Evaluation and Management of Adrenal Masses

Sergio Gugisch Moreira, Jr, MD, and Julio M. Pow-Sang, MD

Disclosures

Cancer Control. 2002;9(4) 

In This Article

Etiology

Incidentalomas are adrenal tumors discovered on an imaging study performed for indications exclusive of adrenal-related conditions.[4] The frequent use of imaging studies, particularly computed tomography (CT) scans, which consistently detect adrenal lesions greater than 1 cm, has resulted in the detection of incidentalomas in 0.35% to 5% of studies.[5] The majority of incidentalomas are biochemically nonfunctional and benign. However, in approximately 10% of cases, an incidental adrenal mass may be functional.[6]

Several reports have addressed the topic of incidentalomas, and many controversies exist regarding evaluation and management methods of these entities. The approach to incidentalomas is directed towards distinguishing benign from malignant neoplasms and determining the functional status of these lesions.

When functional, these masses may manifest as Cushing's syndrome, a rare entity that describes the symptom complex caused by an excess of circulating glucocorticoids. It is also important to rule out an exogenous source of hormone excess since therapeutic corticosteroids are the most common cause. The term preclinical Cushing's syndrome was introduced in 1981 to describe adrenal incidentalomas with autonomous cortisol-secreting cortical adenomas in patients who lacked the typical signs and symptoms of hypercortisolism.[7] The incidence of preclinical Cushing's syndrome is approximately 5% to 10%.[8]

Primary aldosteronism is another disorder of excess adrenal hormone production to consider in a patient with an adrenal incidentaloma. In 1955, Conn[9] described the clinical syndrome consisting in hypertension, hypokalemia, hypernatremia, alkalosis, and periodic paralysis caused by an aldosterone-secreting adenoma. Primary aldosteronism is a rare but important cause of secondary hypertension. Recent data suggest that this pathology may be more common than previously reported (as much as 5% to 15% of the hypertensive population) and may become the most common form of curable hypertension.[10] The hallmark of primary aldosteronism is hypertension with hypokalemia, suppressed plasma renin activity, and elevated plasma aldosterone. All patients with adrenal incidentalomas who have hypertension should be evaluated for primary aldosteronism.

Clinically silent pheochromocytomas are a third disorder of excess adrenal hormone to consider in a patient with an adrenal incidentaloma. Approximately 5% of patients with adrenal incidentalomas have pheochromocytomas, and 10% of adrenal pheochromocytomas have presented as adrenal incidentalomas.[11] The clinical features of pheochromocytomas are discussed later.

Distinguishing adenoma from carcinoma by pathologic examination can be challenging for pathologists. All large adrenal lesions do not behave biologically as carcinomas. Some lesions that appear benign on histologic evaluation eventually metastasize. Hence, surgical removal is recommended for all lesions larger than 5 cm.

Adrenal adenomas often manifest on CT scans as smooth, well defined, homogeneous, smaller than 4 cm in diameter, and low in attenuation. Several reports in the literature indicate that an adrenal mass with a value of 10 Hounsfield units (HU) or fewer on unenhanced CT scan is likely to be an adenoma.[12] The low attenuation of these lesions is attributed to their rich lipid content. Radiological findings are discussed later.

Benign neoplasms are composed of mature adipose cells and hemopoietic tissue in varying proportions, and most are hormonally inactive. They are generally small (<5 cm) and unilateral. The most common symptom is pain. The fatty component is evident and characterized on CT scans by low-density and inhomogeneous images (Fig 1). On magnetic resonance imaging (MRI), the fat appears hyperintense on T1-weighted images and intermediate on T2-weighted images. The treatment for these lesions, if asymptomatic, is conservative unless there is a possibility that they may be confused with necrotic adrenal carcinoma. Tumor progression or hemorrhage is uncommon.

Myelolipoma of the left adrenal (arrow).

Adrenal carcinoma is a rare disease that carries a poor prognosis and accounts for 0.2% of all cancer deaths.[13] Adrenal tumors are classified as either functional or nonfunctional. Approximately 80% are functional, and they are usually larger than 6 cm. In a recent series published by Kendrick et al,[14] cortisol-secreting tumors were the most common functional tumors (67%), followed by mixed hormonal-secreting tumors (15%), sex hormonal excess (11%), and aldosteronesecreting tumors (7%). It is important to note that nonfunctional tumors may eventually become functional.

Due to the infrequency of adrenal carcinoma and the lack of randomized prospective trials, determining the optimal treatment can be difficult. Surgical resection is the principal treatment for stage I to II disease. For patients with stage III or IV disease, adjuvant therapy may improve survival, with mitotane being the agent of choice. Patients diagnosed at an earlier stage have an improved 5-year survival. However, the clinical benefits are questionable.

Adrenal cysts are rare, often unilateral lesions, and more prevalent in women. Endothelial cysts account for almost 50% of adrenal cysts. Pseudocysts, which are less common (40%), result from previous adrenal hemorrhages and may compress adjacent structures. Epithelial and parasitic cysts are uncommon.[15]

Adrenal hemorrhage presents as a unilateral or bilateral mass on CT scan. It may occur spontaneously or may be the result of anticoagulation or trauma. On MRI in the acute phase, a signal loss is observed on T1 and T2 images due to the presence of deoxyhemoglobin. In the subacute and chronic phases, the intensity on both T1 and T2 images is increased due to calcification and hemosiderin deposition.[4]

Pheochromocytomas are tumors of neuroendocrine origin that arise in the adrenal medulla in approximately 80% to 90% of cases. They are the cause of hypertension in less than 1% of the hypertensive population. Detection of these tumors is critical, not only to cure the hypertension, but also to avoid the potential lethal effects of the tumor. Pheochromocytomas can be large, ranging in size from 2 g to 3,600 g. Symptoms associated with these tumors usually are referable to their production of catecholamines.[16] The catecholamineinduced symptoms are mediated by the normal sympathetic neural pathway and not primarily by serum catecholamines. Any direct stimulus to the sympathetic nervous system can induce a crisis without a large rise in serum catecholamine levels. Hypertension is the most consistent sign, involving three basic patterns: sustained, paroxysmal, and sustained with superimposed paroxysms.[15] The signs and symptoms of pheochromocytoma are variable,[17] and 10% are found in normotensive patients. In addition to hypertension, the sequelae of chronic exposure to catecholaminic excess include plasma volume contraction and catecholamine-induced cardiomyopathy. Approximately 10% to 20% of pheochromocytomas are malignant. Although some patients may live decades, the mean 5-year survival rate is 40%.[18] Malignancy may be reflected in local invasion or by metastatic spread in decreasing frequency to the bone, lymph nodes, liver, lungs, or brain.

Several syndromes of familial pheochromocytoma have been described. The most common are multiple endocrine neoplasia type 2 and von Hippel-Lindau disease. A lower incidence of pheochromocytoma is seen in patients with neurofibromatosis type 1. Some families seem to have familial disorders characterized by pheochromocytomas without other abnormalities.

Manifestations of pheochromocytomas in children vary from those in adults and are not addressed here. The radiological and laboratory diagnosis is discussed later. Preoperative medical preparation is essential and includes expansion of plasma volume and alpha-adrenergic receptor blockade, with either selective alpha-blockers (prazosin)[19] or nonselective alpha-blockers (phenoxybenzamine). Beta-blockers are used to protect this patient against arrhythmias and should be started only after alpha-blockade has been established to avoid a significant rise in the total peripheral vascular resistance. Another option is alpha-methylparatyrosine, which decreases the rate of catecholamine synthesis.

Metastatic tumors to the adrenal gland are more common than primary adrenocortical carcinoma. The most common tumors to metastasize to the adrenal gland are melanomas, carcinomas of the breast and lung, and renal cell carcinoma. Other tumors include carcinomas of the contralateral adrenal, bladder, colon, esophagus, gallbladder, liver, pancreas, prostate, stomach, and uterus.[20] In general, the adrenal lesion is part of the clinical picture of diffuse metastatic disease. Therefore, the finding of an unsuspected adrenal mass should heighten the clinical suspicion of a neoplasm elsewhere. Adrenal insufficiency may occur.[21]

Rare causes of benign nonfunctioning masses include adrenolipoma, amyloidosis, angiomyolipoma, ganglioneuroma, fibroma, neurofibroma, teratoma, and granuloma. Rare causes of malignant nonfunctioning masses include ganglioneuroblastoma, neuroblastoma, lymphoma, lymphangioma, liposarcoma, malignant schwannoma.

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