Focal lesions of the adrenal glands are incidentally detected in approximately 5% of cases by modern imaging techniques. Fewer than 5% of these adrenal incidentalomas are malignant and approximately 10% have endocrine activity. Reliable differentiation of malignant versus benign and hormonally active versus nonfunctional adrenal incidentalomas significantly influences therapeutic management and the outcome of affected individuals. Therefore, each adrenal incidentaloma should undergo a standardized diagnostic work-up to exclude malignancy and endocrine activity. This position statement of the World Federation of Ultrasound in Medicine and Biology (WFUMB) summarizes the available evidence on the management of adrenal incidentaloma and describes efficient management strategies with particular reference to the role of ultrasound techniques.
The definition of an adrenal incidentaloma (AI) encompasses any focal adrenal lesion, independent of size, discovered by any imaging method including ultrasonography (US), endoscopic ultrasonography (EUS), computed tomography (CT), or magnetic resonance imaging (MRI), in the absence of adrenal disease.
Due to the fact that the adrenal glands are the fourth most frequent site of metastasis, independent of the location of the primary tumor (prevalence of metastases: 27%) [
After detection of an AI, there are a few important questions to be answered to determine the need for treatment: (1) What is the prevalence?; (2) Is the AI malignant?; (3) Does the AI have endocrine activity?
The prevalence of AIs of any size with imaging is reported to be about 5%, ranging from 1% to 12% (with higher rates in older age groups) and the frequency of AIs has approached 8.7% in autopsy series [
As shown for focal liver lesions [
Importantly, the size and some imaging features are helpful in determining whether an AI is benign or malignant [
On the contrary, the smaller the size at the time of diagnosis, the better the prognosis [
In addition to size, some imaging features should be considered. Most important are the smooth border of a lesion and the amount of fat (attenuation values below 10 Hounsfield units [HU] in unenhanced CT) in benign lesions [
MRI is less often used, but the so-called chemical-shift imaging techniques give equivalent results for the estimated amount of fat. The descriptive features for benign AI are an oval or round shape, sharp margins and smooth contour, and homogeneous echo pattern (US) or density (CT). In conclusion, an approach combining size (<40 mm) and HU values (≤10 HU) excludes malignancy in almost all cases [
Results of studies using contrast enhancement for all imaging methods, including contrast-enhanced US, are less convincing [
With contrast-enhanced US, the combination of early arterial hyperenhancement and rapid wash-out was described to be highly sensitive for the diagnosis of malignancy, but specificity was only moderate [
With all imaging techniques, the typical imaging features of adrenocortical carcinoma and metastases are a size >40-60 mm, irregular shape, inhomogeneous echo pattern, calcifications and non-enhancing spontaneous hemorrhage necrosis. Metastases tend to be bilateral [
Combining various parameters from unenhanced and contrast-enhanced CT and patient-related clinical data significantly improves the diagnostic performance for differentiating between benign and malignant adrenal lesions beyond that of single parameters [
Other differential diagnoses (e.g., adrenal cysts and myelolipoma) show typical imaging features and do not need further work-up [
In contrast to patients with suspected or proven malignant disease with solid adrenal tumors, in AI the role of image-guided biopsy is limited. Recent guidelines do not recommend image-guided sampling for routine work-up of AIs [
In case of equivocal results of imaging, image-guided sampling aiming at histological specimens may be preferred over adrenalectomy [
Most AIs are nonfunctional (about 90%) [
Pheochromocytoma and (subclinical) Cushing's syndrome should be excluded in all patients with AI. In patients with arterial hypertension with or without hypokalemia, Conn syndrome should be excluded.
Pheochromocytomas (3% of AIs) are typically >40 mm at time that significant hormone production is diagnosed [
All patients with proven pheochromocytoma should undergo surgery. Multiple endocrine neoplasia should be considered [
Subclinical Cushing's syndrome (SCS) is defined by autonomous cortisol secretion (detected by ≥2 abnormalities in a basal or dynamic test of the hypothalamic-pituitary-adrenal axis in patients who do not have the typical signs and symptoms of hypercortisolism). SCS is excluded by performing the 1 mg overnight dexamethasone suppression test (DST) [
An abnormal DST indicates ACTH-independent cortisol production (positive if cortisol concentration >5 μg/dL [>138 nmol/L]). As a consequence, 24-hour urinary free cortisol and serum ACTH concentrations should be tested and evaluation of dehydroepiandrosterone sulfate metabolism should be performed, as well as a high-dose (8 mg) overnight DST. Clinically significant glucocorticoid secretory autonomy is confirmed by a test of early-morning DST serum cortisol levels. Autonomous glucocorticoid function may also develop over time; therefore, follow-up testing should be considered [
The indications for unilateral (or very rarely bilateral) adrenalectomy [
Aldosteronomas (<1% of AIs) are typically <20 mm at the time of diagnosis, poorly vascularized, and most often circumscribed. Diffuse mild hyperplasia <10 mm can be encountered. The diagnosis is achieved by measuring the plasma aldosterone concentration to plasma renin activity ratio [
In younger patients with unilateral aldosterone-producing adenoma, surgery should be offered to cure the aldosterone excess, whereas aldosterone-antagonistic drugs are the treatment of choice in cases of bilateral hyperplasia with hyperaldosteronism and generally in older patients with comorbidities [
Nonfunctional AI (NFAI) should be considered for surgery if >40 mm due to the risk of malignancy, in particular adrenal cortical carcinoma (ACC) [
Adrenal myelolipoma (AML) is a slowly growing benign tumor composed of hematopoietic elements and fat elements with eye-catching imaging features [
Many other rare focal adrenal lesions may be encountered.
Patients with bilateral AI should be investigated for Cushing's disease, congenital adrenal hyperplasia, and BMAH [
Follow-up by repeat imaging and hormonal work-ups is recommended by most recent guidelines for individuals with AI with a benign imaging phenotype and no hormonal activity at initial presentation [
Adrenalectomy for NFAI <60 mm is most often performed laparoscopically (less pain, shorter hospitalization, less blood loss, and faster recovery compared to open surgery), but the endoscopic posterior approach [
All procedures are reported to be relatively safe [
US has a high sensitivity for the detection of adrenal mass lesions (in particular for the right gland), even in tumors <20 mm [
Therefore, in addition to a hormonal work-up, unenhanced CT should be performed in lesions ≥10 mm. If endocrine activity is lacking and CT findings are highly predictive for a benign lesion, further imaging or regular follow-up is not necessary. In cases of equivocal CT findings or hormonal activity, further management should be based on a multidisciplinary expert board discussion. Further management options in cases of functional AI are described above. In cases of an incidental adrenal mass with equivocal CT criteria or a diameter of >40 mm and <60 mm, an individualized decision should be made, considering close follow-up, surgery, or further imaging (chemical phase-shift MRI) [
In AIs detected using cross-sectional imaging techniques, the role of US and EUS is limited. Performing US may be useful if, as a result of further work-up, surgery is not the appropriate management strategy for the patient and follow-up is required. If US enables appropriate visualization and measurement of the lesion, due to the absence of radiation exposure, US may be preferable to CT for surveillance [
All patients with an AI >10 mm should be evaluated at initial presentation to exclude malignancy and hormonal hyperfunction according to recent guideline recommendations [
Conceptualization: Dietrich CF, Jenssen C. Data acquisition: Dietrich CF, Correas JM, Dong Y, Nolsoe C, Westerway SC, Jenssen C. Data analysis or interpretation: Dietrich CF, Correas JM, Dong Y, Nolsoe C, Westerway SC, Jenssen C. Drafting of the manuscript: Dietrich CF, Correas JM, Jenssen C. Critical revision of the manuscript: Dietrich CF, Correas JM, Dong Y, Nolsoe C, Westerway SC, Jenssen C. Approval of the final version of the manuscript: all authors.
No potential conflict of interest relevant to this article was reported.
The anatomical landmarks are the right liver lobe (RLV, right liver vein), the right diaphragm (D), and the inferior caval vein (vena cava inferior [VCI]). Layering of the adrenal gland with a hyperechoic central echo representing the medulla, the hypoechoic cortex and hyperechoic capsule are depicted. The thickness of the adrenal gland is less than 7 mm (in this case: 5 mm).
The anatomical landmarks are the pancreatic body and tail (P), upper pole of the left kidney (K), and the left diaphragm (D).
There was no history or suspicion of malignant disease, unenhanced computed tomography showed an attenuation value of below 10 Hounsfield unit, and an endocrine work-up did not reveal any endocrine activity (nonfunctional adenoma).
The lesion was not found with computed tomography, and an endocrine work-up did not show any endocrine activity.
The lesion had smooth borders, but a central area was more hypoechoic than the periphery of the tumor. Contrast-enhanced ultrasonography reveals the high vascularity of the peripheral parts of the tumor, whereas the central area is without any contrast enhancement (hemorrhage, necrosis, marked by arrows). This pattern indicates the diagnosis of pheochromocytoma, which was established by an endocrine work-up and finally by surgical pathology.
This finding is typical for the rare diagnosis of adrenal angiomyolipoma.