Recommended Laboratory Workup for Adrenal Nodules
For all adrenal nodules, a complete hormonal evaluation is mandatory before any intervention, including tests for cortisol excess, pheochromocytoma, and primary aldosteronism to prevent potentially life-threatening complications. 1, 2
Comprehensive Hormonal Evaluation
1. Glucocorticoid Excess Assessment (minimum 3 of 4 tests)
- 1mg overnight dexamethasone suppression test
- 24-hour urinary free cortisol
- Basal serum cortisol
- Basal plasma ACTH
2. Catecholamine Excess (Pheochromocytoma Screening)
- Plasma free metanephrines and normetanephrines (preferred)
- Alternatively: 24-hour urinary fractionated metanephrines
- Consider plasma methoxytyramine (if available) to assess likelihood of malignancy
3. Mineralocorticoid Excess
- Serum potassium
- Aldosterone-to-renin ratio (especially in patients with hypertension and/or hypokalemia)
4. Sex Steroids and Steroid Precursors
- DHEA-S (serum)
- 17-OH-progesterone (serum)
- Androstenedione (serum)
- Testosterone (serum)
- 17-beta-estradiol (serum, only in men and postmenopausal women)
- Consider 24-hour urine steroid metabolite examination
Imaging Evaluation
Initial Imaging
- Non-contrast CT (primary modality)
- HU ≤10 indicates benign adenoma with high specificity
- HU >10 requires further evaluation
Additional Imaging (as indicated)
- Contrast-enhanced CT with washout protocol
60% washout at 15 minutes suggests benign lesion
- MRI with chemical-shift imaging
- Signal intensity loss in opposed-phase images indicates benign adenoma
- CT of chest, abdomen, and pelvis (if malignancy suspected)
- Consider FDG-PET for indeterminate lesions or suspected malignancy
- Bone scintigraphy if skeletal metastases are suspected
Clinical Pitfalls and Caveats
Failure to rule out pheochromocytoma before any intervention can cause life-threatening crisis 1, 2
- Always screen for pheochromocytoma regardless of symptoms
Low adherence to guidelines for hormonal evaluation 3, 4
- Only 8.8% of patients with incidental adrenal masses receive any hormonal evaluation
- 27.3% of evaluated patients have functional masses
Needle biopsy contraindication 2
- Performing needle biopsy of potentially resectable adrenal masses is contraindicated and potentially harmful
Multidisciplinary approach needed for:
- Imaging inconsistent with benign lesion
- Evidence of hormone hypersecretion
- Nodules ≥4 cm
Perioperative management
- Patients with autonomous cortisol secretion require perioperative hydrocortisone replacement
- Patients with pheochromocytoma require preoperative alpha-blocker treatment for 10-14 days
Follow-up Recommendations
- Annual hormonal evaluation for 4-5 years for patients with adrenal nodules under surveillance
- Repeat imaging at 6-12 months for non-functional masses ≥4 cm or with suspicious features
- Clinical, radiological, and biochemical surveillance for at least 10 years after adrenalectomy for adrenal tumors
The comprehensive evaluation of adrenal nodules is essential as approximately 8.5% of patients may have hyperfunctioning nodules (cortisol-producing, aldosterone-producing, or pheochromocytoma) that require specific management 3.