What laboratory tests are recommended for evaluating adrenal nodules?

Laboratory Tests for Evaluating Adrenal Nodules

All patients with adrenal nodules should undergo a comprehensive hormonal evaluation including tests for cortisol excess, catecholamine excess, and aldosterone excess, regardless of imaging appearance. 1

Recommended Hormonal Tests

For All Adrenal Nodules:

1. Cortisol Assessment

   • 1mg overnight dexamethasone suppression test 1
   • Normal response criteria:
     • Control plasma cortisol level should exceed 5 μg/100 mL
     • 30-minute level should show an increment of at least 7 μg/100 mL above basal level
     • 30-minute level should exceed 18 μg/100 mL 2

2. Catecholamine Assessment

   • Plasma-free or 24-hour urinary fractionated metanephrines 3, 1
   • Additional measurement of plasma methoxytyramine provides useful information to assess likelihood of malignancy 3

3. Aldosterone Assessment (especially in hypertensive patients)

   • Aldosterone-to-renin ratio 1

Additional Tests Based on Clinical Suspicion:

• For suspected adrenocortical carcinoma (ACC): Extensive steroid hormone work-up assessing:
  • Glucocorticoids
  • Mineralocorticoids
  • Sex hormones
  • Steroid precursors 3

Clinical Rationale for Hormonal Testing

• Multiple purposes of hormonal evaluation:

  • Provides orientation to the nature of the adrenal mass
  • Rules out pheochromocytoma (critical before any intervention)
  • Identifies hormone excess that may impact survival and quality of life
  • Establishes biological markers for follow-up
  • Assesses adrenal function in case of large bilateral masses 3

• Prevalence of hormone-producing tumors:

  • Cortisol-secreting adenomas: 5.3% of adrenal masses
  • Aldosterone-secreting adenomas: 1% of adrenal masses
  • Pheochromocytomas: 5.1% of adrenal masses 1

Importance of Complete Evaluation

• Studies show that when radiologists include specific recommendations for hormonal evaluation in their reports, adherence to guidelines improves significantly (48% vs 13.9%, p<0.0001) 4

• In one study, 8.5% of patients with adrenal incidentalomas had hyperfunctioning nodules (4 cortisol producing, 6 aldosterone producing, and 1 pheochromocytoma) 4

Special Considerations

• For ACTH stimulation testing: Cosyntropin (synthetic ACTH) can be administered to assess adrenal function:

  • Standard dose: 0.25 mg intramuscularly or intravenously
  • For pediatric patients ≤2 years: 0.125 mg may suffice
  • Blood samples collected at baseline and 30 minutes after administration 2

• Timing considerations:

  • Patients receiving cortisone, hydrocortisone, or spironolactone should omit pre-test doses on the day of testing
  • Women taking estrogen-containing medications may exhibit abnormally high basal plasma cortisol levels 2

Pitfalls to Avoid

• Don't skip hormonal evaluation based on benign imaging appearance - even radiologically benign-appearing lesions can be hormonally active 1

• Don't forget to rule out pheochromocytoma before any invasive procedure, as these tumors can induce life-threatening crises 3

• Avoid biopsy of suspected adrenal masses - biopsies of suspected ACC or pheochromocytoma are usually not informative and should be avoided 3

• Be aware of medication effects - certain medications can affect test results:

  • Cortisone/hydrocortisone may cause paradoxical responses
  • Spironolactone or estrogen may cause abnormally high basal cortisol levels 2

By following these comprehensive laboratory testing recommendations, clinicians can effectively evaluate adrenal nodules, identify functional tumors, and guide appropriate management decisions to improve patient outcomes.