8.4 Adrenal Masses & Incidentalomas
Key Takeaways
Assess hormone excess with a 1-mg overnight DST, except where frailty and limited life expectancy make it inappropriate. Test metanephrines when imaging is not typical of a benign adenoma, and aldosterone–renin ratio in hypertension or unexplained hypokalemia.
A homogeneous adrenal mass with unenhanced CT attenuation ≤10 HU has a benign imaging phenotype and requires no further routine imaging, regardless of size. Hormonal assessment remains a separate decision.
For indeterminate masses, select additional imaging or interval assessment through multidisciplinary review. Traditional 15-minute washout cutoffs (APW ≥60% or RPW ≥40%) support adenoma but do not conclusively exclude pheochromocytoma or malignancy.
Avoid routine adrenal biopsy. Consider it only when the lesion is hormonally inactive, imaging remains indeterminate and histology would change management. Exclude pheochromocytoma first; avoid biopsy when resectable ACC is suspected.
For a non-adrenal retroperitoneal mass, determine its origin and differential before treatment; suspected sarcoma needs specialist review and planned image-guided core biopsy.
8.4 Adrenal Masses & Incidentalomas
An adrenal incidentaloma is defined as an unsuspected, asymptomatic adrenal lesion measuring ≥ 1.0 cm identified on cross-sectional imaging (ultrasound, CT, or MRI) performed for indications other than suspected adrenal disease. Driven by the widespread utilization of high-resolution computed tomography, adrenal incidentalomas are detected in approximately 3% to 7% of the adult population, with the frequency rising to nearly 10% in elderly individuals. When an adrenal mass is discovered, the clinical evaluation must answer two fundamental questions:
- Is the lesion hormonally functional (hypersecreting catecholamines, cortisol, aldosterone, or sex steroids)?
- Is the lesion malignant (primary adrenocortical carcinoma or solitary metastasis from an extra-adrenal primary)?
1. Etiological Spectrum of Adrenal Incidentalomas
The majority of adrenal incidentalomas are benign, non-functional adrenocortical adenomas, but a structured diagnostic pathway is mandatory to detect life-threatening hyperfunctioning tumours and malignancies:
- Non-Functioning Adrenocortical Adenoma: The commonest diagnosis; most adrenal incidentalomas are benign cortical lesions.
- Mild Autonomous Cortisol Secretion (MACS): Cortisol nonsuppression without overt Cushing signs; prevalence varies with population and definition.
- Pheochromocytoma: An important minority of incidentalomas (frequently clinically silent or lacking classical paroxysms).
- Primary Aldosteronism (Conn Adenoma): Often accompanied by hypertension, with or without hypokalemia.
- Adrenocortical Carcinoma (ACC): Uncommon, but important to recognize from imaging and steroid findings.
- Metastatic Disease: More likely with an extra-adrenal malignancy, including lung, breast, colon, melanoma or RCC; a cancer history does not make every adrenal lesion a metastasis.
- Benign Non-Adenomatous Lesions: Myelolipoma (contains macroscopic fat, negative HU < -20), adrenal cyst, hematoma, ganglioneuroma.
2. Systematic Biochemical Screening Protocol
European Society of Endocrinology (ESE) and European Network for the Study of Adrenal Tumors (ENSAT) guidelines recommend clinical and biochemical assessment tailored to hormone risk. Routine metanephrine testing may be omitted for a homogeneous lipid-rich adenoma (unenhanced CT ≤10 HU); test other indeterminate lesions, even without classical symptoms.
Mild Autonomous Cortisol Secretion (MACS) Screening
- The 1 mg Overnight Dexamethasone Suppression Test (DST): The usual first-line test for cortisol excess. It may be omitted in frail patients with limited life expectancy; overt Cushing signs require appropriate endocrine evaluation.
- Protocol: 1.0 mg dexamethasone is administered orally at 23:00; fasting serum cortisol is measured the following morning at 08:00.
- Diagnostic Interpretation:
- Post-DST Serum Cortisol ≤ 50 nmol/L (≤ 1.8 µg/dL): Normal cortisol suppression. Excludes autonomous cortisol secretion.
- Post-DST Cortisol >50 nmol/L (>1.8 µg/dL), without overt Cushing signs: MACS. Confirm ACTH independence, consider test confounders and repeat DST. ESE2023 no longer splits results at 138 nmol/L.
- Clinical Significance: MACS is associated with metabolic syndrome, hypertension, type 2 diabetes, osteoporotic fractures, and increased cardiovascular mortality. Patients undergoing unilateral adrenalectomy with cortisol nonsuppression require perioperative glucocorticoid coverage to prevent fatal acute adrenal crisis due to suppression of the contralateral adrenal axis.
Pheochromocytoma Screening
- Diagnostic Test: Measurement of plasma free metanephrines (normetanephrine and metanephrine) or 24-hour urinary fractionated metanephrines.
- Diagnostic Accuracy: Extremely high sensitivity (>97%) and specificity (>93%). Marked elevations (>3–4 times the reference limit) strongly support pheochromocytoma; interpret in clinical context.
- False-Positive Precautions: For plasma testing, sample after supine rest using matched reference intervals. Severe acute illness, pain, stress, and specific medications (tricyclic antidepressants, acetaminophen, labetalol, alpha-methyldopa, phenoxybenzamine) can provoke false-positive elevations and should be addressed prior to re-testing.
Primary Hyperaldosteronism (Conn Syndrome) Screening
- Screening Population: Indicated in all patients with an adrenal incidentaloma who have concomitant arterial hypertension and/or unexplained hypokalemia (not required in normotensive, normokalemic individuals).
- Diagnostic Test: The Aldosterone-to-Renin Ratio (ARR), measured in the morning in a seated, ambulatory patient.
- Protocol: Concomitant serum aldosterone concentration (SAC) and plasma renin activity (PRA) or direct renin concentration (DRC). Correct hypokalemia and review interfering drugs; withdrawal is individualized to safety (commonly MRAs/diuretics for four weeks and beta-blockers for two). Suppression testing is selective, not mandatory after every positive screen. Establish lateralization, usually with adrenal venous sampling, before surgical treatment.
Adrenocortical Carcinoma (ACC) Steroid Profiling
- In patients with clinical or imaging features suspicious for ACC, screening should include sex steroids and steroid precursors: DHEA-S, androstenedione, 17-hydroxyprogesterone, and total testosterone (in females) or estradiol (in males and postmenopausal females).
3. Radiological Characterization & Washout Dynamics
Radiological imaging determines the malignant potential of an adrenal lesion, relying on intracytoplasmic lipid content and contrast clearance kinetics.
Unenhanced Computed Tomography (NCCT)
- The 10-HU Benchmark: Many benign cortical adenomas contain abundant intracytoplasmic lipid. On unenhanced CT, lipid attenuation reduces X-ray absorption.
- Diagnostic Cutoff: An unenhanced attenuation value of ≤ 10 Hounsfield Units (HU) has a sensitivity of ~71% and a specificity of ~98% for benign adenoma.
- Clinical Implication: A homogeneous adrenal lesion with unenhanced attenuation ≤10 HU is considered benign on imaging, irrespective of size. If non-functioning biochemically, no further dynamic contrast imaging or radiological follow-up is required.
Contrast-Enhanced Washout CT (Triphasic Protocol)
Approximately 30% of benign adrenocortical adenomas are 'lipid-poor' and exhibit unenhanced attenuation values > 10 HU, overlapping with pheochromocytomas, ACC, and metastases. Further assessment is individualized; washout CT, chemical-shift MRI, FDG-PET/CT or interval imaging may be selected. A traditional washout protocol uses unenhanced, 60–70-second enhanced and 15-minute delayed acquisitions.
- Physiological Basis: Adenomas often lose contrast enhancement relatively quickly, but washout overlaps with pheochromocytomas and malignant lesions.
- Absolute Percentage Washout (APW) (when unenhanced CT is available):
- APW = [(Enhanced HU - Delayed HU) / (Enhanced HU - Unenhanced HU)] × 100%
- APW ≥60%: Traditionally supports adenoma; not conclusive by itself.
- APW <60%: Indeterminate; some benign adenomas also wash out slowly.
- Relative Percentage Washout (RPW) (when unenhanced CT is unavailable):
- RPW = [(Enhanced HU - Delayed HU) / Enhanced HU] × 100%
- RPW ≥40%: Traditionally supports adenoma; does not exclude pheochromocytoma or malignancy.
- RPW <40%: Does not establish malignancy; assess the whole imaging and clinical picture.
Chemical Shift Magnetic Resonance Imaging (MRI)
Utilizes dual in-phase and out-of-phase gradient-echo imaging. Intracellular lipid and water protons oscillate at slightly different frequencies. A signal intensity drop on out-of-phase images compared to in-phase images confirms the presence of microscopic intracytoplasmic lipid, supporting a lipid-rich adenoma in the appropriate imaging context.
Features of Adrenocortical Carcinoma (ACC)
- Size: Larger size increases concern, but size alone does not diagnose malignancy or mandate resection of a clearly benign lesion.
- Morphology: Irregular, lobulated margins, heterogeneous internal density, central areas of cystic necrosis and hemorrhage, and coarse, irregular calcifications.
- Attenuation & Washout: Unenhanced CT attenuation > 20 to 30 HU, heterogeneous contrast enhancement, and slow washout (APW < 60%).
4. Strict Biopsy Rules & Contraindications
Percutaneous image-guided fine-needle aspiration or core biopsy of an adrenal mass is not a routine incidentaloma investigation. Two key precautions are:
- Unexcluded Pheochromocytoma: Biopsying a pheochromocytoma can provoke catastrophic massive intra-tumoral hemorrhage, capsular rupture, and massive systemic dumping of catecholamines, precipitating malignant hypertensive crisis, cerebral hemorrhage, and fatal cardiac arrhythmias.
- Suspected Adrenocortical Carcinoma: Avoid biopsy when complete resection of suspected ACC is feasible: tissue sampling may disseminate tumour and does not reliably distinguish cortical adenoma from carcinoma. Tissue may be needed when unresectable disease requires systemic treatment.
Caution
Biopsy may be considered, usually with known extra-adrenal cancer, when the lesion remains indeterminate, is hormonally inactive (especially excluding pheochromocytoma), and histology would change treatment. PET-CT or resection may be more appropriate after multidisciplinary review.
5. Surgical Management & Preoperative Adrenergic Blockade
Indications for Adrenalectomy
- Hormonally Active Tumours: Pheochromocytoma, lateralized unilateral primary aldosteronism or clinically significant cortisol excess; individualize surgery for MACS with relevant comorbidity.
- Suspected Adrenocortical Carcinoma: Assess in an expert team; a mass ≥4 cm that is heterogeneous or >20 HU usually merits surgery, while clearly benign imaging does not require surgery solely for size.
- Growing Masses: Non-functioning lesions that demonstrate growth >20% plus at least 5 mm in maximum diameter on repeat CT/MRI at 6–12 months.
Preoperative Management of Pheochromocytoma: Adrenergic Blockade
Surgeons and urologists must adhere strictly to a mandatory pharmacological protocol to prevent intraoperative hypertensive crises during tumour manipulation and circulatory collapse following vein ligation:
- Alpha-Adrenergic Blockade First: Usually started 7–14 days before surgery, allowing titration.
- Agent: Phenoxybenzamine (non-selective, non-competitive alpha-1 and alpha-2 blocker, titrated from 10 mg BID to 60–100 mg daily) or selective alpha-1 blockers (doxazosin, prazosin).
- Target: Control blood pressure (< 130/80 mmHg seated) and restore intravascular volume.
- Aggressive Volume Expansion: Chronic high catecholamine levels cause severe systemic vasoconstriction and contracted intravascular volume. Salt and fluid loading restore volume; individualize these in heart or renal failure to avoid overload.
- Beta-Adrenergic Blockade Second: Add only if needed for tachycardia, and ONLY AFTER adequate alpha-blockade (often 2–3 days preoperatively) (propranolol, metoprolol).
Warning
Never administer a beta-blocker prior to establishing complete alpha-blockade. Blocking vasodilatory beta-2 receptors in the presence of unblocked alpha-1 receptors leaves catecholamine-mediated vasoconstriction completely unopposed, precipitating catastrophic hypertensive crisis, acute coronary syndrome, and pulmonary edema.
Surgical Techniques: Laparoscopic vs Open
- Laparoscopic Adrenalectomy: Performed via a transperitoneal or posterior retroperitoneal approach. It is the gold standard for benign functional adenomas, pheochromocytomas < 6 cm, and small indeterminate masses without signs of local invasion.
- Open Adrenalectomy: Standard for suspected ACC with local invasion, aiming for intact R0 en bloc excision. Expert minimally invasive resection can be considered for selected suspicious masses ≤6 cm without invasion; other cases require individualized planning.
6. Adrenal Incidentaloma Diagnostic & Management Algorithm
| Clinical Finding / Imaging Parameter | Biochemical Screening Result | Working Diagnosis | Guideline-Endorsed Management Protocol |
|---|---|---|---|
| Homogeneous unenhanced CT ≤10 HU, any size | Cortisol screen normal; ARR negative if hypertensive/hypokalemic | Benign nonfunctioning lesion | No routine imaging follow-up or adrenalectomy; reassess new endocrine signs |
| Benign imaging phenotype | Post-DST cortisol >50 nmol/L without overt Cushing signs; ACTH independence confirmed | MACS | Assess cortisol-related comorbidity; individualized surgery and perioperative steroids if operated |
| Unenhanced CT >10 HU, without definitive benign characterization | Appropriate hormonal assessment negative | Indeterminate lesion | Multidisciplinary selection of additional imaging or 6–12-month reassessment; washout alone is not proof |
| Adrenal mass with catecholamine excess | Markedly elevated plasma/urinary metanephrines | Pheochromocytoma | Alpha-blockade and volume preparation; beta-blocker only if needed after alpha-blockade; appropriate adrenalectomy |
| Heterogeneous/invasive mass, especially ≥4 cm and >20 HU | Hormone profile may be normal or show steroid excess | Suspected ACC | Avoid biopsy if resectable; specialist surgery, open for local invasion |
| Indeterminate adrenal mass with known extra-adrenal cancer | Hormonally inactive; pheochromocytoma excluded | Possible metastasis | PET-CT, resection or biopsy according to management impact and multidisciplinary review |
A 51-year-old female with newly diagnosed hypertension undergoes an abdominal CT scan following a motor vehicle collision. The scan reveals a well-circumscribed, homogeneous 2.6 cm right adrenal mass. The unenhanced CT attenuation of the lesion is measured at 5 Hounsfield Units (HU). Biochemical screening reveals a 1 mg overnight dexamethasone suppression test with a morning cortisol of 35 nmol/L (< 1.8 ug/dL), and plasma free normetanephrine and metanephrine levels are completely normal. Serum potassium is 4.4 mmol/L, and an appropriately performed aldosterone–renin screen is negative. What is the most appropriate next step in clinical management according to European guidelines?
Perform image-guided percutaneous core needle biopsy to definitively establish histology
Perform a dynamic contrast-enhanced CT with 15-minute delayed washout calculations
Schedule an elective laparoscopic right adrenalectomy
Reassure the patient that the mass is a benign, non-functioning adenoma and discharge from further routine imaging follow-up
A 46-year-old male with paroxysmal episodes of severe throbbing headache, profuse diaphoresis, palpitations, and labile hypertension is found to have a 4.5 cm heterogeneous left adrenal mass on non-contrast CT. Plasma free normetanephrines are elevated at 9 times the upper limit of normal, and plasma free metanephrines are elevated at 4 times the upper limit of normal. He is scheduled for laparoscopic left adrenalectomy. Which of the following preoperative medical preparation sequences is mandatory to avoid intraoperative hypertensive catastrophe?
Initiate alpha-adrenergic blockade (e.g., phenoxybenzamine or doxazosin) for 10 to 14 days, accompanied by volume expansion, adding a beta-blocker for persistent tachycardia only after adequate alpha-blockade
Initiate immediate high-dose intravenous propranolol monotherapy to control tachycardia and prevent perioperative arrhythmias
Administer high-dose intravenous dexamethasone combined with fludrocortisone for 72 hours prior to surgical exploration
Administer oral spironolactone and an angiotensin-converting enzyme (ACE) inhibitor without adrenergic blockade
A 62-year-old male with a history of surgically resected non-small cell lung cancer 18 months ago undergoes routine surveillance imaging, which demonstrates an asymptomatic, newly enlarged 3.6 cm left adrenal mass. Unenhanced CT attenuation is 26 Hounsfield Units (HU). Triphasic CT with 15-minute delay demonstrates an enhanced attenuation of 80 HU and a delayed attenuation of 62 HU, resulting in an Absolute Percentage Washout (APW) of 33%. Plasma free metanephrines and 1 mg dexamethasone suppression test are completely normal. After complete staging and multidisciplinary review, no radiological features specifically suggest resectable ACC. Tissue confirmation is needed because it would alter lung-cancer treatment versus local management. Which option is appropriate?
Reassure the patient that the lesion represents a benign lipid-poor adenoma and discharge from care
Perform image-guided core biopsy to establish whether the indeterminate lesion is a metastasis, because histology will change management
Perform emergent open bilateral adrenalectomy with retroperitoneal lymphadenectomy
Administer immediate empiric systemic combination immunotherapy with nivolumab plus ipilimumab without tissue biopsy
Non-Adrenal Retroperitoneal Masses
First establish whether a retroperitoneal mass arises from kidney, adrenal gland or other soft tissue. The differential includes liposarcoma, leiomyosarcoma, lymphoma, germ-cell tumour, nerve-sheath tumour and paraganglioma. Renal or adrenal proximity alone does not establish the organ of origin.
Contrast-enhanced CT of the abdomen and pelvis defines the mass, its solid/fatty components and its relationship to viscera and vessels. Chest CT contributes to sarcoma staging. Refer a suspected retroperitoneal sarcoma promptly to an experienced multidisciplinary sarcoma service.
Plan tissue diagnosis after imaging review. Image-guided coaxial core biopsy usually precedes treatment, targeting viable solid components and using a route planned with the specialist team; avoid an unplanned open biopsy or piecemeal excision. Histology matters because these diseases require different treatment. A potential catecholamine-secreting paraganglioma needs biochemical assessment and specialist precautions before invasive manipulation, as with suspected pheochromocytoma.
Worked decision: CT shows a heterogeneous fatty mass displacing, rather than arising from, the kidney. Suspect a retroperitoneal liposarcoma and arrange specialist imaging review and planned core biopsy. Neither the presence of fat nor adjacency to the kidney proves a benign renal angiomyolipoma.
Primary references: TARPSWG differential and management consensus, GEIS retroperitoneal-sarcoma recommendations, CAR/CSAR imaging and biopsy consensus, 2026 and Endocrine Society pheochromocytoma/paraganglioma guideline.
CT shows a large heterogeneous retroperitoneal fatty mass displacing the left kidney, with an enhancing solid component. What is the most appropriate next pathway?
Diagnose benign renal angiomyolipoma from fat alone and discharge
Refer to a sarcoma specialist team for imaging review and planned image-guided core biopsy
Perform an unplanned piecemeal excision through a small incision
Start adrenal replacement therapy without establishing the organ of origin
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