What is the recommended hormonal work‑up and imaging follow‑up for an incidentally discovered 1 cm adrenal adenoma?

Management of a 1 cm Adrenal Adenoma

All patients with a 1 cm adrenal incidentaloma require comprehensive hormonal screening regardless of imaging characteristics, and benign-appearing lesions <4 cm with attenuation ≤10 HU on non-contrast CT require no further imaging or repeat hormonal testing after initial evaluation. 1

Initial Hormonal Work-Up (Mandatory for All Patients ≥1 cm)

Every patient must undergo biochemical screening for hormone excess, even when imaging suggests a benign lesion. 1

Required Tests for All Patients:

• 1 mg overnight dexamethasone suppression test to screen for autonomous cortisol secretion 1
  • Administer 1 mg dexamethasone at 11 PM, measure serum cortisol at 8 AM
  • ≤50 nmol/L (1.8 μg/dL): excludes autonomous cortisol secretion 2
  • 51-138 nmol/L (1.9-5.0 μg/dL): suggests possible autonomous cortisol secretion 2
  • >138 nmol/L (>5.0 μg/dL): confirms autonomous cortisol secretion 2

Conditional Hormonal Testing:

• Pheochromocytoma screening (plasma free metanephrines or 24-hour urinary fractionated metanephrines) is indicated only if: 2

  • The lesion measures >10 HU on non-contrast CT, OR
  • Patient has symptoms of catecholamine excess (episodic hypertension, headaches, palpitations, diaphoresis, anxiety, tremor, pallor)
  • Do not screen if the mass is <10 HU and patient lacks adrenergic symptoms 2

• Primary aldosteronism screening (aldosterone-to-renin ratio) should be performed if: 2, 3

  • Patient has hypertension or hypokalemia
  • Ratio >20 ng/dL per ng/mL/hr indicates primary aldosteronism 3

• Androgen testing (DHEAS, testosterone, 17-hydroxyprogesterone, androstenedione) is reserved for: 2

  • Clinical signs of virilization or feminization (hirsutism, deepening voice, clitoromegaly, gynecomastia)
  • Suspected adrenocortical carcinoma
  • Not routinely indicated for a 1 cm mass without virilization 2

Imaging Follow-Up Algorithm

If Non-Contrast CT Shows ≤10 HU:

No further imaging is required. 1, 4

• A homogeneous, well-circumscribed mass with ≤10 HU attenuation has essentially 0% risk of malignancy and can be confidently diagnosed as a benign adenoma 1
• No repeat imaging or hormonal testing is needed for benign-appearing, non-functional adenomas <4 cm 4

If Non-Contrast CT Shows >10 HU:

• Proceed with second-line imaging: contrast-enhanced CT with washout protocol or chemical-shift MRI 1, 2
• Adenomas demonstrate >60% absolute washout or >40% relative washout at 15 minutes 3

Clinical History and Physical Examination Targets

Focus specifically on identifying signs and symptoms of hormone excess and malignancy: 1

Signs of Cortisol Excess (Cushing's Syndrome):

• Weight gain, central obesity, moon facies, buffalo hump, purple striae (>1 cm wide), easy bruising, proximal muscle weakness, hypertension, diabetes, osteoporosis 1, 3

Signs of Aldosterone Excess:

• Resistant hypertension, hypokalemia, muscle weakness, cramping 4, 3

Signs of Catecholamine Excess (Pheochromocytoma):

• Episodic or sustained hypertension, headaches, palpitations, diaphoresis, anxiety, tremor, pallor 4

Signs of Androgen/Estrogen Excess:

• Virilization in women, feminization in men, hirsutism, deepening voice, clitoromegaly, gynecomastia, testicular atrophy 4

Assess for Malignancy Risk:

• History of extra-adrenal malignancy (lung, colon, melanoma, lymphoma, renal cell carcinoma) 1
• Rapid growth or constitutional symptoms 1

Management Based on Results

For Non-Functional, Benign-Appearing 1 cm Adenoma (≤10 HU):

No further action required. 4

• No repeat imaging 4
• No repeat hormonal testing 4
• Patient can be reassured

For Functional Lesions:

• Autonomous cortisol secretion: Consider adrenalectomy, especially in younger patients with progressive metabolic comorbidities (weight gain, hypertension, diabetes) after shared decision-making 2
• Pheochromocytoma: Surgical resection after appropriate alpha-blockade 1
• Primary aldosteronism: Surgical resection if unilateral disease confirmed 1

For Indeterminate Lesions (>10 HU):

• Complete second-line imaging characterization 1
• Consider multidisciplinary review 1

When to Involve Multidisciplinary Team

Obtain consultation with endocrinology, surgery, and radiology when: 1, 4

• Imaging is not consistent with a benign lesion
• Evidence of hormone hypersecretion is confirmed
• Tumor growth exceeds 5 mm per year during surveillance
• Adrenal surgery is being considered

Critical Pitfalls to Avoid

• Do not omit hormonal screening based solely on benign-appearing imaging; up to 12-23% of incidentalomas exhibit subclinical hormone secretion 2
• Do not perform adrenal biopsy unless metastatic disease from a known extra-adrenal malignancy would change management and pheochromocytoma has been definitively excluded 1, 4, 3
• Do not screen for pheochromocytoma if the mass is <10 HU and the patient lacks adrenergic symptoms 2
• Hold interfering medications before testing when possible: beta-blockers, ACE inhibitors, and ARBs affect aldosterone/renin ratio; tricyclic antidepressants and decongestants affect metanephrine testing; estrogen and rifampin affect cortisol testing 4

Size-Based Context

• A 1 cm mass is well below the 4 cm threshold at which size alone raises concern for malignancy 2, 5
• Lesions <3 cm in patients without known malignancy have a malignancy rate of approximately 1.5% 2
• Most small adrenal masses (<3 cm) are benign, but endocrinologic evaluation remains mandatory because subclinical hyperfunction is present in 5% of adrenal incidentalomas 1