What is the management plan for patients with adrenal nodules?

Management of Adrenal Nodules

Adrenal nodules require a systematic evaluation focusing on malignancy risk and hormonal status, with surgical management indicated for lesions >4 cm with suspicious features, hormone-producing tumors, or growth >5 mm/year on follow-up imaging. 1

Initial Evaluation

Imaging Assessment

• Non-contrast CT is the first-line imaging modality:
  • HU ≤10 indicates benign adenoma (0% risk of adrenocortical carcinoma)
  • Homogeneous lesions with HU ≤10 are benign regardless of size and require no additional imaging 2
  • Lesions with HU >10 require contrast-enhanced CT with washout protocol

    • 60% washout at 15 minutes suggests benign lesion 1

• Chemical-shift MRI is highly appropriate (rating 8) for characterizing adrenal masses when CT is indeterminate 1
• Risk stratification based on size and imaging features:
  • <3 cm: Extremely low risk of malignancy (87% benign even in patients with history of malignancy)

  • 4 cm with inhomogeneous appearance or HU >20: High risk of malignancy

  • 6 cm: Surgery usually indicated regardless of appearance 1, 2

Hormonal Evaluation

All patients with adrenal nodules require comprehensive hormonal evaluation:

1. Cortisol assessment:

   • 1mg overnight dexamethasone suppression test (cutoff value ≤50 nmol/L or ≤1.8 µg/dL) 1, 2
   • Values >138 nmol/L (>5 µg/dL) indicate "autonomous cortisol secretion" 3

2. Catecholamine assessment:

   • Plasma free metanephrines or 24-hour urinary fractionated metanephrines
   • Values >2× upper limit of normal strongly suggest pheochromocytoma 1

3. Aldosterone assessment (in patients with hypertension/hypokalemia):

   • Aldosterone-to-renin ratio (ARR)
   • ARR >20 ng/dL per ng/mL/hr has >90% sensitivity/specificity for hyperaldosteronism 1

4. Sex hormone evaluation (in patients with suspected adrenocortical carcinoma or virilization):

   • DHEAS, testosterone, and potentially 17β-estradiol, 17-OH progesterone, and androstenedione 1

Management Recommendations

Surgical Management

Surgery is recommended for:

1. Based on size and imaging features:

   • Lesions >4 cm with inhomogeneous appearance or HU >20
   • All masses >6 cm regardless of appearance
   • Any lesion with growth >5 mm/year on follow-up imaging 1, 2

2. Based on hormonal status:

   • Biochemically confirmed pheochromocytomas
   • Aldosterone-secreting adenomas
   • Cortisol-secreting adenomas
   • Patients with "mild autonomous cortisol secretion" (MACS) who have relevant comorbidities (hypertension, type 2 diabetes) 1, 2

3. Surgical approach:

   • Minimally invasive surgery (MIS) preferred for benign adenomas
   • Open adrenalectomy for larger tumors or those with features concerning for malignancy 1
   • For adrenocortical carcinoma, surgical resection with removal of adjacent lymph nodes is recommended 4

Medical Management

1. For primary hyperaldosteronism:

   • Spironolactone is indicated for long-term maintenance therapy in patients with bilateral adrenal hyperplasia or those who are not surgical candidates 5

2. For cortisol-producing lesions:

   • Ketoconazole (400-1200 mg/d) can be used when surgery is contraindicated 4

3. For metastatic adrenal carcinoma:

   • Options include mitotane monotherapy or combinations of cisplatin, carboplatin, etoposide, doxorubicin, and streptozocin 4

Follow-up Recommendations

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

   • <4 cm with HU ≤10: No further follow-up imaging or functional testing required 1, 2
   • ≥4 cm: Repeat imaging in 6-12 months 1

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

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

3. For patients with adrenal carcinoma:

   • Follow-up imaging and biomarkers (for functioning tumors) every 3-6 months 4

Special Considerations

Bilateral Adrenal Masses

• Represent 10-20% of incidentally discovered adrenal masses 6
• Follow same protocol as unilateral masses but consider:
  • Possibility of familial syndromes
  • Risk of adrenal insufficiency if bilateral adrenalectomy is considered 6

ACTH-Dependent Nodules

• Adrenal nodules in conditions like congenital adrenal hyperplasia may regress with adequate hormonal control 7
• Consider underlying endocrine disorders in patients with bilateral adrenal hyperplasia

Pitfalls to Avoid

• Fine-needle aspiration (FNA) is not recommended as initial evaluation due to significant risks (4-12% complication rate) and limited diagnostic benefit 1
• Avoid unnecessary follow-up for clearly benign lesions (HU ≤10) as modern imaging techniques can reliably identify benign adenomas 1, 8
• Don't overlook hormonal evaluation even in apparently non-functioning lesions, as subclinical hormone production can cause significant morbidity 1