Philip W. Smith and John B. Hanks

Indications and Contraindications

Adrenal masses are common and are frequently found incidentally on imaging obtained for other reasons.⁷ The workup of an adrenal mass is straightforward and is focused on determining if a mass is functional or may represent malignancy, both indications for adrenalectomy (Table 15-1). The specifics of this workup are discussed in detail elsewhere in this text. Although the majority of adrenal masses are benign, the finding of malignant adrenal masses is not uncommon, and as many as 15% of incidentally found adrenal masses are functionally active.⁸ Benign adrenal masses include the nonfunctioning (“incidentaloma”) and the functioning adrenal mass (Conn’s Syndrome, Cushing’s tumor, pheochromocytoma, or an androgen-secreting tumor). Primary malignancies of the adrenal may have their own characteristic imaging finding; however, this is often difficult to determine with certainty preoperatively, and size of the mass is used as an important predictor. A final class of adrenal masses includes metastatic lesions.

Much of the workup and diagnostic decision making depends on biochemical studies and image review (e.g., CT, MIBG, MRI, CT, arteriogram, PET, or other specialized studies). Fine-needle aspiration biopsy has very limited application in the evaluation of adrenal lesions, unlike its utility in thyroid nodules. The primary use of fine-needle aspiration is for suspicion of an extraadrenal malignancy metastatic to the adrenal. Fine-needle aspiration of an adrenal mass should never be considered until completing a workup for pheochromocytoma, because inadvertent fine-needle aspiration of such a lesion may lead to catastrophic, uncontrolled hypertension.

Of the benign lesions mentioned, pheochromocytoma has an increased chance of being bilateral or ectopic. Careful evaluation should be made prior to the initial operation, documenting the location of ectopic tissue. Previously, MEN2 patients underwent bilateral adrenalectomy and retroperitoneal exploration. In 1993, Wells and colleagues advocated that if a unilateral lesion is found, it may be reasonable to resect it, followed by surveillance of the remaining adrenal.⁶ Only 50% of patients with unilateral pheochromocytoma in the MEN2 population will require contralateral adrenalectomy within 5 years, thereby decreasing their exposure to exogenous corticosteroid replacement for that time. This allows for less invasive, more direct approaches, including flank incision (and later, laparoscopy), with greatly reduced morbidity and mortality.

Contraindications to adrenal surgery after appropriate selection are relatively few. It has been emphasized that prior to considering resection, several factors must be taken into account. For example, a 2-cm, nonfunctioning incidentaloma should not (in general) be surgically removed, whereas a 6-cm lesion should.⁹ A 2-cm functioning tumor should be removed, whereas a 2-cm metastasis to the adrenal should be carefully considered with regard to prognosis. An asymptomatic angiomyelolipoma of almost any size need not be resected if the diagnosis is certain. Therefore, although the surgical capability to perform adrenalectomy is usually available, it must be tempered by presurgical judgment. If the laparoscopic approach is to be considered, it is clear that experience is needed both in endocrine surgery and in laparoscopy. Caution should be used in the appropriate choice of technique for adrenal or retroperitoneal procedures.

Laparoscopy has emerged as the standard for surgical removal of most lesions of the adrenal gland.3–5 Although no prospective randomized trial has been reported comparing laparoscopic adrenalectomy to open adrenalectomy, in multiple reviews, laparoscopy has proven to be as safe and effective as the open approach and offers less pain, shorter hospital stay, and more rapid convalescence.⁵ Gagner et al. had suggested that increased intraoperative catecholamine secretion occurs during laparoscopic surgery, possibly related to CO₂ insufflation.¹⁰ Other studies have not shown that CO₂ had any different effect than helium insufflation, and most recent studies have confirmed the intraoperative safety of the technique.¹¹

Metastatic or regionally advanced carcinoma of the adrenal, or the presence of regionally metastatic pheochromocytoma, makes the laparoscopic approach less appropriate.¹² Such a clinical situation might require en bloc resection, possibly involving kidney or other organs as well as regional lymph nodes. Despite advances in minimally invasive techniques, it still is believed that adrenal masses that demonstrate evidence of local invasion should be approached with an open resection, and reported series of laparoscopic adrenalectomy have excluded these patients.

The size of the adrenal lesion may affect the choice of operative approach. There are two primary concerns regarding resecting large adrenal lesions through minimally invasive techniques. The first is the technical difficulty of safely dissecting and removing bulky lesions. The second major concern is the possibility of laparoscopically resecting a known or unknown adrenocortical carcinoma, which remains a debated practice. The likelihood of an undiagnosed lesion harboring malignancy increases dramatically with the size of the lesion. According to the NIH consensus statement for the management of undiagnosed adrenal masses, the incidence of adrenocortical carcinomas increases from 2% in lesions ≤40 mm, to 6% in lesions 41 to 60 mm, to 25% in lesions >60 mm.¹³

Adrenocortical carcinomas are rare and have poor prognoses, with 12% to 38% 5-year survival.¹⁴ Complete resection offers the only hope of cure (see Chapter 11). Therefore, patients with carcinomas often require more extensive resection, which may include local lymph nodes, kidney, spleen, and/or partial resection of the pancreas or liver. The standard approach for documented adrenal malignancy has been an open laparotomy. Early, limited reports of laparoscopic resections of primary adrenal malignancies were associated with very high rates of early recurrence, including in laparoscopic port sites as well as peritoneal carcinomatosis.¹⁵ It was believed that insufflation, which is necessary for laparoscopy, contributed to disease spread. This belief now has been replaced by an understanding that the operation must follow basic oncologic principles regardless of the technique employed for resection. As additional experience has accumulated, improved outcomes are now reported with laparoscopy for primary adrenal malignancy.¹⁵ Table 15-2 summarizes 15 publications that included laparoscopic resections for primary adrenal malignancies, all published between 2002 and 2008 (adapted from McCauley¹⁵). This aggregate includes 60 primary adrenal malignancies; the low number is reflective of the rarity of these tumors. In this analysis, six of the reported tumor recurrences and all five instances of port-site recurrence and carcinomatosis occurred in a single series.¹⁶ Of note, those five patients represent a highly selected group, all of whom presented with recurrent disease prior to the resection reported in this series, identifying them as high risk for aggressive tumor behavior. Even including these five patients, oncologic results in the overall group compare favorably to open series; 35% had recurrence during approximately 3 years of mean follow-up. This compares well with results reported in open series which report similar or higher recurrence rates.^15,16

Although the question is not settled, there is a growing consensus in the literature that minimally invasive techniques may be employed for excision of primary adrenal malignancy in appropriately selected cases. It also is now becoming evident that laparoscopy provides similar long-term results to open adrenalectomy when employed for solitary metastases to the adrenal.¹⁵ Appropriate planning and patient selection are imperative. If preoperative imaging suggests invasion into surrounding structures or vena caval thrombus, one should proceed with open resection. Principles of resection that apply in open surgery must be maintained in laparoscopy, including preservation and dissection of tissue planes and avoidance of fracture or rupture of the lesion. The specimen should be removed from the body in an impermeable retrieval bag to avoid exposure of the port site. It is obvious that the surgeon must be experienced in both laparoscopy and endocrine surgery. Because malignancy may be undiagnosed prior to resection, all of these principles should be applied to laparoscopic and open adrenalectomy in general, with particular attention in large or suspicious lesions.

There remains debate in the literature regarding how large of a lesion should be approached laparoscopically, both for oncologic and technical reasons. A large lesion makes the operation more challenging. Most series reporting resection of large masses, including those in Table 15-1, emphasize the lateral transperitoneal technique, which allows the greatest visualization and operative space. Even with this approach, however, visualization can be a challenge in large lesions. Large lesions also may have aberrant vascular supply, thus leading to potential for operative bleeding. While lesions as large as 15 cm have been resected laparoscopically,¹⁷ the appropriate size restrictions for laparoscopic adrenalectomy has not been universally agreed upon. Multiple series have now been published of laparoscopic adrenalectomy for lesions over 6 cm.^15,18–21 Hospital length of stay, operative blood loss, and overall morbidity are not necessarily worsened following laparoscopic resections of large lesions. Rosoff’s review concludes that tumor size alone should not preclude laparoscopic approaches, but that larger lesions should be managed by experienced laparoscopic surgeons who also are adept at the open procedure, should conversion be required. The review also emphasizes the importance of adhering to the oncologic principles discussed earlier.²² Previous upper-abdominal surgery such as nephrectomy, splenectomy, or hepatic resection is not an absolute contraindication to laparoscopy but does make the procedure more difficult. This could necessitate conversion to an open procedure, potentially in an urgent fashion if difficult dissection leads to operative bleeding. Retroperitoneal laparoscopic approach has been reported to circumvent these problems, but this procedure is technically challenging and not widely practiced.

Robotic surgery is a fairly recent development in adrenal surgery. Robotic computer-assisted telemanipulation systems were developed to overcome some of the limitations of standard laparoendoscopic techniques and to facilitate surgeon hand motions in limited operating spaces. The surgeon operates from a remote console, and hand motions are reproduced in scaled proportion through robotically controlled microwrist instruments inserted through the body wall. Purported advantages of robotic-assisted laparoscopic surgery over conventional laparoscopy include hand motions intuitive even to the nonlaparoscopic surgeon,²³ seven degrees of freedom of motion (compared to four with standard laparoscopy), three-dimensional image projection, tremor suppression, motion scaling, and the potential to perform remote “telesurgery.”

Robotic approaches have been applied in a wide variety of urologic, cardiothoracic, gynecologic, and general surgical procedures. The first report of robotic adrenalectomy was by Piazza et al. in 1999.²⁴ Hanly and colleagues reported 30 robotic adrenalectomies without any conversions to open procedures.²⁵ They felt that the robotic system permitted improved identification and control of the multiple adrenal arteries. Although all other reports of robotic adrenalectomy have been for benign lesions, a robotic resection of an 8-cm adrenal lesion that proved to be adrenocortical carcinoma with clean margins has now been reported, with good early results.²⁶

Several reports have compared robotic to laparoscopic adrenalectomy. No difference was found in perioperative quality of life measures between laparoscopic and robotic adrenalectomy.²⁷ An earlier randomized series compared one hospital’s first 10 robotic adrenalectomies to 10 laparoscopic adrenalectomies²⁸ and reported that laparoscopy was superior to robotics in terms of morbidity and cost. More recently, a retrospective review of prospectively collected data compared 50 patients undergoing robotic unilateral adrenalectomy to 59 patients undergoing laparoscopic unilateral transperitoneal adrenalectomy.²⁹ They found that the robotic approach was associated with lower blood loss but longer operative times early in their series. Interestingly, they reported a learning curve of 20 robotic adrenalectomies, after which the difference in operative time was absent. Furthermore, operative times were not affected by obesity or large tumors in the robotic group, while these factors led to significantly longer operative times in the laparoscopic group. Conversion rate, morbidity, and hospital stay were similar between groups.

Limitations of robotics and robotic adrenalectomy include the high cost of the permanent equipment and the semi-reusable instruments, the absence of good data for benefit compared to standard laparoscopy, the learning curve, and the lack of tactile feedback to the surgeon. While the role and future of this technology remain to be determined, one expects that the lessons and advances from robotics will allow further advances in adrenal surgery.

Preoperative History and Evaluation

Patients with functional adrenal tumors may present with characteristic metabolic disorders. Patients with nonfunctional masses or malignancies should undergo routine evaluation for general anesthesia, which is required for either minimally invasive or open adrenalectomy. In the patient with a functioning adrenal mass, specific attention may be needed to correct any metabolic abnormality. The patient with an aldosterone-secreting tumor, hypertension, and significant hypokalemia will require medical correction. Potassium replacement with oral supplementation is usually sufficient. Hypertension treatment can be undertaken with a variety of medications, including calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors. Hyperglycemia occurs in as many as 15% of these patients, and they may require insulin treatment. The patient presenting with Cushing’s syndrome and a unilateral adrenal mass may have suppression of the contralateral adrenal. Therefore, preoperative preparation with stress-dose steroids (e.g., 100 mg of hydrocortisone) is generally indicated. This dose is also adequate for patients undergoing bilateral adrenalectomy for persistent ACTH-secreting syndromes. The former group of patients will require postsurgical steroid tapering, whereas the latter group will require lifelong exogenous steroid replacement.

The patient with pheochromocytoma deserves particular attention (see Chapter 14). Once this diagnosis is made, medical management must address hypertension, decreased intravascular volume, and possible cardiac arrhythmias. The use of phenoxybenzamine, a long-acting α-adrenoceptor blocker, is usually suggested for 1 to 3 weeks prior to surgery (see also Chapter 14). More recently, some groups have reported the use of preoperative blockade with selective postsynaptic α₁-adrenergic receptor antagonists such as prazosin hydrochloride or doxazosin. Such selective agents are thought not to produce reflex tachycardia and have a shorter half-life. These agents may avoid postoperative hypotension that are associated with the longer-acting drugs. These are important considerations, yet phenoxybenzamine remains a standard and time-tested preoperative blockade. The use of calcium channel blockers or ACE inhibitors has also gained acceptance. Because these medications are given in the preoperative period, attention should be given to oral salt and fluid intake to address expansion of intravascular volume prior to surgery. This preoperative regimen must be closely watched. During this time, patients will retain fluid and demonstrate side effects of the medication, possibly including sinus discomfort and orthostatic hypotension. Additionally, a small subset of patients may have arrhythmias which may require β-adrenoceptor blockade. Effective β-blockers include propranolol and nadolol.³⁰ Our group has had excellent experience with metyrosine, 1 to 4 g/day for 10 to 14 days prior to surgery, in addition to phenoxybenzamine. Metyrosine is a tyrosine hydroxylase inhibitor and is very effective in reducing blood pressure; it is associated with fatigue and sinus discomfort. Patients need to be instructed carefully about its side effects.

Preoperative imaging must be evaluated by expert interpretation and also should be studied by the operating surgeon. CT and MRI form the cornerstones of workup and preoperative diagnosis. These films must be of adequate technique and quality to allow investigation of the retroperitoneum and the contralateral adrenal, as well as any other anatomy relevant to the diagnostic workup (e.g., the lung fields, in the case of metastasis). In the case of aldosterone excess, the diagnosis of a solitary adrenal mass must be made to secure the diagnosis of Conn’s syndrome. If both adrenals are not investigated, occasional macronodular bilateral hyperplasia might present with a unilateral nodule that, although appearing to be dominant, might draw attention away from less discrete nodularity in the contralateral gland (Figs. 15-1, 15-2). This situation might require bilateral adrenal vein sampling for aldosterone levels (see Chapter 12). In the case of the pheochromocytoma, multicentric tumors in the retroperitoneum and the contralateral adrenal must be excluded. Any suspicious masses may require MIBG radionuclide study or T1- and T2-weighted MRI scanning (Fig. 15-3).

The experienced endocrine surgeon should personally investigate any or all preoperative laboratory and imaging studies, using local or regional expertise in imaging. Repeat studies are warranted if there is any doubt as to the diagnosis, since operative and perioperative management vary with different pathologies.

Surgical Anatomy, Approaches, and Techniques

The surgical approach to the adrenal requires a complete understanding of the surgical anatomy and the available preoperative and intraoperative options. One of several approaches can be chosen. The open technique allows access to both adrenals and the retroperitoneum (transabdominal). The lateral techniques (open, laparoscopic, or robotic) allow a more focused approach to unilateral adrenal masses and to retroperitoneal areas and kidney. The posterior approach (open or laparoscopic) allows fairly limited access to the adrenal gland on either side but is thought to be associated with fewer postoperative complications.