In a 53-year-old woman whose serum testosterone rose from 47 ng/dL to 390 ng/dL over two months, what is the appropriate evaluation and management?

Urgent Evaluation for Androgen-Secreting Tumor Required

This 53-year-old woman with testosterone rising from 47 to 390 ng/dL over 2 months requires immediate workup for an androgen-secreting ovarian or adrenal tumor, as this dramatic elevation—particularly the 390 ng/dL level which is 8-fold above normal—strongly suggests neoplasm rather than benign hyperandrogenism.

Critical First Steps

1. Verify the Testosterone Level

• Repeat testosterone measurement using a specialty laboratory with mass spectrometry (not standard hospital immunoassays, which are notoriously inaccurate in women) 1
• Draw early morning, ideally days 4-10 of cycle if still menstruating
• The 390 ng/dL level is approximately 8-fold the upper limit of normal for women (normal ~10-50 ng/dL), placing this in the tumor range

2. Complete Hormonal Panel

Obtain the following to localize the source:

Adrenal markers:

• DHEAS: If >600 µg/dL (16,000 nmol/L), suggests adrenal cortical adenoma 2
• 17-hydroxyprogesterone (early morning): Rules out nonclassic congenital adrenal hyperplasia
• Cortisol: Assess for concurrent hypercorticism

Ovarian/pituitary markers:

• Free testosterone and SHBG
• LH and FSH (typically suppressed with androgen-secreting tumors)
• Consider AMH (markedly low in recent case reports of ovarian tumors) 3

Imaging Protocol

Even if initial imaging is negative, proceed with comprehensive evaluation:

1. Pelvic MRI with contrast (superior to ultrasound for small ovarian tumors) 3, 4

   • Transvaginal ultrasound frequently misses small androgen-secreting tumors 5, 4, 6
   • Multiple recent case reports document negative ultrasound/CT with positive MRI findings

2. Abdominal CT with contrast if DHEAS >600 µg/dL to evaluate adrenal glands 2

Critical Clinical Assessment

Assess for virilization features that increase tumor likelihood 1:

• Rapid onset/progression (present in this case—2 months)
• Clitoromegaly
• Deepening voice
• Male-pattern baldness
• Increased muscle mass
• Severe hirsutism

Diagnostic Algorithm Based on Results

If DHEAS >600 µg/dL:

• Abdominal CT → likely adrenal source
• Surgical referral for adrenalectomy

If DHEAS normal but testosterone remains >200 ng/dL:

• Ovarian source most likely 2
• Pelvic MRI mandatory
• Strong consideration for bilateral salpingo-oophorectomy even with negative imaging 5, 4, 6

Special Consideration for This Postmenopausal-Age Patient

At 53, if perimenopausal/postmenopausal:

• Lower threshold for surgical exploration given multiple 2025-2026 case reports of bilateral Leydig cell tumors, steroid cell tumors, and ovarian hyperplasia presenting with testosterone 300-1500 ng/dL and negative or minimal imaging findings 5, 4, 6
• These tumors are often <1 cm and easily missed on imaging
• Bilateral oophorectomy is both diagnostic and therapeutic, with immediate testosterone normalization post-operatively

Common Pitfalls to Avoid

1. Relying on negative ultrasound: Multiple recent cases show normal TVUS with confirmed ovarian tumors 4, 6
2. Being misled by adrenal incidentalomas: Check DHEAS to confirm adrenal vs ovarian source 3
3. Using standard hospital testosterone assays: These are unreliable in women 1
4. Delaying surgery awaiting positive imaging: In postmenopausal women with testosterone >200 ng/dL and negative imaging, diagnostic bilateral oophorectomy is indicated 4, 6

Definitive Management

For testosterone levels twice the upper limit of normal (>100 ng/dL), particularly with rapid rise as in this case:

• Endocrine surgery referral
• If ovarian source suspected and patient is postmenopausal: bilateral salpingo-oophorectomy
• If premenopausal with negative imaging: consider GnRH antagonist suppression test (cetrorelix) to confirm ovarian source before surgery 7

The 8-fold elevation to 390 ng/dL over just 2 months represents a medical urgency requiring rapid tumor workup, as delays in diagnosis of androgen-secreting tumors lead to irreversible virilization (voice changes, clitoral enlargement) and potential malignancy progression.