What is the best course of action to manage Hyperandrogenism in a 23-year-old female with elevated DHEA and Testosterone levels?

Management of Hyperandrogenism in a 23-Year-Old Female

The most appropriate next step for this 23-year-old female with significantly elevated testosterone (664.3 ng/dL) and DHEA (291) levels is referral for imaging studies of both adrenal glands and ovaries to rule out androgen-secreting tumors.

Laboratory Interpretation and Clinical Significance

The patient's hormone profile shows:

• Testosterone: 664.3 ng/dL (markedly elevated; normal female range is typically 15-70 ng/dL)
• DHEA: 291 (elevated)
• Estrogen: 41 (within normal range)
• FSH: 4.9 (within normal range)
• LH: 7.0 (within normal range)

These values indicate significant hyperandrogenism that requires immediate evaluation due to:

• Testosterone level >200 ng/dL, which strongly suggests the possibility of an androgen-secreting tumor
• Elevated DHEA, which may indicate adrenal involvement

Diagnostic Algorithm

1. Immediate imaging studies:

   • Adrenal CT scan with contrast to evaluate for adrenal adenoma or carcinoma
   • Transvaginal ultrasound to evaluate for ovarian pathology (such as polycystic ovary syndrome or ovarian tumors)

2. Additional laboratory testing:

   • 17-hydroxyprogesterone to rule out congenital adrenal hyperplasia
   • Androstenedione levels for complete androgen profile
   • 24-hour urinary free cortisol to rule out concurrent hypercortisolism
   • ACTH level to help differentiate between adrenal and pituitary causes

3. If imaging is inconclusive:

   • Consider selective venous sampling from adrenal and ovarian veins to localize the source of androgen excess

Potential Diagnoses Based on Current Findings

1. Androgen-secreting tumor - Most likely given the markedly elevated testosterone level

   • Adrenal adenoma/carcinoma (elevated DHEA suggests adrenal involvement)
   • Ovarian tumor (Sertoli-Leydig cell tumor, hilar cell tumor)

2. Severe PCOS - Less likely with testosterone >600 ng/dL

   • PCOS typically presents with testosterone levels <200 ng/dL 1

3. Congenital adrenal hyperplasia (non-classical) - Would require elevated 17-hydroxyprogesterone

Treatment Approach

Treatment depends on the underlying cause:

1. For androgen-secreting tumors:

   • Surgical removal is the definitive treatment 2
   • Laparoscopic approach for adrenal adenomas when feasible
   • Oophorectomy or ovarian tumor resection for ovarian sources

2. For severe PCOS (if tumor is ruled out):

   • Combined hormonal contraceptives to suppress ovarian androgen production
   • Anti-androgens such as spironolactone may be added
   • Metformin if insulin resistance is present

Important Clinical Considerations

• Testosterone levels >200 ng/dL in women strongly suggest neoplastic etiology and warrant immediate investigation 3
• Pure testosterone-secreting adrenal adenomas are rare but can cause severe hyperandrogenism even with normal DHEAS 2
• Concurrent adrenal and ovarian pathology can coexist, as reported in case studies 4
• The positive predictive value of elevated testosterone (>250 ng/dL) for neoplasm is only about 9%, but the negative predictive value is 100% 1

Pitfalls to Avoid

1. Do not assume PCOS without ruling out neoplasm - Testosterone levels >200 ng/dL are uncommon in PCOS and should trigger tumor workup
2. Do not rely solely on DHEAS to rule out adrenal pathology - Some adrenal tumors can produce predominantly testosterone with minimal DHEAS elevation 2
3. Do not delay imaging studies - Early detection and treatment of androgen-secreting tumors is essential for preventing progression of virilization
4. Do not overlook the possibility of dual pathology - Both adrenal and ovarian sources can coexist 4

Follow-up Plan

• Repeat hormone levels after treatment to confirm normalization
• Monitor for resolution of clinical hyperandrogenism symptoms
• If surgical treatment is performed, ensure pathological confirmation of tumor type