA-S of 515.7 μg/dL is moderately elevated but well below the threshold (>600 μg/dL) that raises concern for adrenocortical carcinoma 1
• Free testosterone of 5.2 ng/dL is elevated above normal female ranges, confirming biochemical hyperandrogenism 2
• Testosterone bioavailability of 11.4 ng/dL is elevated, further confirming androgen excess 2

These levels suggest polycystic ovary syndrome (PCOS) as the most likely diagnosis, which accounts for 95% of hyperandrogenism cases in women 2. However, the elevation pattern requires systematic exclusion of other causes 2, 3.

Critical Red Flags to Assess Immediately

Evaluate for signs of androgen-secreting tumor, which would require urgent imaging:

• Rapid onset of symptoms (developing over weeks to months rather than years) suggests tumor rather than PCOS 2, 4
• Virilization signs: deepening voice, clitoromegaly, increased muscle mass, or male body habitus 2, 3
• Very high testosterone (>150-200 ng/dL or >5.2 nmol/L) would be more concerning for tumor, though your patient's levels are below this threshold 4

If any virilization or rapid progression is present, order adrenal CT scan immediately to exclude adrenal tumor 3. The DHEA-S level of 515.7 μg/dL makes adrenal tumor unlikely but does not completely exclude it 1, 4.

Complete Diagnostic Workup

First-Line Testing (if not already done)

• Confirm testosterone measurement by repeating total and free testosterone in the morning using LC-MS/MS methodology for highest accuracy 2
• Measure prolactin to exclude hyperprolactinemia, which can cause similar symptoms 2, 3
• Check TSH to rule out thyroid disease 2, 3
• Obtain LH/FSH ratio: a ratio >2 supports PCOS diagnosis 2

Second-Line Testing

• 17-hydroxyprogesterone (17-OHP) to screen for non-classic congenital adrenal hyperplasia, particularly if patient has ethnic background at higher risk 2, 3
• Fasting glucose and 2-hour oral glucose tolerance test to screen for insulin resistance and diabetes 2
• Fasting lipid panel to assess cardiovascular risk 2

Imaging Studies

• Pelvic ultrasound to evaluate for polycystic ovaries, though isolated polycystic ovaries without clinical/biochemical hyperandrogenism and ovulatory dysfunction do not constitute PCOS 2, 3
• Adrenal imaging (CT or MRI) is NOT routinely indicated with DHEA-S <600 μg/dL unless rapid symptom progression or virilization is present 1, 3

Clinical Assessment Required

Document the following to establish diagnosis:

• Menstrual history: oligomenorrhea (cycles >35 days or <8 cycles/year) or amenorrhea supports PCOS 2, 3
• Hirsutism assessment: use modified Ferriman-Gallwey score (≥6 indicates hirsutism) 2, 4
• Acne severity: persistent or treatment-resistant acne suggests hyperandrogenism 2
• Androgenic alopecia: male-pattern hair loss 2
• Metabolic signs: acanthosis nigricans (indicates insulin resistance), truncal obesity, elevated BMI 2, 3
• Timeline of symptom development: gradual onset over years favors PCOS; rapid onset over months raises concern for tumor 2, 4

Management Based on Most Likely Diagnosis (PCOS)

First-Line Treatment

Combined oral contraceptives (COCs) are the first-line treatment for hyperandrogenism in PCOS, effectively regulating menstrual cycles and reducing androgen effects 2, 3. This recommendation comes from the American College of Obstetricians and Gynecologists 2.

Adjunctive Therapies

• Lifestyle modification with weight loss if patient is overweight or obese, as this improves insulin sensitivity and reduces androgen levels 2, 3
• Metformin if insulin resistance is documented on glucose testing 3
• Anti-androgen therapy (spironolactone) for persistent hirsutism or acne despite COC therapy 3

Important Caveat About DHEA-S in PCOS

Only 8-33% of PCOS patients have elevated DHEA-S, with higher rates in certain phenotypes and ethnic groups 2. The presence of elevated DHEA-S does not change the diagnosis or management of PCOS, as it represents adrenal androgen contribution that is still part of the PCOS spectrum 2, 5.

Monitoring and Follow-Up

• Repeat DHEA-S and testosterone levels every 3-6 months until normalized or stable 3
• Monitor clinical symptoms of androgen excess for improvement 3
• Screen for metabolic complications including diabetes and dyslipidemia annually 2
• Address psychological impact of hyperandrogenism symptoms as part of comprehensive care 2

Key Clinical Pitfalls to Avoid

• Do not assume PCOS without excluding other causes: hyperprolactinemia, non-classic CAH, Cushing's syndrome, and tumors must be ruled out 2, 3
• Do not rely on DHEA-S alone for diagnosis: it has poor specificity (67%) compared to testosterone measurements 2
• Do not order adrenal imaging reflexively: with DHEA-S <600 μg/dL and no virilization, imaging is not indicated 1, 3
• Do not use direct immunoassay for free testosterone: LC-MS/MS or calculated free androgen index are required for accuracy 2
• Do not attribute all symptoms to PCOS without confirming ovulatory dysfunction: isolated polycystic ovaries on ultrasound without clinical/biochemical hyperandrogenism and menstrual irregularity do not meet PCOS criteria 2