Residency · Residency · Urology

Adrenal Incidentaloma: Workup and Surveillance

Introduction

An adrenal incidentaloma refers to an adrenal mass that is discovered incidentally during imaging studies performed for reasons unrelated to adrenal disease. With the widespread use of abdominal computed tomography (CT) and magnetic resonance imaging (MRI), adrenal incidentalomas are found in approximately 4-5% of abdominal imaging studies, with prevalence rising to about 10% in elderly populations. The main clinical challenge is to determine whether the mass is hormonally active and whether it is benign or malignant. Employing a systematic approach helps avoid unnecessary interventions for benign, non-functional adenomas while ensuring that potentially dangerous conditions such as pheochromocytoma, adrenocortical carcinoma, or cortisol-secreting tumors are not missed.

Epidemiology

Adrenal incidentalomas are detected in about 4-5% of CT scans and 6-9% of autopsy series. They are rare before age 30 but become increasingly common with advancing age. Bilateral incidentalomas occur in 10-15% of cases and raise concern for metastatic disease, congenital adrenal hyperplasia, or bilateral adenomas. Histologically, most incidentalomas are adenomas (approximately 80%), followed by myelolipomas (5-7%), pheochromocytomas (5%), adrenocortical carcinomas (2-5%), metastases (2-5%), and less commonly cysts, ganglioneuromas, or other lesions.

Imaging Characteristics

CT Features

Unenhanced CT attenuation measured in Hounsfield units (HU) is the most important initial imaging characteristic. A lesion with attenuation less than 10 HU is considered a lipid-rich adenoma and is benign with over 98% specificity, requiring no further imaging. Lesions with attenuation greater than 10 HU are indeterminate and warrant further evaluation with contrast-enhanced CT washout studies or MRI. In the washout study, an absolute washout greater than 60% and a relative washout greater than 40% at 15 minutes post-contrast are consistent with adenoma. Low washout values suggest non-adenoma lesions such as pheochromocytoma, adrenocortical carcinoma (ACC), or metastasis.

Size is another critical factor: lesions smaller than 4 cm carry a low risk of malignancy (less than 2%), those between 4 and 6 cm have an intermediate risk (6-10%), and lesions larger than 6 cm have a high risk of malignancy (around 25%), generally warranting surgical resection. Morphologically, smooth and well-defined borders favor benign lesions, whereas irregular margins, heterogeneity, calcification, necrosis, and local invasion suggest malignancy.

MRI Features

Chemical shift MRI, which compares in-phase and opposed-phase images, is useful in characterizing adrenal masses. A signal drop on opposed-phase images indicates intracellular lipid, consistent with adenoma, analogous to low HU on CT. Lack of signal drop on opposed-phase images is indeterminate and may represent pheochromocytoma, ACC, or metastasis. MRI is particularly helpful when CT washout studies are inconclusive or when intravenous contrast cannot be administered.

PET/CT

Fluorodeoxyglucose positron emission tomography combined with CT (FDG-PET/CT) can detect increased metabolic activity. Lesions with standardized uptake values (SUV) higher than liver uptake suggest malignancy, such as ACC or metastasis. However, FDG-PET/CT has limitations due to false positives in pheochromocytomas and false negatives in low-grade ACC. Therefore, it is not a routine first-line study but is reserved for indeterminate lesions or when metastatic disease is suspected.

<image>CT imaging comparison panel showing: (1) a homogeneous 2 cm left adrenal mass with attenuation of 5 HU on unenhanced CT (classic lipid-rich adenoma), (2) a 3 cm right adrenal mass with 25 HU on unenhanced CT with contrast-enhanced and delayed washout images demonstrating absolute washout of 65% (adenoma), and (3) a 7 cm heterogeneous right adrenal mass with necrosis, irregular borders, and 35 HU (suspicious for adrenocortical carcinoma), with Hounsfield unit measurements annotated</image>

Hormonal Evaluation

Required for All Adrenal Incidentalomas

Screening for pheochromocytoma is mandatory in all patients with adrenal incidentalomas. The preferred test is plasma free metanephrines (metanephrine and normetanephrine), which has a sensitivity exceeding 96%. Alternatively, 24-hour urine metanephrines and catecholamines can be used for confirmation. It is critical to exclude pheochromocytoma before any intervention because undiagnosed pheochromocytoma during surgery can precipitate a life-threatening hypertensive crisis. False positives can occur due to stress or certain medications such as tricyclic antidepressants, monoamine oxidase inhibitors, decongestants, and acetaminophen in some assays.

Assessment for autonomous cortisol secretion, also known as subclinical Cushing syndrome, is performed using the 1 mg overnight dexamethasone suppression test (DST). This involves administering 1 mg dexamethasone at 11 PM and measuring serum cortisol at 8 AM. A cortisol level below 1.8 mcg/dL indicates normal suppression and excludes autonomous secretion. Levels between 1.8 and 5.0 mcg/dL suggest possible autonomous cortisol secretion (PACS), while levels above 5.0 mcg/dL indicate autonomous cortisol secretion (ACS), warranting confirmatory testing. PACS and ACS are the most common hormonal abnormalities in adrenal incidentalomas, occurring in 5-20% of cases, and are associated with metabolic syndrome, type 2 diabetes, hypertension, osteoporosis, and possibly increased cardiovascular mortality. Additional tests such as ACTH levels (which are suppressed in autonomous secretion), midnight salivary cortisol, and dehydroepiandrosterone sulfate (DHEA-S, which is suppressed in ACTH-independent cortisol excess) may be helpful.

Screening for aldosterone-producing adenoma is indicated only in patients with hypertension or unexplained hypokalemia. The aldosterone-to-renin ratio (ARR) is used, with an ARR greater than 30 and aldosterone levels above 15 ng/dL raising suspicion for primary aldosteronism. Confirmatory testing with salt loading or fludrocortisone suppression tests is required. Adrenal vein sampling (AVS) is the gold standard for lateralizing aldosterone secretion before surgery, especially when CT shows bilateral adenomas or discordant findings.

Additional Tests Based on Clinical Context

If adrenocortical carcinoma is suspected, elevated DHEA-S and 17-hydroxyprogesterone levels may be present. In cases of virilization or feminization, measuring sex hormones such as testosterone and estradiol is important, as these findings suggest ACC with sex hormone secretion.

Differential Diagnosis

Adrenal adenomas typically measure less than 4 cm, have attenuation below 10 HU, demonstrate washout greater than 60%, and show lipid content on MRI. Myelolipomas contain macroscopic fat with attenuation values between -30 and -100 HU, which is pathognomonic and requires no further workup. Pheochromocytomas are heterogeneous, have attenuation greater than 10 HU, lack washout, and are associated with elevated metanephrines. Adrenocortical carcinomas are usually larger than 4 cm, heterogeneous, with necrosis and invasion, and elevated DHEA-S. Metastases often occur in patients with a history of malignancy (lung, breast, melanoma, renal), are frequently bilateral, have attenuation above 10 HU, and lack washout. Adrenal cysts appear as thin-walled, homogeneous lesions with water density and are benign. Ganglioneuromas are well-circumscribed, homogeneous, and show delayed enhancement; they are benign.

<image>Flowchart algorithm for adrenal incidentaloma workup: initial CT characterization by size and HU, hormonal evaluation (plasma metanephrines, 1 mg DST, ARR if hypertensive), decision pathways for benign adenoma (observation), indeterminate lesion (MRI/washout CT/PET), functional tumor (surgery after appropriate preparation), and suspected malignancy (adrenalectomy), with surveillance intervals for benign non-functional lesions</image>

Management Decisions

Surgical Indications

Surgery is indicated for all pheochromocytomas after appropriate alpha-blockade preparation. Patients with primary aldosteronism and lateralized secretion confirmed by AVS are candidates for surgery. Autonomous cortisol secretion associated with cortisol-related comorbidities such as diabetes, hypertension, or osteoporosis requires individualized decision-making regarding surgery. Lesions larger than 4-6 cm carry an increased risk of ACC, and resection is generally recommended for most lesions over 4 cm with suspicious features and for all lesions larger than 6 cm. Imaging features suspicious for malignancy, including heterogeneity, invasion, or growth on follow-up, also warrant surgical intervention. Interval growth greater than 1 cm or more than 20% increase in maximum diameter on surveillance imaging should prompt surgical consultation.

Observation and Surveillance (Non-Functional, Benign-Appearing)

According to the European Society of Endocrinology (ESE) and European Network for the Study of Adrenal Tumors (ENSAT) 2016 guidelines, clearly benign lesions less than 4 cm with attenuation below 10 HU and homogeneous appearance do not require routine repeat imaging. However, hormonal re-evaluation with the 1 mg DST should be performed annually for five years to detect evolving autonomous cortisol secretion. The American Urological Association (AUA) and Endocrine Society recommend repeat imaging at 6 to 12 months and then annually for up to five years for indeterminate lesions. Stability in size over one to two years is reassuring, while growth greater than 1 cm or development of suspicious features necessitates surgical consultation.

Adrenal Biopsy

Adrenal biopsy has a very limited role and is only indicated when the results will change management. The primary indication is suspected adrenal metastasis in a patient with known extra-adrenal malignancy where tissue diagnosis would alter treatment. It is essential to exclude pheochromocytoma before biopsy because puncturing a pheochromocytoma can cause a hypertensive crisis. Biopsy is not helpful in differentiating adenoma from ACC, as histology alone is unreliable for this distinction. Risks of biopsy include hemorrhage, pneumothorax, and rare tumor seeding.

<image>Comparison MRI images showing chemical shift imaging of an adrenal adenoma: in-phase image with normal signal intensity and opposed-phase image demonstrating marked signal dropout (India ink artifact at organ-fat interfaces), confirming intracellular lipid content diagnostic of a benign adenoma, with ROI measurements annotated on both sequences</image>

Key Clinical Pearls

All adrenal incidentalomas require hormonal evaluation, including mandatory screening for pheochromocytoma using plasma metanephrines and assessment of cortisol secretion with the 1 mg dexamethasone suppression test, even if the mass appears benign on imaging. Unenhanced CT attenuation below 10 HU is the single most useful imaging characteristic, identifying lipid-rich adenomas with over 98% specificity. Biopsy of an adrenal mass should never be performed without first excluding pheochromocytoma, as this can precipitate a life-threatening hypertensive crisis. Autonomous cortisol secretion, or subclinical Cushing syndrome, is more common than overt Cushing syndrome in incidentalomas and contributes to cardiometabolic morbidity. Lesions larger than 4 cm with indeterminate imaging features warrant surgical resection due to the increasing risk of adrenocortical carcinoma. Myelolipomas, characterized by macroscopic fat on CT, are pathognomonic and require no further workup or surveillance.

References

1. Fassnacht M, Arlt W, Bancos I, et al. Management of adrenal incidentalomas: European Society of Endocrinology clinical practice guideline. Eur J Endocrinol. 2016;175(2):G1-G34.
2. Zeiger MA, Thompson GB, Duh QY, et al. The American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocr Pract. 2009;15(Suppl 1):1-20.
3. Young WF. The incidentally discovered adrenal mass. N Engl J Med. 2007;356(6):601-610.
4. Bancos I, Prete A. Approach to the patient with adrenal incidentaloma. J Clin Endocrinol Metab. 2021;106(11):3331-3353.

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