What are the typical levels of androstenedione in women with androgen-secreting tumors?

Androstenedione Levels in Women with Androgen-Secreting Tumors

Women with androgen-secreting tumors typically present with androstenedione levels exceeding 1,000 ng/dL (>34.7 nmol/L), often accompanied by markedly elevated testosterone levels above 200 ng/dL, and these extreme elevations distinguish tumors from more common causes of hyperandrogenism like PCOS. 1, 2

Typical Androstenedione Levels by Diagnosis

Androgen-Secreting Tumors

• Androstenedione levels frequently exceed 1,000 ng/dL in women with ovarian steroid cell tumors, with documented cases showing levels >1,738 ng/dL alongside testosterone levels of 485 ng/dL 2
• One reported case demonstrated androstenedione >34.7 nmol/L (approximately >1,000 ng/dL) with concurrent testosterone of 28.3 nmol/l in an ovarian steroid-cell tumor 1
• Testosterone levels >200 ng/dL should prompt urgent evaluation for androgen-producing tumors, as this threshold distinguishes neoplastic from functional causes 2

Comparative Context: PCOS vs. Tumors

• In PCOS, androstenedione levels are typically mildly elevated with sensitivity of 75% and specificity of only 71% for diagnosing hyperandrogenism, making it a second-line test 3
• Only 8-33% of PCOS patients have elevated DHEAS, whereas tumors typically present with markedly elevated androgens across multiple pathways 3
• The key distinguishing feature is rapid-onset virilization with extreme androgen elevations in tumors versus gradual symptom development in PCOS 3

Clinical Presentation Patterns

Tumor-Specific Features

• Rapidly progressive virilization (developing over weeks to months rather than years) is the hallmark clinical presentation 4
• Associated findings include clitoromegaly, deepening voice, and severe hirsutism that develop quickly 5, 3
• Postmenopausal women with new-onset virilization should be considered high-risk for androgen-secreting neoplasms 5, 4

Hormonal Patterns

• Tumors may produce isolated testosterone elevation (>700 ng/dL) with normal DHEAS and androstenedione in rare pure testosterone-secreting adenomas 5
• More commonly, tumors produce elevations across multiple androgens including testosterone, androstenedione, DHEAS, and 17-hydroxyprogesterone 1
• DHEAS >600 μg/dL indicates adrenal source and raises concern for adrenocortical carcinoma 3

Diagnostic Approach

Initial Screening Thresholds

• Testosterone >200 ng/dL (>8.7 nmol/L) warrants imaging evaluation for neoplasm, though this threshold has only 9% positive predictive value due to low tumor prevalence 4, 2
• The sensitivity of testosterone >250 ng/dL for detecting tumors is 100%, but specificity is only 98% with many false positives 4
• Androstenedione should be measured alongside testosterone and DHEAS when clinical suspicion for tumor exists, particularly with rapid symptom onset 6

Recommended Testing Panel

• First-line tests: DHEAS and testosterone to assess for suspected adrenocortical carcinoma (ACC) or virilization 6
• Ancillary testing should include: 17β-estradiol, 17-OH progesterone, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol 6
• Higher androgen levels suggest greater tumor burden, making serial measurements useful for monitoring 6

Important Clinical Pitfalls

Limitations of Biochemical Screening

• Testosterone and DHEAS screening alone is not cost-effective for tumor detection due to low disease prevalence (2.3% in hyperandrogenic populations) 4
• Clinical evaluation is often sufficient screening, with imaging reserved for those with testosterone >200 ng/dL or rapid virilization 4
• Normal DHEAS, androstenedione, and 17-hydroxyprogesterone do not exclude adrenal tumors, as rare pure testosterone-secreting adenomas exist 5

Source Localization Challenges

• Elevated testosterone alone does not reliably distinguish ovarian from adrenal source, requiring imaging of both sites in postmenopausal women with virilization 5
• Transvaginal ultrasound and adrenal CT imaging should be performed when testosterone exceeds 200 ng/dL or androstenedione exceeds 1,000 ng/dL 2
• PET-CT may help differentiate benign from malignant lesions and exclude ectopic androgen-producing tumors 5

Post-Surgical Outcomes

• Androgen levels normalize rapidly (within 13-30 days) following tumor removal, confirming the diagnosis 7, 2
• Normal ovulatory cycles resume within 30 days to 4 months after successful tumor resection 7, 2
• Fertility is preserved with appropriate surgical management, with documented spontaneous pregnancies following tumor removal 2