5.2 Adrenal surgery

The indications for adrenal surgery and techniques employed have evolved significantly in the last 20 years. The need for adrenalectomy has increased due to:

The operative approach has changed with the availability of minimal access surgery; this has significant advantages for the patient in terms of reduced morbidity and faster recovery (1).

Despite these changes, the fundamental principles of adrenal surgery have remained unchanged:

This chapter will focus on the surgical aspects of treatment. The pathology of adrenal disease, details of biochemical and radiological investigations, and the nonsurgical modalities of treatment are covered elsewhere.

The existence of the adrenal glands has been known for several centuries but its importance as an endocrine organ was only highlighted in the 19th century after the description by Thomas Addison of the clinical features of patients with adrenal insufficiency. The first reported adrenalectomy was performed by Knowsley-Thornton, in London in 1889, for a 9-kg tumour where the adrenal and the kidney were removed via an anterior transperitoneal operation. The patient survived the operation despite significant postoperative sepsis. The posterior approach was initially described by Hugh Young, a urologist from Baltimore, who attempted this approach when he was unable to access the adrenals at laparotomy. Surgery for phaeochromocytomas, first performed successfully in 1926 by Cesar Roux in Switzerland, was considered a formidable challenge and associated with a high mortality until the advent of adrenergic receptor blockers in the 1960s (2).

Adrenal surgery underwent a rapid transformation with the advent of laparoscopic adrenalectomy in the early 1990s. First described by surgeons in Japan and Canada, it was initially adopted for small tumours and soon became rapidly accepted as the gold standard of treatment for most adrenal tumours.

The adrenal glands are located in the retroperitoneum in relation to the upper poles of the kidneys at the levels of T11–T12 vertebrae (Fig. 5.2.1). The right adrenal is pyramidal in shape and located partly behind the inferior vena cava with the base of the pyramid abutting the upper pole of the right kidney. The left adrenal gland is semilunar in shape and situated anteromedial to the upper pole of the left kidney. The adrenal glands are enclosed in a layer of fat within Gerota’s fascia. During adrenalectomy for Cushing’s disease, the surgeon will remove the adrenal glands with their fatty envelope to ensure complete removal of hyperfunctioning adrenocortical tissue. The close relationship of the adrenal gland to the inferior vena cava and liver on the right side and the aorta, spleen, stomach, and tail of the pancreas on the left side requires special care during dissection. Clinicians should also be aware of ectopic adrenal tissue or adrenal rests which may exist along the path of testicular descent in males and near the broad ligament and uterus in females. This can be a source of continued cortisol production after bilateral adrenalectomy.

Superior, middle, and inferior adrenal arteries arise from the inferior phrenic, aorta, and renal arteries respectively. The middle adrenal artery is the most variable and not uncommonly absent. Venous drainage is usually via a single, large vein which drains into the inferior vena cava on the right, and the upper border of the renal vein on the left side. The vein on the right side is short and if torn or inadequately secured during surgery can cause profuse bleeding from the vena cava. Additional accessory veins are sometimes found draining into the inferior phrenic veins, renal, and portal veins. The lymphatic drainage of the adrenal glands is to adjacent para-aortic and paracaval lymph nodes.

The adrenal gland has an outer cortex derived from the embryonic mesoderm and an inner medulla derived from ectoderm. The cortex in turn is divided into three layers: the outer zona glomerulosa, the middle zona fasciculata, and the inner zona reticularis. These layers predominantly secrete aldosterone, cortisol, and sex steroids, respectively. The adrenal medulla is part of the sympathetic nervous system and functions as postganglionic neural tissue, secreting catecholamines and their metabolites.

The adrenal glands are the site of pathology in 15% of patients with hypercortisolism. Of these, adenoma (two-thirds) and carcinoma (one-thirds) are the usual causes. Rarely, other lesions such as bilateral nodular hyperplasia, primary pigmented nodular adrenal disease, and McCune–Albright syndrome are encountered (3). Surgery offers the potential for complete biochemical cure. Cushing’s syndrome-related symptoms and signs can be expected to improve after surgery, although this can take from a few weeks to years (4). Surgery is also of benefit in patients with subclinical Cushing’s syndrome. A recent randomized controlled trial of 45 patients compared surgery with nonintervention. Adrenalectomy resulted in significant ‘improvement’, not only of biochemical parameters, but also associated medical conditions such as diabetes, hypertension, hyperlipidaemia, and obesity (5).

Pituitary tumours are the commonest (70%) cause of cortisol excess. The primary treatment of the pituitary lesion is trans-sphenoidal excision, associated with recurrence rates of up to 10% at 5 years and 20% at 10 years (6). Although persistent or recurrent Cushing’s disease can be treated with reoperative pituitary surgery or pituitary radiotherapy, bilateral laparoscopic adrenalectomy is an alternative that provides rapid control of the hormonal syndrome with low morbidity (3, 6). In patients with ectopic ACTH secretion, the primary source of ACTH may not be identified. In such patients and in patients where the primary source is unresectable due to extensive or metastatic disease, bilateral adrenalectomy may be indicated to control symptoms of cortisol excess (7).

Adrenalectomy is indicated in unilateral disease (Conn’s syndrome) and in some patients with bilateral disease when there is evidence of unilateral dominant secretion on selective venous sampling. Adrenal morphology on CT/MRI may be inconclusive or misleading as the adrenals are often nodular in hypertensive patients and ‘obvious nodules’ are not always the source of hormone hypersecretion. The key issues for the surgeon are that unilateral disease is distinguished from bilateral disease, and the laterality is clearly defined in all cases prior to operation. This is achieved in many centres by the performance of selective venous sampling before a decision is made to proceed with adrenalectomy (8). Laparoscopic adrenalectomy for unilateral disease results in significant long-term benefits. Hypertension is cured in one-third of patients and in the majority of the remainder there is a significant reduction in the dosage and number of antihypertensive medications (9, 10).

Surgery is indicated in patients with phaeochromocytoma/extra-adrenal chromaffin tumours (paraganglioma). Malignant phaeochromocytomas are very rare and account for less than 10% of all cases. Despite earlier concerns, the laparoscopic approach is now considered safe for patients with phaeochromocytoma (11). Recurrent phaeochromocytoma and extra adrenal phaeochromocytomas (paragangliomas) can also be effectively treated with surgery (Fig. 5.2.2).

Surgery is indicated in adrenal tumours that are potentially or overtly malignant. A ‘curative resection’ has a favourable impact on outcome in this uncommon disease, which has an overall 5-year survival of 38% (12). Clinical features that indicate an increased risk of malignancy include young age, rapid onset of hormonal symptoms/signs, pain, mixed hormonal secretion, virilizing or feminizing features, and other organ metastases. CT features of malignancy include large tumour size, heterogeneous tumour with bleeding or necrosis, rapidly enlarging tumour on serial scans, invasion into adjacent structures, and regional lymph node enlargement. An MRI scan can sometimes help in evaluating lesions that are indeterminate (lesions with a density of more than 10 Hounsfield units on unenhanced CT). Features of malignancy on MRI include reduced fat content, isointensity to liver on T1 images, intermediate to moderate intensity on T2 images, and enhancement after gadolinium contrast with slow washout. Surgery should be considered in patients with locally advanced or recurrent tumours as resection may improve survival and help in the control of hormonal symptoms (13).

Patients with recently diagnosed cancer or a past history of cancer have a 50% chance of an incidentally discovered adrenal lesion being a metastasis (14). Adrenal metastases most frequently arise from primary malignancy in the lung, kidneys, gastrointestinal tract, and melanoma (15). Adrenalectomy in selected patients with isolated adrenal metastasis may be associated with an improvement in survival (15, 16).

An adrenal lesion detected on cross-sectional imaging performed for an unrelated indication requires thorough biochemical and radiological assessment. Surgery should be considered in all patients with functioning lesions (clinical and subclinical syndromes) and patients with malignant or potentially malignant tumours. The size of an incidentaloma correlates with the risk of malignancy— less than 2% in lesions smaller than 4 cm in size, compared with 25% in lesions larger than 6 cm in size (17). Surgery is indicated for all lesions larger than 6 cm in size, while nonfunctioning lesions smaller than 4 cm may be managed conservatively. For NIH guidelines from 2002 state that surgery or observation are reasonable options. However, in many centres, an incidentaloma larger than 4cm in size is an indication for surgery. Decision making in such cases is also based on considerations such as radiological features, increasing tumour size on sequential scans, and patient choice (17).

Adrenal cysts may be neoplastic (cystic degeneration of cortical or medullary neoplasms) or non-neoplastic, the latter being very rare. Non-neoplastic cysts may be lined by an endothelial or epithelial layer or simply fibrous tissue (as in pseudocysts). Large adrenal cysts, if symptomatic, can be successfully treated by image-guided aspiration alone. This is done after exclusion of a cystic phaeochromocytoma by biochemical tests. Recurrent cysts that are symptomatic may be considered for excision both to treat symptoms and to exclude cystic neoplasms.

Virilizing/feminizing syndromes result from adrenocortical tumours that secrete sex hormones. Cosecretion of androgens/ androgen precursors in conjunction with corticosteroids indicates an increased risk of adrenocortical cancer. Surgery is curative in benign tumours.

Other rare lesions in adults that require surgery include adrenal sarcoma and medullary tumours such as ganglioneuroma, ganglioneuroblastoma, and neuroblastoma. Ganglioneuroma is a benign tumour that may present with symptoms of catecholamine excess. Ganglioneuroblastoma and neuroblastomas are malignant tumours which occur more frequently in children. These conditions are amenable to surgery, but patients with neuroblastoma often need chemotherapy and carry a poor prognosis.

I would like to see the day when somebody would be appointed surgeon somewhere who had no hands, for the operative part is the least part of the work.

(Harvey Cushing)

All patients require a thorough preoperative clinical assessment to determine comorbidities that may need optimization prior to surgery. A full blood count, renal and liver function tests, clotting screen, and blood grouping are performed. Prophylaxis against venous thromboembolism with low molecular weight heparin (especially in patients with hypercortisolism) is given unless specifically contraindicated. For patients with large tumours/phaeochromocytoma, the availability of critical care facilities in the early postoperative period is recommended.

Hypertension, diabetes, and ischaemic heart disease are commonly associated with cortisol excess; measures should be taken to reduce their adverse impact on surgical outcomes. A single dose of prophylactic antibiotics is given at induction because of the increased risk of wound infection. Patients with cortisol excess have fragile skin and special care is required to avoid soft tissue injury during patient movement, positioning on the operating table, and during surgery. Adhesive dressings and sticky tape are best avoided in this situation. All patients should receive perioperative hydrocortisone before surgery. Our practice is to give 100 mg intramuscular hydrocortisone 6-hourly starting on the morning of surgery, continuing with parenteral administration at a reducing dose until the patient can take steroids orally (tds). On the third postoperative day, the evening dose of hydrocortisone (20 mg) is omitted and basal cortisol levels measured the following morning prior to the first daytime dose. In patients who have undergone bilateral adrenalectomy, undetectable cortisol levels confirm cure. These patients require lifelong glucocorticoid and mineralocorticoid replacement therapy. In patients who have undergone adrenalectomy for unilateral disease, low levels of cortisol mandate that a short synacthen test is performed to identify contralateral adrenal hypofunction (observed in 75% of patients). These patients require glucocorticoid replacement for a variable period of time ranging from months to years until recovery of the HPA axis is confirmed on biochemistry. Post operative in hospital care is provided in conjunction with endocrinologists according to clearly defined local protocols, robust arrangements should be in place for subsequent follow-up. Patients on steroid replacement must be counselled on the need for compliance with steroid medication and the need for increased steroid requirements during acute illness. The patient should be given an emergency ‘steroid’ pack and a card detailing their steroid regimen.

Hypokalaemia is corrected preoperatively. Aldosterone antagonists are stopped postoperatively followed by regular monitoring of blood pressure and appropriate modification of antihypertensive medications. Preoperative biochemical screening sometimes identifies concomitant cortisol secretion in patients with aldosteronomas. For these patients, appropriate perioperative steroid cover and postoperative testing for contralateral adrenal suppression is performed. Plasma aldosterone concentrations and renin activity are also measured in the follow up period to confirm biochemical cure.

The principles of preoperative preparation of a patient with phaeochromocytoma include ‘maximum tolerated’ α-blockade and adequate hydration. In our practice, patients are started on phenoxybenzamine (10 or 20 mg twice daily) at diagnosis and the dose is increased until symptoms are controlled. Patients are admitted to the ward a week prior to surgery. Lying and standing blood pressure is monitored at 6-hourly intervals. Each dose of phenoxybenzamine is increased by 10 mg every 48 h until symptomatic postural hypotension and nasal stuffiness occurs. β-blockers are only used to limit tachycardia, and only when α-blockade has been achieved. An adequate oral fluid intake is encouraged and patients are prescribed 1–2 litres of intravenous fluids over 12 h prior to the operation. Intraoperative invasive monitoring of central venous pressure, arterial blood pressure and the judicious use of vasodilators and inotropes by an experienced anaesthetist minimizes the risk of cardiovascular instability during surgery. In the immediate postoperative period (up to several hours), patients should be monitored for hypoglycaemia and appropriately treated.

As with any operative procedure, it is the duty of the surgeon to ensure that the patient scheduled to undergo adrenalectomy understands the indications, implications, and risks of surgery (see below). In primary hyperaldosteronism and subclinical Cushing’s syndrome, the alternative (nonsurgical) options should be discussed so that a fully informed choice can be made by the patient with appropriate guidance from the surgeon. Patients should be made aware that some clinical features of their illness (e.g. hypertension in Conn’s syndrome and features of Cushing’s syndrome) may persist after surgery. Conversion to open surgery may be required with the laparoscopic approach in up to 10% of patients. This is a consequence of intraoperative complications or technical limitations of the laparoscopic approach, the most significant predictor of conversion being a large tumour size (18).

Laparoscopic adrenalectomy should be the standard surgical approach to most adrenal lesions (Fig. 5.2.3). This is due to the distinct advantages seen with laparoscopy in large observational studies. The advantages include reduction in postoperative pain, blood loss, wound infection, hospital stay, and time to return to normal activity.

The choice of an open or laparoscopic surgical approach for the ‘potentially’ malignant adrenal mass is controversial (19). Proponents of the open approach quote the risk of peritoneal seeding and local recurrence after laparoscopic adrenalectomy (20). In contrast, laparoscopic surgery is associated with lower postoperative morbidity (21) and in selected patients has the same potential for complete resection as open surgery (22). Our practice is to use an open approach for patients with obvious radiological features of malignancy and lesions larger than 10 cm in size. The latter tumours have a significant risk of cancer and are often difficult to mobilize without capsular rupture at laparoscopy (23). Some surgeons who perform laparoscopic adrenalectomy for large tumours make use of a hand-assist device which enables direct handling and aids the dissection of large tumours (24).

Both open and laparoscopic procedures can be performed via the anterior, lateral, or posterior approach. In the ‘open’ era, the approach adopted was based on the underlying pathology, unilateral or bilateral disease, and the likelihood of ectopic or extra-adrenal lesions. The posterior approach was an option for small to medium sized tumours thought to be benign. The lateral approach was adopted in the case of large unilateral lesions as this approach is suited to a thoracic extension (thoracoabdominal approach) when a large malignant tumour infiltrates the diaphragm and/or vena cava. The anterior transperitoneal approach was used most frequently, in patients with bilateral tumours, or in patients with malignancy when abdominal exploration for metastatic disease was required. Preoperative imaging with CT/MRI has changed the decision-making process in many of these cases.

The approach in the ‘laparoscopic’ era is principally determined more by the surgeon’s experience and his/her familiarity with a specific procedure. The transperitoneal (Fig. 5.2.3) and the posterior retroperitoneal approach (Fig. 5.2.4) are most commonly used. No significant difference in clinical outcomes have been demonstrated in randomized controlled trials of these two approaches (25, 26); surgeons familiar with both techniques base their choice upon specific patient characteristics. In patients with bilateral tumours and/or previous intra-abdominal surgery, the posterior approach would be preferred and in patients with large tumours the anterior approach has the advantage of a larger working space. Table 5.2.1 gives a flavour of the approaches used in our practice in different clinical situations and their underlying rationale.

The key steps to performing adrenalectomy are correct positioning of the patient, use of appropriate port sites or incisions, identification of the anatomical landmarks and careful dissection of the adrenal gland. The term ‘radical adrenalectomy’ is often used to describe the surgical approach in adrenal malignancy. The nature and extent of this procedure is poorly defined. An en bloc resection of the entire adrenal gland, periadrenal fat, and involved lymph nodes is usually performed. Occasionally, resection of involved adjacent organs such as the liver and kidney may be required for complete macroscopic clearance. Cortical-sparing adrenalectomy can be performed in patients with bilateral (i.e. genetically determined) phaeochromocytoma. These patients would otherwise undergo bilateral (total) adrenalectomy, which necessitates lifelong steroid replacement and places them at risk of adrenal insufficiency. Inadvertently retained adrenal medulla in patients treated by cortex-sparing surgery can however result in recurrent disease. Other proposed indications for subtotal adrenalectomy include patients who have previously undergone contralateral adrenalectomy and those with Conn’s adenomas where tumours are small, benign, and eccentrically located (27). The tumour is excised with surrounding normal tissue aiming to preserve sufficient adrenal tissue to preserve cortical function.

General complications of adrenalectomy include venous thromboembolism, and respiratory and cardiac failure. The reported overall postoperative mortality of adrenalectomy is up to 2.8% (28). Specific risks of adrenalectomy are:

Adrenal surgery is required for the treatment for syndromes of ho rmonal excess arising from the adrenal gland and adrenal neoplasms. A multidisciplinary approach, careful preoperative planning, and an experienced surgeon are essential for a good outcome. Several areas in the surgical treatment of adrenal disease are still in evolution. These include

The rarity of adrenal disease, the heterogeneity of clinical conditions, and the multifactorial influences on outcome will make it difficult (if not impossible) for surgical strategies to be based on evidence from randomized trials. Good quality data from observational series and the insight and judgement of experienced endocrine surgeons should be considered an acceptable alternative.