What is the recommended workup for an adrenal nodule?

Adrenal Nodule Workup

All patients with adrenal nodules should undergo both comprehensive imaging and hormonal evaluation to rule out malignancy and hormone excess, regardless of how the nodule was discovered. 1

Hormonal Evaluation

1. Initial hormonal screening (required for ALL adrenal nodules):

   • 1mg overnight dexamethasone suppression test (cortisol ≤50 nmol/L or ≤1.8 µg/dL indicates normal suppression) 1
   • Plasma free metanephrines OR 24-hour urinary fractionated metanephrines (values >2× upper limit of normal strongly suggest pheochromocytoma) 1
   • Aldosterone-to-renin ratio (ARR) in patients with hypertension and/or hypokalemia (ARR >20 ng/dL per ng/mL/hr has >90% sensitivity/specificity for hyperaldosteronism) 1

2. Additional hormonal testing (based on clinical suspicion):

   • Sex hormone evaluation (DHEAS, testosterone, 17β-estradiol, etc.) in patients with suspected adrenocortical carcinoma or virilization 1
   • Further cortisol evaluation: ACTH levels, 24-hour urinary free cortisol, midnight salivary cortisol 1

Imaging Evaluation

1. Initial imaging characteristics to assess:

   • Non-contrast CT: HU < 10 indicates benign adenoma (risk of adrenocortical carcinoma 0%) 1
   • Size: Critical thresholds are 4 cm and 6 cm 1
   • Appearance: Homogeneity vs. inhomogeneity, margins (regular vs. irregular) 1

2. Additional imaging (when indicated):

   • Contrast-enhanced CT: >60% washout at 15 minutes suggests benign lesion 1
   • Chemical-shift MRI: Signal intensity loss in opposed-phase images indicates benign adenoma 1
   • Chest CT: For evaluating metastatic disease 1
   • Specialized imaging: MIBG scintigraphy, DOTA-TATE-PET, or Dopa/Dopamine PET for suspected pheochromocytoma 1
   • Bone scintigraphy: If skeletal metastases are suspected 1

Management Algorithm Based on Nodule Characteristics

Surgical Consideration Criteria:

• Size-based criteria:

  • All masses >6 cm regardless of appearance 1
  • Masses >4 cm with inhomogeneous appearance or HU >20 1

• Imaging-based criteria:

  • Irregular margins or heterogeneous appearance
  • High attenuation (>10 HU) on non-contrast CT with poor contrast washout (<60% at 15 minutes)
  • Growth >5 mm/year on follow-up imaging 1

• Functional criteria:

  • Any hormone-producing tumor (pheochromocytoma, aldosterone-secreting adenoma, cortisol-secreting adenoma) 1
  • Mild autonomous cortisol secretion (MACS) with relevant comorbidities 2

Surgical Approach:

• Minimally invasive surgery (MIS): Preferred for benign adenomas when feasible 1
• Open adrenalectomy: For larger tumors or those with features concerning for malignancy 1

Follow-up Recommendations

1. For non-operated patients with benign-appearing adenomas <4 cm:

   • If clearly benign (HU ≤10): No further follow-up imaging or functional testing required 1

2. For non-operated patients with benign-appearing adenomas ≥4 cm:

   • Repeat imaging in 6-12 months
   • Consider surgery if growth >5 mm/year (after repeating functional workup) 1

3. For non-operated patients with non-functioning masses:

   • Consider repeat screening for pheochromocytoma and hypercortisolism at 1-2 years 1

Common Pitfalls and Caveats

• Underestimation of hormone excess: All adrenal nodules require hormonal evaluation, even if they appear benign on imaging 1
• Overreliance on washout CT: Recent research shows washout CT has limited utility in evaluating incidental adrenal nodules in patients without known malignancy 3
• Inadequate hormonal testing: Studies show that despite guidelines, only 30% of patients with adrenal incidentalomas receive appropriate hormonal testing, with even lower rates (18%) for patients not seen by endocrinologists 4
• Growth patterns: Most nodules that will show growth do so within the first 12 months after detection 4
• Terminology clarification: For patients without clinical signs of overt Cushing's syndrome but with serum cortisol levels post dexamethasone >50 nmol/L (>1.8 µg/dL), the term "mild autonomous cortisol secretion" (MACS) is now preferred 2