Adrenal

Robert Udelsman

Anatomy

The adrenal glands are paired retroperitoneal organs located in close contact to the superior surface of either kidney. They are surrounded by a loose layer of areolar connective tissue and have multiple fibrous bands and vascular attachments through which they are associated with the superior poles of the kidneys. They are recognizable by their firm texture and chromate yellow color, which is distinctly darker than the pale retroperitoneal fat. The normal adrenal gland is slightly nodular and generally weighs between 4 and 5 g in the adult. The presence of adrenal nodules is not uncommon, and their frequency increases with age. The anatomical relationships of the adrenal glands are important and have significant surgical ramifications. The CT findings of the normal adrenal glands are easily visualized on most CT scans, and the width of each adrenal gland limb is similar to that of the nearby diaphragm. Their anatomical relationships have been summarized by Mihai and Farndon (Table 29.1). The location of the adrenal gland deep in the retroperitoneum has in the past made them relatively inaccessible. However, laparoscopic adrenalectomy has dramatically changed the surgical management of adrenal tumors. Each adrenal gland is supplied by small arterial branches that originate from three distinct sources. The major supplying vessels are the inferior phrenic artery, the aorta, and the ipsilateral renal artery. Occasional additional sources include the intercostal and ovarian vessels. The arterial branches ramify over the capsule of the gland and form a subcapsular plexus. The major source of adrenal medullary blood appears to be via the adrenal cortex from which blood rich in glucocorticoids flows from the cortical layers into the medulla. This intraadrenal “portal venous” circulation has significant physiological ramifications. The final pathway for the catacholamine epinephrine requires the enzyme phenylethanolamine N methyltransferase (PNMT), and glucocorticoids are required for this final step. Thus, there is significant functional interaction between the adrenal medulla and cortex. The venous drainage of the adrenal gland is more constant than the arterial supply. The right adrenal gland usually drains by one short vein, which empties directly into the vena cava. Accessory adrenal veins are not infrequently present. The left major adrenal vein is often joined by the inferior phrenic vein, which drains into the left renal vein. There may be associated small additional veins. Lymphatic drainage from the adrenal glands drains directly into adjacent, periaortic and paracaval nodes. These structures are important when operating for malignant adrenal lesions.3

Physiology

The adrenal gland is composed of two distinct organs, the adrenal cortex and the adrenal medulla. The cortex is divided into three functional zones: the outer glomerulosa, the intermediate fasciculata, and the inner reticularis. These three zones are associated with the production of mineralocorticoids, glucocorticoids, and sex steroids, respectively. Of these three hormone classes, the only one absolutely required for life is glucocorticoids. Glucocorticoids exert a myriad of effects on essentially every tissue in the body. A partial list of the effects of glucocorticoids is presented in Table 29.2. Cortisol is the major glucocorticoid in humans. The rate-limiting step in adrenal steroid synthesis, which is controlled by adrenocorticotropic hormone (ACTH), is the cleavage of the cholesterol side chain to yield p regnenolone. Glucocorticoids are secreted directly into the circulation immediately upon their synthesis. Cortisol circulates in both the bound form (95%) and in a free unbound state (5%). The free form passes into target cells by diffusion and binds to cytosolic receptors. All physiological actions of glucocorticoids are mediated through binding to steroid receptors, which are present in virtually every nucleated cell. The actions of glucocorticoids are both “permissive,” allowing other hormones to function in the basal state, as well as “regulatory,” which are observed under stress-induced conditions. The autonomic nervous system develops in parallel to the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal medulla is embryologically analogous to a peripheral sympathetic ganglia. The medullary chromaffin cells have rudimentary nerve fibers and the ability to synthesize, store, and secrete catecholamines. The primary secretory product of the adrenal medulla is epinephrine. The proximity of the adrenal medulla and the adrenal cortex results in a unique site of catecholamine-glucocorticoid interactions.

The biosynthetic pathway for catecholamines is demonstrated in Figure 29.2. Epinephrine constitutes approximately 80% of adrenal medullary secretion.

Adrenal Imaging

The adrenal glands are relatively inaccessible retroperitoneal organs that are surrounded by perinephric fat. Plain abdominal films have a very limited role in adrenal imaging. However, they can detect calcifications, especially in children who have had neonatal hemorrhage or have neuroblastoma. In adults, calcifications of the adrenal glands are highly suggestive of granulomatous disease including tuberculosis, histoplasmosis, and sarcoidosis. Ultrasonography can detect adrenal lesions and is a relatively inexpensive method to serially follow small adrenal adenomas. Adrenal ultrasound has a limited role for diagnostic purposes and is largely supplemented by computed tomography (CT) or magnetic resonance imaging (MRI) scans. Intraoperative ultrasound performed during laparoscopic adrenalectomy has proven to be a useful modality. It can identify the location of small adrenal glands and delineate their vasculature.

CT Scans

Computed tomography scanning of the adrenal gland has proven to be the diagnostic procedure of choice for most patients. Simple cysts and myelolipomas can be diagnosed with virtual certainty based on their CT characteristics. Intravenous contrast is generally not required, and a low attenuation value on an unenhanced CT scan can help differentiate benign (low density) from malignant lesions as well as metastases, which generally have a higher density. Lesions with low Hounsfield units (HU) are most likely benign, whereas lesions that have a HU density greater than 20 are more likely to be malignant. Accordingly, it has been suggested that a cutoff point of 30 HU should be accepted for discriminating malignant and benign lesions.

MRI Scan

Magnetic resonance imaging (MRI) has a significant role in the evaluation of adrenal tumors. Nonfunctioning adenomas appear on T2-weighted images like normal adrenal tissue. Functional adenomas tend to demonstrate a slightly increased signal intensity, whereas adrenal metastases or primary adrenal cortical carcinomas tend to be relatively bright. Enhancement on T2-weighted images is particularly useful for pheochromocytomas and therefore MRI appears to be the imaging study of choice in patients with suspected pheochromocytomas.

Radioisotope Scan

Iodocholesterol-labeled agents including 131I-6-_-iodomethyl- 19-norcholesterol (NP59) are incorporated into steroidogenesis pathways in the form of intracellular cholesterol and therefore have the ability to visualize functional adrenal cortical lesions. However, NP59 is not readily available at most institutions and dexamethasone pretreatment is required. These two factors limit its clinical utility. Meta-iodobenzylguanidine (MIBG) is frequently used for the evaluation of pheochromocytoma as well as neuroblastoma. 131I-MIBG and 123I-MIBG are concentrated in catecholamine storage vesicles and therefore are useful in suspected cases of pheochromocytoma. In cases of extraadrenal disease, which has a lower propensity for MIBG uptake, positron emission tomography (PET) utilizing 2-fluorine-18-fluoro-2-deoxy-D-glucose (FDG) may be useful.

Angiography

Angiography and venography were at one time more commonly employed for the evaluation of adrenal tumors. These procedures have been largely replaced by noninvasive imaging.

Pertucaneous Biopsy

Percutaneous biopsy of the adrenal gland can be performed under either CT or ultrasound guidance. However, there are very few appropriate indications for this procedure. A percutaneous biopsy cannot reliably distinguish between an adrenal adenoma and an adrenal carcinoma. The most common indication is in the setting of suspected metastatic disease to the adrenal gland. In such a case, when a fine-needle aspiration demonstrates nonadrenal malignant tissue the diagnosis of metastasis is confirmed. This procedure should never be performed in a patient until a biochemical workup has been completed to rule out a pheochromocytoma because sudden death has been reported following biopsy of unsuspected pheochromocytoma.

Incidentaloma

Adrenal “incidentalomas” are adrenal tumors discovered on an imaging study that has been obtained for indications exclusive of adrenal-related conditions. The frequent use of CT scans, which can detect adrenal lesions greater than 1 cm, has resulted in their detection in 0.35% to 5% of studies. The evaluation and decision paradigm for an incidentaloma hinges on three issues: (1) Is it functional? (2) Is it likely to be a malignant adrenal tumor? (3) Is it metastatic? The evaluation is focused on answering each of the foregoing questions.

Hormone Evaluation

All evaluations begin with a detailed history and physical examination. If symptoms or signs suggesting a functional adrenal neoplasm are detected, then, in addition to a routine screening evaluation, specific hormone studies are indicated. However, most patients are asymptomatic. The CT findings of a specific subset of adrenal masses including simple adrenal cysts and myelolipomas can be pathognomonic. In these instances, hormonal screening studies are not required. Screening studies are directed at three specific syndromes: pheochromocytoma, aldosteronoma, and Cushing's syndrome. Pheochromocytomas are rare. However, because the risk of complications associated with an occult pheochromocytoma is significant, virtually all investigators agree that all incidentaloma patients should be screened for catecholamine hypersecretion. Most commonly, urinary collections over 24 h are obtained in bottles containing acid. These collections are analyzed for metanephrines, vanillylmandelic acid (VMA), or fractionated catecholamines. The screen for aldosteronoma in the setting of an incidentaloma is often limited. If the patient is normotensive and not receiving hypertension or diuretic therapy and has a normal serum potassium (_3.5 mEq/l), then an aldosteronoma is very unlikely. If the patient does not satisfy these criteria, then an aldosteronoma evaluation is performed as delineated later in this chapter. Cushing's syndrome is important to consider in all patients with adrenal tumors. Patients with advanced Cushing's syndrome present with classic symptoms and signs of glucocorticoid excess and are therefore not difficult to diagnose. However, patients not uncommonly present with subtle stigmata of Cushing's syndrome or with occult or “subclinical” disease. In this situation the patient has an adrenal adenoma that has attained functional autonomy in its ability to secrete glucocorticoids but has not yet manifest findings of Cushing's syndrome. This silent but subtle hypercortisolism occurs in approximately 15% of patients with incidentalomas. It is important to rule out subclinical Cushing's syndrome for two reasons: (1) if one elects not to perform an adrenalectomy, then the endocrinopathy will continue and deleterious effects will occur, and (2) if one does perform an adrenalectomy, the contralateral adrenal will be suppressed, and if perioperative glucocorticoids are not administered the patient will be at risk for Addisonian crisis. It is important to recognize that an incidentaloma may represent a metastatic lesion in the adrenal gland. The majority of patients with metastatic disease to one or both adrenal glands have both a history of malignant disease and metastases to multiple additional sites. In the setting of widespread metastatic disease, the adrenal disease is not treated directly as it represents only a small focus of total tumor burden. Patients with bilateral adrenal metastases are at some risk for adrenal insufficiency. An important and unresolved issue in the management of incidentalomas is the determination of what size of adrenal tumor is in itself an indication for extirpation. In the absence of scientific trials an empiric approach has been employed. Virtually all experts agree that any lesion greater than 5 cm on initial presentation should be excised because of the risk of malignancy. Lesions less than 3 cm are generally followed with serial imaging studies. Several experienced investigators have recommended excision of all adrenal tumors greater than 4 cm. If one elects not to excise an incidentaloma, then a follow-up imaging study should be obtained at a relatively short interval (approximately 3 months) to determine if serial growth has occurred. Lesions that grow should be excised. An algorithm for the evaluation of incidentally discovered adrenal masses is depicted in Figure 29.3. It is based upon a systematic literature review and the acceptance of 4.0 cm as a size that is in itself an indication for adrenalectomy.

Hyperaldosteronism

Excessive secretion of aldosterone results in hypertension and hypokalemia. It may be caused by primary aldosteronism, an intrinistic abnormality of one or both adrenal glands. It can also be caused by excessive renin secretion, which results from a low effective arterial blood volume, in which case it is termed secondary aldosteronism. Primary aldosteronism is rare, with a prevalence among hypertensive patients estimated to range between 0.05% and 2%. Aldosteronomas occur in approximately 65% of patients with primary aldosteronism. They are almost always unilateral and are often less than 2 cm in size.

It is extremely important to distinguish a unilateral aldosteronoma from idiopathic hyperaldosteronism (IHA), which occurs in 25% of patients with primary aldosteronism and is caused by bilateral adrenal hyperplasia. In this case both adrenal glands contain multiple macro- and microscopic nodules. Importantly, unilateral adrenalectomy in the setting of IHA is not curative. Unfortunately, the distinction between aldosterone-producing adenoma (APA) and IHA can be difficult. Additional, but less common, surgically correctable causes of primary aldosteronism include primary adrenal hyperplasia and renin-response aldosterone-producing adenoma. Primary adrenal hyperplasia may be unilateral or bilateral, and the glands appear histologically like those seen in patients with IHA. The biochemical profile, however, is similar to that seen in an APA and unilateral adrenalectomy appears to be beneficial in patients with unilateral lesions. Renin-responsive aldostrone-producing adenomas appear biochemically like IHA, and they also respond to surgical resection. Adrenal cortical aldosterone-producing carcinoma is extremely rare and represents another surgically treatable form of primary aldosteronism.

Clinical Presentation

The signs and symptoms of primary aldosteronism are nonspecific and include hypertension and hypokalemia. The mean age at presentation ranges from 30 to 50 years, and it is twice as common in women. The hypertension is generally indistinguishable from that seen in the population with essential hypertension.

Screening for Primary Aldosteronism

The presence of spontaneous hypokalemia in a hypertensive individual strongly suggests the diagnosis. Unfortunately, the common use of diuretics, as well as antihypertensive agents including angiotension-converting enzyme inhibitors and spironolactone, interfere with the ability to establish the diagnosis. Most endocrinologists recommend discontinuation of all diuretic and antihypertensive therapy for at least 4 weeks before a diagnostic evaluation. If the patient's blood pressure requires control during this interval, prazosin can be used as it will not interfere with the workup. A wide variety of biochemical tests have been recommended, but there is no clear consensus as to which tests are the most appropriate. Hypokalemia, although highly suggestive of the diagnosis, should not be considered as a necessary criterion.

PLASMA ALDOSTERONE/RENIN RATIO

Excess autonomous secretion of aldosterone results in salt retention, hypertension, and suppression of plasma renin activity. However, single isolated measurements of either plasma renin or aldosterone are of limited diagnostic value. Because primary aldosteronism results in elevated aldosterone and suppressed plasma renin levels, simultaneous determination appears more useful and is less affected by physiological or pharmacological variables.

SALINE INFUSION TEST

The saline infusion test is used to demonstrate autonomous aldosterone secretion that does not decrease appropriately following sodium loading. Failure to suppress plasma aldosterone below 8.5 mg/dl after 2 l of intravenous normal saline is considered diagnostic of primary aldosteronism.

DISTINCTION BETWEEN APA AND IHA The majority of cases of primary aldosteronism are caused by either an APA (65%) or IHA (25%). It is important to discriminate between these as an APA is treated by unilateral adrenalectomy, whereas IHA is generally treated with spironolactone. A variety of biochemical and imaging studies are available to make this distinction (Table 29.3).

Localization

Once the biochemical criteria for an APA have been satisfied, the next step is tumor localization. High-quality CT scans have simplified this workup for the majority of patients. If a unilateral adrenal mass is detected and the contralateral adrenal gland is normal, then proceeding directly to unilateral adrenalectomy appears reasonable.

Treatment

There is an ever-expanding body of literature to suggest that laparoscopic adrenalectomy is the procedure of choice for aldosteronomas. This technique results in improvement in length of stay, morbidity, and costs. In addition the patient is able to return to normal activity in a much shorter interval. The traditional surgical treatment has required a unilateral total adrenalectomy. Recently, aldosteroma enucleation or subtotal adrenalectomy has been suggested as an equally effective technique.

Results

The surgical treatment of APA results in correction of hypokalemia in almost all cases. Hypertension is usually improved, but may persist, particularly if the patient has longstanding hypertension at the time of surgery. The incidence of persistent hypertension is approximately 30%. Risk factors associated with persistent hypertension include age greater than 50 at the time of surgery, male sex, and the presence of “multiple adenomas” or inappropriately diagnosed IHA.

Cushing's Syndrome

Harvey Cushing described eight patients in 1932 with moon facies, truncal obesity, hypertension, polyphagia, polydipsia, polycythemia, and pulmonary infections. Pituitary basophil adenomas were noted in autopsy in four of these patients, and he correctly associated this syndrome with pituitary adenomas. The most common cause of Cushing syndrome is iatrogenic administration of glucocorticoids. Endogenous Cushing syndrome is, for the most part, either ACTH dependent or ACTH independent (Table 29.4). The most common cause of endogenous Cushing's syndrome, accounting for nearly 85% of all cases, is Cushing's disease, glucocorticoid excess caused by a pituitary adenoma. The majority of ACTH-independent causes of Cushing's syndrome are adrenal in origin, consisting of adrenal adenoma and rare adrenal carcinomas. The management of ACTH-dependent Cushing's syndrome requires accurate tumor identification and extirpation whenever possible. In some circumstances, pituitary surgery is unsuccessful or the source of the ectopic ACTH secretion cannot be identified. In this situation bilateral adrenalectomy may be required to alleviate the sequela of life-threatening glucocorticoid excess.

The treatment of choice of ACTH-independent Cushing's syndrome is surgical resection. Patients with endogenous Cushing's syndrome caused by a unilateral adrenal tumor will have an elevated 24-h urinary free cortisol and 17-hydroxycorticosteroid levels. Because these tumors produce glucocorticoids in the absence of ACTH stimulation, the normal pituitary secretion of ACTH is suppressed. Therefore, an elevated plasma ACTH level in this setting is inconsistent with the diagnosis. The dexamethasone suppression test can be extremely useful in discriminating between ACTH-dependent and ACTH-independent causes of Cushing's syndrome. It is also crucial to carefully evaluate the imaging studies. In the setting of an adrenal adenoma one anticipates unilateral adrenal enlargement and a contralateral normal or slightly suppressed adrenal gland. In the setting of adrenocortical carcinoma, the ipsilateral adrenal gland should be significantly enlarged and may be associated with local tumor invasion. The contralateral adrenal gland should be normal in size. In addition, in the setting of an adrenal carcinoma one is likely to find elevated levels of adrenal androgens. Surgical treatment of adrenal causes of Cushing syndrome has undergone significant changes. Adrenal surgery can be performed safely with low morbidity and operative mortality in the 2% to 3% range. The recent advent of laparoscopic adrenalectomy has dramatically changed the management of these patients. Unilateral adrenalectomy is the treatment of choice for most patients with a tumor causing ACTHindependent endogenous Cushing's syndrome.

Bilateral Adrenalectomy

Bilateral adrenalectomy will continue to play a small but significant role in the management of selected patients with Cushing's disease. These include patients who have not been cured following pituitary resection, patients with primary pigmented nodular adrenal dysplasia, and patients with macronodular adrenal hyperplasia refractory to medical management with receptor blockers. Bilateral adrenalectomy is associated with significant long-term morbidity. These patients require lifelong replacement with both mineralocorticoids and glucocorticoids. Occult adrenal insufficiency may occur and can be life threatening.

Pheochromocytoma

Pheochromocytomas are rare tumors that arise from the neuroectodermally derived chromaffin cells. The majority of pathologists believe that all pheochromocytomas are of adrenal origin, and they refer to extraadrenal chromaffin tumors as paragangliomas, which may or may not be functional. However, most clinicians designate catecholamine-secreting tumors as either adrenal or extraadrenal pheochromocytomas. The majority of pheochromocytomas (90%) in adults are located in the adrenal gland. However, in children the incidence of extraadrenal pheochromocytomas is much higher (35%). Most pheochromocytomas (90%) are unilateral. However, the incidence of synchronous or metachronous pheochromocytomas are more common in patients with familial forms of pheochromocytomas. These syndromes and their associated findings are listed in Table 29.5. The majority of pheochromocytomas (90%) are thought to be benign. However, because the criteria for malignancy requires the demonstration of distant metastasis or direct invasion into surrounding organs, it is possible that surgical extirpation of a subset of presumptively benign pheochromocytomas results in excision of a malignant lesion that has not yet satisfied the requisite malignant criteria. Functional pheochromocytomas secrete a variety of vasoactive compounds either continually or episodically. Norepinephrine is the most common.

Clinical Manifestations

The classic presentation of a symptomatic pheochromocytoma is episodic attacks of headaches, diaphoresis, and palpitations. Although hypertension is commonly present during an attack, it is important to remember that between attacks approximately 50% of affected individuals are normotensive. The hypertension can result in stroke, renal insufficiency, and cardiac failure.

DIAGNOSIS

The most commonly employed biochemical screening tests require 24-h urinary collections for the measurement of vanillymandelic acid (VMA), metanephrines, or fractionated catecholamines. In addition, recent studies indicate that plasma levels of metanephrine and normetanephrine are sensitive and specific for pheochromocytoma. In select circumstances, additional pharmacological tests are required to yield an unequivocal biochemical diagnosis. However, the clonidine suppression test and the glucagon stimulation test are not routinely required.

Imaging

Once the diagnosis of a pheochromocytoma has been made, the next step is tumor localization using imaging studies including ultrasound, CT, MRI, and MIBG scans. MRI scans have several unique characteristics that make them the imaging study of choice. The MRI scan will enhance on T2- weighted images, and administration of i.v. contrast agents are not.

Treatment

Because of chronic hypersecretion of catecholamines, patients with pheochromocytomas are often severely volume contracted. In the past, when these patients underwent general anesthesia, it was not uncommon for them to experience severe hemodynamic instability. Accordingly, it is necessary to initiate a 1- to 4-week period of preoperative alpha-adrenergic receptor blockade. The most commonly used agent is the selective alpha-1-adrenergic receptor blocker, phenoxybenzamine. Occasional patients will also require beta-adrenergic receptor blockade because of breakthrough tachycardia. However, beta receptor blockade should not be administered in the absence of prior alpha receptor blockade because of the risk of unapposed alpha receptor-induced malignant hypertension.

The anesthestic and surgical care of these patients is critical and requires a concerted effort. Patients may experience both hypertension and hypotension (following tumor removal), and the anesthesiologist must be prepared to treat preciptious changes in blood pressure. Infusions of phentolamine and sodium nitroprusside are often required. In addition, anesthestic agents that lower the threshold of catecholamine- induced arrhythmias (halothane) or histamine release (morphine) should be avoided. Surgical treatment in the past required an open laparotomy with early control of the main adrenal vein and bilateral as well as extraadrenal exploration. This practice has been changed by the exquisite sensitivity of current imaging techniques and the use of laparoscopic adrenalectomy. At many institutions, laparoscopic adrenalectomy has become the procedure of choice.

Malignant Pheochromocytoma

Complete surgical excision is the only potentially curative therapy for malignant pheochromocytoma. However, the criteria for malignancy, invasion into adjacent tissue or distant metastases, are not always demonstrable at the time of surgery or on pathological review of the specimen. It is for this reason that initial total tumor extirpation as well as longterm follow-up are essential. Patients with malignant pheochromocytomas, even in the setting of metastatic disease, can have prolonged survival. The mean 5-year survival ranges from 30% to 40%. Surgical resection is indicated whenever feasible. The most effective chemotherapeutic regiment includes cyclophosphamide, vincristine, and dacarbazine. Although pheochromocytomas are not generally radiosensitive, treatment with 131I-MIBG has been shown to be of benefit in selected patients.

Familial Pheochromocytoma

Pheochromocytomas occur in association with several genetic syndromes including MEN2, von Hippel-Lindau disease, and von Recklinghausen's disease (see Table 29.5). When individuals from an affected family are identified they should undergo screening. If they are found to have biochemical evidence of catecholamine excess, localization procedures are indicated. Bilateral adrenalectomy has been generally recommended in familial patients because at the time of biochemical abnormalities at least bilateral adrenal medullary hyperplasia has already developed. Recent evidence suggests that it may be prudent to perform a unilateral adrenalectomy for macroscopically normal glands in the setting of familial pheochromocytomas. Serial follow-up is required.

Adrenocortical Carcinoma

Adrenocortical carcinoma is rare, with an incidence of 0.6 to 2 cases per million individuals per year. The prognosis is poor, and most series report a 5-year mortality between 55% and 90%. It accounts for approximately 0.2% of cancer deaths. Because of its rare incidence, controlled clinical trials have not addressed major issues in the diagnosis or treatment of this disease.

Presentation

The majority of patients (68%-80%) present with an endocrinopathy, most commonly Cushing's syndrome. Patients often have advanced disease at the time of presentation with almost 40% presenting with metastatic disease. The most common sites of distant metastases are the liver, lung, bone, and brain. However, local invasion into adjacent organs including the kidney, liver, diaphragm, spleen, pancreas, and vena cava are common at the time of diagnostics. A female predominance of at least 2:1 is noted in most series, and the mean age at presentation ranges from 30 to 50 years. The staging criteria for adrenocortical carcinoma are shown in Table 29.6. The majority of patients present with tumors greater than 5 cm in size with local invasion into adjacent organs with or without distant metastases (stage II or III).

Surgery is the mainstay of therapy and remains the only potential for cure. Aggressive local resection is indicated whenever feasible. Adjacent organs including lymph nodes, kidney, spleen, diaphragm, distal pancreas, liver, and vena cava are often resected in continuity with the primary tumor. MRI scans, especially MRI “angiograms,” are used when there is a suspicion of major vascular involvement. The role of adjuvant chemotherapy is somewhat controversial. The single most effective agent, mitotane (o,p_- DDD or 1,1-dichlorodiphenyldichloroethane), has been used since 1960 with moderate success. It is the only agent associated with long-term remissions and regression of metastases. The overall prognosis for adrenal cortical carcinoma remains poor. Mean survival rates are approximately 22 to 47 months. However, long-term survival can occur. Patients who develop locally recurrent disease can benefit from reoperative surgery.

Laparoscopic Adrenalectomy

There are multiple surgical approaches to the adrenal gland, including anterior transabdominal, flank, thoracoabdominal, supracostal, posterior, and the newer laparoscopic techniques via a transperitoneal or retroperitoneal approach. The traditional techniques of adrenalectomy are well described and are beyond the scope of this review. Laparoscopic adrenalectomy has already had a major impact on the management of adrenal neoplasms. In skilled hands this technique is appropriate for virtually all nonmalignant adrenal tumors. Most, but not all, endocrine surgeons agree that large tumors and clearly malignant tumors should be excised using an open technique.

Laparoscopic adrenalectomy appears to have distinct advantages compared to traditional open techniques. Avoidance of large incisions and decreased tissue trauma appears to decrease morbidity and mortality. Interestingly, even pheochromocytomas have been successfully managed with this technique. Several investigations have compared various anatomical approaches with laparoscopic adrenalectomy. It is now clear that in skilled hands laparoscopic adrenalectomy can be performed safely, resulting in decreased hospital stays, increased patient comfort, and a shorter interval until the resumption of normal activity.

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