specific for pheochromocytoma (Fig. 77-10B,C). MRI is useful in suspected malignant

pheochromocytoma to evaluate for inferior vena cava thrombus or liver invasion.

Functional nuclear imaging with iodine-131-metaiodobenzylguanidine (131-I MIBG) is a useful

adjunct to cross-sectional imaging for pheochromocytoma (Fig. 77-10D). MIBG resembles

norepinephrine and is taken up by adrenergic tissues including pheochromocytoma. An MIBG scan can

detect tumors not detected by CT or MRI or multiple tumors when CT or MRI is positive. Multiinstitutional experience with this technique has demonstrated an overall sensitivity of 77% to 87% and a

specificity of 96% to 100%. This test is usually not necessary for sporadic pheochromocytoma unless

urinary or plasma catecholamines and metabolites are marginally elevated, or if malignant or

extraadrenal pheochromocytoma is suspected. 131-I MIBG scanning is also useful to screen patients with

metastatic pheochromocytoma for high-dose 131-I MIBG therapy. 111-In-pentetreotide scintigraphy may

also identify pheochromocytoma and can be used therapeutically as with 131-I MIBG.

Figure 77-10. Imaging of pheochromocytoma (arrows). A: Computed tomography scan shows well-circumscribed left adrenal mass.

B: T2-weighted magnetic resonance imaging shows the mass to be heterogeneously bright, consistent with pheochromocytoma.

C,D: Coronal contrast enhanced MRI and near-simultaneous

131I-metaiodobenzylguanine (131I-MIBG) scanning show location of the

pheochromocytoma and relationship to surrounding structures.

Treatment

Surgical resection is the only cure for pheochromocytoma. When the diagnosis of pheochromocytoma

has been established and localization studies are completed, preoperative preparation of the patient

centers on blood pressure control. Usually 1 to 3 weeks before operation alpha-adrenergic blockade is

performed first with phenoxybenzamine, starting at 10 mg twice a day and increasing by 10 to 20 mg

per day until blood pressure normalizes. Side effects of alpha blockade include postural hypotension,

reflex tachycardia, nasal congestion, and an inability to ejaculate. Preoperative alpha blockade also

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reverses the relative hypovolemia that is usually present in patients with pheochromocytoma and also

prevents severe blood pressure swings during intraoperative manipulation of the tumor. Metyrapone

added preoperatively to phenoxybenzamine can achieve a greater degree of sympathetic blockade.

Beta-adrenergic blockade with propranolol added after alpha blockade can manage patients who

develop tachycardia or who have inducible cardiac arrhythmias or ischemia. Propranolol may enhance

pressor response to endogenous norepinephrine and thus should not be given until adequate alpha

blockade has been established. Propranolol can also produce profound bradycardia, myocardial

depression, and congestive heart failure. Newer drug regimens to manage hypertension in

pheochromocytoma include selective alpha-1-adrenergic antagonists (terazosin and doxazosin) and

calcium channel blockers (nifedipine and nicardipine).

Patients with pheochromocytoma can be expected to have blood pressure volatility and high

intravascular volume requirements during and immediately after surgery. Elderly patients or those with

history of heart disease may require pulmonary catheter insertion and arterial line placement for careful

monitoring of blood pressure and arterial pH. Anesthetic agents may trigger the release of

catecholamines from pheochromocytomas. The anesthetic plane is now considered more important than

the choice of agent, and both enflurane and isoflurane have been used successfully. Magnesium

administration during surgery is an effective way to control blood pressure in patients with

pheochromocytoma. Intraoperative hypertension is best treated with a sodium nitroprusside drip, and

cardiac arrhythmias are best managed with short-acting beta-blockers (esmolol) or lidocaine.

Formerly, an anterior approach through either a midline or bilateral subcostal incisions was used

exclusively to resect pheochromocytomas. Today, CT, MRI, and nuclear scans permit preoperative

localization of tumor in 95% or more of cases, so that the surgical approach may be more directed using

a laparoscopic approach. Regardless of approach, important common principles include minimal

handling of the tumor, early isolation and ligation of the adrenal vein, and avoidance of capsular

rupture. Recurrence following resection of benign pheochromocytoma is infrequent, and its presence

indicates malignancy.

Recurrent, malignant pheochromocytoma can include locally advanced disease or metastasis to bone,

liver, lymph nodes, lungs, and the central nervous system. Treatment of malignant pheochromocytoma

involves resection of metastases when feasible and medical control of hypertension. Radiation therapy

may be helpful to ameliorate pain from bony metastases. Ablative therapy with 131-I MIBG may also

produce partial responses and palliation of hormonal symptoms. Radiofrequency ablation of hepatic and

bone metastases can be effective in selected patients. Combination chemotherapy with

cyclophosphamide, vincristine, and dacarbazine can also be effective. Overall 5-year survival for

patients with malignant pheochromocytoma ranges from 36% to 60%.

Metastasis to the Adrenal Glands

The adrenal glands are frequent sites for metastases from many cancers. Carcinoma of the lung and

breast account for most adrenal metastases; however, virtually any cancer including melanoma,

lymphoma, and kidney and ovarian carcinoma can spread to the adrenals. Autopsy series of patients

with carcinoma show that the adrenal glands are involved in more than 25% of cases. Among cancer

patients, 50% to 75% of newly discovered adrenal masses represent metastases. Usually, either a

primary site is obvious, or widespread disease is apparent. Biopsy of adrenal masses in patients with a

history of carcinoma may be performed after pheochromocytoma is excluded. Resection of isolated

adrenal metastases in select patients with long disease-free intervals from lung cancer, renal cell

carcinoma and melanoma can be considered, although subsequent extraadrenal disease usually develops.

Median survival after complete resection of isolated adrenal metastases from a variety of tumors ranges

from 13 to 60 months with actuarial 2- and 5-year survival of 40% to 50% and 20%, respectively.

Incidental Adrenal Mass

9 Clinically inapparent adrenal masses (also called adrenal incidentalomas) have become commonplace

over the past 20 years with the increased use of abdominal imaging such as CT and MRI. The estimated

prevalence of incidental adrenal neoplasms varies by population studied and method of detection.

Unsuspected adrenal masses are detected by CT in between 0.6% and 1.9% of healthy patients, a figure

that is somewhat lower than the estimated prevalence of up to 8.7% based on unselected autopsy data.

Patients with a prior history of malignancy have a prevalence of adrenal masses of up to 4.4%. Adrenal

masses increase in frequency with advancing age, ranging from 3% in midlife to 10% in the elderly. The

combination of an aging population and increased application of abdominal imaging promises to create

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a significant public health challenge.

Over the past 10 years, increased awareness of morbidity associated with subclinical hormone

overproduction as well the increased availability of minimally invasive, laparoscopic adrenalectomy has

resulted in a lower threshold for treatment of adrenal masses. The goal of evaluation is to distinguish

and remove those adrenal masses that are functioning or likely to be malignant versus those that are

neither and may be observed.

Expectations of the yield for the workup of adrenal masses may be informed by epidemiologic reports

and reports of pathologic findings in resected incidentalomas. Epidemiologic data indicate that up to

6.5% of incidentalomas are pheochromocytoma, 7% produce aldosterone, 0.035% produce cortisol, and

0.06% is carcinoma. A recent review of 44 reports describing over 3,000 such cases reported that 41%

were cortical adenomas, 19% were metastases from other primary cancers, 10% were adrenocortical

carcinomas, and 8% were pheochromocytomas, with the remainder including myelolipomas and cysts.

Diagnosis

The evaluation of incidental adrenal masses, previously considered controversial, can now be

standardized. Two simple questions must be answered: Is it functional? Is it malignant? The diagnostic

approach should proceed to answer these questions sequentially (Table 77-6). Current opinion is that all

asymptomatic patients with adrenal masses should be screened for pheochromocytoma,

hypercortisolism, and hyperaldosteronism (Algorithm 77-3).

Table 77-6 Diagnosis Summary of Tests for Evaluation of Incidental Adrenal Mass

All patients require a complete history and physical examination, biochemical evaluation of pertinent

hormones, and select imaging studies. Attention must be paid to episodes of hypertension, tachycardia,

and anxiety that suggest pheochromocytoma. Physical findings such as muscle wasting, purple striae,

hirsutism, and gynecomastia may suggest either Cushing syndrome or a virilizing tumor. Secondary

metastases from underlying malignancy must be considered and evaluated with appropriate history,

physical examination, and select tests including mammograms in women and chest radiography in all

patients, especially smokers.

Biochemical testing should routinely exclude pheochromocytoma, hypercortisolism, and

hyperaldosteronism. Pheochromocytoma is evaluated either by 24-hour urine collection for

catecholamines, metanephrines, and 3-methoxy-4-hydroxy-mandelic acid, or by plasma fractionated

metanephrines. Subclinical or clinically apparent Cushing syndrome is best evaluated with the overnight

1 mg dexamethasone suppression test. Hyperaldosteronism is best assessed by concurrent measurement

of serum or plasma aldosterone and PRA.

Imaging studies usually include cross-sectional imaging with either CT or MRI. CT is the best test for

identifying and characterizing most adrenal masses. Using a fast scanner and 1-m scanning intervals,

both adrenal glands can be identified in 97% to 99% of patients and lesions as small as 5 mm can be

readily identified. Currently, attenuation values expressed in Hounsfield units (HU) have better

performance than size or other criteria to differentiate adenomas from adrenal malignancy and

nonadenomas such as pheochromocytoma. Adenomas are usually lipid rich and have attenuation values

less than 18 HU on unenhanced CT, a threshold with high sensitivity and specificity (85% to 95% and

93% to 100%, respectively). Generally, further workup is unnecessary when an adrenal lesion has an

attenuation of less than 10 HU suggesting lipid-rich adrenal adenoma. A notable exception is lipid poor

adenoma, which has higher HU density. In these cases, rapid washout of intravenous contrast suggests

an adenoma. Using a 10- to 15-minute delayed enhanced CT, a washout value of 50% to 60% of the

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initial enhancement is used to distinguish adenoma from nonadenoma.

MRI can differentiate adenomas, metastases and pheochromocytomas, although the best MRI

technique for evaluating adrenal masses is complex and controversial. Adenomas usually show a loss in

signal intensity on chemical shift MRI because of high lipid content. Malignant masses tend to be bright

on T2-weighted images because of higher fluid content. Secondary metastases to the adrenal are

hypointense to liver on T1-weighted images and are brighter than liver on T2-weighted images.

Metastases also typically show strong contrast enhancement. Pheochromocytomas most often have low

lipid content and high water content, giving low T1 signal intensities and very bright T2 signal

intensities. Comparison of the adrenal mass to liver and spleen intensities on various sequences adds to

specificity and sensitivity of the test.

Algorithm 77-3. Diagnosis and management of the incidental adrenal mass. PRA, plasma renin activity; PAC, plasma aldosterone

concentration; HTN, hypertension; CT, computed tomography; MRI, magnetic resonance imaging; FNA, fine-needle aspiration.

Masses that appear cystic may be aspirated under CT guidance. Fine-needle aspiration biopsy may be

of value in patients with known extraadrenal malignancy; however, it is not indicated in the evaluation

of primary adrenal neoplasms and is contraindicated if pheochromocytoma is suspected.

Treatment

Resection is indicated for all functioning adrenal incidentalomas and those suspected of harboring

primary adrenal cancer. Size cutoff for resecting adrenal incidentalomas has drifted to include smaller

and smaller lesions. The prevalence of primary adrenal carcinoma in adrenal incidentalomas is related

to mass size. The risk of primary adrenal carcinoma is less than 2% in lesions under 4 cm while the

incidence rises to 25% for lesions larger than 6 cm. Lesions larger than 6 cm and smaller lesions with

suspicious criteria on imaging should be resected. Lesions smaller than 4 cm with benign imaging

characteristics should be followed. For lesions between 4 and 6 cm, either resection or observation is

acceptable. Decisions should not be based on size alone, but also on imaging characteristics including CT

attenuation values. Resection of secondary adrenal malignancy is not generally recommended except for

highly select patients.

Adrenal Insufficiency

Adrenal insufficiency reflects inadequate glucocorticoid and mineralocorticoid production by the

adrenals, either secondary to suppression of the HPA axis or by destruction or removal of the adrenal

glands. The most common causes of primary adrenal insufficiency are autoimmune adrenalitis,

infection, and gland replacement with metastatic disease. Chronic exogenous steroid use with HPA

suppression and surgical resection of adrenal glands are important causes of secondary adrenal

insufficiency.

Clinical signs and symptoms usually do not become manifest until at least 90% of the gland is

destroyed. Adrenal insufficiency usually occurs gradually unless the patient experiences stress which

may precipitate acute crisis.

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