What is the recommended endocrine workup for adrenal nodules?

Recommended Endocrine Workup for Adrenal Nodules

All patients with adrenal incidentalomas should undergo a complete endocrine workup to evaluate for hormone hypersecretion, regardless of nodule size or imaging characteristics. 1

Initial Evaluation

Required Hormonal Testing

1. Autonomous Cortisol Secretion 1, 2

   • 1 mg overnight dexamethasone suppression test (DST) - primary screening test
   • Interpretation: Cortisol ≤50 nmol/L (≤1.8 µg/dL) excludes autonomous cortisol secretion
   • Values >50 nmol/L indicate mild autonomous cortisol secretion (MACS)

2. Pheochromocytoma Screening 1

   • Required for:
     • Adrenal masses with >10 HU on non-contrast CT
     • Any patient with signs/symptoms of catecholamine excess
   • Test options:
     • 24-hour urinary fractionated metanephrines
     • Plasma free metanephrines
   • Not required for unequivocal adrenocortical adenomas (<10 HU) without symptoms

3. Primary Aldosteronism Screening 1

   • Required for patients with:
     • Hypertension
     • Hypokalemia
   • Test: Aldosterone-to-renin ratio (ARR)
   • If positive, adrenal vein sampling is recommended before surgery

4. Androgen Excess Testing 1

   • Required for:
     • Suspected adrenocortical carcinoma
     • Clinical signs of virilization
   • Tests: Serum DHEA-S, androstenedione, testosterone

Special Considerations for Bilateral Adrenal Incidentalomas

• Evaluate each lesion separately using the same criteria as unilateral nodules 1
• Additional testing:
  • Serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 1, 3
  • Assess for adrenal insufficiency in cases of suspected bilateral infiltrative disease, metastases, or hemorrhage 1

Management Algorithm Based on Hormonal Results

1. Cortisol-secreting adenomas:

   • Overt Cushing's syndrome: Unilateral adrenalectomy 1
   • Mild autonomous cortisol secretion (MACS): Consider adrenalectomy in younger patients with progressive metabolic comorbidities 1, 2

2. Aldosterone-secreting adenomas:

   • Unilateral adrenalectomy after confirmation with adrenal vein sampling 1

3. Pheochromocytomas:

   • Surgical resection required 1
   • Preoperative alpha-blockade essential

4. Non-functional adenomas:

   • <4 cm with benign imaging features: No further follow-up required 1
   • ≥4 cm but radiologically benign (<10 HU): Repeat imaging in 6-12 months 1
   • Growing >5 mm/year: Repeat functional workup and consider adrenalectomy 1
   • Growing <3 mm/year: No further imaging or functional testing required 1

Common Pitfalls and Caveats

1. Poor adherence to guidelines: Only 30% of patients with adrenal incidentalomas undergo proper hormonal evaluation, with even lower rates (18%) among patients not seen by endocrinologists 4. Consider using standardized reporting templates to improve adherence.

2. Biopsy risks: Adrenal mass biopsy should not be performed routinely and must be avoided in suspected pheochromocytoma due to risk of hypertensive crisis 1.

3. Washout CT limitations: About 1/3 of pheochromocytomas may washout in the characteristic range of an adenoma, and approximately 1/3 of adrenal adenomas do not washout in the adenoma range 1.

4. Follow-up timing: Growth of malignant lesions typically occurs within 12 months of detection 5, making appropriate timing of follow-up imaging crucial.

5. Indeterminate lesions: For non-functional adrenal masses that remain indeterminate after imaging, shared decision-making between clinicians and patients should guide management (repeat imaging in 3-6 months versus surgical resection) 1.

By following this systematic approach to the endocrine workup of adrenal nodules, clinicians can appropriately identify functional tumors requiring intervention while avoiding unnecessary procedures for benign, non-functional lesions.