Evaluation of adrenal incidentalomas: Current approaches, caveats, and unexplored issues

Abstract

The widespread use of high-resolution cross-sectional imaging over the past two decades has resulted in a marked increase - estimated at nearly ten-fold - in the incidental detection of adrenal masses greater than 1 cm, commonly termed adrenal incidentalomas (ADIs). A fundamental principle in their evaluation is the distinction between “true ADIs” - identified in patients without a history of malignancy or clinical suspicion of adrenal disease - and adrenal lesions detected during oncologic staging. This distinction is critical because the pre-test probability of malignancy differs substantially between these groups. In patients undergoing cancer staging, approximately half of adrenal masses may represent metastatic disease, whereas in true ADI populations, the risk of malignancy is typically below 1%. Failure to differentiate these populations risks inappropriate extrapolation of benign-prevalence data into high-risk oncologic contexts. The evaluation of an ADI has two primary objectives: Exclusion of malignancy and identification of hormonal hypersecretion. Although most ADIs are benign and nonfunctional, biochemical screening remains mandatory in most patients, except in those with limited life expectancy or critical illness. Mild autonomous cortisol secretion is the most prevalent functional abnormality, affecting 20% to 50% of patients, and is associated with increased cardiovascular, metabolic, and osseous morbidity. Cardiovascular event rates of 15.5% over approximately 50-60 months have been reported in affected populations. Radiological paradigms are evolving. A homogeneous lesion with attenuation ≤ 10 Hounsfield units on non-contrast computed tomography remains highly specific for a benign lipid-rich adenoma and, according to current European Society of Endocrinology guidance, requires no further imaging follow-up irrespective of size. Emerging evidence, however, suggests that in true ADIs < 4 cm, expanding the benignity threshold to ≤ 20 Hounsfield units may maintain a positive predictive value of 99.4%-99.8% while reducing unnecessary follow-up imaging. Conversely, the historical reliance on adrenal washout computed tomography is increasingly questioned due to limitations in excluding pheochromocytoma and concerns regarding cost-effectiveness. Future research priorities include prospective validation of expanded radiological thresholds, rigorous cost-effectiveness analyses, systematic assessment of psychiatric and quality-of-life outcomes, and evaluation of proposed etiological hypotheses.

Keywords: Adrenal incidentaloma; Mild autonomous cortisol secretion; Non-contrast computed tomography attenuation; Adrenal washout computed tomography; Adrenal venous sampling; Cardiometabolic risk

Core Tip: Incidental adrenal masses are increasingly identified through modern imaging, and physicians must differentiate benign from malignant lesions while excluding hormonal hypersecretion. Mild autonomous cortisol secretion is common and carries cardiometabolic/skeletal risks, warranting biochemical evaluation. Current evidence supports a conservative radiologic approach: Homogeneous adrenal lesions with non-contrast computed tomography attenuation ≤ 10 Hounsfield units are considered benign, and emerging data suggest this threshold may safely extend to ≤ 20 Hounsfield units. The utility of adrenal washout computed tomography is increasingly questioned due to its poor discrimination of pheochromocytoma and limited cost-effectiveness. Future research should address psychiatric consequences and novel etiological factors.