Adrenal glands are a common site of disease.
The detection of adrenal masses has increased with the expanding use of cross-sectional imaging.
Adrenal incidentalomas are asymptomatic masses discovered on imaging studies performed for reasons unrelated to adrenal disease,
and have a prevalence in the general population of 3% to 7%.
The majority of incidental adrenal masses are benign and are most commonly adenomas.
However,
adrenal gland is also a common site of metastases.
Additionally,
primary malignant adrenal neoplasms can also occur.
Once an adrenal lesion is detected,
the goal of adrenal imaging is to characterize and to differentiate the benign “leave-alone” lesions from masses that require treatment.
Imaging plays an essential role in the characterization of adrenal lesions,
suggesting their benign or malignant nature,
and should always be integrated with patient oncologic background.
In the imaging workup of adrenal lesions several morphologic aspects assess the risk of malignancy such as the identification of intracellular lipid,
macroscopic fat,
hemorrhage,
cystic changes,
vascularity (namely washout values),
calcifications,
shape,
size and change in size.
The clinical context is also crucial in the interpretation of these lesions,
particularly with regard to patient history of malignancy.
Benign adrenal masses generally are homogenous low density lesions,
that present smooth margins,
and that usually remain stable in size.
Certain adrenal lesions have specific benign imaging features that are diagnostic at detection and do not warrant further workup,
like adrenal myelolipomas (easily recognized by the presence of macroscopic fat),
and adrenal cysts (simple cyst without enhancement after contrast administration).
Certain imaging features are suspicious for malignancy,
such as large size,
growth,
irregular margins,
heterogeneous attenuation and central necrosis.
In patients without history of malignancy,
the main concern for a large adrenal mass is adrenal cortical carcinoma,
although it is rare in the general population.
Usually,
adrenal masses larger than 4 cm are surgically resected in patients without history of malignancy,
unless a definitive benign diagnosis,
such as myelolipoma,
adrenal cyst,
typical adenoma,
or hemorrhage,
can be established.
Patient history of malignancy is one of the most important aspects in the workup of incidental adrenal lesion.
It is extremely rare for an incidental adrenal mass to be metastatic disease of unrecognized primary malignancy.
Characterization of incidental adrenal lesions in patients with cancer is essential to predict prognosis of the primary disease,
to assess staging,
and to direct therapy.
CT and MRI are the most commonly used imaging studies for evaluating an incidental adrenal mass.
These techniques reflect physiologic differences distinguishing adenoma from malignant masses,
by evaluating intracytoplasmic lipid content and contrast washout pattern.
On CT,
the distinction between benign from malignant adrenal masses is based on density measurement on unenhanced CT and on the determination of their different contrast washout characteristics.
Density measurement on unenhanced CT is based on the fact that adrenal adenomas have a varying amount of intracytoplasmic lipid (mainly cholesterol,
fatty acids,
and neutral fat),
and an inverse relationship exists between the lipid content of the adenoma and its density measurement on CT.
Approximately 70% of adenomas have sufficient intracytoplasmic lipid to be diagnosed on unenhanced CT,
and the threshold of 10 HU allow the diagnosis of adenoma with 71% sensitivity and 98% specificity,
being currently the standard threshold used to diagnose a lipid-rich adenoma on CT.
Conversely,
almost all nonadenomatous lesions are low intracytoplasmic lipid content,
and their CT attenuation is consequently higher.
Up to 30% of adenomas are lipid poor and have an attenuation value greater than 10 HU on unenhanced CT scans,
as do almost all malignant lesions.
Therefore,
these lesions require further evaluation to be characterized.
Contrast washout characteristics also permit to differentiate adenoma from other lesions.
After enhancement with intravenous contrast,
adenomas enhance rapidly and also show a rapid loss of contrast medium,
aphenomenon termed “contrast washout”; despite malignant lesions also enhance rapidly,
they usually show a slower washout of contrast medium due to leaky capillaries.
The ratio of attenuation values on the washout-delayed scan,
after 15 minutes,
when compared with the initial dynamic contrast-enhanced study can help to accurately characterize adrenal lesions.
Adenomas can be distinguished from nonadenomas by:
Absolute percentage washout (APW) is calculated by a formula (see Fig.
1)
An APW value of 60% or greater at 15 minutes is diagnostic of an adenoma.
In the absence of unenhanced series,
a relative percentage washout (RPW) is calculated by a formula (see Fig.
1)
An RPW value greater than 40% is diagnostic of adenoma.
Contrast washout is independent of the amount of lipid content and allows accurate diagnosis of both lipid-rich and lipid-poor adenoma.
Fig. 1: Percentage Washout Formulas for 15-minute Delayed Contrast-enhanced CT Scans:
These threshold percentage washout values can be used to accurately differentiate adenoma from malignancy. APW = absolute percentage washout, RPW = relative percentage washout D= delayed enhanced value, E= enhanced attenuation value, U= unenhanced attenuation value.
In general,
a combination of unenhanced CT and washout characteristics correctly discriminates nearly all adrenal adenomas from malignant lesions.
On MR technique,
the principle of adrenal evaluation is based on chemical shift imaging which is obtained as dual-echo breath-hold gradient echo acquisition.
As CT density measurement,
this technique also depends on the presence of intracytoplasmic lipid in adenomas to distinguish them from nonadenomas.
Chemical shift MRI (CS-MR) is based in the different resonant frequency rates of protons in fat and water molecules,
with fat protons resonating at a slower frequency.
By choosing the “correct” TE (echo time),
the signal from lipid will oppose that from water,
causing signal drop-off in voxels containing both lipid and water on opposed-phase imaging.
Most adrenal adenomas contain sufficient amount of lipid and lose signal (become darker) on the opposed-phase images imaging when compared with in-phase images.
With CS-MR,
adenomas are differentiated from metastasis with sensitivity and specificity of 81% to 100% and 94% to 100%,
respectively.
The paired in-phase and opposed-phase images can be analyzed using quantitative methods such as signal intensity index or chemical shift ratio.
Although,
simple visual analysis is as effective and easier to use,
being more commonly used in clinical practice.
Occasionally,
heterogeneous signal suppression may be seen in an adenoma because of a heterogeneous population of lipid-rich cells.
Fig. 2: Morphologic and Imaging Characteristics of Incidental Adrenal Lesions.
Fig. 3: Morphologic and Imaging Characteristics of Incidental Adrenal Lesions. APW, absolute percentage washout; RPW, relative percentage washout; SI, signal intensity.
Adrenal Biopsy
The number of imaging-guided biopsies necessary to diagnose an adrenal mass has decreased,
with the recent advances in their characterization.
However,
they may still be necessary to exclude or confirm metastases if imaging findings are inconclusive,
or to evaluate enlarging adrenal masses.
Adrenal biopsy is usually performed with CT guidance and has been shown to be safe,
with a 85% to 96% diagnostic accuracy and 3% to 9% complication rate.
Plasma-free metanephrine level should be obtained prior to biopsy,
if there is any suspicion of a pheochromocytoma,
because this procedure may induce a hypertensive crisis in that situation.
Diagnostic Algorithm of Incidental Adrenal Lesions
Recently,
White Paper of the American College of Radiology (ACR) Committee on Incidental Findings presented an adrenal imaging algorithm.
According to this,
in:
- An incidental adrenal mass of any size that has diagnostic features of a benign lesion,
such as a myelolipoma,
cyst,
or a lipid-rich adenoma,
a specific benign diagnosis can be made and no additional imaging is needed.
- Adrenal masses smaller than 4 cm with no diagnostic imaging features for which prior imaging is available and that have been stable for at least a year are likely benign and do not need follow-up imaging.
- Enlarging lesions,
biopsy or resection should be considered because they may be malignant.
- Patients with no history of cancer,
if no prior CT or MRI is available for comparison and the lesion has benign imaging features (low density,
homogeneous with smooth margins),
then the mass can be presumed to be benign and a follow-up unenhanced CT or CS-MR in 12 months may be considered.
- The cases where suspicious imaging features are present,
unenhanced CT or CS-MR could be performed.
If these are not diagnostic of an adenoma,
then adrenal CT protocol with washout analysis may be helpful.
If the lesion does not have imaging and washout features of a benign lesion,
then biopsy may be appropriate.
- Oncologic patients,
if the adrenal mass does not have imaging features diagnostic of a benign lesion and no prior imaging is available to establish stability,
unenhanced CT,
CS-MR,
or PET/PET-CT can be considered.
If these studies do not confirm the mass to be an adenoma,
then adrenal CT with washout analysis may be helpful.
If these imaging studies are not diagnostic of a benign lesion,
then biopsy should be considered.
- An adrenal mass larger than 4 cm without a definitive benign diagnosis is usually resected in patients without history of cancer,
because there is concern for an adrenal cortical carcinoma.
In patients with a history of cancer,
PET/PET-CT or biopsy is recommended because the large adrenal mass could represent a metastasis.
Fig. 4: Recommended algorithm for managment of incidental adrenal masses . ↓ = decreased; APW = absolute percentage washout; CS-MR = chemical shift MRI; HU = Hounsfield unit; RPW = relative percentage washout; a If patient clinical signs or symptoms of adrenal hyperfunction, consider biochemical evaluation. b Consider biochemical testing to exclude pheocromocytoma. c Benign imaging features: homogeneous, low density, smooth margins. d Suspicious imaging features: heterogeneous, necrosis, irregular margins.