What tests are used to diagnose an adrenal adenoma?

Diagnostic Testing for Adrenal Adenoma

All patients with suspected adrenal adenoma require comprehensive hormonal evaluation including cortisol, aldosterone, and catecholamine testing, combined with CT or MRI imaging to characterize the mass. 1

Mandatory Hormonal Testing

Cortisol Excess Screening (Required for All Patients)

• Perform a 1 mg overnight dexamethasone suppression test as the preferred initial screening method, administering 1 mg dexamethasone at 11 PM and measuring serum cortisol at 8 AM the following morning 1, 2
• Measure plasma ACTH levels as part of cortisol assessment 3, 1
• Consider 24-hour urinary free cortisol excretion for additional confirmation 3
• Serum cortisol ≤50 nmol/L after dexamethasone excludes hypersecretion; 51-138 nmol/L suggests possible autonomous secretion; >138 nmol/L indicates cortisol excess 2

Aldosterone Excess Screening (For Hypertensive or Hypokalemic Patients)

• Measure aldosterone-to-renin ratio in all patients with hypertension and/or hypokalemia 1, 2
• Check serum potassium levels 3, 1
• An aldosterone/renin ratio >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity for primary aldosteronism 2
• A plasma aldosterone concentration to active renin concentration ratio >62 (when aldosterone >200 ng/L) reliably screens for primary hyperaldosteronism 4

Catecholamine Excess Screening (Critical to Avoid Surgical Crisis)

• Test plasma free metanephrines or 24-hour urinary fractionated metanephrines in all patients with adrenal masses >10 HU on non-contrast CT or symptoms of catecholamine excess 1, 2
• Plasma metanephrines measured by radioimmunoassay demonstrate high sensitivity and specificity for pheochromocytoma, superior to other biochemical parameters 4
• Include normetanephrine and methoxytyramine measurements when available, as methoxytyramine provides useful information about malignancy likelihood 3

Androgen/Sex Steroid Testing (Selective Cases)

• Measure DHEA-S, 17-OH-progesterone, androstenedione, testosterone, and 17-beta-estradiol in patients with virilization signs, suspected adrenocortical carcinoma, or bilateral masses 3, 1, 2
• Consider 24-hour urine steroid metabolite examination when adrenocortical carcinoma is suspected 3

Imaging Studies

First-Line Imaging

• Obtain non-contrast CT as the initial imaging modality to assess Hounsfield units (HU), with <10 HU strongly suggesting benign adenoma 3, 2
• CT is less expensive than MRI and should be the first choice for suspected adenoma 3

Second-Line Imaging for Indeterminate Masses

• Perform contrast-enhanced CT with 15-minute delayed washout imaging when initial non-contrast CT is indeterminate; rapid washout suggests benign tumor 3
• Use chemical-shift MRI showing signal intensity loss on opposed-phase imaging as an alternative to characterize lipid-rich adenomas 3, 2
• Choose MRI over CT when pheochromocytoma is suspected to avoid hypertensive crisis from intravenous contrast 3

Advanced Imaging

• FDG-PET is useful for distinguishing potentially malignant lesions from benign tumors in radiologically indeterminate masses 3
• Consider bone scintigraphy when skeletal metastases are suspected 3

Critical Pitfalls to Avoid

• Never perform adrenal biopsy without first excluding pheochromocytoma, as biopsy of undiagnosed pheochromocytoma triggers life-threatening hypertensive crisis 3, 1
• Do not skip hormonal testing even in apparently non-functioning tumors, as subtle hormone production impacts surgical management and perioperative care 1
• Radiological appearance cannot reliably predict hormone secretion status 1
• Fine needle biopsy of suspected adrenocortical carcinoma is almost never justified due to risk of tumor spill 3
• Be aware that medications can interfere with hormone testing results; hold interfering medications before testing when possible 2

Additional Laboratory Tests

• Obtain basic metabolic panel to assess electrolyte abnormalities accompanying hormone-secreting tumors 1
• Perform complete blood count to identify hematologic abnormalities affecting surgical planning 1

Important Clinical Context

Approximately 5.3% of adrenal incidentalomas are cortisol-secreting adenomas, 1% are aldosterone-secreting, and 5.1% are pheochromocytomas 2. Rare cases demonstrate co-secretion of multiple hormones from single or bilateral adenomas 5, 6. Even micro-pheochromocytomas as small as 3 mm can express catecholamine biosynthetic enzymes despite normal biochemical levels 7, reinforcing the need for comprehensive screening before any surgical intervention.