What is the recommended workup for a 16 mm adrenal adenoma?

Workup for a 16 mm Adrenal Adenoma

A 16 mm adrenal adenoma requires comprehensive hormonal evaluation to exclude autonomous hormone secretion and dedicated imaging characterization to assess malignancy risk, regardless of whether the patient has symptoms. 1, 2, 3

Mandatory Hormonal Evaluation

Every patient with an adrenal incidentaloma ≥1 cm requires biochemical screening for hormone excess, even in the absence of clinical symptoms. 1, 2, 3

Cortisol Assessment (Required for All)

• Perform 1 mg overnight dexamethasone suppression test with a cortisol cutoff of ≤50 nmol/L (≤1.8 μg/dL) to rule out autonomous cortisol secretion. 1, 2
• If cortisol post-dexamethasone is >50 nmol/L (>1.8 μg/dL), this indicates mild autonomous cortisol secretion (MACS), which carries increased morbidity and mortality risk even without overt Cushing syndrome. 3
• Consider additional tests: 24-hour urinary free cortisol, basal serum cortisol, and plasma ACTH if initial screening is abnormal. 4

Pheochromocytoma Screening (Required for All)

• Measure plasma free metanephrines OR 24-hour urinary fractionated metanephrines to systematically exclude pheochromocytoma, as unrecognized tumors can cause life-threatening hypertensive crises during any intervention. 1, 5, 2
• Plasma free metanephrines have the highest sensitivity (96-100%) and should ideally be collected from an indwelling catheter after 30 minutes supine to minimize false positives. 5
• If available, measure plasma methoxytyramine as elevated levels indicate higher malignancy risk. 4, 1, 5

Mineralocorticoid Assessment (Conditional)

• Only screen if the patient has hypertension and/or hypokalemia by measuring aldosterone-to-renin ratio. 4, 1, 2
• Check serum potassium in all hypertensive patients. 4

Additional Steroid Evaluation (If Malignancy Suspected)

If imaging features suggest possible adrenocortical carcinoma (inhomogeneous, HU >20, or concerning features), perform comprehensive steroid workup including: 4

• DHEA-S, 17-OH-progesterone, androstenedione, testosterone
• 17-beta-estradiol (in men and postmenopausal women)
• 24-hour urine steroid metabolite examination if available

Imaging Characterization

Initial CT Assessment

• Measure Hounsfield units (HU) on unenhanced CT to determine malignancy risk. 2, 3, 6
  • HU ≤10: Benign adenoma—no further imaging needed regardless of size. 2, 3
  • HU 11-20: Intermediate risk (0.5% malignancy rate)—proceed to second-line imaging. 2
  • HU >20: Higher risk (6.3% malignancy rate)—proceed to second-line imaging. 2
• Assess for homogeneity—inhomogeneous lesions carry higher malignancy risk. 2, 3

Second-Line Imaging (If HU >10)

For indeterminate masses with HU >10, obtain either: 2, 6

• Contrast-enhanced CT with washout protocol: Absolute washout ≥60% or relative washout ≥40% indicates benign adenoma. 6
• Chemical-shift MRI: Signal loss on opposed-phase imaging indicates lipid-rich adenoma. 6

Additional Imaging Considerations

• CT chest should be obtained if there is concern for malignancy or metastatic disease. 4
• FDG-PET is optional but may help differentiate benign from malignant lesions in equivocal cases. 4, 6

Management Algorithm Based on Findings

If Radiologically Benign (HU ≤10, Homogeneous)

• No further imaging required if nonfunctioning and <4 cm. 2, 3
• If MACS is present, screen for cortisol-related comorbidities (hypertension, type 2 diabetes, osteoporosis) and consider surgery if these are difficult to control medically. 2, 3

If Indeterminate Features (HU >10 but <4 cm)

• Repeat imaging in 6-12 months to assess for growth. 2, 7
• If growth >5 mm/year, repeat hormonal workup and consider surgery. 2
• Approximately 17% of adenomas may increase in size during follow-up, and 6% of initially nonfunctioning adenomas may develop subclinical hormone secretion. 7

If High-Risk Features Present

Surgery is indicated if: 2, 3

• Lesion >4 cm with inhomogeneous appearance or HU >20
• Confirmed hormone-secreting tumor (pheochromocytoma, aldosteronoma, or symptomatic cortisol excess)
• Growth >5 mm/year on surveillance imaging

Critical Pitfalls to Avoid

• Never perform adrenal biopsy before biochemically excluding pheochromocytoma, as this can precipitate fatal hypertensive crisis. 5, 2
• Do not rely solely on size to determine malignancy risk—13.5% of adrenocortical carcinomas are <5 cm, and 26% of benign tumors are >5 cm. 8
• Do not skip hormonal evaluation even if imaging appears benign, as functional tumors require different management. 1, 3
• Do not use beta-blockers alone if pheochromocytoma is suspected—always establish alpha-blockade first to prevent hypertensive crisis. 5