Case Files Surgery, (LANGE Case Files) 4th Ed.

SECTION II. Clinical Cases

CASE 44

A healthy 53-year-old woman was involved in a low-speed automobile collision and brought to the emergency department 4 weeks ago. Because the patient’s physical examination revealed mild abdominal tenderness, she underwent a computed tomographic (CT) scan of her abdomen that revealed an incidental 3.5-cm solid mass in the left adrenal gland. The patient was discharged from the emergency department with instructions to follow up for an outpatient evaluation of the left adrenal mass. During her office visit, she indicates she is feeling well and is asymptomatic. Her heart rate is 70 beats/min and blood pressure 138/82 mm Hg. Her physical examination reveals no abnormal findings.

Images What is the differential diagnosis for an incidental adrenal mass?

Images What are the important elements of the history and physical examination in a patient with an adrenal mass?

Images What is the most likely diagnosis?

ANSWERS TO CASE 44: Adrenal Incidentaloma and Pheochromocytoma

Summary: A 53-year-old woman is found to have an incidental 3.5-cm solid adrenal mass.

• Differential diagnosis: May include a variety of primary malignant tumors, metastatic tumors, and benign functioning and nonfunctioning tumors.

• History and physical examination: The history should describe symptoms of hypertension, previous malignancies, prior endocrinopathies, and previous imaging studies, as well as family medical history. The physical examination should include an abdominal examination and a blood pressure reading, and the patient’s general appearance should be noted.

• Most likely diagnosis: Nonfunctioning adenoma.

ANALYSIS

Objectives

1. Learn the prevalence of clinically inapparent adrenal masses otherwise referred to as adrenal incidentalomas.

2. Become familiar with nonfunctioning and functioning adrenal tumors as well as the other clinical entities that may manifest as an incidentaloma.

3. Learn the diagnostic evaluation and management of an adrenal incidentaloma.

4. Become familiar with the clinical presentation of a patient with pheochromocytoma.

5. Learn to outline a diagnostic plan for pre-, intra-, and postoperative treatment of a patient with a pheochromocytoma.

APPROACH TO: Adrenal Incidentalomas

CLINICAL APPROACH

The term “adrenal incidentaloma” refers to a clinically inapparent adrenal mass that is discovered inadvertently in the course of diagnostic testing for other conditions. Incidental adrenal masses are found in 0.7% to 4.3% of patients undergoing abdominal CT scans and in 1.4% to 8.7% of patients at autopsy. Most adrenal incidentalomas are nonfunctioning adenomas, accounting for 55% to 94% of all cases. Functioning tumors, which include pheochromocytoma, aldosterone-producing adenoma, and cortisol-producing adenoma, are less common. Other adrenal tumors that can appear as incidentalomas are ganglioneuroma, adrenocortical carcinoma, and metastases. The differential diagnosis also includes myelolipoma, cysts, and hemorrhage, which are entities that can be diagnosed on the basis of CT criteria alone. An adrenal hematoma is not an infrequent finding in a patient who sustains abdominal trauma, and the diagnosis is confirmed with resolution of the mass on follow-up CT scanning.

The evaluation of a patient with an adrenal incidentaloma consists of obtaining a history, performing a physical examination, and making a functional and anatomic assessment of the adrenal mass. (See Table 44–1.) Specific signs and symptoms of excess catecholamines, aldosterone, cortisol, and androgens should be actively sought in the history and on physical examination. At minimum, patients should be asked about a history of hypertension and whether or not they have been experiencing headaches, palpitations, profuse sweating, abdominal pain, or anxiety. All patients should be questioned about a prior history of malignancy. When present, adrenal masses are metastases in up to 75% of patients. In addition to obtaining a resting heart rate and a blood pressure reading, patients should be examined for features suggestive of Cushing syndrome such as truncal obesity, moon facies, thin extremities, prominent fat deposition in the supraclavicular areas and the nape of the neck, hirsutism, bruising, abdominal striae, and facial plethora.

Table 44–1 • BIOCHEMICAL EVALUATION OF PATIENTS WITH ADRENAL INCIDENTALOMA

Images

The functional assessment consists of the following: measurement of plasma-free metanephrine levels; a 24-hour urine collection for detection of vanillylmandelic acid (VMA), metanephrine, and normetanephrine to evaluate for pheochromocytoma. Measurement of aldosterone and plasma renin activity can be performed to evaluate for an aldosterone-producing adenoma, where an aldosterone-renin ratio of greater than 30 is suggestive of hyperaldosteronism. An overnight 1-mg dexamethasone suppression test (DST) is useful during the initial evaluation for hypercortisolism.

Once it has been determined whether an adrenal mass is functioning or nonfunctioning, the next step is an anatomic assessment, preferably with unenhanced CT or magnetic resonance imaging (MRI). Positron emission tomography (PET) scanning is used for the evaluation of an adrenal mass in a patient with a known extra-adrenal cancer because it is of value in separating benign lesions from metastases. It is also important in excluding the presence of other metastases. Myelolipomas, cysts, and hemorrhage of the adrenal gland can be identified on the basis of CT criteria alone. However, certain imaging characteristics are suggestive of adrenocortical carcinoma, including irregular margins, inhomogeneous density, scattered areas of decreased attenuation, and local invasion. Other CT criteria that increase the probability of malignancy include large tumor size and tumor enlargement over time. Primary adrenocortical carcinomas are rare, and the majority of them are 6 cm or greater. The two CT characteristics have been reported to be highly specific for adrenal adenomas and can be applied to rule out adrenal malignancies, and these are adrenal glands exhibiting Hounsfield units less than 10 during noncontrast CT and early contrast washout during a CT with intravenous contrast (defined as >60% contrast clearance at 10-15 minutes after contrast injection); any tumor that exhibits one or both of these CT features has extremely low probability of being malignant and therefore can be managed with observation only (high negative predictive values).

For nonfunctioning tumors of the adrenal gland, selecting a tumor size for which surgery will be recommended requires a determination of the risks and benefits. The larger the size of threshold for surgery, the lower the number of unnecessary operations on patients with benign disease; however, rare patients with small adrenocortical carcinomas will be missed. The smaller the tumor threshold, the greater the likelihood that all carcinomas will be resected but at the expense of performing increasing number of unnecessary operations for patients with nonfunctioning, benign tumors. No consensus exists for a recommended size cutoff for surgery. In patients with adrenal incidentaloma, surgery is recommended for all functioning tumors, nonfunctioning tumors 4 cm or greater, tumors less than 4 cm that are enlarging (growth of >0.8-1.0 cm during a 3- to 12-month period), tumors of any size with imaging characteristics suggestive of carcinoma, and a solitary adrenal metastasis.

Treatment in Patients with Other Malignancies

The adrenal gland is well recognized as a site of metastasis. The most common tumor metastasizing to the adrenal gland is lung carcinoma. Other tumors include carcinoma of the breast, kidney, colon, and stomach, and melanoma. The patient with adrenal incidentaloma and a prior history of malignancy should undergo a biochemical assessment to exclude a functioning tumor. Whole-body PET scanning is performed in patients with a nonfunctioning tumor to exclude the presence of other metastases. Surgery is recommended for a solitary lesion of 4 cm or greater. Fine-needle aspiration (FNA) biopsy is reserved for a solitary nonfunctioning lesion smaller than 4 cm because the result will alter treatment. Patients with negative results from an FNA biopsy are treated nonoperatively. Finally, nonsurgical treatment is recommended for patients with diffuse metastases (Figure 44–1).

Images

Figure 44–1. Algorithm for the evaluation of patients with an adrenal incidentaloma. CT, computed tomography; DST, dexamethasone suppression test; FNA, fine-needle aspiration; MRI, magnetic resonance imaging.

Follow-up

A patient with a nonfunctioning adrenal incidentaloma smaller than 4 cm usually undergoes follow-up CT scans at 3 and 15 months. If there is no change in the size of the mass, the patient is followed annually by reviewing the history and performing a physical examination. Repeated biochemical testing is reserved for abnormal findings from the history or the physical examination. A change in size greater than 1 cm may prompt adrenalectomy.

APPROACH TO: Pheochromocytoma

Pheochromocytoma is a tumor that most commonly arises from the chromaffin cells of the adrenal medulla and secretes catecholamines. Pheochromocytoma is known as the “10% tumor” because 10% are bilateral, extra-adrenal, multiple, malignant, or familial. The hallmark clinical manifestation of pheochromocytoma is hypertension that can be either paroxysmal or sustained. Headache, palpitations, and profuse sweating are other common manifestations. Anxiety and abdominal pain may also occur. Because of the increasing application of CT imaging, up to half of the patients with pheochromocytoma are identified during biochemical testing for clinically silent incidentaloma.

The diagnosis of pheochromocytoma usually requires a demonstration of excess catecholamine production by one of two methods: a 24-hour urine collection to test for metanephrine, normetanephrine, and VMA and/or measurement of plasma-free metanephrine levels. Measurements of plasma-free metanephrine levels have a sensitivity of 99% and a specificity of 89% and as a result have been advocated by some as the initial biochemical test for the diagnosis of pheochromocytoma.

Imaging and Localization

Once a pheochromocytoma has been diagnosed by biochemical studies, tumor localization is the next step. Preoperative imaging studies are also important to exclude multiple, bilateral, or extra-adrenal pheochromocytomas. Abdominal CT imaging and MRI have at least 95% sensitivity in detecting an adrenal pheochromocytoma. A pheochromocytoma usually appears bright on a T2-weighted MRI. Both CT imaging and MRI have a specificity of as low as 50% in some studies related to the high frequency of adrenal masses that are not pheochromocytomas. An iodine-131 metaiodobenzylguanidine (MIBG) scan is usually obtained for confirmation of pheochromocytoma because of its superior specificity of 90% to 100%. PET imaging can be used when conventional imaging studies cannot localize the tumor.

Patient Preoperative Preparation

A preoperative chest radiograph should be obtained for all patients because the lung is one of the most common sites for metastasis. An electrocardiogram and an echocardiogram are frequently useful because chronic catecholamine excess may cause cardiomyopathy. Preoperative blood pressure control is essential to minimize the risk of a hypertensive crisis. The preferred method is to administer an α-adrenergic–blocking agent 1 to 2 weeks before surgery. This allows for relaxation of the constricted vascular tree and correction of the reduced plasma volume, which helps prevent the hypotension that can often occur following tumor removal. A β-adrenergic–blocking agent is added to oppose the reflex tachycardia associated with α-blockade. In general, administration of a β-blocking agent should not be started without prior α-blockade because this may precipitate a hypertensive crisis related to unopposed α-receptor stimulation.

Traditionally, phenoxybenzamine has been the preferred α-adrenergic antagonist. α-Methyl-p-tyrosine, which is often used in combination with phenoxybenzamine, competitively inhibits tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. Newer, selective α1-blocking agents have also been used with good results.

Surgical Concerns

The intraoperative management is critical because of the danger of large fluctuations in blood pressure, heart rate, and fluid balance. Continuous blood pressure monitoring usually is accomplished with an arterial line, and central venous and Foley catheters are inserted for volume assessment and intravenous fluid replacement. An intravenous nitroprusside continuous infusion is often administered for the control of hypertension, and a short-acting β-blocker, such as esmolol, is used to control any tachycardia. Adrenalectomy can be accomplished either laparoscopically or through an open technique. Acute hypotension may occur following excision of a pheochromocytoma related to sudden diffuse vasodilatation. Continuous intravenous Neo-Synephrine is used when the blood pressure fails to respond to fluid administration. Postoperatively, a normotensive state is achieved in approximately 90% of patients following tumor excision.

Follow-up

Because histopathologic studies cannot always identify whether a tumor is benign or malignant, all patients are followed for life. In general, plasma-free metanephrine levels are measured 1 month after surgery and at yearly intervals thereafter.

COMPREHENSION QUESTIONS

44.1 A 44-year-old otherwise healthy man has a 3-cm left adrenal mass found during CT evaluation for acute appendicitis. Following his appendectomy, a serum metanephrine level during his hospitalization revealed mild elevation in value. Which of the following is the most appropriate next step?

A. A 24-hour urine collection for VMA, metanephrine, and normetanephrine

B. MIBG scan

C. CT-guided needle biopsy of the adrenal gland

D. Alpha blockage for 1 week followed by laparoscopic adrenalectomy

E. Monitor the lesion with CT scans annually

44.2 A 3.5-cm right adrenal mass was discovered incidentally on an abdominal CT scan obtained for a 62-year-old man who was a victim of motor vehicular trauma. His medical history was notable for a right upper lobe lung resection 3 years previously for a stage I carcinoma. He is asymptomatic. Which of the following is the next most appropriate step in the evaluation?

A. FNA biopsy of the adrenal mass.

B. Repeated CT scanning in 3 months.

C. A functional assessment of the adrenal mass.

D. MRI of the adrenal gland.

E. Perform a PET scan to look for other sites of possible metastatic disease.

44.3 For which of the following patients is observation alone appropriate?

A. A 53-year-old healthy man with a 8-cm nonfunctioning left adrenal mass

B. A 46-year-old man with a history of hypertension and unexplained hypokalemia

C. A 32-year-old woman with elevated serum metanephrines and urinary VMA, metanephrines, and an asymptomatic 2-cm right adrenal mass

D. A 66-year-old man with a history of malignant melanoma on the leg at age 50, who presents with a newly diagnosed 4-cm right adrenal mass

E. A 44-year-old woman with a 8-cm left adrenal mass that appears to be a myolipoma based on CT

44.4 Which of the following is the most appropriate management for an 85-year-old nursing home resident, with severe dementia and congestive heart failure (CHF), and a 6-cm left adrenal mass?

A. Evaluate for the tumor for functionality and treat with laparoscopic adrenalectomy.

B. Evaluate the tumor for functionality and perform CT-guided biopsy.

C. Expectant management.

D. Medically optimize the patient and perform laparoscopic adrenalectomy.

E. Monitor the lesion with repeat CT scan every 6 months.

44.5 Which of the following statements regarding adrenalectomy for a pheochromocytoma is most correct?

A. It results in blood pressure improvement, but blood pressure rarely normalizes.

B. It corrects hypertension only in patients with benign disease.

C. It may lead to profound intraoperative hypotension.

D. It should be reserved for patients with hypertension refractory to drug therapy.

E. Preoperative management is not needed if laparoscopic surgery is planned.

44.6 Which of the following imaging studies has the highest specificity when used to confirm the presence of a pheochromocytoma?

A. MIBG imaging

B. CT imaging

C. MRI

D. PET

E. Ultrasonography

ANSWERS

44.1 A. A 24-hour urinary collection for VMA, metanephrines, and normetanephrine is needed in this patient to confirm the diagnosis of pheochromocytoma. While a normal serum metanephrine level has a high negative predictive value for the absence of pheochromocytoma, elevated serum values do not always indicate the presence of a pheochromocytoma, and the possibility of a pheochromocytoma needs to be further explored with the more specific urinary catecholamine analyses. If the biochemical analysis confirms pheochromocytoma, the lesion should be removed rather than observed.

44.2 C. The initial step in evaluating an adrenal mass is performing functional studies. The presence of an adrenal mass in a patient with a prior history of early-stage lung cancer cannot be assumed to be metastatic disease.

44.3 E. CT is accurate for the diagnosis of myolipoma of the adrenal gland. To be more complete, it is not unreasonable to obtain biochemical studies to rule out functional adrenal adenoma and pheochromocytoma in this patient. The patient with a prior history of melanoma may have an adrenal metastasis and needs biochemical evaluations first to rule out the usual causes, followed by biopsy of the mass. The patient with hypertension and unexplained hypokalemia needs biochemical analysis to rule out aldosterone-producing adrenal adenoma.

44.4 C. Expectant management is acceptable for this patient with severe comorbidities and asymptomatic adrenal mass. While the possibility of an adrenocortical carcinoma exists in this patient, the risks of treatment would exceed the potential benefits associated with further diagnostic studies and/or treatment.

44.5 C. Excision of a pheochromocytoma may result in immediate intraoperative hypotension. Preoperative treatment of the patients with α-blockers is critical prior to laparoscopic and open adrenalectomy.

44.6 A. An MIBG scan is highly specific in confirming pheochromocytoma.

CLINICAL PEARLS

Images Assessment of functional studies is the first step in the evaluation of any patient with an adrenal mass.

Images The functional assessment consists of evaluation for pheochromocytoma, aldosterone-producing adenoma, and a cortisol-producing tumor.

Images Biopsy of an adrenal mass is indicated only when the mass is suspected of being a metastatic lesion.

Images The most common tumor metastasizing to the adrenal gland is lung carcinoma. Other tumors include carcinoma of the breast, kidney, colon, and stomach, and melanoma.

Images Once a pheochromocytoma is diagnosed, CT imaging is the initial test used to localize the tumor. An iodine-131 MIBG scan is usually obtained for the confirmation of pheochromocytoma because of its superior specificity of 90% to 100%.

Images Pheochromocytoma is known as the 10% tumor because 10% are bilateral, extra-adrenal, multiple, malignant, or familial.

Images During surgery, there is significant danger of large fluctuations in blood pressure, heart rate, and fluid balance. Notably, acute hypotension may occur following excision of a pheochromocytoma related to sudden diffuse vasodilation.

REFERENCES

Mazzaglia PJ, Miner TJ. Adrenal incidentaloma. In: Cameron JL, Cameron AM, eds. Current Surgical Therapy. 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:565-570.

Silberfein E, Perrier ND. Management of pheochromocytoma. In: Cameron JL, Cameron AM, eds. Current Surgical Therapy. 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:579-584.

Young WF. The incidentally discovered adrenal mass. N Engl J Med. 2007;356:601-610.