Adrenal incidentaloma

01Purpose and principlesWhat the assessment is for and the core concepts behind it.

Most incidentally detected adrenal lesions are non-functioning adenomas, yet a small minority represent phaeochromocytoma, autonomous cortisol secretion, aldosterone excess, metastasis or primary adrenal malignancy. The work-up therefore combines dedicated imaging, a targeted endocrine history and reproducible biochemical testing rather than using size alone.

Cortisol autonomy is a spectrum. A post-dexamethasone cortisol above the assay-endorsed exclusion threshold, without overt Cushing features, can indicate mild autonomous cortisol secretion. Interpretation must verify dexamethasone exposure and account for oestrogen therapy, enzyme-inducing drugs, alcohol, depression and acute illness before a lifelong label or surgery is proposed.

Management reflects phenotype. Clearly benign, non-functioning lesions may need no repeated imaging under current pathways, whereas indeterminate or enlarging masses require expert radiology review. Hormone-producing lesions and suspected malignancy belong in an adrenal multidisciplinary team that can coordinate blockade, surgical technique and postoperative steroid planning.

Key points

An adrenal incidentaloma is discovered on imaging performed for an unrelated reason; lesions found during known cancer staging require a modified metastasis pathway rather than casual use of the label.
Answer two questions promptly: does imaging suggest malignancy, and does the lesion produce cortisol, catecholamines, aldosterone or, less commonly, sex steroids.
Retrieve the original images and report unenhanced attenuation, homogeneity, size, margins, calcification, necrosis and growth; a generic adrenal nodule description is not adequate characterisation.
A homogeneous lipid-rich lesion with unenhanced CT attenuation at or below 10 Hounsfield units is strongly benign, but local follow-up policy and the full clinical context still govern disposition.
Use an overnight 1 mg dexamethasone suppression test to evaluate autonomous cortisol secretion unless frailty or limited life expectancy makes testing disproportionate.
Check plasma or urinary metanephrines whenever phaeochromocytoma has not been confidently excluded by the endorsed imaging-hormone pathway, and always before biopsy or adrenal intervention.
Measure aldosterone and renin in hypertension or unexplained hypokalaemia, adjusting interfering medicines and interpretation with endocrine advice rather than relying on potassium alone.
Biopsy rarely distinguishes benign adrenal cortex from adrenocortical carcinoma and can trigger a catecholamine crisis; consider it only for a non-adrenal malignancy when phaeochromocytoma is excluded and histology would change care.

02Indications, selection and cautionsWhen it is useful, when urgency changes and important limitations.

Cortisol phenotype

Hypertension, diabetes, proximal weakness, easy bruising, osteoporosis or unexplained fractures can accompany autonomous cortisol, although classical Cushing stigmata may be absent.

Catecholamine phenotype

Episodic headache, palpitations, sweating, pallor, tremor or labile hypertension should heighten suspicion, but an asymptomatic lesion can still be a phaeochromocytoma.

Aldosterone phenotype

Resistant or young-onset hypertension, suppressed renin or hypokalaemia points toward primary aldosteronism; normal serum potassium does not exclude it.

Androgen or oestrogen effect

Rapid virilisation, feminisation or combined steroid features are unusual in a benign adenoma and warrant urgent assessment for adrenocortical malignancy.

Concerning imaging

Heterogeneity, irregular margins, necrosis, invasion, high unenhanced attenuation or meaningful interval growth increases concern and requires dedicated adrenal radiology review.

Bilateral disease

Bilateral nodules broaden the differential to macronodular hyperplasia, metastases, lymphoma, infection or haemorrhage and may create adrenal insufficiency as well as hormone excess.

Red flags requiring action

A planned adrenal biopsy or operation without biochemical exclusion of phaeochromocytoma creates a preventable risk of hypertensive crisis, arrhythmia and death.
Rapid virilisation, severe new Cushing features, unexplained weight loss or invasive imaging characteristics requires urgent referral to a specialist adrenal cancer pathway.
Paroxysmal hypertension with chest pain, neurological deficit, pulmonary oedema or shock may represent catecholamine crisis and needs emergency endocrine and critical-care input.
Acute flank pain with hypotension, falling haemoglobin or bilateral adrenal enlargement raises haemorrhage and possible adrenal crisis; treat physiological instability immediately.
Large bilateral infiltrative lesions with hyponatraemia, hyperkalaemia, hypoglycaemia or shock require urgent cortisol assessment and empirical hydrocortisone when crisis is suspected.

03Method and interpretationA systematic approach to the test and its findings.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Dedicated unenhanced adrenal CTFirst step
Why
Characterise lipid content, morphology and features that determine benignity or MDT review.
Interpretation and limitations
Homogeneous attenuation of 10 HU or less strongly supports a benign lipid-rich adenoma; higher attenuation, heterogeneity or invasion needs a pathway-specific contrast CT, MRI or expert review.
02
Overnight 1 mg dexamethasone suppression test
Why
Screen for autonomous cortisol production from the adrenal lesion.
Interpretation and limitations
A morning cortisol at or below 50 nmol/L generally excludes autonomy with current immunoassays; higher results require confirmation of conditions, ACTH context and assessment of cortisol-related comorbidity.
03
Plasma free or urinary fractionated metanephrines
Why
Exclude clinically important catecholamine production before intervention and in lesions not clearly benign by the endorsed pathway.
Interpretation and limitations
Marked elevation is concerning, while modest results require posture, stress, medicine and assay review; never dismiss a suspicious lesion from one poorly collected sample.
04
Aldosterone renin ratio
Why
Screen a hypertensive or hypokalaemic patient for primary aldosteronism.
Interpretation and limitations
Interpret aldosterone, renin and potassium together after considering posture, salt intake and interfering antihypertensives; a positive screen needs specialist confirmation and subtype planning.
05
Sex steroids and steroid precursors
Why
Evaluate virilisation, feminisation or imaging concern for adrenocortical carcinoma.
Interpretation and limitations
A mixed or precursor-rich secretion pattern increases suspicion but is not independently diagnostic; route results rapidly to the adrenal cancer MDT.
06
Interval imaging comparison
Why
Detect biologically meaningful growth when an indeterminate lesion is managed non-operatively.
Interpretation and limitations
Use the same modality and expert measurements where possible; absolute size, proportional growth and morphological change matter more than millimetre variation between unrelated reports.

04Clinical next stepsHow the result changes management or prompts escalation.

01FOUNDNew incidental adrenal lesionFirst stepAn adrenal mass is reported on imaging obtained outside a known adrenal diagnostic pathway.

1Confirm why imaging was performed, whether extra-adrenal cancer is present and whether prior scans establish stability.
2Request dedicated radiological characterisation and take a focused history for cortisol, catecholamine, aldosterone and sex-steroid features.
3Arrange hormone testing proportional to phenotype and imaging, ensuring phaeochromocytoma is addressed before any invasive plan.
4Discuss indeterminate, functioning, bilateral, enlarging or suspicious lesions in an adrenal endocrine-radiology MDT with a documented follow-up owner.

02CORTISOLAbnormal dexamethasone suppressionMorning cortisol is above the local exclusion threshold after the overnight test.

1Verify dexamethasone was taken correctly and identify oestrogen, enzyme-inducing medicine, alcohol, psychiatric, sleep or acute-illness confounding.
2Confirm ACTH-independent physiology and assess blood pressure, glucose, lipids, weight, bone and fracture consequences rather than chasing cortisol alone.
3Classify overt Cushing syndrome separately from mild autonomous secretion and review proportional treatment options with endocrinology.
4If surgery is selected, establish perioperative glucocorticoid cover and postoperative axis testing because the contralateral gland may be suppressed.

03UNCERTAINIndeterminate imagingThe lesion is not unequivocally lipid-rich or displays size, morphology or growth requiring further definition.

1Obtain adrenal-protocol CT, chemical-shift MRI or another MDT-selected modality instead of repeating non-dedicated scans reflexively.
2Complete the relevant functional work-up and assess previous malignancy, age, frailty, operative risk and patient priorities.
3Choose surveillance interval or expert adrenalectomy according to the combined imaging-hormone risk, documenting the rationale and stop rule.
4Avoid percutaneous biopsy unless suspected metastasis or lymphoma would change management and catecholamine excess has been safely excluded.

04BILATERALBilateral adrenal lesionsMasses or infiltrative abnormalities affect both adrenal glands.

1Characterise each lesion individually and seek systemic clues such as malignancy, infection, haemorrhage or hereditary endocrine disease.
2Assess cortisol excess and, when destructive disease is plausible, test adrenal reserve without delaying crisis treatment in an unwell patient.
3Use targeted oncological, infectious or genetic testing rather than assuming two benign adenomas.
4Coordinate surveillance, biopsy or treatment through specialists because removing or damaging both glands creates lifelong steroid dependence.

05Procedure and medicine safetyRelevant preparation, treatment and contraindications.

Test whether physiological glucocorticoid feedback suppresses endogenous cortisol production from the adrenal axis.

Dexamethasone for overnight suppression testing

Give 1 mg orally at the locally specified late-evening time and measure serum cortisol the following morning within the laboratory window.

Check adherence, timing, enzyme inducers, oestrogen and absorption; this is a diagnostic administration, and an abnormal result should not trigger treatment without endocrine interpretation.

Reduce catecholamine-mediated vasoconstriction and perioperative cardiovascular instability before definitive adrenal surgery.

Alpha-adrenoceptor blockade

Initiate and titrate phenoxybenzamine or a selective alpha blocker only through the specialist phaeochromocytoma preoperative protocol with fluid and salt planning.

Never start beta blockade before adequate alpha blockade; monitor postural hypotension, tachycardia, renal or cardiac comorbidity and coordinate anaesthetic preparation in an experienced centre.

Prevent adrenal crisis while the hypothalamic-pituitary-adrenal axis recovers after removal of a cortisol-autonomous gland.

Perioperative hydrocortisone

Use the endocrine and anaesthetic stress-dose regimen for cortisol-producing lesions or patients at risk of postoperative adrenal suppression, then taper by testing.

Avoid both abrupt withdrawal and prolonged unnecessary over-replacement; provide sick-day education, an emergency card and a clearly owned postoperative cortisol plan.

06Risks, monitoring and follow-upComplications, safety checks and further assessment.

For non-operated mild autonomous cortisol secretion, review blood pressure, glycaemia, lipids, weight and bone or fracture risk rather than repeating hormone tests without a clinical question.
When imaging surveillance is chosen, state modality, interval, growth definition and which MDT will review a change; open-ended annual scanning is not a plan.
After adrenalectomy, monitor haemodynamics, electrolytes, glucose and cortisol replacement, with later axis recovery testing directed by endocrinology.
In primary aldosteronism or phaeochromocytoma, follow the disease-specific biochemical, blood-pressure and genetic pathway after the incidental discovery is reclassified.
Record new cancer diagnoses, virilisation, catecholamine symptoms or cortisol comorbidity because these can change the risk category between scheduled reviews.
Communicate a benign discharge decision explicitly to primary care and the patient to prevent repeated scans being generated from the same unchanged lesion.

07Special situationsVariants, exceptions and circumstances that change the usual approach.

Incidental is not trivial

The discovery mechanism says nothing about biological importance; a silent phaeochromocytoma or cortisol-producing adenoma can be found during unrelated imaging.

Density can outperform diameter

A small heterogeneous high-attenuation lesion may require more scrutiny than a larger unequivocally lipid-rich homogeneous adenoma, so size must not act alone.

Cortisol treatment is comorbidity-led

For mild autonomy, improvement likelihood in hypertension, diabetes or bone disease and the patient's operative risk are more meaningful than one biochemical number.

Biopsy answers a narrow question

Percutaneous sampling can confirm metastasis or lymphoma in selected cases, but it is poor at proving or excluding primary adrenocortical malignancy.

Bilateral lesions change both directions

They can produce excess hormone through hyperplasia or destroy cortex through infiltration, so screening only for secretion misses adrenal insufficiency.

08Common pitfallsFrequent interpretation and management errors.

01
Do not order biopsy because a lesion is indeterminate until phaeochromocytoma is excluded and a result would materially alter treatment.
02
Do not call every post-dexamethasone cortisol elevation Cushing syndrome without reviewing test validity, ACTH dependence and clinical phenotype.
03
Do not use normal potassium to rule out primary aldosteronism in a hypertensive patient who otherwise meets screening criteria.
04
Do not repeat non-dedicated abdominal imaging indefinitely when expert adrenal characterisation can establish benignity or define a rational interval.
05
Do not assume two adrenal nodules are simply bilateral adenomas when cancer, lymphoma, infection, haemorrhage or adrenal insufficiency is plausible.
06
Do not refer a suspicious mass for routine laparoscopic removal without an adrenal cancer MDT considering tumour rupture and oncological surgical technique.