What initial lab work is recommended for a patient with an adrenal nodule?

Initial Laboratory Workup for Adrenal Nodules

All patients with adrenal incidentalomas should undergo screening for autonomous cortisol secretion with a 1 mg overnight dexamethasone suppression test as the first-line hormonal evaluation, regardless of nodule characteristics. 1

Comprehensive Hormonal Evaluation

The initial laboratory workup for a patient with an adrenal nodule should be guided by both imaging characteristics and clinical presentation:

For All Adrenal Nodules:

• Cortisol evaluation:
  • 1 mg overnight dexamethasone suppression test (DST)
    • Take 1 mg dexamethasone at 11 PM, measure serum cortisol at 8 AM
    • Interpretation:
      • ≤50 nmol/L (≤1.8 μg/dL): Excludes cortisol hypersecretion
      • 51-138 nmol/L (1.9-5.0 μg/dL): Possible autonomous cortisol secretion

      • 138 nmol/L (>5.0 μg/dL): Evidence of cortisol hypersecretion 1

For Patients with Hypertension and/or Hypokalemia:

• Aldosterone evaluation:
  • Aldosterone-to-renin ratio (ARR)
    • Collect in morning after patient has been out of bed for 2 hours and seated for 5-15 minutes
    • Ensure patient is potassium-replete and not on interfering medications
    • ARR ≥20 ng/dL per ng/mL/hr suggests hyperaldosteronism (>90% sensitivity and specificity) 1

For Nodules with ≥10 HU on Non-contrast CT or Patients with Symptoms of Catecholamine Excess:

• Pheochromocytoma screening:
  • Plasma free metanephrines OR
  • 24-hour urinary metanephrines
  • Values >2× upper limit of normal are diagnostic 1

For Suspected Adrenocortical Carcinoma or Virilization:

• Androgen evaluation:
  • DHEAS (dehydroepiandrosterone sulfate)
  • Testosterone
  • Additional tests if indicated: 17β-estradiol, 17-OH progesterone, androstenedione 1

Clinical Approach Based on Imaging

For Nodules <10 HU on Non-contrast CT:

• Screen for cortisol excess only, unless clinical symptoms suggest other hormone excess 1

For Nodules ≥10 HU on Non-contrast CT:

• Complete hormonal workup including cortisol, catecholamines, and if indicated, aldosterone and androgens 1

For Nodules ≥4 cm:

• Complete hormonal workup regardless of imaging characteristics
• Higher suspicion for adrenocortical carcinoma (ACC) warrants more extensive androgen testing 1

Pitfalls and Caveats

1. Medication interference: Many medications can affect hormone test results. Consider stopping drugs affecting pituitary or adrenocortical function before testing (at least 5 half-lives) 2

2. False negatives in cortisol testing: Mild autonomous cortisol secretion may be missed with a single test. Consider additional testing (24-hour urinary free cortisol, midnight salivary cortisol) when clinical suspicion is high 1

3. Timing matters: For aldosterone testing, proper patient positioning and timing are crucial for accurate results 1

4. Size matters for malignancy risk: The prevalence of malignancy is significantly higher in nodules ≥4 cm (21.1%) compared to those <4 cm (0.3%) 3

5. Coexisting conditions: Adrenal incidentalomas and unilateral adrenal hyperplasia may coexist, potentially leading to incorrect identification of the source of hormone excess 4

6. Imaging limitations: While non-contrast CT with <10 HU suggests a benign adenoma, heterogeneous microscopic fat on chemical-shift MRI typically indicates benignity but requires caution in patients with prior malignancy 5, 6

7. Poor compliance with guidelines: Studies show that only 30% of patients with adrenal incidentalomas undergo appropriate hormonal testing, highlighting the importance of following established protocols 7

By following this systematic approach to laboratory evaluation of adrenal nodules, clinicians can effectively identify functional tumors requiring intervention while avoiding unnecessary testing in patients with clearly benign lesions.