In a 55‑year‑old postmenopausal woman with prior Cushing’s syndrome, Conn’s syndrome, mild autonomous cortisol secretion (MACS), and primary aldosteronism who had a unilateral adrenalectomy 10 weeks ago and no ovarian pathology, how should the markedly elevated total testosterone (~236 ng/dL) and free testosterone (~2.7 ng/dL) be evaluated and managed?

Urgent Evaluation for Residual or Contralateral Adrenal Pathology

This patient's markedly elevated testosterone (236 ng/dL, >2× upper normal limit for postmenopausal women) 10 weeks post-unilateral adrenalectomy requires immediate investigation for a testosterone-secreting tumor in the remaining adrenal gland or an occult ovarian source, despite prior ovarian clearance.

Immediate Diagnostic Workup

The testosterone level of 236 ng/dL is profoundly elevated—approximately 4-5 times the upper limit of normal for postmenopausal women (typically <70 ng/dL). When testosterone exceeds twice the upper limit of normal, guidelines mandate specific evaluation 1, 2:

First-Line Testing

• DHEAS measurement (essential next step): DHEAS >600 μg/dL indicates an androgen-secreting adrenal cortical adenoma 2. This is critical because:

  • The patient had bilateral adrenal pathology (Cushing's, Conn's, MACS, primary aldosteronism)
  • Only one adrenal was removed
  • The remaining adrenal may harbor an androgen-secreting lesion

• Repeat pelvic ultrasonography: Despite prior ovarian clearance, testosterone this elevated warrants re-imaging to exclude:

  • Ovarian hyperthecosis (typically associated with insulin resistance) 2
  • Androgen-secreting ovarian tumor that may have been missed or developed 1

Critical Imaging

• Adrenal protocol CT of the remaining adrenal gland: Given this patient's complex adrenal pathology history (Cushing's, MACS, Conn's, primary aldosteronism), the contralateral adrenal requires immediate high-resolution imaging 1. The coexistence of multiple hormone-secreting pathologies in adrenal tumors is well-documented 3, 4.

Clinical Context and Pitfalls

Common pitfall: Assuming unilateral adrenalectomy resolved all endocrine abnormalities. This patient's history reveals:

• Bilateral disease was likely present: She had both Cushing's syndrome AND primary aldosteronism, which can represent bilateral pathology 5, 6
• Aldosterone- and cortisol-co-secreting tumors are increasingly recognized and may also produce androgens 4
• Tumors >2.5 cm with multiple hormone secretion patterns suggest complex adrenal pathology 4

Key consideration: The testosterone elevation at 10 weeks post-op is NOT a transient post-surgical phenomenon—this represents active androgen production requiring source identification.

Algorithmic Approach

1. If DHEAS >600 μg/dL: Diagnosis is androgen-secreting adrenal adenoma in remaining gland → CT adrenal protocol → consider completion adrenalectomy with endocrinology consultation

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

   • Pelvic imaging for ovarian source
   • Consider ovarian hyperthecosis (check for insulin resistance markers)
   • Assess for androgen-secreting ovarian tumor

3. If both adrenal CT and pelvic imaging negative: Measure androstenedione and consider dynamic testing (ACTH stimulation, dexamethasone suppression) to localize source 1

Additional Laboratory Assessment

• SHBG level: Rarely, elevated testosterone with markedly elevated SHBG can occur with certain medications (tamoxifen, raloxifene) or hyperthyroidism 2. However, free testosterone is also elevated here (2.72 ng/dL), confirming true hyperandrogenism.

• Early morning repeat total and free testosterone: Confirm values in a reliable specialty laboratory 1

Management Implications

Do not delay imaging: Testosterone levels this elevated in a postmenopausal woman represent tumor until proven otherwise. The patient's history of multiple hormone-secreting adrenal pathology increases the likelihood of:

• Residual disease in the remaining adrenal
• A previously undetected androgen-secreting component
• Bilateral adrenal disease requiring completion adrenalectomy 3, 4

The 10-week timeframe post-adrenalectomy is sufficient for any surgical stress response to resolve, making these values pathologic rather than reactive.