Illustrative case series

Incidental Adrenal Mass

By Bindu Kanapuru, MD, Institute for Advanced Studies in Aging and Geriatric Medicine, Falls Church Va. Dr. Kanapuru reports no relationships to this field of study.

A 70-year-old man undergoing preoperative evaluation for abdominal aortic aneurysm surgery was noted to have a 3 cm mass in the right adrenal gland with heterogeneous texture but clear margins. Past medical history was significant for hypertension, hypercholesterolemia, and coronary artery disease. He has 40-pack per year smoking history but quit 2 years ago. Laboratory tests revealed K+ level of 4.0 mmol/L and blood sugar levels of 100 mg/dL. He was referred to an oncologist for further evaluation.

CASE DISCUSSION

Detection of asymptomatic adrenal masses has become very common of late due to widespread use of abdominal imaging studies for a wide range of indications. The prevalence of incidental adrenal mass ranges from 0.2% in those younger than 30 years of age to as high as 7% in those 70 years of age or older. In 80% of the cases, adrenal incidentalomas are non-secreting benign adrenocortical adenomas such as lipoma or myolipoma. For the remaining 20%, the question to be addressed is whether there is malignancy and/or whether the nodular mass is functionally active.

DIFFERENTIATING BENIGN FROM MALIGNANT LESIONS

Malignant adrenal masses may be metastatic from a distant site or primary adreanal carcinoma. For those with metastatic disease, a clinical history of prior or current cancer diagnosis is almost always present. In fact, adrenal metastasis as the primary presentation of a malignancy is extremely rare (approximately 1%). In contrast, more than 60% of metastatic adrenal lesions are discovered at the time the primary tumor is diagnosed. Nearly two-thirds of adrenal metastases are from primary tumors of the breast or lung. Other common sites include melanomas, renal cell carcinoma, and GI tract cancers. However, even in those patients with a known malignancy, adrenal masses are more commonly benign and definitive diagnosis may require biopsy, especially in cases where this would be the only site of metastatic disease.

There are no specific symptoms or signs that clearly define a benign from malignant lesion. Although benign adenomas are more likely to present with symptoms of hormonal hypersecretion, adrenocortical carcinomas also may be associated with hyperglycemia, cushingoid features, hypertension, and symptoms of virilization or feminization. Alternatively about 5% of cortical secreting adenomas and pheochromocytomas are clinically silent and are identified by further functional testing.

IMAGING

The size and specific characteristics of the adrenal mass on CT scan may help in differentiating benign from malignant adrenocortical neoplasms. Adrenocortical carcinomas were diagnosed in more than 25% of lesions greater than 6 cm compared to only 2% in lesions less than 4 cm. Adrenocortical carcinomas and functioning adenomas are likely to be unilateral whereas metastatic adrenal masses are more often bilateral.

Both adrenocortical carcinomas and metastatic adrenal lesions appear as large heterogeneous masses in contrast to the small circumscribed homogeneous density that typify benign cortical adenomas. Pheochromocytomas are difficult to distinguish from malignant lesions by routine imaging as they are often relatively large (size > 3 cm) with heterogeneous signal and include both hemorrhagic and cystic areas. Nonetheless, unlike malignant adrenal lesions, pheochromocytomas more often appear round or oval and have clear margins. On an unenhanced CT, an attenuation coefficient of < 10 HU is reported to have specificity of 100% in ruling out malignancy. A contrast CT with enhancement washout of < 60% can further help in differentiating a non-lipid-rich adenoma from malignancy. Although a chemical shift MRI is equally effective in differentiating adrenal masses, it does not provide any additional information beyond what is provided by CT imaging. However, if CT imaging is unsuccessful in establishing the phenotype, an MRI may be of value. Pheochromocytoma, adrenal carcinoma, and metastatic lesions appear hyper-intense on T2 images, whereas benign lesions and adrenal cortisol-producing adenomas are iso-intense.

FDG-PET is reported to have 100% sensitivity and 94% specificity in characterizing adrenal lesions in patients with a current or suspected cancer. In a small study involving 10 patients with adrenocortical cancer, the sensitivity and specificity for FDG-PET was 100% and 95% respectively. However, it is not routinely recommended in the evaluation of pure adrenal incidentalomas.

Fine needle biopsy is a safe procedure with a complication rate of less than 3%. It is indicated to discriminate between metastatic disease and adrenal neoplasm, but is often insufficient to distinguish adrenal adenoma from carcinoma. It is imperative that a functional pheochromocytoma be ruled out to avoid a hypertensive crisis. An alpha-adrenergic blocker followed by a beta-blocker should be administered for about 2 weeks prior to the fine needle procedure.

EVALUATION OF HORMONAL HYPER SECRETION

The initial history and physical examination should be directed to identify the three most common hormonal abnormalities in these patients: Cushing's syndrome, pheochromocytoma, and primary aldosteronism. In addition, it is important to inquire about a family history of cancer and look for symptoms suggestive of syndromes associated with MEN2A, MEN 2B, and Von Hippel Lindau disease, all of which are associated with pheochromocytoma.

Most patients with autonomous cortical secreting adenomas have subclinical Cushing's and do not have the florid clinical signs and symptoms typically seen with Cushing's syndrome. As such, evaluation by 24-hour urinary cortisol may fail to identify these patients. Although false positives occur, the most commonly employed test to rule out a cortisol-producing adenoma is an overnight 1 mg dexamethasone suppression test. Failure to suppress serum cortisol to < 5mg/dL (although some suggest a value of 1.8 µg/dL) is considered a positive screening test and is followed by confirmatory testing. Recently the late-night salivary cortisol test has been shown to be a very early and sensitive marker for Cushing's syndrome with an elevated nighttime cortisol level having sensitivity and specificity of 90%-95%. A urinary-free cortisol level 4 times the normal level is also an excellent screening test. If the 1 mg dexamethasone suppression test is negative but the clinical suspicion for Cushing's is still high, all three tests can be done to effectively exclude this diagnosis. In patients with subclinical Cushing's, confirmatory testing with 2 mg dexamethasone test may be required.

Pheochromocytoma, the second most common functional adrenal tumor, accounts for > 10% of the cases. The measurements of plasma-free metanephrines and normetanephrines have a sensitivity of (97%-100%) and specificity (85%-89%) and represent the best screening tests for this disorder. In patients with hypertension, plasma renin activity ratio of > 20 and a plasma aldosterone concentration of >10 ng/dL suggest primary aldosteronism, which may be present in 1% of adrenal incidentalomas.

CURRENT CASE DISCUSSION

In the case presented, the medical history and physical examination were unrevealing with regard to hormonal hypersecretion. Although he had an extensive smoking history, he had no prior history of cancer or symptoms suspicious for a cancer diagnosis at the time of presentation.

Serum cortisol at 8 a.m. after 1 mg dexamethasone suppression test was 1.5 µg/dL and plasma renin aldosterone level was 15. Plasma-free metanephrines and normetanephrines were normal.

How should this patient be followed?

Although surgical resection is recommended for any adrenal incidentalomas larger than 6 cm after appropriate biochemical testing, the optimal management of lesion 4-6 cm is still unclear. Surgery is still a reasonable option in masses > 4 cm, especially if the imaging studies are suspicious for malignancy. In patients with masses < 4 cm, or > 4 cm and no suspicious features, a reasonable approach would be to repeat imaging in 3-6 months and then annually for 1-2 years. If there is no growth of the mass in 2 years, it is highly unlikely that it is malignant. Biochemical testing, however, should be repeated yearly for at least 5 years.

This patient underwent abdominal aortic aneurysm surgery uneventfully and is now scheduled for follow-up imaging studies and biochemical markers at regular intervals.

Resources

1. National Institutes of Health. Consensus Development Program. Management of the Clinically Inapparent Adrenal Mass ("Incidentaloma"). February 4–6, 2002. Available at: http://consensus.nih.gov/2002/2002AdrenalIncidentalomasos021main.htm. Accessed Sept. 16, 2011.

2. Gopan T, et al. Evaluating and managing adrenal incidentalomas. Cleve Clin J Med 2006;73:561-568.

3. Hamrahian AH, et al. Clinical utility of noncontrast computed tomography attenuation value (hounsfield units) to differentiate adrenal adenomas/hyperplasia from nonadenomas: Cleveland Clinic experience. J Clin Endocrinol Metab 2005; 90:871-877.

4. Yun M, et al. 18F-FDG PET in characterizing adrenal lesions detected on CT or MRI. J Nucl Med 2001;42:1795-1799.

5. McLean K, et al. Management of isolated adrenal lesions in cancer patients. Cancer Control 2011;18:113-126.

6. Zeiger MA, et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas. Endocr Pract 2009;15(Suppl 1). Available at: https://www.aace.com/sites/default/files/AdrenalGuidelines.pdf. Accessed Sept. 16, 2011.