What tests should be done for a patient with a lesion on the adrenal gland?

Laboratory and Imaging Workup for Adrenal Lesions

All patients with an adrenal lesion ≥1 cm require comprehensive biochemical screening for hormone excess, regardless of imaging characteristics or symptoms. 1

Mandatory Hormonal Testing for All Patients

Autonomous Cortisol Secretion (Universal Screening)

• Perform a 1 mg overnight dexamethasone suppression test in every patient with an adrenal incidentaloma. 1, 2
• Administer 1 mg dexamethasone at 11 PM and measure serum cortisol at 8 AM the next morning 2
• Interpretation thresholds:
  • ≤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 Based on Clinical Features

Pheochromocytoma Screening

• 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 (episodic hypertension, headaches, palpitations, diaphoresis, anxiety, tremor, pallor). 1, 2
• Do NOT screen patients with unequivocal adrenocortical adenomas (<10 HU on non-contrast CT) who lack symptoms of adrenergic excess. 1
• Use plasma free metanephrines or 24-hour urinary metanephrines and normetanephrines 1, 2
• Critical pitfall: Never perform adrenal biopsy without first excluding pheochromocytoma, as this can precipitate a hypertensive crisis 1, 3

Primary Aldosteronism Screening

• Screen patients with hypertension and/or hypokalemia using the aldosterone-to-renin ratio. 1, 2
• A ratio >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity for hyperaldosteronism 2
• If positive, proceed with adrenal vein sampling before considering adrenalectomy 1
• Medication interference: Hold beta-blockers, ACE inhibitors, and ARBs before testing when possible, as these affect the aldosterone/renin ratio 2, 3

Androgen/Sex Hormone Testing

• Perform serum androgen testing (DHEAS, testosterone, androstenedione, 17-hydroxyprogesterone, estradiol) only when:
  • Suspected adrenocortical carcinoma is present 1, 2
  • Clinical signs of virilization or feminization are evident (hirsutism, deepening voice, clitoromegaly in women; gynecomastia, testicular atrophy in men) 1, 2, 4
• For bilateral adrenal masses specifically, measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia. 2, 3

Imaging Protocol

First-Line Imaging

• Obtain non-contrast CT as the first-line imaging test to characterize the adrenal mass. 1, 2
• Benign features: homogeneous, well-circumscribed, <10 HU 2, 4
• Masses <10 HU on non-contrast CT are lipid-rich adenomas and require no further imaging characterization 1

Second-Line Imaging for Indeterminate Masses

• If the mass remains indeterminate on non-contrast CT (≥10 HU), proceed with either washout CT or chemical-shift MRI. 1
• Washout CT and chemical-shift MRI are equally effective for distinguishing benign from malignant lesions 1

Follow-Up Imaging Strategy

• For radiologically benign (<10 HU) non-functional lesions <4 cm: no further imaging or functional testing required 2
• For benign-appearing lesions ≥4 cm: repeat imaging in 6-12 months 2, 5
• For indeterminate masses: repeat imaging in 3-6 months to assess growth 1, 6
• If growth >5 mm/year: repeat functional workup before considering surgery 2

Clinical History and Physical Examination Targets

Signs of Cortisol Excess

• Weight gain, central obesity, moon facies, buffalo hump, purple striae, easy bruising, proximal muscle weakness, hypertension, diabetes, osteoporosis 4

Signs of Aldosterone Excess

• Resistant hypertension, hypokalemia, muscle weakness, cramping 4

Signs of Catecholamine Excess

• 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

When to Involve Multidisciplinary Team

Engage endocrinology, surgery, and radiology when:

• Imaging is not consistent with a benign lesion 1, 2
• Evidence of hormone hypersecretion is present 1, 2
• Tumor growth is >5 mm/year during surveillance 2, 4
• Adrenal surgery is being considered 1, 2

Role of Biopsy

Adrenal mass biopsy should NOT be performed routinely for workup of an adrenal incidentaloma. 1

• Consider biopsy only when diagnosis of metastatic disease from an extra-adrenal malignancy would change management 1, 2
• Always exclude pheochromocytoma biochemically before any biopsy attempt 1, 3

Common Pitfalls to Avoid

• Do not skip dexamethasone suppression testing even in small, benign-appearing masses—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 1
• Do not perform routine androgen testing unless virilization, feminization, or suspected adrenocortical carcinoma is present 2
• Do not forget to measure 17-hydroxyprogesterone in bilateral adrenal masses to exclude congenital adrenal hyperplasia 2, 3
• Hold interfering medications before testing: beta-blockers/ACE inhibitors/ARBs affect aldosterone/renin ratio; tricyclic antidepressants/decongestants affect metanephrines; estrogen/rifampin affect cortisol 2, 4, 3