Adrenal Lesion Evaluation and Management

Introduction to Adrenal Lesion Workup

The American Urological Association recommends that all patients with an adrenal lesion ≥1 cm require comprehensive biochemical screening for hormone excess, regardless of imaging characteristics or symptoms 1

Perform a 1 mg overnight dexamethasone suppression test in every patient with an adrenal incidentaloma, as recommended by the Endocrine Society 1, 2
The dexamethasone suppression test should be interpreted 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, and >138 nmol/L (>5.0 μg/dL) confirms autonomous cortisol secretion 1, 2

Screen for pheochromocytoma if the adrenal mass measures ≥10 Hounsfield Units (HU) on non-contrast CT or if any symptoms of catecholamine excess are present, as recommended by the American College of Radiology 1, 2
Use plasma free metanephrines or 24-hour urinary metanephrines and normetanephrines for pheochromocytoma screening, with a sensitivity of 97% and specificity of 91% 1, 2
Screen patients with hypertension and/or hypokalemia using the aldosterone-to-renin ratio, with a ratio >20 ng/dL per ng/mL/hr having excellent sensitivity and specificity for hyperaldosteronism 1, 2

Obtain non-contrast CT as the first-line imaging test to characterize the adrenal mass, as recommended by the American College of Radiology 1, 3, 2
Masses <10 HU on non-contrast CT are lipid-rich adenomas and require no further imaging characterization, with a sensitivity of 71% and specificity of 98% 1, 3

Look for signs of cortisol excess, including weight gain, central obesity, moon facies, buffalo hump, purple striae, easy bruising, proximal muscle weakness, hypertension, diabetes, and osteoporosis, which are present in 50-70% of patients with Cushing's syndrome 4
Look for signs of aldosterone excess, including resistant hypertension, hypokalemia, muscle weakness, and cramping, which are present in 50-70% of patients with primary aldosteronism 4

Adrenal mass biopsy should not be performed routinely for workup of an adrenal incidentaloma, as recommended by the American Urological Association, due to the risk of precipitating a hypertensive crisis in patients with pheochromocytoma 1
Consider biopsy only when diagnosis of metastatic disease from an extra-adrenal malignancy would change management, with a sensitivity of 80-90% and specificity of 90-95% 1, 2

Do not skip dexamethasone suppression testing, even in small, benign-appearing masses, as autonomous cortisol secretion is present in 5.3% of incidentalomas 4
Do not screen for pheochromocytoma in patients with confirmed lipid-rich adenomas (<10 HU) who lack symptoms, as the risk of pheochromocytoma is low in this population 1
Do not perform routine androgen testing unless virilization, feminization, or suspected adrenocortical carcinoma is present, as the yield of this testing is low in asymptomatic patients 2

Screen for pheochromocytoma with plasma free metanephrines or 24‑hour urinary fractionated metanephrines/normetanephrines when the adrenal lesion measures ≥10 HU on non‑contrast CT or when catecholamine‑excess symptoms are present (e.g., hypertension, headaches, palpitations, sweating, pallor) 5.
Plasma methoxytyramine measurement can be added to improve assessment of the likelihood of malignancy in suspected pheochromocytoma 5.
Primary aldosteronism screening using the aldosterone‑to‑renin ratio is recommended in patients with hypertension and/or unexplained hypokalemia; a ratio > 20 ng/dL per ng/mL/hr provides excellent sensitivity and specificity 6.
If the aldosterone‑to‑renin ratio is positive, confirm the diagnosis with a saline suppression test 6.

Obtain a non‑contrast abdominal CT as the first‑line imaging modality to characterize any adrenal mass 6.
Adrenal lesions larger than 4 cm are associated with a higher risk of malignancy and generally warrant surgical evaluation 6.
For lesions with HU > 10 or otherwise indeterminate on non‑contrast CT, perform contrast‑enhanced CT with a washout protocol (10–15 min delayed images) or a chemical‑shift MRI 6.
An enhancement washout greater than 50 % at 10–15 minutes strongly suggests a benign adenoma 6.
Before any therapeutic intervention, obtain cross‑sectional CT of the chest, abdomen, and pelvis to assess for local invasion, venous extension, lymph‑node involvement, or distant metastases 5.

Pheochromocytoma screening must never be omitted before surgical or medical treatment of an adrenal mass, as undiagnosed disease can precipitate a fatal hypertensive crisis 7.

In pregnant patients, children, and individuals younger than 40 years, urgent evaluation is recommended because of a higher malignancy risk; magnetic resonance imaging is preferred over CT to limit radiation exposure 6.