In a 55-year-old postmenopausal woman 10 weeks after left adrenalectomy for a renal tumor, with markedly elevated total and free testosterone, what could be causing this high testosterone and what diagnostic tests should be performed?

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Last updated: September 28, 2026 • View editorial policy

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Elevated Testosterone in Postmenopausal Woman After Adrenalectomy

This patient requires urgent evaluation for a residual or contralateral adrenal tumor, an androgen-secreting ovarian tumor, or ovarian hyperthecosis, with immediate comprehensive hormonal testing and imaging to exclude malignancy.

Most Likely Causes

Given the clinical context of recent adrenalectomy with incomplete tumor removal (3/4 resected), the differential diagnosis includes:

High-Priority Malignant/Serious Causes

  • Residual adrenal tumor tissue - The incompletely resected tumor may be producing androgens, particularly if it was an adrenocortical carcinoma (ACC) 1, 2
  • Contralateral adrenal pathology - New or previously undetected adrenal adenoma or carcinoma
  • Androgen-secreting ovarian tumor - Leydig cell tumor, steroid cell tumor, or hilus cell tumor 3, 4, 5

Functional Causes

  • Ovarian hyperthecosis - Benign but significant ovarian stromal hyperplasia producing excess androgens 4, 6, 5
  • Polycystic ovary syndrome (PCOS) - Can persist into menopause, though less likely with this degree of elevation 7, 8

Critical Red Flags Present

Your patient has markedly elevated testosterone (332.86 ng/dL is approximately 11.5 nmol/L, which is >5-fold above normal postmenopausal range). This level of elevation strongly suggests:

  • Tumor source (ovarian or adrenal) rather than functional hyperandrogenism 9, 7
  • Testosterone >150 ng/dL (5.2 nmol/L) requires aggressive investigation for neoplasm 6, 8
  • The recent incomplete adrenalectomy raises concern for residual ACC or other androgen-secreting adrenal pathology

Required Diagnostic Testing

Immediate Hormonal Evaluation

Complete androgen panel 1, 2:

  • Repeat early morning total testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS) - not immunoassay, as automated assays are unreliable in women 9
  • Free testosterone (calculated from total testosterone and SHBG)
  • SHBG
  • DHEA-S (dehydroepiandrosterone sulfate)
  • Androstenedione
  • 17-hydroxyprogesterone

Additional steroid hormones to assess for ACC 1, 2, 10:

  • 11-deoxycortisol
  • 17-hydroxypregnenolone
  • Estradiol (in postmenopausal women)
  • 24-hour urinary free cortisol
  • 1 mg dexamethasone suppression test
  • Basal ACTH

Rule out pheochromocytoma (should have been done pre-adrenalectomy, but verify) 1:

  • Plasma free metanephrines and normetanephrine
  • Or 24-hour urinary fractionated metanephrines

Imaging Studies

Immediate imaging required 1, 2, 10:

  • High-quality CT or MRI of abdomen and pelvis with contrast to evaluate:
    • Residual adrenal tissue at surgical site
    • Contralateral adrenal gland
    • Both ovaries (even small ovarian tumors can produce massive androgen excess)
    • Lymph nodes and liver for metastases
  • CT chest to evaluate for metastatic disease if ACC suspected
  • FDG-PET/CT if malignancy suspected or imaging indeterminate 1, 2

Functional Testing to Localize Source

If imaging is unrevealing but testosterone remains markedly elevated 3, 4, 6:

GnRH analogue suppression test 3, 4:

  • Administer single dose of GnRH analogue (e.g., leuprolide)
  • Measure testosterone and gonadotropins at baseline and 2-4 weeks post-injection
  • Suppression of testosterone indicates ovarian source
  • Lack of suppression suggests adrenal source

Dexamethasone suppression test (2-day protocol) 11:

  • If testosterone suppresses >40% and DHEA-S >60%: adrenal source
  • If testosterone fails to suppress but cortisol does: ovarian source
  • If neither suppresses: autonomous tumor production

Selective venous sampling 3, 6:

  • Ovarian vein sampling (if available and imaging non-diagnostic)
  • Adrenal vein sampling (if bilateral adrenal pathology suspected)
  • High technical failure rate but can be definitive when successful

Management Algorithm

Step 1: Urgent Evaluation (Within 1-2 Weeks)

  1. Obtain complete hormonal panel with LC-MS/MS testosterone
  2. CT abdomen/pelvis with contrast
  3. Review original adrenal tumor pathology - was it ACC, adenoma, or other?

Step 2: Risk Stratification Based on Initial Results

If imaging shows mass lesion:

  • Multidisciplinary tumor board discussion 1, 10
  • Surgical resection if:
    • Residual/recurrent adrenal mass (concern for ACC)
    • Ovarian mass with elevated testosterone
    • Any heterogeneous mass >4 cm
  • Open adrenalectomy preferred if ACC suspected (not laparoscopic) 12

If imaging is negative but testosterone markedly elevated:

  • Proceed to GnRH analogue test 3, 4
  • If ovarian source confirmed: bilateral salpingo-oophorectomy
  • Consider ovarian vein sampling if available and patient surgical candidate 6, 5

Step 3: Surgical Intervention

For ovarian source 4, 5:

  • Bilateral salpingo-oophorectomy (even if imaging negative)
  • Small Leydig cell tumors, steroid cell tumors, and hyperthecosis often not visible on imaging
  • Testosterone normalizes within days to weeks post-surgery

For adrenal source:

  • Complete resection of residual tumor
  • Staging for ACC if pathology confirms malignancy
  • Consider mitotane therapy if ACC 1, 2

Common Pitfalls to Avoid

  1. Using immunoassay testosterone - Automated hospital assays are inaccurate in women; demand LC-MS/MS 9
  2. Assuming imaging rules out ovarian tumor - Small androgen-secreting ovarian tumors (<2 cm) frequently invisible on CT/MRI/ultrasound 3, 4, 5
  3. Delaying surgery when testosterone >150 ng/dL - This level mandates tumor exclusion; functional causes rarely produce this degree of elevation 7, 6, 8
  4. Performing unilateral oophorectomy - Bilateral procedure required as source may be bilateral hyperthecosis or contralateral small tumor 4, 5
  5. Not reviewing original adrenal pathology - If original tumor was ACC, this represents recurrence/metastasis requiring oncologic management 1, 2

Prognosis and Follow-up

  • If benign ovarian or adrenal source: testosterone normalizes within 2-4 weeks post-surgery, symptoms improve over months 4, 5
  • If ACC: requires long-term oncologic surveillance with imaging and tumor markers 1, 2
  • Monitor for cortisol-related comorbidities (diabetes, hypertension, osteoporosis) given potential prior hypercortisolism 10

References

8
Research

Approach to the patient: investigation of postmenopausal androgen excess.

The Journal of clinical endocrinology and metabolism, 2026

10
Guideline

imaging of adrenal masses.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologist, 2025

11
Guideline

american association of clinical endocrinologists medical guidelines for the clinical practice for the diagnosis and treatment of hyperandrogenic disorders.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologist, 2001

12
Guideline

the american association of clinical endocrinologists and american association of endocrine surgeons medical guidelines for the management of adrenal incidentalomas.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologist, 2009

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