Early observations and pilot data that first suggested a new direction
The widespread use of abdominal imaging led to detection of adrenal masses in up to 5% of CT scans performed for unrelated reasons. Early management varied widely, with some centers performing extensive workups and frequent follow-up imaging for all incidentalomas. The NIH State of the Science Conference in 2002 provided the first structured approach, establishing that the two key questions for every adrenal incidentaloma were whether the mass was malignant and whether it was hormonally active.
Landmark RCTs and pivotal trials that established the evidence base
The 2016 ESE/ENSAT Clinical Practice Guideline, led by Fassnacht, provided the first comprehensive evidence-based European guideline for adrenal incidentaloma management. The guideline addressed four key questions: assessing malignancy risk (imaging characteristics, size thresholds), defining and managing autonomous cortisol secretion, identifying surgical candidates, and determining appropriate follow-up. The recommendation for a 1 mg overnight dexamethasone suppression test as the standard screening for cortisol excess (with a 50 nmol/L cutoff) standardized the hormonal evaluation approach.
Follow-up studies, subgroup analyses, and real-world validation
The 2023 updated ESE/ENSAT guidelines refined the approach with new evidence on several fronts: the introduction of CT washout criteria for characterizing lipid-poor adenomas, updated data on the natural history of autonomous cortisol secretion (previously termed subclinical Cushing syndrome), and evidence that routine follow-up imaging was unnecessary for masses with clearly benign imaging characteristics. Studies demonstrating the association between autonomous cortisol secretion and cardiometabolic morbidity strengthened the rationale for systematic hormonal screening.
Integration into clinical practice guidelines and recommendations
The ESE/ENSAT guidelines remain the primary international reference, recommending: (1) non-contrast CT as the initial imaging modality with Hounsfield unit assessment; (2) 1 mg dexamethasone suppression test for all patients; (3) plasma or urinary metanephrines if clinical suspicion for pheochromocytoma; (4) surgery for hormonally active tumors or those with imaging features suspicious for malignancy; and (5) limited follow-up for clearly benign lesions.
ESE/ENSAT
Systematic hormonal evaluation with 1 mg DST; imaging characterization by HU and washout; surgery for lesions >4 cm or with suspicious features; limited follow-up for benign-appearing lesions
AACE/AAES
Size-based approach with hormonal workup including DST, metanephrines, and aldosterone-renin ratio if hypertensive
Now
Current standard of care and ongoing research directions
Adrenal incidentaloma management has matured into a structured, risk-stratified approach that balances the need to identify malignancy and hormone excess against the harms of over-investigation. The updated 2023 ESE/ENSAT guidelines reduced unnecessary follow-up imaging for clearly benign lesions. The clinical significance and optimal management of mild autonomous cortisol secretion remains the most debated area, with growing evidence linking it to cardiometabolic outcomes but insufficient randomized trial data to guide surgical versus medical management.
What workup is needed for an adrenal incidentaloma?+
Per ESE/ENSAT 2023 guidelines: (1) non-contrast CT to assess Hounsfield units (≤10 HU suggests lipid-rich adenoma); (2) 1 mg overnight dexamethasone suppression test to screen for cortisol excess (cutoff ≤50 nmol/L); (3) plasma or urinary metanephrines if pheochromocytoma is suspected; (4) aldosterone-renin ratio if hypertensive. Surgery is recommended for lesions >4 cm, imaging features suspicious for malignancy, or confirmed hormone excess.
How often does an adrenal incidentaloma require follow-up?+
The 2023 ESE/ENSAT guidelines reduced follow-up requirements. Clearly benign lesions (homogeneous, ≤10 HU, <4 cm) may not require routine imaging follow-up. Indeterminate lesions warrant repeat imaging at 6-12 months. Hormonal re-evaluation is recommended only if clinical features of cortisol or catecholamine excess develop.
