What lab tests are used to identify adrenal adenomas?

Laboratory Tests for Identifying Adrenal Adenomas

All patients with adrenal incidentalomas should undergo biochemical testing for hormonal hypersecretion, including 1 mg dexamethasone suppression test (DST) for cortisol excess, plasma or 24-hour urinary metanephrines for pheochromocytoma, and aldosterone-to-renin ratio for primary aldosteronism in hypertensive patients. 1, 2

Hormonal Evaluation

Cortisol Secretion (Required for All Patients)

• 1 mg overnight dexamethasone suppression test (DST) - preferred screening test 1
  • 1 mg taken at 11 PM, serum cortisol measured at 8 AM
  • Interpretation:
    • ≤50 nmol/L: excludes cortisol hypersecretion
    • 51-138 nmol/L: possible autonomous cortisol secretion

    • 138 nmol/L: evidence of cortisol hypersecretion

• Ancillary testing when DST is abnormal:
  • Plasma ACTH (to confirm ACTH independence)
  • 24-hour urinary free cortisol
  • Midnight salivary cortisol
  • DHEAS levels

Catecholamine Excess (Required for Specific Patients)

• Plasma free metanephrines or 24-hour urinary metanephrines 1, 2
  • Required for:
    • Patients with adrenal masses ≥10 HU on non-contrast CT
    • Patients with signs/symptoms of catecholamine excess
  • Interpretation: >2× upper limit of normal is diagnostic
  • Additional test: plasma methoxytyramine (useful for assessing malignancy risk) 2

Primary Aldosteronism (For Hypertensive/Hypokalemic Patients)

• Aldosterone-to-renin ratio (ARR) 1, 2
  • Best performed:
    • In the morning
    • After patient has been out of bed for 2 hours
    • Seated for 5-15 minutes before testing
    • Patient should be potassium-replete
    • Interfering medications should be substituted
  • Interpretation: ≥20 ng/dL per ng/mL/hr has >90% sensitivity and specificity for hyperaldosteronism
  • Confirmatory tests:
    • Adrenal vein sampling for lateralization
    • Saline suppression test
    • Salt loading with 24-hour urine aldosterone measurement

Androgen Excess (For Specific Patients)

• DHEAS and testosterone 1
  • Indicated for:
    • Suspected adrenocortical carcinoma (ACC)
    • Clinical signs of virilization
  • Additional tests when indicated:
    • 17β-estradiol
    • 17-OH progesterone
    • Androstenedione
    • 17-OH pregnenolone
    • 11-deoxycorticosterone
    • Progesterone
    • Estradiol

Imaging Characteristics to Guide Laboratory Testing

• Non-contrast CT is essential to determine Hounsfield Units (HU) 2

  • HU <10: indicates benign adenoma (risk of adrenocortical carcinoma 0%)
  • HU >10: requires screening for pheochromocytoma
  • HU >20: increases suspicion for malignancy

• Contrast-enhanced CT washout study for indeterminate lesions 2

  • 60% washout at 15 minutes suggests benign lesion

  • Sensitivity >95% and specificity >97% for adenoma detection

• Chemical shift MRI for patients with contraindications to CT contrast 2

  • Signal intensity loss in opposed-phase images indicates benign adenoma

Common Pitfalls and Caveats

• Never perform adrenal biopsy without excluding pheochromocytoma first, as this can trigger a life-threatening hypertensive crisis 2

• Medication interference with hormonal testing must be addressed:

  • Antihypertensives can affect aldosterone and renin measurements
  • Patients should be potassium-replete before aldosterone testing

• Subclinical hormone production is common in adrenal adenomas and may require treatment despite lack of overt clinical symptoms 3, 4

• Post-surgical adrenal insufficiency is a major risk in patients with cortisol-producing adenomas, even those with subclinical hypercortisolism 4

• ACTH stimulation testing may be useful in differentiating aldosterone-producing adenomas from idiopathic hyperaldosteronism when adrenal vein sampling is not available 5

By following this comprehensive laboratory evaluation approach, clinicians can accurately identify the functional status of adrenal adenomas and determine appropriate management strategies to reduce morbidity and mortality associated with these tumors.