What investigations should be ordered for a patient with an adrenal mass before initiating medical management?

Laboratory and Imaging Tests for Adrenal Mass Before Medical Management

Every patient with an adrenal mass requires comprehensive hormonal screening and dedicated imaging before any medical management, regardless of size or appearance, to exclude life-threatening conditions like pheochromocytoma and to guide appropriate treatment. 1

Mandatory Hormonal Testing (All Patients)

Cortisol Screening

• Perform a 1 mg overnight dexamethasone suppression test in every patient with an adrenal mass ≥1 cm, administering 1 mg dexamethasone at 11 PM and measuring serum cortisol at 8 AM the next morning 2, 1, 3
• Interpret results as follows: ≤50 nmol/L (≤1.8 μg/dL) excludes autonomous cortisol secretion; 51-138 nmol/L (1.9-5.0 μg/dL) suggests possible autonomous cortisol secretion (mild autonomous cortisol secretion); >138 nmol/L (>5.0 μg/dL) confirms autonomous cortisol secretion 2, 3

Pheochromocytoma Screening

• Measure plasma free metanephrines or 24-hour urinary fractionated metanephrines and normetanephrines if the mass measures ≥10 Hounsfield Units (HU) on non-contrast CT or if any symptoms of catecholamine excess are present (hypertension, headaches, palpitations, sweating, pallor) 4, 2, 1
• This testing is critical before any intervention to prevent life-threatening hypertensive crisis 4
• Plasma methoxytyramine measurement provides additional information about malignancy likelihood 4

Conditional Hormonal Testing (Based on Clinical Features)

Primary Aldosteronism Screening

• Measure aldosterone-to-renin ratio in patients with hypertension and/or unexplained hypokalemia, with a ratio >20 ng/dL per ng/mL/hr having excellent sensitivity and specificity 4, 2, 1
• Confirm diagnosis with saline suppression testing if screening is positive 4

Sex Hormone and Steroid Precursor Testing

• Measure serum androgens (DHEAS, testosterone, androstenedione), 17-hydroxyprogesterone, and estradiol only if clinical signs of virilization, feminization, or suspected adrenocortical carcinoma are present 4, 1
• For bilateral adrenal masses, measure 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 4, 2
• If adrenocortical carcinoma is suspected on initial imaging, obtain comprehensive steroid hormone panel including sex hormones and precursors 4

Mandatory Imaging Studies

First-Line Imaging

• Obtain non-contrast (unenhanced) CT of the abdomen as the first-line imaging test to characterize the adrenal mass 4, 2, 1
• Measure Hounsfield Units (HU): masses <10 HU are lipid-rich adenomas and require no further imaging characterization (sensitivity 71%, specificity 98%) 1, 3
• Assess size: masses >4 cm have increased malignancy risk and typically require surgical evaluation 4, 3

Second-Line Imaging (For Indeterminate Masses)

• For masses with HU >10 or indeterminate features, proceed with contrast-enhanced CT with washout protocol (10-15 minute delayed imaging) or chemical-shift MRI 4, 2
• Enhancement washout >50% at 10-15 minutes suggests benign lesion 4, 5

Cross-Sectional Imaging for Staging

• Obtain CT imaging of chest, abdomen, and pelvis to detect local invasion, vena cava extension, lymph node involvement, or distant metastases (lung, liver) before planning any intervention 4

Clinical Assessment Targets

Signs of Cortisol Excess

• Look for weight gain, central obesity, moon facies, buffalo hump, purple striae (>1 cm wide), easy bruising, proximal muscle weakness, hypertension, diabetes, and osteoporosis 1, 6

Signs of Catecholamine Excess

• Assess for hypertension (particularly paroxysmal), headaches, palpitations, diaphoresis, pallor, and anxiety 4, 6

Signs of Aldosterone Excess

• Evaluate for resistant hypertension, hypokalemia, muscle weakness, and cramping 1

Signs of Androgen/Estrogen Excess

• In suspected adrenocortical carcinoma, look for virilization (hirsutism, deepening voice, clitoromegaly), feminization (gynecomastia), or precocious puberty 6

Critical Pitfalls to Avoid

• Never skip pheochromocytoma screening before any surgical or medical intervention, even if the mass appears benign, as undiagnosed pheochromocytoma can cause fatal hypertensive crisis 4, 1
• Do not perform adrenal biopsy routinely—it is contraindicated until pheochromocytoma is excluded and should only be considered when diagnosis of metastatic disease from extra-adrenal malignancy would change management 2, 1
• Do not skip dexamethasone suppression testing even in small, benign-appearing masses, as autonomous cortisol secretion occurs in 5.3% of incidentalomas and is associated with increased cardiovascular morbidity 1, 7
• Be aware that medications can interfere with hormone testing results; consider holding interfering medications when possible before testing 2

Special Population Considerations

• Pregnant women, children, and patients <40 years old require urgent assessment due to greater malignancy risk; MRI is preferred over CT when possible to minimize radiation exposure 4, 6
• For pediatric masses, surgical resection is typically indicated regardless of size given the 30.8% malignancy rate, but complete hormonal workup must precede intervention 6