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Pathophysiology
Clinical meaning
An adrenal incidentaloma is an adrenal mass ≥ 1 cm discovered on imaging performed for indications other than suspected adrenal disease. Prevalence is 3-7% on abdominal CT (increases with age — up to 10% in elderly). Most are non-functioning cortical adenomas (80%). The two critical questions in evaluation are: (1) Is it hormonally active? (subclinical Cushing > pheochromocytoma > primary aldosteronism > adrenal carcinoma; functional tumors require treatment regardless of size), and (2) Is it malignant? (adrenocortical carcinoma is rare but aggressive; size > 4-6 cm, irregular borders, heterogeneous enhancement, washout < 50% on delayed CT are concerning features). CT characteristics guide risk assessment: Hounsfield units (HU) < 10 on unenhanced CT indicates lipid-rich adenoma (benign — no further imaging needed); HU > 10 requires contrast washout study (absolute washout > 60% and relative washout > 40% at 15 minutes suggests adenoma). MRI signal drop on out-of-phase compared to in-phase images (India ink artifact at tumor-tissue interface) indicates intracellular lipid = adenoma.
Diagnostics & workup:
- Hormonal workup (ALL adrenal incidentalomas ≥ 1 cm require functional assessment):
- 1. Pheochromocytoma screening: plasma free metanephrines (MANDATORY — undiagnosed pheo is life-threatening during any future surgery, even non-adrenal)
- 2. Cortisol excess: 1 mg overnight dexamethasone suppression test (DST) — cortisol > 1.8 mcg/dL at 8 AM = abnormal (possible autonomous cortisol secretion); cortisol > 5.0 = likely Cushing syndrome
- 3. Aldosterone/renin ratio: ONLY if hypertensive or hypokalemic (not needed if normotensive with normal K+)
- 4. Sex steroids (DHEA-S, testosterone, estradiol): if large mass (> 4 cm) or clinical virilization — elevated androgens suggest adrenocortical carcinoma
- CT adrenal protocol: unenhanced HU < 10 = lipid-rich adenoma (benign — high specificity); HU > 10 → enhanced CT with 15-minute delayed washout (absolute washout > 60% = adenoma, < 60% = indeterminate/suspicious)
- MRI chemical shift imaging: signal dropout on opposed-phase = intracellular lipid = adenoma; no dropout = indeterminate (may be metastasis, carcinoma, or pheo)
- PET/CT with FDG: may differentiate benign from malignant — adenomas typically non-avid; carcinomas and metastases are FDG-avid
- Biopsy: ONLY when metastasis is suspected (known primary malignancy) AND pheochromocytoma has been biochemically excluded — never biopsy without excluding pheo first (life-threatening hypertensive crisis)
Risk factors:
- Age (prevalence increases with age — up to 10% by age 70)
- Obesity and metabolic syndrome (associated with non-functioning adenomas)
- Hypertension, diabetes (may indicate subclinical autonomous cortisol secretion)
- Known extra-adrenal malignancy (adrenal metastasis is common — lung, breast, melanoma, kidney, lymphoma)
- Large mass size > 4-6 cm (increased malignancy risk)
- Rapid growth on serial imaging
- Young age with large adrenal mass (higher index of suspicion for adrenal carcinoma)
Management
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Prescribing & monitoring
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Takeaways
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