What laboratory tests should be ordered to follow up on an adrenal incidentoma?

Laboratory Tests for Adrenal Incidentaloma Follow-up

All patients with adrenal incidentalomas should undergo screening for autonomous cortisol secretion with a 1 mg overnight dexamethasone suppression test, and additional hormone testing should be performed based on clinical presentation and imaging characteristics. 1

Core Laboratory Evaluation

Screening for Cortisol Excess (Required for ALL patients)

• 1 mg overnight dexamethasone suppression test (DST) is the preferred initial screening test for autonomous cortisol secretion 1
  • Administer 1 mg dexamethasone at 11 PM, measure serum cortisol at 8 AM the next morning 1
  • Interpretation:
    • ≤50 nmol/L excludes cortisol hypersecretion
    • 51-138 nmol/L suggests possible autonomous cortisol secretion

    • 138 nmol/L indicates evidence of cortisol hypersecretion 1

• For abnormal results, additional testing may include:
  • Plasma ACTH (to confirm ACTH independence) 1
  • 24-hour urinary free cortisol 1
  • Midnight salivary cortisol 1
  • DHEAS 1

Screening for Primary Aldosteronism (For patients with hypertension/hypokalemia)

• Aldosterone/renin ratio (ARR) is the preferred initial test 1
  • Best performed in the morning after the patient has been out of bed for 2 hours and seated for 5-15 minutes 1
  • Patient should be potassium-replete and off interfering medications 1
  • ARR >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 1
• For positive screening, confirmatory testing may include:
  • Adrenal vein sampling for lateralization 1
  • Saline suppression test 1
  • Salt loading with 24-hour urine aldosterone measurement 1

Screening for Pheochromocytoma (Based on imaging and symptoms)

• Plasma free metanephrines or 24-hour urinary metanephrines and normetanephrines 1
• Testing is indicated for:
  • Adrenal masses with ≥10 HU on non-contrast CT 1
  • Patients with signs/symptoms of catecholamine excess (headaches, anxiety attacks, sweating, palpitations) 1
• Not routinely needed for masses with <10 HU on unenhanced CT without clinical signs of adrenergic excess 1, 2

Screening for Adrenocortical Carcinoma (For suspicious masses or virilization)

• Serum androgen testing should be performed when adrenocortical carcinoma is suspected or when clinical signs of virilization are present 1
• Tests include:
  • DHEAS and testosterone (primary tests) 1
  • Additional testing may include 17β-estradiol, 17-OH progesterone, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol 1

Algorithm for Laboratory Testing

1. For ALL adrenal incidentalomas:

   • 1 mg overnight dexamethasone suppression test 1

2. For patients with hypertension and/or hypokalemia:

   • Aldosterone/renin ratio 1

3. For patients with adrenal masses ≥10 HU on non-contrast CT or with symptoms of catecholamine excess:

   • Plasma free metanephrines or 24-hour urinary metanephrines 1

4. For patients with suspected adrenocortical carcinoma or virilization:

   • DHEAS, testosterone, and other sex hormone testing 1

Important Considerations and Pitfalls

• Medications can interfere with hormone testing results; consider holding interfering medications before testing when possible 1, 3
• Patients with mild autonomous cortisol secretion (serum cortisol 51-138 nmol/L after DST) should be monitored for metabolic comorbidities that could be related to cortisol excess 4
• Follow-up hormone testing is not required for benign non-functional adenomas <4 cm, myelolipomas, and other small masses containing macroscopic fat 1
• For indeterminate masses, repeat functional testing should be performed if the mass grows >5 mm/year 1
• Studies have shown that approximately 5% of initially non-functional adrenal incidentalomas may develop hormonal activity (primarily subclinical hypercortisolism) during follow-up, justifying periodic reassessment 5

By following this systematic approach to laboratory testing for adrenal incidentalomas, clinicians can effectively identify functional tumors that may require surgical intervention or medical management to reduce morbidity and mortality.