What is the significance of a testosterone level of 1056 ng/dL in a 47-year-old female?

Evaluation and Management of Significantly Elevated Testosterone in a 47-Year-Old Female

A testosterone level of 1056 ng/dL in a 47-year-old female is extremely high and requires urgent evaluation for an androgen-secreting tumor, most likely ovarian in origin. This value is dramatically above the normal female range of 20-50 ng/dL and warrants immediate investigation.

Clinical Significance and Diagnostic Approach

• Normal testosterone ranges for women:

  • Total testosterone: 20-50 ng/dL (or up to 70 ng/dL depending on the laboratory)
  • Free testosterone: 0.3-1.9 pg/mL

• A level of 1056 ng/dL is:

  • More than 20 times the upper limit of normal for women
  • Within the normal range for adult males (300-950 ng/dL) 1
  • Strongly suggestive of pathological androgen production

Initial Evaluation

1. Confirm the result:

   • Repeat the testosterone measurement to rule out laboratory error
   • Consider diethyl-ether extraction prior to immunoassay to eliminate potential assay interference 2
   • Use mass spectrometry if available (gold standard method) 3

2. Clinical assessment:

   • Evaluate for virilization signs (hirsutism, male-pattern baldness, deepening voice, clitoromegaly)
   • Note: Some patients may have selective peripheral tissue response without obvious virilization despite high testosterone 2
   • Assess menstrual history (amenorrhea is common with such high levels)

3. Additional laboratory tests:

   • DHEAS (to evaluate adrenal source)
   • FSH and LH (typically suppressed with androgen-secreting tumors) 4
   • Complete metabolic panel
   • Complete blood count (evaluate for erythrocytosis)

Imaging Studies

• Ovarian imaging: Transvaginal ultrasound and pelvic MRI to evaluate for ovarian tumors

  • Steroid cell tumors and other sex cord-stromal tumors are common causes 2, 4

• Adrenal imaging: CT scan of adrenal glands

  • To rule out adrenal androgen-secreting tumors 4

Diagnostic Pearls

• Testosterone levels ≥1.4 ng/mL (140 ng/dL) in postmenopausal women increase the likelihood of tumor by 8.4 times 4
• FSH levels ≤35 IU/L in postmenopausal women increase tumor likelihood by 10.8 times 4
• The combination of very high testosterone and suppressed gonadotropins strongly suggests a hormone-secreting tumor

Management

1. Referral:

   • Immediate referral to endocrinology and gynecologic oncology
   • Consider urology consultation if adrenal pathology is suspected

2. Definitive treatment:

   • Surgical resection of identified tumor is the primary treatment
   • Testosterone levels typically normalize within 24 hours post-surgery if tumor is completely removed 2

3. Follow-up:

   • Monitor testosterone levels post-intervention
   • Assess for return of normal menstrual function
   • Long-term surveillance based on tumor pathology

Important Caveats

• Commercial laboratory reference ranges for testosterone in women are often inappropriately high, which can lead to missed diagnoses of hyperandrogenism 5
• Some patients may have discordance between laboratory values and clinical presentation (high testosterone without virilization) 2
• 25-43% of ovarian steroid cell tumors are clinically malignant, emphasizing the need for prompt evaluation 2
• Non-tumoral causes of hyperandrogenism may be identified through immunohistochemical analysis with anti-P450c17α antibody if no tumor is found 4

This level of testosterone requires urgent evaluation as it represents a potentially serious underlying condition that could impact both morbidity and mortality if not promptly addressed.