What is the recommended further workup for a patient with an adrenal mass, particularly one being treated for anxiety?

Workup for Adrenal Mass

All patients with an adrenal mass require comprehensive hormonal evaluation regardless of imaging characteristics, including screening for pheochromocytoma, cortisol excess, and aldosterone excess (in hypertensive/hypokalemic patients), combined with non-contrast CT imaging as the initial radiologic assessment. 1, 2

Mandatory Hormonal Testing for All Patients

Pheochromocytoma Screening (Universal)

• Measure plasma-free metanephrines or 24-hour urinary fractionated metanephrines in all patients before any intervention 1, 2
• This testing is critical because undiagnosed pheochromocytoma can trigger life-threatening hypertensive crisis during biopsy or surgery 2, 3
• Include plasma methoxytyramine measurement when available, as levels >3-fold above normal suggest malignancy risk 1
• Never skip this test even if the mass appears benign on imaging—radiological appearance cannot predict hormone secretion status 2, 3

Cortisol Excess Screening (Universal)

• Perform 1 mg overnight dexamethasone suppression test (DST) as the preferred screening method: give 1 mg dexamethasone at 11 PM, measure serum cortisol at 8 AM 1, 2, 3
• Interpretation: ≤50 nmol/L excludes hypersecretion; 51-138 nmol/L suggests possible autonomous secretion; >138 nmol/L indicates cortisol excess 1, 3
• Measure plasma ACTH to confirm ACTH-independent secretion if considering intervention 1, 2, 3
• Consider 24-hour urinary free cortisol and midnight salivary cortisol for additional confirmation 1, 3
• Measure DHEAS as ancillary testing 1

Aldosterone Excess Screening (Selective)

• Screen patients with hypertension and/or hypokalemia using aldosterone-to-renin ratio (ARR) 1, 2
• Perform testing in the morning after patient has been upright for 2 hours and seated for 5-15 minutes 1
• Ensure potassium repletion and substitute interfering medications when possible 1, 2, 3
• ARR >20 ng/dL per ng/mL/hr has >90% sensitivity and specificity for primary aldosteronism 1, 3
• Perform adrenal vein sampling for lateralization before offering adrenalectomy in confirmed primary aldosteronism 1

Androgen Excess Screening (Selective)

• Test DHEA-S, 17-OH-progesterone, androstenedione, testosterone, and 17-beta-estradiol when: 1, 2, 3
  • Clinical signs of virilization are present
  • Adrenocortical carcinoma is suspected
  • Large bilateral masses are present
• Consider 24-hour urine steroid metabolite examination in suspected adrenocortical carcinoma 1

Radiologic Evaluation

Initial Imaging

• Obtain non-contrast CT as first-line imaging to measure Hounsfield units (HU) 1, 3
• Masses <10 HU are confidently benign (lipid-rich adenomas) and require no further imaging characterization 1, 3
• Masses 10-20 HU have 0.5% risk of adrenocortical carcinoma; >20 HU have 6.3% risk 1

Second-Line Imaging for Indeterminate Masses (>10 HU)

• Perform either contrast-enhanced CT with 10-15 minute delayed washout imaging OR chemical-shift MRI 1
• Rapid washout on CT (absolute washout >60% or relative washout >40%) suggests benign adenoma 1
• Signal intensity loss on opposed-phase MRI indicates lipid-rich adenoma 1
• Choose MRI over contrast CT if pheochromocytoma is suspected to avoid hypertensive crisis from IV contrast 3

Staging Imaging for Suspected Malignancy

• Obtain cross-sectional imaging of chest, abdomen, and pelvis before planning surgery 1
• Look for local invasion, inferior vena cava extension, lymph node involvement, and distant metastases (lung, liver) 1
• Consider FDG-PET for distinguishing malignant from benign lesions in radiologically indeterminate masses 1, 3
• Consider bone scintigraphy when skeletal metastases are suspected 1, 3

Functional Imaging for Pheochromocytoma

• Indicated when: tumor ≥5 cm, extra-adrenal paraganglioma, SDHB mutation, or plasma methoxytyramine >3-fold elevated 1
• Options include MIBG scintigraphy, DOTA-TATE-PET, or Dopa/Dopamine PET 1

Additional Laboratory Testing

• Obtain basic metabolic panel to assess electrolyte abnormalities (particularly potassium) 1, 2, 3
• Perform complete blood count to identify hematologic abnormalities affecting surgical planning 2, 3

Critical Pitfalls to Avoid

• Never perform adrenal biopsy without first excluding pheochromocytoma—this can trigger fatal hypertensive crisis 2, 3
• Do not skip hormonal testing based on benign imaging appearance—subtle hormone production impacts perioperative management 2, 3
• Adrenal biopsy should only be considered in patients with known extra-adrenal malignancy to confirm metastasis, and only after pheochromocytoma is excluded 1, 4
• Fine needle biopsy of suspected adrenocortical carcinoma is almost never justified due to tumor spill risk 3
• Be aware that medications (especially antihypertensives) can interfere with hormone testing; adjust medications before testing when possible 1, 3

Multidisciplinary Review

• Maintain low threshold for multidisciplinary review by endocrinologists, surgeons, and radiologists when: 1, 2
  • Imaging is not consistent with benign lesion
  • Evidence of hormone hypersecretion exists
  • Tumor has grown significantly during follow-up
  • Adrenal surgery is being considered

Special Consideration for Anxiety

In this patient being treated for anxiety, pheochromocytoma screening is particularly important as catecholamine excess can mimic or exacerbate anxiety symptoms (headaches, palpitations, sweating, anxiety attacks) 1. The anxiety diagnosis should be reconsidered if pheochromocytoma is confirmed 1.