Adrenal Adenoma and Carcinoma

Adrenal tumors present either as a result of their clinical symptoms or as incidental findings during radiologic imaging studies. The nomenclature “adrenal incidentaloma” describes adrenal tumors discovered inadvertently by radiologic imaging in the absence of clinical indication.
The objectives of this chapter are to discuss the various aspects of adrenal incidentaloma and adrenocortical carcinoma with regard to the epidemiology, natural history, investigation, diagnosis, and treatment with particular emphasis on their surgical management. Aldo-steronoma, pheochromocytoma, Cushing’s disease and syndrome, and laparoscopic adrenalectomy have been purposely excluded from this chapter because they are reviewed in detail in Chapter 1, Chapter 3, Chapter 4, and Chapter 132.
EPIDEMIOLOGY AND NATURAL HISTORY
The prevalence of adrenal incidentalomas is estimated to approach 2%,3 similar to the 1.9% figure of autopsy series, considering the increasing and widespread use of various radiologic images such as ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI).1,3,10 The incidence of adrenocortical carcinoma, on the other hand, is extremely rare, with an estimated annual rate of 0.00006% to 0.00017% in the population, i.e., approximately one in a million.4 Because the majority of adrenal carcinomas present late, and approximately half are hormonally active, it is calculated that the chance of detecting an adrenocortical carcinoma is one in 1,700 adrenal incidentalomas. Adrenocortical carcinomas occur in all age groups but are most common in the fifth to seventh decades of life.
The vast majority of adrenal incidentalomas are benign, remain asymptomatic, and have favorable outcome. On the other hand, the opposite is true in adrenocortical carcinoma, which is an aggressive malignant disease with ominous prognosis. The majority present late with local invasion, regional lymph node involvement, or distant metastases (stages III and IV) rather than early, i.e., confined to the adrenal gland (stages I and II). Approximately half of these tumors are hormonally active and release excessive secretions of glucocorticoids, estrogens, androgens, and, rarely, mineralocorticoids.
DIAGNOSIS
Biochemical Evaluation
Incidentally discovered adrenal tumors found by radiologic imaging can exhibit hormonal activity that initially may not be clinically apparent. Subsequent detailed endocrine clinical assessment may reveal, for the first time, clinical features suggestive of hormonal activity.
In these patients, further evaluation with appropriate biochemical testing is indicated according to the clinical suspicion. On the other hand, 15% of adrenal incidentalomas may be totally asymptomatic in a setting of subclinical hormonal activity. Much debate currently exists regarding the recommended biochemical evaluation in this latter group. It is to be emphasized that before embarking on an extensive and exhaustive biochemical evaluation, one must consider the expected detection rate and cost/benefit ratio of such an empirical approach. The overall low prevalence of hormonal activity in these adrenal incidentalomas and the type of hormonal dysfunction likely to be encountered call for a more selective approach. The calculated possibility of uncovering a pheochromocytoma or aldosteronoma is one per 15 adrenal incidentalomas, and for a glucocorticoid-producing adenoma or adrenal carcinoma, it is one per 1,700 to 2,800.9 It therefore seems reasonable to initiate biochemical screening for primary hyperaldosteronism with serum potassium first and for pheochromocytoma with urinary VMA, catecholamines, and metanephrines. Biochemical assessment for glucocorticoid and sex hormones should be reserved for patients with clinical features suggestive of such hormonal dysfunction.
Radiologic Evaluation
Computerized tomography (CT) is the standard radiologic imaging modality for adrenal tumors. It is utilized to delineate the anatomy and characterize the morphology of adrenal tumors. Although CT is reliable in the diagnosis of certain benign adrenal masses such as myelolipoma (Fig. 2-1) and simple cysts, its dependability in accurately differentiating between benign and malignant tumors is limited. Certain CT features suggestive of a malignant process include a tumor >6 cm, inhomogeneity, irregular contours, thickened walls, and calcification, as illustrated in Fig. 2-2.
Magnetic resonance imaging (MRI) is increasingly becoming a valuable radiologic tool in the evaluation of adrenal tumors. The MRI provides better visual clarity and resolution than CT imaging. Furthermore, the utilization of coronal planes in MRI (Fig. 2-3 and Fig. 2-4) offers superior images for understanding anatomy and for assessing vena cava involvement. More recent advances in the MRI technique have revealed encouraging results in distinguishing between benign and malignant adrenal tumors.2,5,6,7 and 8 This is achieved by the manipulation of fat and water MRI signals (chemical shift technique), which allows for the detection of microlipids within the tumor; these are a hallmark for benign adrenal adenomas. A significant subtraction of microlipids from the adrenal mass tissue on MRI as illustrated in Fig. 2-5 implies a benign adrenal adenoma. Conversely, lack of microlipid subtraction from the adrenal tissue, i.e., an area of hyperintensity, correlates with the presence of malignancy (Fig. 2-6). Further clinical experience and future refinements of this technique hold a real potential for MRI to become the imaging modality of choice in the evaluation of adrenal masses.

Fine Needle Aspiration Cytology
When clinical, biochemical, and radiologic evaluation fail to provide sufficient diagnostic information for an appropriate management decision, fine needle aspiration (FNA) cytology may play a role. Difficulty in tissue sampling, preparation, and interpretation can lead to false-negative results and limit its reliability. Potential indications for FNA cytology include atypical adrenal cysts, i.e., with thick, irregular walls or inhomogeneous fluid content, and differentiation between primary and metastatic deposits in individual cases.
Other Evaluation
Recent advances in noninvasive radiologic imaging such as CT and MRI have replaced the need for scintigraphy as well as NP-59 and MIBG, venography, and arteriography. The previously recommended use of venography in the assessment of inferior vena caval involvement has been superseded by the less invasive MRI. In rare circumstances, preoperative arteriography may have a role in delineating the vascular supply of large adrenal masses to aid in planning surgical resection.
INDICATIONS FOR SURGERY
Generally, there are two definitive indications for surgical excision: (a) symptomatic and hormonally active adrenal tumor and (b) adrenal carcinoma.
The dilemma arises in patients with asymptomatic adrenal tumors and unconfirmed diagnosis despite extensive evaluation. These constitute a gray zone into which fall the majority (>80%) of adrenal incidentalomas. Conservative management of these patients by observation and serial imaging poses certain concerns about the possibility of delayed or missed diagnosis of a biologically active lesion. To date, the controversies continue with no clear answers to the primary concern of whether or not a tumor is malignant.
As a result of the available epidemiologic data, the influence of radiologic features, and FNA cytology, certain guidelines are becoming available for management decisions in an attempt to minimize unnecessary surgical excisions without compromising the final outcome.
Surgical resection continues to be the treatment of choice for adrenal masses with features suggestive of malignancy such as large size (>6 cm), inhomogeneity, irregular contours, thickened walls, calcification, regional lymphadenopathy, lack of microlipids on chemical-shift MRI, and suspicious FNA cytology. Conservative management with observation and serial imaging is recommended for small tumors (<3 cm) with benign radiologic features and negative FNA cytology (Fig. 2-7).
In the midst of this spectrum reside the 3- to 6-cm tumors that pose the greatest diagnostic difficulties, especially when their imaging features and FNA cytology are equivocal.
The decision whether to observe or operate should be carefully tailored in each individual case, keeping in mind the possibility of small adrenocortical carcinoma. In patients with a metastatic deposit to the adrenal gland, the decision for surgical excision should be meticulously evaluated, and surgical excision should be limited to patients with solitary metastatic deposits in whom the primary malignancy has been adequately treated.
SURGICAL TECHNIQUE
Surgical Approaches to the Adrenal Gland
Adrenalectomy can be performed through a number of surgical approaches. These include posterior (with and without rib resection); posterior transthoracic; lateral flank (with and without rib resection); anterior transabdominal through subcostal, transverse, Chevron, or midline incisions; thoracoabdominal; and laparoscopic approaches. The choice of surgical approach is influenced by the tumor pathology, size of the adrenal tumor, and patient’s habitus as well as by the surgeon’s preference, familiarity, and experience with the surgical technique. This chapter focuses primarily on the lateral flank approach because the remaining surgical approaches are discussed in detail in the other chapters.
General Considerations
Regardless of the surgical approach, it is of paramount importance for the urologist to fully understand the anatomic position and relation, the blood supply of the adrenal glands, and the difference between the two sides. Each adrenal is a delicate and friable gland located superior to the upper pole of the kidney on the right but in a more superomedial position on the left. They lie adjacent to their respective great vessels, with the right posterolateral to the inferior vena cava and the left adrenal lateral to the aorta (Fig. 2-8 and Fig. 2-9). Other structures in close anatomic proximity include the duodenum on the right and the stomach, spleen, and pancreas on the left (Fig. 2-9). The sympathetic chain and ganglia are also closely located posteromedially to the adrenal glands, particularly on the left side.
The arterial blood supply originates from three sources: the inferior phrenic artery superiorly, the aorta centrally, and the renal artery inferiorly (Fig. 2-8). This rich blood supply enters the adrenal gland in a stellate fashion, primarily superomedially, while the base and the posterior surface of the gland often lack vasculature. Each adrenal has one central vein; the one on the right is short and drains directly into the inferior vena cava, and that on the left is longer and drains into the left renal vein.
The Posterior, Modified Posterior, and Posterior Transthoracic Approaches
The posterior surgical approach is performed through a subcostal incision, though resection of a rib (12th or 11th) is frequently required for better exposure. This approach was favored in the past in bilateral adrenal surgery for diagnostic exploration and total ablative adrenalectomy. However, with better preoperative radiologic diagnosis and localization of adrenal masses and the decline of bilateral surgical adrenalectomy in cancer therapy, the use of this approach has diminished. The posterior approach provides a limited surgical field, and the incidence of pleurotomy increases with rib resection, which may prove challenging and unsuitable for excision of large adrenal masses and in overweight patients. Nonetheless, it provides a relatively direct access to the adrenal gland, is potentially less traumatic, is well tolerated by patients, and causes less postoperative ileus. In our opinion, the posterior approach to adrenalectomy is best reserved for thin patients with small well-localized benign adrenal tumors in anatomically favorably positioned glands.
Modifications of the standard posterior approach have been utilized for excision of larger adrenal masses. Such modifications include an upward extension of the medical end of the standard posterior oblique skin incision, rib resection, and transthoracic accesses. A superior surgical exposure is achieved at the expense of more extensive dissection and the need for chest tubes postoperatively.
Lateral Flank Approach
The lateral flank approach offers better and larger operative exposure for excision of larger tumors in adrenal glands positioned in less favorable anatomic locations. In general, urologists tend to be more familiar with this approach because of its frequent utilization in renal surgery.
Following the administration of general anesthesia with endotracheal intubation, a Foley catheter is used to drain the bladder, and sequential compression devices (SCD) are placed on the legs. The patient is then placed in the lateral position with the flank over the flexion/kidney rest site of the operating table with the patient’s back close to the edge. Both arms are kept extended, with the contralateral one resting on an arm rest with an axillary roll and the ipsilateral arm on a stand adjusted to the appropriate height and angle. A pillow is placed between the legs, keeping the contralateral leg flexed, and the ipsilateral leg is allowed to remain straight. The kidney rest is then raised, and the table is flexed to 30 to 45 degrees (Fig. 2-10). The patient position is then further secured by the use of wide adhesive tape over the hip and shoulder.
Following skin preparation and draping, a flank skin incision is made along the rib extending from sacrospinalis muscle posteriorly to lateral border of the rectus abdominis muscle anteriorly. The incision is deepened through the subcutaneous fat layer, exposing the external oblique muscle anterolaterally and the latissimus dorsi muscle posteriorly, under which lies the internal oblique muscle and inferior part of the serratus posterior muscle. The muscles are incised with diathermy along the line of the incision to expose the rib, thoracodorsal fascia, and the transversus abdominis muscle. Two spring retractors are placed to retract the muscle edges and facilitate the exposure. The periosteum over the rib is incised and elevated using a periosteal elevator or diathermy. The tip of the rib is freed and gently retracted outward with the aid of a Kocher clamp to expose its undersurface. The rib is dissected off its bed along its entire length, starting at the tip. It is then transected at its proximal end with the aid of a guillotine rib resector. The use of diathermy instead of conventional periosteal elevators during rib dissection allows for better control of hemostasis and decreases the chance of accidentally injuring the neurovascular bundle or the pleura. The lumbodorsal fascia and the transversus abdominus muscle are incised, exposing the peritoneum and its preperitoneal fat. The peritoneum is bluntly dissected off the abdominal wall using the index finger in gentle sweeping motions, and the dissection is continued to free the undersurface of the rib bed. Starting anteriorly, the rib bed is carefully incised to complete the access into the flank. Careful attention should be practiced to avoid injury to the neurovascular bundle inferiorly, pleura, and diaphragm superiorly, and a Finochietto self-retaining retractor is then placed.
Once in the flank, the kidney is partially mobilized by blunt dissection of the overlapping peritoneum and colon off Gerota’s fascia. Crossing vessels along the dissection plane are coagulated or ligated to secure hemostasis as the dissection is continued medially toward the renal hilum. The renal vein is visualized laterally and inferiorly to further mobilize the lower pole of the kidney. The superior pole of the kidney and the adrenal gland are purposely kept attached together to aid in the dissection later; this allows the adrenal gland to be brought down by gentle inferior traction of the kidney and thus facilitates the identification of its vessels and surrounding attachments. The vessels and the surrounding attachments of the adrenal are then secured with 3-0 silk ligatures, surgical clips, or electrocautery, resulting in mobilization of the adrenal gland (Fig. 2-11 and Fig. 2-12). It is to be stressed that the adrenal vessels are small, short, and easily traumatized, especially on the right, thus demanding gentle retraction and careful dissection. Finally, unless simultaneous nephrectomy is not indicated, the adrenal gland is dissected off the upper pole of the kidney and removed (Fig. 2-13 and Fig. 2-14).
In the treatment of adrenocortical carcinomas, surgical treatment also necessitates additional en bloc radical nephrectomy. The renal vessels and ureter are therefore identified, ligated with 2-0 silk, and transected. The kidney is removed en bloc with its Gerota’s fascia and attached adrenal gland. Surgical excision of the regional lymph nodes is performed by removing the retroperitoneal tissue surrounding the adjacent great vessels. Drains are not used unless there is some residual bleeding. The flank musculature and fascia including the periosteum of the rib bed are closed in layers using running 0 polyglycolic (Dexon) or polygalactic polymer (Vicryl) sutures. Subcutaneous tissue is closed with interrupted or running fine (3-0) plain catgut sutures, and the skin is closed with standard skin staples.
Anterior Transabdominal and Thoracoabdominal Approaches
For large adrenal tumors, where a posterior or flank approach offers a limited and relatively inadequate exposure, the transabdominal or transthoracic surgical approach is a preferred alternative because of its superior operative exposure. The anterior abdominal approach can be performed through subcostal, transverse, chevron, or midline incisions. The use of these approaches is dictated by the size and pathology of the adrenal tumor as well as patient habitus and operator preference. In general, adrenocortical carcinomas are excised through such approaches to ensure ample exposure, control, and the ability to accurately stage the disease intraoperatively.
Laparoscopic Approach
The demand for minimally invasive alternative surgical therapies and for cost savings in our current health care system has initiated the concept of laparoscopic adrenalectomy. To date, the experience with this approach is limited to a few medical centers with specific interest in laparoscopic surgery. Technical difficulties, limited instrumentation, and the low volume of surgical adrenalectomies have restricted the utilization of this approach. Laparoscopic adrenalectomy is discussed in detail in Chapter 132.
OUTCOMES
Complications

Preoperatively, patients with hormonally active adrenal tumors should undergo careful preparation to control their hormonal dysfunction and optimize their fluid and electrolyte status. These are essential prerequisites in pheochromocytoma, aldosteronoma, and Cushing’s syndrome. In pheochromocytoma, a blockers are used to decrease vascular tone and control hypertension while intravenous fluid hydration is used to counteract the potential of vasodilation and vascular collapse on excision of the tumor. In aldosteronoma, hypokalemia is treated with spironolactone and potassium supplements. Such preparation should be instituted for a number of weeks to ensure adequate correction and recovery of the suppressed zona glomerulosa of the contralateral adrenal gland. In glucocorticoid-secreting adrenal tumors, glucocorticoid is given intraoperatively and continued postadrenalectomy because the zona fasciculata of the contralateral adrenal function may be suppressed by negative feedback from the excessive glucocorticoid secreted by the tumor. Careful monitoring during the postoperative period is mandatory to recognize and correct such potential adverse events. It should also be emphasized that healing in patients with Cushing’s syndrome may be slow because of the compromised tissue status from excessive glucocorticoid and associated glucose intolerance and the increased potential risks for wound infection, dehiscence, and the development of postoperative incisional hernia. The use of prophylactic antibiotics, meticulous wound closure, and careful postoperative wound care should decrease the risk for such adverse events. Early ambulation and aggressive pulmonary toilet are encouraged to minimize the development of postoperative respiratory complications as well as venous thrombosis and pulmonary embolism.
Intraoperatively, injury to adjacent structures may result, including a pneumothorax, which can be recognized by the formation of bubbles at the site of pleurotomy. Treatment includes closure of the pleural tear with running 4-0 chromic catgut suture and removal of the air and fluid from the pleural cavity through a soft catheter at time of closure. The use of suction or an underwater seal system during hyperinflation of the lung by the anesthesiologist aids in accomplishing this task. Rarely, a chest tube is required for larger pneumothorax (greater than 10%) or when respiratory compromise results. Careful follow-up with serial chest x-rays is needed to ensure resolution of the pneumothorax.
Other structures at risk for injury during adrenalectomy include the kidney, spleen, liver, and pancreas. A tear of the renal capsule may result from forceful retraction of the kidney during dissection and may be treated with gentle tamponading in minor injuries; larger tears may require repair by suturing. Splenic capsular injuries may also occur as a result of retraction or direct dissection, and the use of pressure tamponade is usually sufficient, though occasionally hemostatic gel packing, splenic repair, cauterization with an argon beam coagulator, or even splenectomy may be indicated. Liver injuries may also occur through the same mechanism and should be handled by hemostatic gel packing or repair. Injuries to the pancreas and subsequent pancreatic inflammation may occur during dissection at the region of the upper pole of the left kidney, leading to the postoperative pancreatitis. Rarely, however, a more substantial injury may result in fulminant pancreatitis and significant pancreatic leak and fistula.
Avulsion of the adrenal vessels, especially the delicate central veins, can lead to significant bleeding. Hemostasis is secured by packing and suture ligation. With all such injuries in which there is a potential of delayed bleeding, the use of postoperative drains is recommended.
Results
Generally, convalescence of patients undergoing adrenal surgery is surprisingly smooth. Careful preoperative preparation of the patient, meticulous intraoperative surgical technique, and proper postoperative care are mandatory for successful outcome and complication-free recovery.
The prognosis of adrenalectomy in benign adrenal disease is most favorable once the tumor is completely excised and recovery is uneventful. Complete cure from the disease process and return to normal function are expected in the majority of patients.
The prognosis of adrenalectomy in malignant disease, however, is variable depending on the stage of the disease and on whether or not complete surgical excision is achieved. The potential for a cure can be achieved only in early-stage adrenocortical carcinoma on complete excision of the disease without tumor spillage or positive surgical margins. The 5-year survival in early (stage I or II) adrenocortical carcinoma is 50%, which drops to 5% to 10% in the advanced (stage III or IV) disease.

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