Updated October 2025

Endocrinology | Adrenal

Adrenal Incidentalomas: Biochemical Workup and Surgical Indications

Most adrenal incidentalomas are benign and nonfunctioning, but all lesions ≥1 cm warrant structured hormonal screening and imaging risk stratification. Priorities are to exclude pheochromocytoma, autonomous cortisol secretion, and primary aldosteronism when indicated, and to identify imaging features concerning for malignancy. Surgery is indicated for functional tumors and for lesions with high malignant potential based on size, growth, and radiographic phenotype.

Clinical question

What is the evidence-based biochemical evaluation and what are the indications for adrenalectomy in patients with adrenal incidentalomas?

Adrenal IncidentalomaCortisolPheochromocytomaPrimary AldosteronismAdrenocortical CarcinomaEndocrine Surgery

Key points

Initial triage

Confirm lesion is adrenal; characterize by unenhanced CT attenuation and washout; screen for hormonal excess in all ≥1 cm lesions ^[5], ^[7].

Hormone excess first

Exclude pheochromocytoma, autonomous cortisol secretion, and primary aldosteronism (when hypertensive/hypokalemic). Positive tests typically warrant adrenalectomy ^[5], ^[7].

Benign imaging phenotype

Homogeneous lipid-rich adenoma (≤10 HU) is very unlikely to be pheochromocytoma; in this context, metanephrine testing may be omitted per newer guidance ^[13], ^[5].

Malignancy risk

Concern rises with size, heterogeneity, irregular margins, HU >20–30, delayed washout, and growth on follow-up. Such features trigger surgical consultation ^[3], ^[4], ^[5].

Evidence highlights

All adrenal masses ≥1 cm: biochemical screening for hormonal excess

Who to test

Pheochromocytoma unless ≤10 HU on noncontrast CT and no suspicious features

Key rule-out

1-mg overnight dexamethasone suppression (DST) for all

Core cortisol test

Screen if hypertension or unexplained hypokalemia

Primary aldosteronism

Evidence-Based Approach

Stepwise Evaluation

Prioritize biochemical screening and imaging characterization to separate functional tumors and malignancy from benign, nonfunctioning adenomas.

Confirm adrenal origin and characterize imaging

Obtain unenhanced CT attenuation (HU), homogeneity, and size. Lipid-rich adenomas are typically homogeneous and ≤10 HU; indeterminate lesions may need contrast-enhanced washout CT or MRI chemical-shift. Concerning features include heterogeneity, necrosis, irregular margins, HU >20–30, and low contrast washout ^[4], ^[5].

Screen all patients for cortisol autonomy

Perform 1-mg overnight dexamethasone suppression test (DST). A post-DST cortisol >1.8 µg/dL (50 nmol/L) indicates possible autonomous cortisol secretion; higher thresholds (e.g., >5 µg/dL) increase specificity. Confirm with ACTH, repeat DST, or late-night salivary cortisol if needed. Clinically significant cortisol autonomy with comorbidities often favors surgery ^[5], ^[3].

Exclude pheochromocytoma

Measure plasma free or urinary fractionated metanephrines. A key exception: if the lesion is a homogeneous lipid-rich adenoma with ≤10 HU on noncontrast CT and no suspicious features, pheochromocytoma is highly unlikely and testing can be omitted per contemporary data and guidelines ^[13], ^[5].

Screen for primary aldosteronism when indicated

If the patient has hypertension or unexplained hypokalemia, obtain aldosterone-renin ratio with appropriate medication management and posture/salt conditions. Positive screening prompts confirmatory testing and lateralization strategy if surgery is contemplated ^[5], ^[7].

Consider other hormones selectively

Androgens/estrogens (e.g., DHEA-S, testosterone, estradiol) if virilization/feminization or suspicion for adrenocortical carcinoma. 17-OHP if congenital adrenal hyperplasia is a consideration. Evaluate for adrenal insufficiency only if bilateral disease or clinical cues ^[3], ^[5].

Multidisciplinary review

Integrate biochemical results with imaging risk to decide surveillance versus adrenalectomy. Engage endocrinology, endocrine surgery, and radiology for indeterminate or high-risk lesions ^[3], ^[5], ^[7].

Actionable Criteria

When to Operate vs Observe

Functional tumors are generally resected. Imaging features guide management for nonfunctioning lesions.

Clear surgical indications

Biochemically confirmed pheochromocytoma: adrenalectomy after alpha-blockade ^[5], ^[7].

Primary aldosteronism with unilateral source: adrenalectomy if surgically fit; otherwise medical therapy ^[5], ^[7].

Autonomous cortisol secretion with clinically relevant comorbidities attributable to cortisol excess (e.g., refractory hypertension, diabetes, osteoporosis): consider adrenalectomy after MDT discussion ^[5], ^[3].

Radiographic concern for malignancy (e.g., size ≥4–6 cm, HU >20–30, heterogeneity, irregular margins, delayed washout, interval growth): surgical evaluation; open approach favored if adrenocortical carcinoma suspected ^[4], ^[5].

Reasonable to observe

Homogeneous, lipid-rich adenoma ≤10 HU and <4 cm with negative hormonal screening: no surgery; limited or no further imaging per risk and patient factors ^[5].

Indeterminate 1–4 cm lesion without suspicious features and negative hormones: short-interval imaging (e.g., 6–12 months) can be considered; stop if stable and benign phenotype confirmed ^[3], ^[5].

Features raising malignancy risk

Size: risk increases with diameter; many centers use ≥4 cm as a surgical threshold when phenotype is indeterminate ^[3], ^[5].

Density: unenhanced HU >20–30, heterogeneous texture, necrosis/hemorrhage ^[4], ^[5].

Washout: relative/absolute washout below benign thresholds.

Growth: increase >5 mm–1 cm or >20% over 6–12 months suggests surgery or biopsy consideration in selected scenarios (avoid biopsy if pheochromocytoma not excluded) ^[4], ^[5].

Biochemical testing essentials

Cortisol: 1-mg DST for all; follow-up ACTH, repeat DST, or other tests if discordant ^[5], ^[3].

Pheochromocytoma: plasma free or urinary fractionated metanephrines unless ≤10 HU homogeneous adenoma on unenhanced CT ^[13], ^[5].

Primary aldosteronism: aldosterone-renin ratio if hypertensive or hypokalemic; confirm positives ^[5], ^[7].

Selective tests: androgens/estrogens, 17-OHP, etc., guided by phenotype ^[3], ^[5].

Follow-up strategy

Nonfunctioning benign adenoma: many can forgo routine serial imaging; consider one follow-up at 6–12 months depending on risk and patient preference ^[5].

Repeat hormonal testing: generally not needed if initial testing negative and phenotype benign; reassess if new symptoms/comorbidities arise ^[5].

Indeterminate lesions under surveillance: reassess imaging at 6–12 months; growth or phenotype change prompts surgical referral ^[3], ^[5].

Perioperative and special considerations

Alpha-blockade for pheochromocytoma before surgery; optimize volume status ^[5], ^[7].

For cortisol autonomy, assess perioperative glucocorticoid coverage and plan taper ^[5].

Bilateral lesions: evaluate for functional status of both glands; avoid precipitating adrenal insufficiency; consider staged approaches ^[11], ^[5].

Avoid percutaneous biopsy unless metastatic disease is suspected and pheochromocytoma is excluded; biopsy does not reliably distinguish adenoma from adrenocortical carcinoma ^[4], ^[5].

References

Source material

Primary literature that informs this article.