What is the appropriate workup and management for incidentally discovered adrenal nodules?

Workup and Management of Incidentally Discovered Adrenal Nodules

All patients with adrenal incidentalomas require both comprehensive hormonal screening and radiological characterization regardless of symptoms or imaging appearance, with management decisions driven by size, imaging characteristics, and functional status. 1, 2

Initial Radiological Assessment

Obtain unenhanced (non-contrast) CT as the mandatory first-line imaging test for all adrenal incidentalomas. 1, 2, 3

Benign Lesions Requiring No Further Workup:

• Homogeneous lesions measuring ≤10 Hounsfield Units (HU) are definitively benign regardless of size and require no additional imaging 1, 2, 3
• Myelolipomas and masses containing macroscopic fat are benign and need no further evaluation 1, 2

Indeterminate or Suspicious Lesions:

• Masses >10 HU on non-contrast CT require second-line imaging with either washout CT or chemical-shift MRI 1
• Lesions >4 cm that are inhomogeneous or have HU >20 carry sufficiently high malignancy risk that surgery is usually the appropriate management 3
• All indeterminate cases warrant multidisciplinary discussion with endocrinology, surgery, and radiology 1, 2

Mandatory Hormonal Evaluation

Every patient requires complete hormonal screening regardless of symptoms or how benign the mass appears on imaging, as approximately 5% of radiologically benign incidentalomas harbor subclinical hormone production requiring treatment. 4, 2

Required Tests for All Patients:

1. Autonomous Cortisol Secretion Screening:

• Perform 1 mg overnight dexamethasone suppression test (1 mg at 11 PM, measure serum cortisol at 8 AM) 1, 5, 2, 3
• Cortisol ≤50 nmol/L (≤1.8 µg/dL) excludes autonomous secretion 5, 2, 3
• Cortisol 51-138 nmol/L suggests possible mild autonomous cortisol secretion (MACS) 5
• Cortisol >138 nmol/L indicates evidence of cortisol hypersecretion 5

2. Pheochromocytoma Screening:

• Measure plasma free metanephrines or 24-hour urinary fractionated metanephrines/normetanephrines in all patients 5, 4, 2
• This test is particularly critical for masses ≥10 HU or patients with symptoms of catecholamine excess (hypertension, headaches, palpitations, sweating) 5
• Never perform adrenal biopsy or surgery without first excluding pheochromocytoma, as failure to do so can be fatal 2

3. Primary Aldosteronism Screening:

• Measure aldosterone/renin ratio in patients with hypertension and/or hypokalemia 5
• Ratio >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity 5

4. Androgen Testing:

• Measure serum DHEAS and testosterone only in patients with suspected adrenocortical carcinoma or clinical signs of virilization/feminization 5, 4
• Not routinely indicated for typical incidentalomas 5

Indications for Surgical Intervention

Surgery is indicated for:

Functional Tumors:

• All pheochromocytomas 4, 2
• Aldosterone-secreting adenomas causing primary aldosteronism 4, 2
• Cortisol-secreting masses with clinically apparent Cushing's syndrome 1, 2
• For MACS (post-dexamethasone cortisol >50 nmol/L without overt Cushing's), consider adrenalectomy in younger patients with progressive metabolic comorbidities (hypertension, type 2 diabetes) attributable to cortisol excess after shared decision-making 4, 3

Suspicious Imaging Features:

• Masses >4 cm with inhomogeneous appearance or >20 HU 1, 2, 3
• Any mass growing >5 mm/year on surveillance (after repeating functional workup) 1, 5, 2

Surgical Approach:

• Use minimally invasive adrenalectomy when feasible for masses that can be safely resected without rupturing the tumor capsule 4
• Consider open adrenalectomy for larger adrenocortical carcinomas or locally advanced tumors 4

Follow-Up Protocol for Non-Surgical Cases

Benign Non-Functional Lesions <4 cm:

• No further imaging or functional testing required for lesions <10 HU, myelolipomas, and other small masses containing macroscopic fat 5, 2

Radiologically Benign (≤10 HU) but ≥4 cm:

• Repeat unenhanced CT at 6-12 months 1, 4, 2
• If growth >5 mm/year, repeat functional workup and consider adrenalectomy 1, 2

Indeterminate Masses:

• Repeat imaging at 3-6 months versus surgical resection based on shared decision-making, considering patient age, comorbidities, and anxiety level 4

Duration of Surveillance:

• Discontinue imaging if no growth after 1-2 years of stability 2
• Perform annual hormonal screening for 4-5 years for masses >3 cm due to risk of new hormone secretion 2

Growth Thresholds:

• Growth <3 mm/year: no further imaging or functional testing required 5
• Growth 3-5 mm/year: continued surveillance may be appropriate 5
• Growth >5 mm/year: repeat functional workup and consider adrenalectomy 1, 5, 2

Special Populations Requiring Expedited Evaluation

Young adults (<40 years), children, and pregnant patients require expedited evaluation because adrenal lesions are more likely malignant in these populations. 4

• Use low-dose CT or chemical-shift MRI to minimize radiation exposure 4

Patients with history of extra-adrenal malignancy require closer evaluation, even for smaller lesions, as metastatic disease to the adrenal gland occurs in 25-72% depending on primary tumor type. 4

Bilateral Adrenal Incidentalomas

Each lesion must be characterized separately using the same protocol as unilateral masses. 4, 2

• Measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 4, 2
• Assess for adrenal insufficiency if bilateral infiltrative disease, metastases, or hemorrhage is suspected 4

Critical Pitfalls to Avoid

Never perform adrenal biopsy routinely. 4, 2

• Only consider biopsy when diagnosis of metastatic disease from extra-adrenal malignancy would directly change management 2
• Biopsy carries risk of tumor seeding in suspected adrenocortical carcinoma 4
• Always exclude pheochromocytoma before any biopsy or surgical intervention 2

Do not skip hormonal evaluation based on benign imaging appearance. 4, 2

• Approximately 5% of radiologically benign incidentalomas have subclinical hormone production requiring treatment 4

Avoid unnecessary repeated imaging. 4

• Leads to increased radiation exposure, patient anxiety, and healthcare costs 4
• Follow evidence-based surveillance intervals outlined above 2

Ensure multidisciplinary discussion when imaging is indeterminate, hormone hypersecretion is present, significant growth occurs, or surgery is considered. 1, 2