Management of Adrenal Nodules
All patients with adrenal nodules require both hormonal screening and imaging characterization to determine if the mass is functional or malignant, followed by size-based and growth-based surveillance protocols. 1
Initial Diagnostic Workup
Mandatory Hormonal Screening
Every patient with an adrenal nodule must undergo hormonal evaluation regardless of imaging appearance, as approximately 5% of radiologically benign lesions harbor subclinical hormone production requiring treatment: 2, 3
1 mg overnight dexamethasone suppression test (give 1 mg at 11 PM, measure serum cortisol at 8 AM): This screens for autonomous cortisol secretion in all patients. Cortisol ≤50 nmol/L (≤1.8 µg/dL) excludes hypersecretion; >138 nmol/L (>5 µg/dL) indicates autonomous cortisol secretion. 1, 3, 4
Plasma free metanephrines or 24-hour urinary metanephrines: Required for all nodules with >10 HU on non-contrast CT or any symptoms of catecholamine excess (palpitations, headaches, sweating). Skipping this test risks undiagnosed pheochromocytoma causing life-threatening hypertensive crisis during any surgical procedure. 1, 2, 3
Aldosterone-to-renin ratio: Only if patient has hypertension and/or hypokalemia. A ratio >20 ng/dL per ng/mL/hr has excellent sensitivity for primary aldosteronism. 1, 3
Serum androgens (DHEA-S, testosterone, 17-OH progesterone): Only if suspected adrenocortical carcinoma or clinical virilization signs present. 1, 3
Imaging Characterization Algorithm
First-line: Non-contrast CT to measure Hounsfield units (HU) 1, 2
HU ≤10: Definitively benign lipid-rich adenoma—no further imaging needed regardless of size (unless >4 cm, see below). 1, 5, 4
HU >10: Proceed to second-line imaging with either washout CT or chemical-shift MRI to further characterize. 1
Critical pitfall: Never perform adrenal biopsy routinely for incidentaloma workup—it is potentially harmful, rarely informative for resectable tumors, and risks tumor seeding. Only consider biopsy when confirming metastatic disease from known extra-adrenal malignancy would change management. 1, 2
Management Based on Functional Status
Functional Adrenal Masses (Require Surgery)
Unilateral adrenalectomy via minimally invasive surgery when feasible for: 1
Clinically apparent Cushing's syndrome: Unilateral cortisol-secreting masses with overt symptoms require immediate surgical resection. 1
Mild autonomous cortisol secretion (MACS): Younger patients with progressive metabolic comorbidities (hypertension, diabetes, vertebral fractures) attributable to cortisol excess can be offered adrenalectomy after shared decision-making. Those not operated require annual screening for new/worsening comorbidities. 1, 4
Pheochromocytomas and aldosterone-secreting adenomas: Surgical resection is mandatory. For aldosteronomas, adrenal vein sampling is required before surgery to confirm lateralization. 1
Suspected Adrenocortical Carcinoma
Surgical approach depends on size and local invasion: 1
Minimally invasive adrenalectomy: Can be offered for suspected ACC that can be safely resected without capsule rupture (generally <6 cm). 1
Open adrenalectomy: Required for larger tumors or those with locally advanced features, lymph node metastases, or tumor thrombus. Complete R0 resection with locoregional lymphadenectomy is the goal. 1
Post-operative surveillance: Every 3 months for 2 years with abdominal CT/MRI, thoracic CT, and hormone monitoring if initially elevated. Continue surveillance for at least 10 years due to late recurrence risk. 1
Management of Non-Functional Masses
Benign Features—No Further Follow-up Required
No additional imaging or hormonal testing needed for: 1, 5
- Non-functional adenomas <4 cm with HU <10
- Myelolipomas (any size with macroscopic fat)
- Other small masses containing macroscopic fat
Size-Based Surveillance Protocol
For non-functional lesions ≥4 cm but radiologically benign (HU <10): 1, 5
- Repeat imaging in 6-12 months (most pheochromocytomas and ACCs are >4 cm at diagnosis, justifying closer surveillance despite benign appearance). 1
For indeterminate non-functional masses: 1
- Shared decision-making between repeat imaging in 3-6 months versus surgical resection, weighing patient age, comorbidities, and anxiety level. 1
Growth-Based Management
Growth rate thresholds determine next steps: 1, 5
<3 mm/year: No further imaging or functional testing required. 1, 5
>5 mm/year: Repeat complete functional workup, then consider adrenalectomy. 1, 5
3-5 mm/year: Continue surveillance with imaging. 5
Important: The 2023 CUA/AUA guidelines do not recommend repeat hormonal testing if initial workup was normal, though older guidelines suggested annual hormonal panels for 5 years—the most recent high-quality evidence supports one-time hormonal evaluation only. 5
Special Populations and Considerations
Bilateral Adrenal Masses
Each lesion requires separate characterization following the same protocol as unilateral masses. Additionally, measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia. 3, 6
Young Adults, Children, and Pregnant Patients
Expedite evaluation as adrenal lesions are more likely malignant in these populations. Consider low-dose CT or chemical-shift MRI to minimize radiation exposure. 1, 5
Patients with Extra-Adrenal Malignancy
Metastatic risk ranges from 25-72% depending on primary tumor. Even smaller lesions require closer evaluation and lower threshold for biopsy (after excluding pheochromocytoma). 5
Critical Pitfalls to Avoid
Never skip initial hormonal evaluation even for benign-appearing lesions—5% harbor subclinical hormone production. 2, 5
Never biopsy before excluding pheochromocytoma—this can precipitate hypertensive crisis. 1
Never assume bilateral masses are metastatic without proper workup—they may represent bilateral adenomas, hemorrhage, or primary bilateral macronodular hyperplasia. 6
Never delay surgery for functional tumors while pursuing additional imaging—hormonal excess drives morbidity and mortality. 1