What is the initial hormone evaluation order for an adrenal lesion?

Initial Hormone Evaluation Order for Adrenal Lesions

All patients with adrenal incidentalomas require universal screening for autonomous cortisol secretion using the 1 mg overnight dexamethasone suppression test (DST), with selective testing for aldosterone excess (if hypertension/hypokalemia present), pheochromocytoma (if ≥10 HU on CT or symptoms present), and androgen excess (if virilization or suspected adrenocortical carcinoma). 1

Universal Testing Required for All Adrenal Lesions

Cortisol Screening (Mandatory for Everyone)

• Perform 1 mg overnight DST as the first-line test: administer 1 mg dexamethasone at 11 PM, measure serum cortisol at 8 AM the following morning 1, 2
• Interpret results as follows: ≤50 nmol/L (1.8 μg/dL) excludes autonomous cortisol secretion; 51-138 nmol/L (1.9-5.0 μg/dL) indicates possible autonomous cortisol secretion; >138 nmol/L (>5.0 μg/dL) confirms cortisol hypersecretion 1
• Measure plasma ACTH levels in all patients considering intervention to confirm ACTH-independency 1, 2

This universal cortisol screening is a strong recommendation with moderate quality evidence and applies regardless of tumor size, appearance, or clinical presentation 1.

Selective Testing Based on Clinical Context

Aldosterone Testing (Only if Hypertension or Hypokalemia)

• Measure aldosterone-to-renin ratio (ARR) in patients with hypertension and/or hypokalemia 1, 2
• Obtain the test in the morning after the patient has been out of bed for 2 hours and seated for 5-15 minutes 1
• Ensure patients are potassium-replete and substitute interfering medications when possible 1
• An ARR >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 1
• Check serum potassium levels concurrently to assess for hypokalemia 2

Pheochromocytoma Screening (If ≥10 HU or Symptoms Present)

• Test plasma free metanephrines or 24-hour urinary fractionated metanephrines in patients with adrenal masses displaying ≥10 HU on non-contrast CT or who have signs/symptoms of catecholamine excess 1, 2
• This is a strong recommendation with moderate quality evidence 1
• Values >2X upper limit of normal are significant 1
• Include normetanephrine and methoxytyramine measurements when available, as methoxytyramine provides information about malignancy likelihood 2

Critical pitfall: Never perform adrenal biopsy without first excluding pheochromocytoma, as biopsy of an undiagnosed pheochromocytoma triggers life-threatening hypertensive crisis 2, 3.

Androgen Testing (If Virilization or Suspected Malignancy)

• Measure DHEA-S and testosterone in cases of suspected adrenocortical carcinoma (ACC) or when clinical signs of virilization are present 1, 2
• Higher levels suggest greater burden of disease 1
• Additional androgens to consider: 17β-estradiol, 17-OH progesterone, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol 1, 2
• ACC is responsible for more than half of androgen hypersecretion cases 1

Ancillary Testing When Initial Screening is Abnormal

For Abnormal Cortisol Results

• 24-hour urinary-free cortisol and midnight salivary cortisol for additional confirmation when DST shows 51-138 nmol/L 1, 2
• DHEAS levels to assess adrenal androgen production 1

For Abnormal Aldosterone Results

• Adrenal vein sampling for lateralization to distinguish unilateral adenoma from bilateral hyperplasia 1
• Saline suppression test or salt loading with 24-hour urine aldosterone measurement for confirmatory testing 1

Supporting Laboratory Tests

• Basic metabolic panel to assess electrolyte abnormalities accompanying hormone-secreting tumors 2, 3
• Complete blood count to identify hematologic abnormalities affecting surgical planning 2, 3

Key Clinical Considerations

Do not skip hormonal testing even in apparently non-functioning tumors, as subtle hormone production impacts surgical management and perioperative care 2, 3. Radiological appearance cannot reliably predict hormone secretion status 2, 3.

Be aware that medications can interfere with hormone testing results; hold interfering medications before testing when possible 2. This is particularly important for aldosterone-to-renin ratio testing, where antihypertensive medications can affect results 1.

The prevalence of functional tumors among adrenal incidentalomas is approximately 5.3% for cortisol-secreting adenomas, 1% for aldosterone-secreting tumors, and 5.1% for pheochromocytomas 2. This justifies the algorithmic approach of universal cortisol screening with selective testing based on clinical features.