MDCT of the Adrenal: 2003-2004

Elliot K. Fishman, M.D.

The evaluation of the adrenal gland has been one of the classic applications in CT for the past 25 years. Specifically, CT has been shown to be able to localize and define the appearance of the adrenal gland in 100% of patients as long as thin collimation (3 mm or less) was used. CT is able to define the size of the gland as well as look for any changes in tissue attenuation. The most common lesion of the adrenal gland is referred to as an incidentaloma and is an adenoma of the adrenal which can occur in up to 10% of patients. Most adenomas are incidentally found on routine CT scans of the chest and abdomen. Specific radiologic signs based on CT criteria for determining the diagnosis an adenoma have been established and will be discussed later on in this manuscript. What is important to recognize is that CT is currently the study of choice for the evaluation of the adrenal gland. By understanding the various appearances of the adrenal gland on non-contrast, contrast and delayed CT scans, one is able to not only detect the presence of adrenal disease but be very specific as to its etiology in most cases. In this manuscript, we will review many of the key diagnostic points that are helpful in differential diagnosis. In addition, there is an accompanying lecture to this chapter which has many excellent case examples. Also, a detailed teaching file of 300 cases is provided as part of this program to allow the reader to see a wide range of various adrenal pathologies and be able to quiz themselves with an interactive teaching file.

There are many logical ways for approaching the CT evaluation of the adrenal gland. We can approach the adrenal gland by dividing diseases up into cortical or medullary origins. This is an interesting way of differentiating different disease processes but it is important to recognize that on CT it is typically impossible to separate the cortex and medulla. One can also look at adrenal disease by determining if it is bilateral or unilateral. This can be helpful in select cases but it is important to remember that bilateral adrenal masses can be due to a range of benign processes including hemorrhage and infection as well as malignancies ranging from lymphoma to metastatic disease. One can review the attenuation of an adrenal mass which may be less helpful as malignant lesions may be cystic or solid. Enhancement patterns are critical particularly for hypervascular lesions, which are typically pheochromocytomas or similar type tumors. Adrenal lesions often have important characteristics in terms of attenuation ranging from fat in adrenal myelolipoma to calcification which can be seen in a range of tumors ranging from neuroblastoma to primary adrenal carcinoma to myelolipoma

Some of the specific potential grouping is noted in the following list. They include:

TABLE 1 Adrenal Medullary Disease

• Neuroblastoma
• Ganglioneuroma
• Ganglioneuroblastoma
• Pheochromocytoma

TABLE 2 Adrenal Cortical Disease

• Cushing syndrome
• Conn syndrome
• Adrenogenital syndrome
• Adrenal cortical carcinoma
• Adrenal hyperplasia

One of the key findings in the differential diagnosis of adrenal masses is whether the lesion is unilateral or bilateral. As noted above, there are many lesions, which can be either unilateral or bilateral, or there are those that tend to be a unilateral process. Unilateral disease is most common and is especially common in adenomas. Unilateral disease is seen in 90% of cases of pheochromocytoma and is more common than bilateral disease in terms of metastatic lesions. The high majority of primary adrenal carcinomas are also unilateral in nature.

If one discovers an adrenal lesion, it is important that we are able to try to determine its etiology. As noted, an adrenal mass can range anywhere from a benign adenoma to a primary adrenal cancer to metastatic disease. The incidental adrenal lesion is more commonly an adenoma but the question is how can we prove this, without a biopsy or follow-up studies.

Many articles in the past have discussed the value of non-contrast CT in determining adrenal attenuation values and ultimately lesion definition. It has been shown that any lesion measuring less than 10 HU on non-contrast CT is a benign adenoma. Many other authors will extend this number to 17 HU. Unfortunately, most CT scans these days are done with IV contrast material. Initially, authors did note that adrenal adenomas could enhance as could other adrenal lesions and felt that it was impossible to determine the nature of an adrenal lesion when IV contrast was given. Later articles did a more careful analysis and found that if a lesion was under 35 or 37 HU on contrast enhanced scans then it was definitely an adenoma.

Further work then went into analysis of adrenal lesion enhancement as well as the consideration that possibly lipid poor adrenal adenomas which could not be diagnosed on non-contrast CT might be diagnosed on contrast enhanced CT with delayed scanning. Much discussion was then made of a washout from a benign lesion. The washout meant that if one took a measurement of the adrenal gland at 1 minute post injection and 15 minutes later then the adenoma should have a greater than 50% washout (i.e. go from 100 HU to less than 50 HU). Even in lipid poor adenomas there is a fast washout. In most malignancies, the washout is slower. This is because these lesions have typically disturbed the capillary bed and so do not washout at a rapid date. Therefore, one can determine if the lesion is indeed an adenoma by obtaining delayed scans at 15 minutes post injection and measuring density values and then calculating the percent washout.

MR has also been used for determining whether a lesion has fat within it and is an adenoma. Korobkin et al. have noted that whether the study is CT or MR that it is the lipid component of the lesion that allows one to make a specific diagnosis of an adenoma.

As noted, adenomas are usually unilateral but can be bilateral. In terms of differential diagnosis, unilateral lesions include:

TABLE 3 Unilateral Adrenal Lesions – Differential Diagnosis

• Adrenal adenoma (incidentaloma)
• Functioning adrenal adenoma
• Metastases
• Hyperplasia
• Infectious disease
• Myelolipoma
• Pheochromocytoma
• Metastases
• Primary adrenal carcinoma
• Hemorrhage

In addition to adrenal adenomas, there are other benign adrenal masses. These include adrenal cyst and adrenal hemorrhage as well as adrenal myelolipoma. Adrenal myolipomas typically have fat within them that measure –20 to –50 HU. The amount of fat present is variable and calcification is not uncommon. Please note that most of these myelolipomas are 1-3 cm in size but large ones have been reported. I have seen several cases of >10 cm masses that displaced structures so that they appear to represent a process like a retroperitoneal liposarcoma.

Adrenal myelolipomas is a benign adrenal tumor consisting of mature fat interspersed with hematopoietic elements. These lesions most commonly occur in the adrenal gland as an incidental finding. CT is the study of choice as it demonstrates the presence of fat within these lesions making the diagnosis fairly straightforward. Please note that the amount of fat in an individual myelolipoma will vary from being nearly 100% fat to having only foci of fat. These lesions can bleed and if they do the fat will be difficult if not impossible to define. Myelolipomas are typically unilateral although bilateral myelolipomas have been reported in the literature. The key differential diagnosis point with myelolipomas is that when they are large they can be confused with retroperitoneal lipomas or liposarcomas. Practically, these lesions are typically discovered in older patients often as part of malignancy work-up. It is therefore important to recognize these lesions for their benign nature and that no biopsy or further evaluation is needed. In select cases, MR may be helpful but typically the diagnosis can easily be made on CT scan once one is familiar with the appearance of myelolipomas.

Myelolipomas as noted can bleed but this typically occurs in lesions that were larger and contained extensive fat. Average lesion size was over 10 cm in lesions that bled.

Although one typically considers myelolipomas to be fatty tumors, it is important to recognize that the presence of calcification is not uncommon. The calcification in the lesions are punctate in nature and typically the presence of calcification is also accompanied by fat. Although CT scanning is the current method of diagnosing myelolipomas it is interesting to note that these tumors were first described in 1905 by Gierke.

Adrenal hemorrhage is another a benign adrenal lesion that has a specific appearance in most cases. Adrenal hemorrhage can be seen due to a number of processes including stress, trauma, and anticoagulant therapy. Adrenal hemorrhage can be unilateral or bilateral with bilateral disease leading to an Addisonian crisis. The appearance of adrenal hemorrhage is an enlarged adrenal gland of high CT attenuation. The CT diagnosis is critical as the clinical diagnosis of adrenal hemorrhage is rarely even suggested by the referring physician.

Finally, another benign adrenal lesion is a lymphangioma. This is an uncommon lesion which is of low CT attenuation and usually measures between 3-5 cm in size.

There are other categories of benign adrenal lesions including old adrenal hematomas and adrenal cysts. There are true adrenal cysts, which are epithelial, or endothelial in nature and range in size from several centimeters to 15-20 cm in size. In our experience these are uncommon. Adrenal hematomas when chronic may look similar to adrenal cysts although a key differential diagnosis point is that they typically have thin calcifications of the cyst wall. This is very helpful in making the diagnosis.

Please note that other adrenal lesions can calcify. Calcification can be seen in unusual infectious diseases like hydatid disease as well as in TB and histoplasmosis. Adrenal hemorrhage, cystic neuroblastoma, lymphangioma, or true cysts may contain some degree of calcification though typically not along the border of the lesion.

A list of potential lesions that do calcify is another differential diagnostic point. These include:

TABLE 4 Adrenal Lesions that Calcify

• Tumor calcification including neuroblastoma, pheochromocytoma, adrenal carcinoma
• Old hematoma
• Infectious etiologies
including tuberculosis, histoplasmosis
• Unusual causes, Wolman disease

Adrenocortical carcinomas are malignant tumors of the adrenal cortex that account for less than 0.2% of all cancers in the United States. They can occur at any age group but classically have a bimodal age distribution with the first peak occurring before age 5 and the second peak in the 4^th and 5^th decade of life. Interestingly, women comprise 65-90% of reported cases. Although most adrenal cortical malignant tumors are unilateral up to 10% may be bilateral.

The most common syndrome associated with adrenocortical tumors are hyperaldosteronism and Cushing syndrome. Cushing syndrome is present in 40% of patients with adrenocortical cancer. Fertilization occurs less frequently in adults than Cushing’s but is the most common hormonal syndrome in children with adrenocortical cancer. Although one often associates adrenocortical neoplasms with abnormal adrenal function, in over half of cases of adult patients there is no recognizable endocrine syndrome. These patients typically present with a large mass or with symptoms due to abdominal pain, palpable mass, weight loss or distant metastases.

Staging for adrenocortical carcinomas is based on tumor size, nodal involvement, invasion of adjacent organs and presence of distant metastasis. Only Stage 1 and Stage 2 lesions are curable surgically and unfortunately most patients are at Stage 3 or Stage 4 at time of diagnosis. The 5-year survival for Stage 3 disease is under 30%. Common sites of metastases from adrenal carcinoma are to the lymph nodes, the lung parenchyma, liver and skeletal system.

Although in the past most adrenal tumors were removed with open laparatomy, there has been increased use of laparoscopic adrenalectomy.

CT staging as well as definition of the tumor bed is helpful in determining the best approach for the individual patient.

Another tumor that can be considered in 10% of patients to be malignant is a pheochromocytoma. Pheochromocytomas are one of the few curable cause of hypertension although they are found in far less than 1% of all hypertensive patients. The prevalence of pheochromocytoma ranges from .3 to .95% in autopsy and so we will discover incidental pheochromocytomas in clinical practice. Radiographically and clinically, there is no way to determine and distinguish benign from malignant pheochromocytomas.

Ninety percent of pheochromocytomas arise in the adrenal medulla and 97% arise below the diaphragm. Roughly 2-3% of all pheochromocytomas are thoracic in location. Pheochromocytomas commonly follow the rule of 10, in that 10% are bilateral, malignant, multifocal, extrarenal or found in children or associated with the familial syndrome. Interestingly, up to 30% of extraadrenal pheochromocytomas are malignant in contrast to about 2.5% of intraadrenal pheochromocytoma which are malignant pheochomocytomas. Pheochromocytomas can be diagnosed because of their excess catecholamines although in some cases the tumors will secrete ACTH. Other causes of ectopic ACTH production include small cell cancer of the lung, and medullary thyroid cancer.

Although as a radiologist we commonly consider CT or MR to be the study of choice for the evaluation of pheochromocytoma, it is important to recognize that biochemical screening for pheochromocytoma can be 100% sensitive and specific. The measurement of catecholamines and their metabolites in 24-hour urine collections approaches 100% sensitivity and specificity. Once laboratory test or biochemical screening focuses on the diagnosis of pheochromocytoma, radiologic imaging studies are done for evaluation. CT and MR are commonly used. CT classically will show 3-5 cm mass which is hypervascular with contrast material. Reports of hypertensive crisis initiated by IV contrast has been reported in the literature and can occur although this far less common with non-ionic contrast material.

When we scan a patient for pheochromocytoma, we obviously will carefully scan the adrenal gland. If no evidence of adrenal lesion is seen, then needs to scan the length from the diaphragm through the aortic bifurcation with specific emphasis on the most common site of extraadrenal pheochromocytoma which is the organ of Zuckerkandl.

As mentioned above, there is the potential that intravenous contrast can elevate plasma catecholamine levels and lead to a hypertensive crisis in patients who have not been treated with a beta blocker.

In cases where CT or MR cannot localize a lesion, MIBG can be used. MIBG has been reported to have a sensitivity between 77-89% in pheochromocytomas.

Another topic worth discussing in regard to the adrenal gland is adrenal insufficiency. Adrenal insufficiency can be considered both primary and secondary in nature. Primary adrenal insufficiency is often described as Addison’s disease and is uncommon but has been seen in such famous patients as President John Kennedy. The most common cause in the past was tuberculous adrenalitis but now is autoimmune adrenalitis. Recently, discovered causes of primary renal insufficiency include AIDS and antiphospholipid syndrome. Secondary causes of adrenal insufficiency include pituitary hypothalmic disorders.

Adrenal insufficiency is often undiagnosed as patient may present with a range of symptoms such as failure to thrive or sepsis. CT may be helpful in suggesting the diagnosis particularly if the underlying cause is hemorrhage of the adrenal glands.