Adrenal Incidentaloma

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Adrenal masses are often discovered incidentally and are then termed adrenal incidentalomas (AIs). They are often discovered after an imaging procedure is performed that is unrelated to the adrenal gland. Usually, the patient has no signs of hormonal excess or obvious underlying malignancy. Incidence has been increasing proportionally to the use of radiographic imaging, as shown in the images below. ^[1] Less commonly, AIs are discovered as part of the clinical workup for suspected adrenal disease (eg, Cushing syndrome). (See Workup, as well as Clinical Presentation.)

The differential diagnosis of AIs includes many primary, metastatic, benign, and malignant entities, most of which are not discussed at length here. (See Diagnosis)

Adrenal cortical adenoma is a common benign tumor arising from the cortex of the adrenal gland. It commonly occurs in adults, but it can be found in persons of any age. Adrenal cortical adenomas are not considered to have the potential for malignant transformation (see the images below).

Because adrenal metastases may be found in as many as 25% of patients with known primary lesions, radiologists frequently face the task of determining whether an adrenal mass is benign or malignant. The question can directly affect the clinical management of the case. For instance, the workup for an otherwise resectable lung cancer may reveal the presence of an adrenal mass and suggest the possibility of metastatic disease. (See Workup.)

The treatment for a hormonally active (functional) adrenal tumor is surgery. The treatment for a malignancy depends on the cell type, spread, and location of the primary tumor. ^[2] Nonfunctional adrenal cortical adenomas are not premalignant, and surgical excision is not indicated. (See Treatment and Management.)

The adrenal glands are located in the perirenal space near the upper pole of each kidney. Their appearance varies: they may be shaped like the letter H, L, Y, T, or V. Typically, they are less than 4 cm in length and less than 1 cm in width.

The biochemical mechanisms depend on the underlying cell type. The cellular mechanisms for primary adrenocortical tumorigenesis are just beginning to be understood.

Some studies report an association with chromosomal and genetic abnormalities (genes coding for p53 and p57). Tumor markers are also present in other syndromes. The multiple endocrine neoplasia (MEN1) gene is linked to multiple endocrine neoplasia type 1. The aldosynthase/11-beta hydroxylase hybrid gene is associated with glucocorticoid-remediable hyperaldosteronism.

Another very rare cause of Cushing syndrome is adrenal-dependent macronodular hyperplasia associated with extremely large adrenal glands.

Adrenal incidentalomas (AIs) are a common finding on cross-sectional abdominal images. In about 1-5% of all cases, abdominal computed tomography (CT) scans that are obtained for reasons other than the evaluation for possible adrenal neoplasm demonstrate an adrenal mass; most of these are AIs. The autopsy prevalence for AIs is 2-9% (see Table 1).

Table 1. Prevalence of AIs (Open Table in a new window)

Author

Method

Sample Size

Prevalence, %

Russl (1941)

Autopsy (>1 cm)

131/9000

1.5

Kokko (1967) ^[3]

Autopsy (>5 mm)

21/1495

1.5

Hedeland (1967)

Autopsy (>2 mm)

64/739

8.7

Glazer (1982) ^[4]

CT scan

16/2200

0.7

Abecassis (1985) ^[5]

CT scan

19/1459

1.3

Belldegrun (1986) ^[6]

CT scan

88/12000

0.7

Herrera (1991) ^[7]

CT scan

259/61054

0.4

Approximately 1-10% of CT scans and magnetic resonance images (MRIs) detect AIs that are 5 mm or larger. An Italian study of incidentally discovered AIs among subjects undergoing chest CT scan found that the prevalence of AIs was approximately 4%. ^[8]

The most important hormonally silent AI is pheochromocytoma. They are present in approximately 1 in 1000 autopsies. If the prevalence of AIs is 10-100 in 1000, then 1-10% of AIs are pheochromocytomas, as noted in the image below.

A study by Falhammar et al of 94 cases of pheochromocytoma, as encountered at a single center, determined that 64% were identified as incidentalomas, while 32% were found in patients suspected of having a pheochromocytoma. In another 4% of cases, patients were screened for the lesion because they were known to have MEN2A. ^[9]

Prevalence increases with age; the rate is less than 1% for patients younger than 30 years and is 7% for patients 70 years or older. Evidence suggests that the incidence in teenage girls is slightly higher than that of teenage boys, but no sex-related predilection is found in adults. AI prevalence is higher in white than in black people and in obese, diabetic, and hypertensive patients. ^[10]

Generally, the prognosis is excellent, but it depends on the type of underlying adrenal disease.

Approximately 85% of AIs are nonfunctional (hormonally silent) and benign. The other 15% of AIs are either functional (hormonally active) or malignant and require further evaluation and treatment to avoid medical complications. ^{[11, 12, 13]}

Patients with a previous history of cancer have a clinical course dictated by the primary tumor. Patients with adrenal cortical carcinomas have poor clinical outcomes, usually a 2- to 5-year 50% overall survival rate.

Approximately 3-7 percent of AIs prove to be pheochromocytomas. ^{[11, 12, 14]} Pheochromocytomas may result in substantial complications, including death if not recognized. A 1981 series reported that less than one quarter of pheochromocytomas found post mortem were diagnosed ante mortem. ^[15] More than 90% of these patients had characteristic symptoms suggesting the unrecognized tumors were not silent. Many of the patients died of causes possibly related to the pheochromocytoma. Approximately 29% died unexpectedly during surgery, 27% died from cardiovascular causes, and 17% died from cerebrovascular causes.

If pertinent, patients should know the signs and symptoms of adrenal insufficiency. Clinical clues include nausea, abdominal pain, fever, and diarrhea.

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Author

Method

Sample Size

Prevalence, %

Russl (1941)

Autopsy (>1 cm)

131/9000

1.5

Kokko (1967) ^[3]

Autopsy (>5 mm)

21/1495

1.5

Hedeland (1967)

Autopsy (>2 mm)

64/739

8.7

Glazer (1982) ^[4]

CT scan

16/2200

0.7

Abecassis (1985) ^[5]

CT scan

19/1459

1.3

Belldegrun (1986) ^[6]

CT scan

88/12000

0.7

Herrera (1991) ^[7]

CT scan

259/61054

0.4

Diagnosis

Features

Biochemical Tests

Pheochromocytoma

High blood pressure, catechol symptoms

Urine-free and plasma-free metanephrines

Primary aldosteronism

High blood pressure, low K⁺, low PRA*

Plasma aldosterone-to-renin ratio

Adrenocortical carcinoma

Virilization or feminization

Urine 17-ketosteroids

Cushing or “silent” Cushing syndrome

Cushing symptoms or normal examination results

Overnight 1-mg dexamethasone test

*Plasma renin activity

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Don S Schalch, MD Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and The Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Stanley Wallach, MD Executive Director, American College of Nutrition; Clinical Professor, Department of Medicine, New York University School of Medicine

Stanley Wallach, MD is a member of the following medical societies: American College of Nutrition, American Society for Bone and Mineral Research, American Society for Clinical Investigation, American Society for Clinical Nutrition, American Society for Nutritional Sciences, Association of American Physicians, and The Endocrine Society

Disclosure: Nothing to disclose.

Adrenal Incidentaloma

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