What is the recommended management for a patient with a newly diagnosed adrenal adenoma?

Management of Newly Diagnosed Adrenal Adenoma

All patients with a newly diagnosed adrenal adenoma require comprehensive hormonal evaluation and risk stratification based on imaging characteristics and size, with benign non-functional adenomas <4 cm requiring no further follow-up after initial characterization. 1

Initial Evaluation Framework

Mandatory Hormonal Testing

Every patient requires complete hormonal screening regardless of imaging appearance, as approximately 5% of radiologically benign lesions harbor subclinical hormone production requiring treatment 1:

• Cortisol assessment: 1 mg overnight dexamethasone suppression test with plasma ACTH levels 2

  • Serum cortisol ≤50 nmol/L (1.8 mg/dL) excludes autonomous secretion 3
  • 51-138 nmol/L (1.9-5.0 mg/dL) indicates possible secretion 3

  • 138 nmol/L (>5.0 mg/dL) confirms autonomous cortisol secretion 3

• Pheochromocytoma screening: Plasma metanephrines or 24-hour urinary metanephrines for all patients, mandatory before any surgical consideration 2

• Aldosterone assessment (if hypertensive or hypokalemic): Aldosterone-to-renin ratio and serum potassium 2

• Androgen testing (if clinically indicated): DHEA-S, 17-OH-progesterone, androstenedione, 17-beta-estradiol 2

Imaging Characterization

Non-contrast CT is the gold standard initial test 3:

• <10 Hounsfield Units (HU): Confidently benign, homogeneous adenoma 3, 1
• 10-20 HU: Low malignancy risk (0.5%) but requires follow-up 3
• >20 HU: 6.3% malignancy risk, indeterminate lesion requiring additional evaluation 3

Management Algorithm Based on Size and Function

Benign Non-Functional Adenomas <4 cm

No further imaging or hormonal testing required after initial characterization if lesion is homogeneous, <10 HU, and hormonally inactive 1. This represents the majority of adrenal adenomas and requires no ongoing surveillance.

Lesions ≥4 cm (Even if Benign-Appearing)

Repeat imaging at 6-12 months is mandatory due to higher malignancy risk 1, 4. Most surgically resected pheochromocytomas and adrenocortical carcinomas were >4 cm at diagnosis 1.

Functional Adenomas

Cortisol-secreting adenomas:

• Screen for comorbidities including hypertension, type 2 diabetes, and asymptomatic vertebral fractures 3
• Consider adrenalectomy based on symptoms, cortisol-induced comorbidities, and overall health status 3
• Surgery not universally recommended for all cases of autonomous cortisol secretion 3

Aldosterone-secreting adenomas:

• Confirm diagnosis with saline suppression test 3
• Perform bilateral adrenal vein sampling (AVS) to lateralize production, even with well-visualized masses on imaging 3
• Laparoscopic adrenalectomy is the treatment of choice 3
• If surgery contraindicated or AVS doesn't lateralize, treat with mineralocorticoid receptor antagonist 3

Pheochromocytoma:

• Mandatory surgical resection 3
• Alpha blocker therapy for 1-3 weeks preoperatively to prevent catecholamine surge 3
• Beta blocker may be added for reflex tachycardia control 3

Indeterminate Imaging Features

For lesions with HU >10 or heterogeneous appearance 3:

• Repeat imaging in 3-6 months initially, then annually for 1-2 years 3
• Consider PET scan if active extra-adrenal malignancy present 3
• Multidisciplinary review by endocrinologists, surgeons, and radiologists 3
• Surgery if appreciable growth on repeat imaging 3

Growth-Based Intervention Thresholds

• <3 mm/year: No further imaging or testing required 1, 4
• >5 mm/year: Consider adrenalectomy after repeating functional workup 1, 4
• Growth of ≥0.8 cm over 3-12 months warrants surgical consideration 5

Follow-Up Hormonal Testing Controversy

The American Urological Association (2023) does not recommend repeat hormonal testing if initial workup was normal 1. However, other guidelines diverge:

• AACE/AAES recommend annual hormonal panels for 5 years 3
• CUA and KES recommend annual testing for 4-5 years if tumor >3 cm 3

Given this discrepancy, prioritize the most recent AUA guideline recommendation of no repeat hormonal testing for initially normal results, particularly for lesions <4 cm with benign imaging characteristics 1.

Special Population Considerations

Patients with history of extra-adrenal malignancy: Metastatic risk ranges 25-72% depending on primary tumor 1. Even with cancer history, 48-52% of adrenal masses represent independent adrenal pathology rather than metastases 6. All patients require standard hormonal evaluation regardless of cancer history 6.

Young adults, children, pregnant patients: Expedited evaluation required as adrenal lesions more likely malignant in these populations 3, 1. MRI preferred over CT when possible 3.

Critical Pitfalls to Avoid

• Never perform adrenal biopsy as part of initial workup - limited clinical value and carries risks including tumor seeding 3, 1
• Never skip pheochromocytoma screening before surgery - undiagnosed pheochromocytoma causes life-threatening intraoperative hypertensive crisis 4, 2
• Do not assume radiologic appearance predicts hormonal status - discordance between imaging and function occurs 7
• Avoid laparoscopic approach for suspected adrenocortical carcinoma - open surgery required for large, invasive tumors to prevent carcinomatosis 3