What is the initial approach to managing adrenal incidentaloma?

Initial Management of Adrenal Incidentaloma

All patients with adrenal incidentalomas require immediate unenhanced CT imaging (if not already performed) and complete hormonal screening regardless of symptoms or imaging appearance. 1, 2, 3

Step 1: Radiological Characterization

First-Line Imaging

• Obtain unenhanced CT to measure Hounsfield Units (HU) and assess lesion characteristics 1, 2, 3
• Lesions ≤10 HU are definitively benign regardless of size—these are lipid-rich adenomas requiring no further imaging workup 1, 2, 3
• Myelolipomas and masses containing macroscopic fat are benign and need no additional evaluation 1, 3

Second-Line Imaging (for indeterminate masses)

• If HU >10 or imaging is equivocal, proceed to enhanced CT with washout protocol (absolute washout ≥60% or relative washout ≥40% suggests benign pathology) 2
• MRI with chemical shift imaging is an alternative, particularly for pregnant women or patients <40 years old 2

Key Imaging Risk Factors

• Size >4 cm significantly increases malignancy risk and warrants closer evaluation 2, 3
• HU >20 carries 6.3% risk of adrenocortical carcinoma versus 0% risk when HU <10 1
• Inhomogeneous appearance, irregular borders, or rapid growth are concerning features 1, 3

Step 2: Mandatory Hormonal Evaluation

Every patient requires complete hormonal screening—this is non-negotiable regardless of symptoms or benign imaging appearance. 1, 2, 4, 3, 5

Required Tests for All Patients

1. 1 mg overnight dexamethasone suppression test (give 1 mg at 11 PM, measure cortisol at 8 AM):

   • Cortisol ≤50 nmol/L (≤1.8 µg/dL) excludes autonomous cortisol secretion 2, 4, 3, 5
   • Cortisol 51-138 nmol/L suggests possible autonomous secretion 4, 5
   • Cortisol >138 nmol/L (>5 µg/dL) indicates autonomous cortisol secretion 4, 5

2. Plasma free metanephrines or 24-hour urinary fractionated metanephrines to exclude pheochromocytoma 2, 4, 3

   • Critical pitfall: Never perform biopsy or surgery without first excluding pheochromocytoma—this can be fatal 3

Conditional Hormonal Tests

1. Aldosterone-to-renin ratio if hypertension or hypokalemia present (ratio >20 ng/dL per ng/mL/hr suggests primary aldosteronism) 2, 4

2. Sex hormones and steroid precursors (DHEAS, testosterone, 17-hydroxyprogesterone, androstenedione) only if:

   • Clinical signs of virilization or feminization present 4
   • Suspected adrenocortical carcinoma 2, 4
   • Bilateral masses (to exclude congenital adrenal hyperplasia) 2, 3

Step 3: Clinical Assessment

Focused History

• Symptoms of cortisol excess: weight gain, easy bruising, proximal muscle weakness, striae, facial plethora 1
• Symptoms of catecholamine excess: episodic headaches, palpitations, diaphoresis, hypertension 1
• Symptoms of aldosterone excess: hypertension, hypokalemia, muscle weakness 1
• Symptoms of sex hormone excess: virilization (hirsutism, acne, menstrual irregularities) or feminization 1
• History of extra-adrenal malignancy (lung, breast, kidney, melanoma, lymphoma) 1

Physical Examination Findings

• Blood pressure measurement (hypertension present in pheochromocytoma, aldosteronoma, Cushing's) 1
• Signs of Cushing's syndrome (central obesity, moon facies, buffalo hump, proximal myopathy) 1
• Signs of virilization or feminization 1

Step 4: Management Algorithm

Immediate Surgical Referral Indicated For:

• Any hormonally active tumor (pheochromocytoma, aldosteronoma, overt Cushing's syndrome) 2, 3, 5
• Masses >4 cm with suspicious imaging features (HU >20, inhomogeneous, irregular borders) 1, 2, 3
• Any mass growing >5 mm/year on surveillance (repeat hormonal workup first) 2, 4, 3
• Radiological features suggesting adrenocortical carcinoma 1, 2

Consider Surgery (Individualized Decision) For:

• Autonomous cortisol secretion (post-dexamethasone cortisol >50 nmol/L) with cortisol-related comorbidities (diabetes, hypertension, osteoporosis, obesity) 3, 5
• Radiologically benign masses ≥4 cm in younger patients (<40 years) 2

No Surgery Required—Follow-Up Protocol:

• Benign masses <4 cm with ≤10 HU: No further imaging or hormonal testing needed 2, 4, 3
• Benign masses ≥4 cm with ≤10 HU: Repeat unenhanced CT at 12 months 2, 3
• Masses 1-4 cm with HU 10-20: Repeat imaging at 12 months, then discontinue if stable 2, 3
• Annual hormonal screening for 4-5 years for masses >3 cm due to risk of developing hormone secretion 3

Step 5: Multidisciplinary Review

Obtain multidisciplinary consultation (endocrinology, surgery, radiology) when: 1, 2, 3

• Imaging not consistent with benign lesion
• Evidence of hormone hypersecretion
• Significant tumor growth during follow-up
• Surgery being considered
• Bilateral adrenal masses (each lesion must be characterized separately) 2, 3

Critical Pitfalls to Avoid

1. Never perform adrenal biopsy routinely—only consider when metastatic disease from extra-adrenal malignancy would change management, and only after definitively excluding pheochromocytoma 3

2. Never skip pheochromocytoma screening—failure to exclude this before intervention can be fatal 3

3. Do not assume benign imaging means non-functional—hormonal evaluation is mandatory for all incidentalomas 1, 2, 3

4. For bilateral masses, measure 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia and characterize each lesion separately 2, 3

5. Medications can interfere with hormone testing—hold interfering medications when possible before testing 4

6. For patients with autonomous cortisol secretion not undergoing surgery, aggressively screen for and treat metabolic comorbidities (hypertension, diabetes, osteoporosis) 3, 5