What investigations are indicated for a patient with an adrenal tumor?

Investigations for Adrenal Tumor

All patients with an adrenal tumor require comprehensive hormonal evaluation and dedicated imaging to exclude hormone excess and assess malignancy risk, regardless of tumor size or appearance. 1, 2

Mandatory Hormonal Testing (All Patients)

Cortisol Excess Screening

• Perform 1 mg overnight dexamethasone suppression test (administer 1 mg dexamethasone at 11 PM, measure serum cortisol at 8 AM) as the preferred initial screening method for all patients 1, 3, 2
• Measure plasma ACTH levels as part of cortisol assessment 3
• Consider 24-hour urinary free cortisol for additional confirmation if dexamethasone suppression test is abnormal 3
• Interpretation: Serum cortisol ≤50 nmol/L (≤1.8 µg/dL) excludes hypersecretion; 51-138 nmol/L suggests possible autonomous secretion; >138 nmol/L indicates cortisol excess 3, 2

Pheochromocytoma/Paraganglioma Screening

• Measure plasma free metanephrines or 24-hour urinary fractionated metanephrines in ALL patients 1, 4, 2
• Critical exception: You may skip pheochromocytoma screening ONLY if the mass has unequivocal adenoma features on unenhanced CT (HU <10) AND the patient has no signs/symptoms of catecholamine excess 1
• Include plasma methoxytyramine measurement when available, as elevated levels indicate higher malignancy risk 1, 4, 3
• For plasma collection: Ideally use an indwelling venous catheter after 30 minutes supine rest to minimize false positives 4

Primary Aldosteronism Screening

• Measure aldosterone-to-renin ratio in all patients with hypertension and/or hypokalemia 1, 3, 2
• Check serum potassium levels 3
• Interpretation: Aldosterone/renin ratio >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity for primary aldosteronism 3

Sex Hormone and Steroid Precursor Testing

• Measure DHEA-S, 17-OH-progesterone, androstenedione, testosterone, and 17-beta-estradiol in patients with: 1, 3
  • Clinical signs of virilization
  • Suspected adrenocortical carcinoma
  • Bilateral adrenal masses

Imaging Studies

First-Line Imaging

• Obtain non-contrast CT as the initial imaging modality to assess Hounsfield units (HU) 1, 3, 2
• Interpretation of HU values: 1, 2
  • HU ≤10: Benign lipid-rich adenoma confirmed; no additional imaging needed regardless of size
  • HU >10 to 20: Indeterminate; requires second-line imaging
  • HU >20: Higher malignancy risk; requires multidisciplinary discussion

Second-Line Imaging (for Indeterminate Masses)

• Perform contrast-enhanced CT with 15-minute delayed washout imaging 1, 3, 2
  • Washout >50% at 10-15 minutes suggests benign lesion 3
• Alternative: Chemical-shift MRI showing signal intensity loss on opposed-phase imaging indicates lipid-rich adenoma 1, 3
• Use MRI instead of CT when pheochromocytoma is suspected to avoid hypertensive crisis from IV contrast 1, 3

Advanced/Functional Imaging

• FDG-PET is useful for distinguishing potentially malignant lesions from benign tumors in radiologically indeterminate masses 3
• Functional imaging (MIBG, FDOPA-PET, or radiolabeled somatostatin analog PET) is indicated when ANY of the following high-risk features are present: 1, 4
  • Tumor size ≥5 cm
  • Extra-adrenal paraganglioma
  • Known SDHB germline mutation
  • Plasma methoxytyramine >3-fold above upper limit of normal
• Consider bone scintigraphy when skeletal metastases are suspected 3

Additional Laboratory Tests

• Obtain basic metabolic panel to assess electrolyte abnormalities accompanying hormone-secreting tumors 3, 5
• Perform complete blood count to identify hematologic abnormalities affecting surgical planning 3, 5

Critical Pitfalls to Avoid

• NEVER perform adrenal biopsy without first excluding pheochromocytoma biochemically - biopsy of undiagnosed pheochromocytoma triggers life-threatening hypertensive crisis 1, 3
• Biopsy is only indicated in patients with: 1
  • History of extra-adrenal malignancy AND no hormone excess (to exclude/prove adrenal metastasis)
  • Active extraadrenal malignancy with single adrenal lesion without suspicion for metastasis elsewhere 6
• Do not skip hormonal testing even in apparently non-functioning tumors, as subtle hormone production impacts surgical management and perioperative care 3, 5
• Radiological appearance cannot reliably predict hormone secretion status 3, 5
• Fine needle biopsy of suspected adrenocortical carcinoma is almost never justified due to risk of tumor spillage 1, 3

Special Considerations for Genetic Testing

• Consider genetic testing in patients with: 1, 4
  • Extra-adrenal tumors
  • Bilateral adrenal tumors
  • Age <30 years at diagnosis
  • Family history of pheochromocytoma or hereditary syndromes (MEN2, VHL, NF1, SDHx mutations)
  • Plasma methoxytyramine elevation (suggests extra-adrenal disease)