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Definitive characterisation of adrenal lesions
J C Miller, medical writer, M A Blake, radiologist, G W L Boland, radiologist

This article explores the radiological investigations for characterising adrenal lesions, focusing on adrenal protocol computed tomography, positron emission tomography, chemical shift magnetic resonance imaging, and nuclear scintigraphy

Learning points

Incidental adrenal lesions are often detected by computed tomography (CT) and magnetic resonance imaging (MRI)

The diagnosis is highly dependent on whether the individual has a known history of cancer, with most lesions proving benign in patients without known cancer

Characterisation of the adrenal lesion is essential in patients with a history of malignancy so that the disease can be staged and treatment decided

Most lesions can be characterised using adrenal protocol CT, although a few indeterminate lesions may require MRI, nuclear imaging, and/or percutaneous biopsy

Functional adenomas and pheochromocytomas are best detected by laboratory tests


The patient
A woman in her 60s presented with a three week history of a productive cough and haemoptysis. A chest x ray film showed a 2.9 cm right upper lobe lung mass. Bronchoscopy and biopsy found non-small cell lung cancer. Staging, contrast enhanced computed tomography (CT) of the chest confirmed the upper lobe lung mass but showed no evidence of metastatic disease in the chest or liver. However, a 2.3 cm smooth walled, left adrenal mass was identified (fig 1). No prior CT examinations were available for comparison; growth of an adrenal mass is highly suggestive of a malignancy, whereas benign lesions are stable or grow very slowly.1 Biochemical analysis was negative for pheochromocytoma and adrenocortical functioning tumour.

Fig 1 Contrast enhanced staging computed tomogram in a 65 year old woman with a recent diagnosis of non-small cell lung cancer showing a 2.3 cm smooth walled left adrenal mass (arrow)

Adrenal masses are common findings whose prevalence increases with age.1 2 3 4 5 In patients without any known cancer, almost all of these masses are benign and have little clinical significance. However, in patients with known cancer, the risk that an adrenal mass is a metastasis is high, estimated at 45-73%.1 A small percentage are hormone secreting or malignant (either primary adrenal carcinoma or metastases from an unknown primary cancer),1 and differentiation using imaging and endocrine function tests is essential for optimising patient care.2 3 4 Most adrenal masses cannot be characterised by simple morphological appearances or enhancement with intravenous contrast agents. However, myelolipomas can often be diagnosed because they show visible fat (fig 2).6 Necrosis, which appears as characteristic irregular hypodensity, is typically indicative of malignancy
Fig 2 Axial non-contrast computed tomogram in a 48 year old woman. The left adrenal gland shows visible areas of fat (long arrow), diagnostic for myelolipoma. The right adrenal gland (short arrow) is normal

What are the next investigations?
If no metastases have arisen from the primary site of cancer, a 2.9 cm lung tumour can be treated with potentially curative surgery; metastatic disease, however, is usually treated with palliative systemic therapy.7 The primary question in this case, therefore, is whether the adrenal mass is a benign adenoma or a distant metastasis. The table shows a comparison of the imaging modalities for evaluating adrenal lesions.

Comparison of imaging modalities for evaluating adrenal lesions




Adrenal protocol CT
A technique known as adrenal protocol CT takes advantage of the differences in fat content and vascular characteristics of benign and malignant lesions.2 8 9 10 11 12 Most adenomas have high levels of intracellular fat (lipid rich adenomas), which is not directly visible on CT scans but can be characterised by measuring the x ray attenuation in Hounsfield units (HU).8 9 Tissues that contain fat have a lower HU value than those that do not. Malignant adrenal lesions with attenuations of <10 HU are extremely rare, and this value is now the generally accepted cut-off value to distinguish an adenoma from a possible malignancy (indeterminate lesion).8 9
Unfortunately, about 30% of adrenal adenomas have low levels of intracellular fat (lipid poor adenomas) and cannot be characterised by this method. However, dual phase contrast enhanced CT can characterise most lesions because even though adenomas and malignancies are enhanced strongly with intravenous contrast agents, the washout rate of administered contrast from malignant tumours is slower than that from adenomas.8 9

Adrenal CT protocol starts with an unenhanced CT scan. If the attenuation of the lesion is <10 HU, no further imaging is necessary. Otherwise, the unenhanced scan is followed by the rapid injection of contrast agent and, 60 seconds later, dynamic contrast enhanced CT. A delayed contrast (washout) scan is obtained 10-15 minutes later. The relative percentage washout is calculated from the HU values of the dynamic and delayed contrast CT, and the absolute percentage washout from the HU values of the precontrast, dynamic contrast enhanced, and delayed contrast CT. In one study using a 10 minute delay protocol, combining all the information available from the protocol gave a sensitivity of 100% and a specificity of 98% for differentiating benign from malignant lesions.8

Positron emission tomography
In some institutions, 2-[18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is used to stage patients with a known lung cancer. This procedure detects adrenal metastases and primary adenocarcinomas with a sensitivity and specificity in the range 93-100% and 78-100% respectively.13 14 False negatives have been reported as a result of haemorrhage and necrosis. False positives can occasionally (<5%) arise from atypical adenomas.14

In addition, FDG-PET can be used to evaluate adrenal masses that are detected incidentally in patients with no known cancer and which are indeterminate after an adrenal protocol CT. Combined FDG-PET and CT (fig 3) using a hybrid scanner has been shown to be better than FDG-PET alone.13

Fig 3 Differentiation of adrenal masses with positron emission tomography and computed tomography. Top: Contrast enhanced CT shows 1.9 cm right adrenal mass (arrow) in a 76 year old man with lung cancer. Bottom: FDG-PET from same patient shows marked uptake of radioactivity into the adrenal mass (arrow), consistent with metastasis




Chemical shift magnetic resonance imaging
Chemical shift magnetic resonance imaging (MRI) can be useful if an adrenal protocol CT examination is equivocal or if an unenhanced CT has been performed and CT contrast agents are contraindicated. In adenomas, out-of-phase signal intensity is typically lower than that of in-phase images (fig 4), which is not the case in lipid poor lesions, such as most metastases. The sensitivity of chemical shift MRI for characterisation of adenomas ranges from 81% to 100% with a specificity of 94-100%.15

Fig 4 Left adrenal mass in a 67 year old man with pancreatic cancer. Top: In-phase chemical shift magnetic resonance imaging (MRI) showing adrenal signal (large arrow) similar to spleen (small arrow). Bottom: Out-of-phase chemical shift MRI showing drop-off in the adrenal signal (large arrow) compared with splenic signal (small arrow), consistent with lipid rich adenoma

Nuclear scintigraphy (other than FDG-PET)
Pheochromocytomas and extra-adrenal catecholamine secreting tumours can be detected by nuclear scintigraphy 24-72 hours after the administration of 131I-meta-iodobenzyl guanidine (MIBG), a structural analog of noradrenaline (norepinephrine). MIBG has a reported 100% specificity for pheochromocytoma but limited sensitivity (80-90%),6 partly as a result of the low image resolution of scintigraphy cameras. An alternative tracer, 111octreotide, an analog of somatostatin, detects pheochromocytoma with lower sensitivity (75-90%) than MIBG but can be useful because some pheochromocytomas are seen with octreotide but not MIBG imaging, and vice versa.6
Adrenal biopsy is regarded as the standard investigation for diagnosis of adrenal disease.2 CT guided percutaneous needle aspiration biopsy has a very high negative predictive value for malignancy16 and is recommended for patients with a history of cancer, no other signs of metastasis, and an adrenal mass that remains indeterminate after imaging studies. Pheochromocytoma must always be excluded to avoid a hypertensive crisis during percutaneous needle aspiration biopsy.2


Outcome
A dedicated adrenal protocol CT was performed. Non-contrast CT yielded an adrenal attenuation of 20 HU (fig 5(A)), consistent with a lipid poor adenoma or a malignant lesion. Dynamic contrast enhanced and 10 minute delayed contrast CT yielded adrenal attenuation measurements of 85 HU and 35 HU respectively (fig 5(B) and (C)). Calculation of the relative and absolute adrenal washout rates were 59% and 77% respectively, consistent with an adrenal adenoma. As there was no evidence of metastatic disease, the patient was referred for curative thoracic surgery.

Fig 5 Adrenal protocol CT examination in the same patient as figure 1, performed two days later (arrows show mass). Left: Unenhanced scan (attenuation of adrenal mass 20 HU). Centre: Dynamic contrast enhanced scan (attenuation 85 HU). Right: Delayed washout scan, performed 10 minutes later (attenuation 35 HU)



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