Residency · Residency · Urology

Surgical Management of Adrenal Tumors

Introduction

Adrenalectomy represents the definitive treatment for functioning adrenal tumors as well as suspected adrenal malignancies. The advent of laparoscopic and robotic-assisted surgical techniques has revolutionized adrenal surgery, making minimally invasive adrenalectomy the standard of care for most adrenal lesions. It is essential for the urologist to be well-versed in preoperative preparation tailored to specific tumor types, the selection of the appropriate surgical approach, and the management of adrenocortical carcinoma, which is a rare but aggressive malignancy that typically requires open surgical resection.

Indications for Adrenalectomy

Adrenalectomy is indicated for both functional and non-functional adrenal tumors, as well as for adrenal metastases under certain conditions. Functional tumors requiring surgery include pheochromocytomas, which mandate resection after adequate alpha-adrenergic blockade. Primary aldosteronism, or Conn syndrome, is treated surgically when a unilateral aldosterone-producing adenoma is confirmed by adrenal vein sampling. Cortisol-producing adenomas causing Cushing syndrome also require adrenalectomy following biochemical confirmation. Autonomous cortisol secretion with related comorbidities may warrant individualized surgical decisions. Sex hormone-secreting tumors that cause virilization or feminization should raise suspicion for adrenocortical carcinoma and prompt surgical intervention.

Non-functional tumors are considered for adrenalectomy based on size, growth, and imaging characteristics. Tumors larger than 4 to 6 cm with indeterminate imaging features, interval growth greater than 1 cm on surveillance imaging, or suspicious imaging findings such as heterogeneity, necrosis, irregular borders, or attenuation greater than 10 Hounsfield units without washout are indications for surgery. Adrenocortical carcinoma suspected on imaging or biopsy also necessitates resection.

Adrenal metastases may be resected in patients with isolated adrenal involvement and controlled primary malignancy, particularly in cases of lung cancer, renal cell carcinoma, or melanoma. The decision to operate is individualized based on oncologic status, disease-free interval, and alternative treatment options.

Preoperative Preparation by Tumor Type

Preoperative preparation varies according to tumor type, with specific protocols to optimize patient safety and surgical outcomes.

For pheochromocytoma, alpha-adrenergic blockade is initiated 10 to 14 days before surgery. Phenoxybenzamine, an irreversible non-selective alpha-blocker, is started at 10 mg twice daily and titrated up to 20-40 mg twice daily. Alternatively, doxazosin, a selective alpha-1 blocker with a shorter half-life and fewer side effects, can be used at doses of 2-8 mg daily. Beta-blockade is added only after adequate alpha-blockade has been established, typically 3 to 5 days before surgery, using propranolol (10-40 mg three times daily) or atenolol (25-50 mg daily). Initiating beta-blockade before alpha-blockade is contraindicated because unopposed alpha stimulation can provoke hypertensive crisis. Calcium channel blockers such as amlodipine or nicardipine may be used as adjuncts or alternatives for blood pressure control. Volume expansion is critical, achieved by a high-sodium diet and liberal fluid intake for 2 to 3 days preoperatively, since patients are chronically volume-depleted due to catecholamine-induced vasoconstriction. Metyrosine, a tyrosine hydroxylase inhibitor, may be employed as an adjunct in refractory cases. The goals before surgery include maintaining blood pressure below 130/80 mmHg when seated, heart rate between 60 and 70 beats per minute, absence of orthostatic hypotension below 80/45 mmHg, and no ST-segment changes on ECG.

In aldosterone-producing adenomas, hypokalemia must be corrected preoperatively with potassium supplementation and mineralocorticoid receptor antagonists such as spironolactone (25-100 mg daily) or eplerenone. Blood pressure optimization with antihypertensives is necessary, although hypertension may not normalize immediately after surgery. Patients should be counseled that 30-60% achieve cure of hypertension, while the remainder experience significant improvement but may still require medication.

For cortisol-producing adenomas causing Cushing syndrome, perioperative stress-dose steroids are essential because the contralateral adrenal gland is suppressed by chronic cortisol excess, leading to adrenal insufficiency immediately after resection. Hydrocortisone is administered as 100 mg intravenously at induction, followed by 50 mg IV every 8 hours, with a taper over weeks to months. Patients require physiologic glucocorticoid replacement (hydrocortisone 15-25 mg/day) until the hypothalamic-pituitary-adrenal axis recovers, typically over 6 to 18 months. Venous thromboembolism prophylaxis is recommended due to the elevated thrombotic risk in Cushing patients, and perioperative glucose management is important because insulin resistance and hyperglycemia are common.

<image>Preoperative preparation timeline chart for pheochromocytoma showing: alpha-blockade initiation 10-14 days before surgery with dose titration, beta-blockade addition 3-5 days preoperatively (only after adequate alpha-blockade), volume expansion with liberal salt and fluid intake in the final 2-3 days, and target hemodynamic parameters (BP less than 130/80, HR 60-70) at the time of surgery, with medication names and dosing annotated</image>

Surgical Approaches

The choice of surgical approach depends on tumor size, location, and suspected pathology.

Laparoscopic transperitoneal adrenalectomy is the most common approach for adrenal tumors smaller than 6 to 8 cm. The patient is positioned in the lateral decubitus position with the affected side up. For left adrenalectomy, 3 to 4 ports are placed; the splenic flexure and spleen are mobilized medially to expose the adrenal gland. The left adrenal vein, which drains into the left renal vein, is identified and ligated early. Right adrenalectomy also uses 3 to 4 ports, with mobilization of the right hepatic lobe to expose the adrenal gland. The short right adrenal vein drains directly into the inferior vena cava (IVC) and requires careful dissection and clip ligation, as it is the most dangerous step due to its short length and proximity to the IVC. The specimen is extracted in an endocatch bag to prevent tumor spillage. Operative time typically ranges from 60 to 120 minutes, with blood loss usually less than 100 mL.

Robotic-assisted adrenalectomy offers advantages such as three-dimensional visualization, wristed instruments, and improved ergonomics. It is particularly useful for larger tumors and bilateral cases. Outcomes are comparable to the laparoscopic approach in experienced hands, and its adoption is growing as it facilitates more complex dissections.

Posterior retroperitoneoscopic adrenalectomy (PRA) involves positioning the patient prone in a jackknife position. A three-trocar approach through the posterior flank directly accesses the retroperitoneum. This approach avoids entering the peritoneal cavity, eliminating the need for bowel mobilization and allowing faster recovery. It is ideal for bilateral simultaneous adrenalectomy and small benign lesions less than 6 cm, including pheochromocytomas, as it avoids manipulation during peritoneal entry. However, PRA has a limited working space for large tumors, a steep learning curve, and limited visualization if bleeding occurs.

Open adrenalectomy is reserved for adrenocortical carcinoma, where an open approach is preferred due to the need for en-bloc resection with negative margins, potential adjacent organ resection, and vascular control. It is also indicated for large tumors greater than 8 to 10 cm where minimally invasive approaches risk capsular violation, and for locally invasive tumors requiring nephrectomy, splenectomy, distal pancreatectomy, or IVC thrombectomy. Approaches include anterior transperitoneal (midline or subcostal) and thoracoabdominal incisions for large right-sided tumors with IVC involvement.

Adrenocortical Carcinoma (ACC)

Adrenocortical carcinoma is a rare malignancy, occurring in 1 to 2 per million people annually, but is highly aggressive. It exhibits a bimodal age distribution, affecting children under 5 years and adults between 40 and 50 years. Approximately 50-60% of ACCs are functional, most commonly producing excess cortisol, but virilization and mixed hormone secretion can also occur. Elevated dehydroepiandrosterone sulfate (DHEA-S) is a characteristic laboratory finding.

The European Network for the Study of Adrenal Tumors (ENSAT) staging system classifies ACC as follows: Stage I tumors are less than 5 cm and confined to the adrenal gland; Stage II tumors are larger than 5 cm but still confined; Stage III involves local invasion into lymph nodes or adjacent organs or tumor thrombus in the renal vein or IVC; Stage IV denotes distant metastases to lung, liver, or bone.

Complete surgical resection with negative margins (R0 resection) is the only potentially curative treatment. Open adrenalectomy is preferred because minimally invasive approaches are associated with higher rates of capsular violation, tumor spillage, and peritoneal carcinomatosis. En-bloc resection of involved adjacent structures such as the kidney, spleen, distal pancreas, or liver segments may be necessary. Regional lymphadenectomy is recommended. If tumor thrombus extends into the renal vein or IVC, thrombectomy may be required, sometimes necessitating cardiopulmonary bypass for suprahepatic extension. Avoiding tumor capsule violation is critical, as breach of the capsule is linked to local recurrence and peritoneal carcinomatosis.

Adjuvant therapy includes mitotane, an adrenolytic agent recommended for all Stage III and IV ACC and considered for Stage II with high-risk features such as Ki-67 greater than 10%, positive margins, or tumor spillage. Mitotane inhibits steroidogenesis and has a direct cytotoxic effect on the adrenal cortex. Target serum levels range from 14 to 20 mg/L, and glucocorticoid and mineralocorticoid replacement are required due to adrenal insufficiency. Side effects include gastrointestinal and neurologic toxicity. Chemotherapy with EDP-M (etoposide, doxorubicin, cisplatin plus mitotane) is used for advanced or metastatic ACC, as demonstrated in the FIRM-ACT trial. Radiation therapy may be applied adjuvantly to the tumor bed in cases of positive margins or locally advanced disease to reduce local recurrence.

<image>Intraoperative illustration of open right adrenalectomy for adrenocortical carcinoma showing a large heterogeneous tumor with en-bloc resection including the ipsilateral kidney (radical nephrectomy), regional lymph node dissection along the IVC, and tumor thrombus extraction from the IVC with vascular clamps positioned above and below the thrombus, with labeled IVC, right renal vein, right renal artery, and hepatic retraction</image>

Intraoperative Considerations

During pheochromocytoma surgery, the anesthesia team must be prepared for hemodynamic instability, with arterial line and central venous access in place. Hypertensive crises during tumor manipulation are managed with intravenous phentolamine, nitroprusside, or nicardipine. Hypotension following adrenal vein ligation requires volume resuscitation and vasopressors such as norepinephrine, as catecholamine levels drop abruptly after ligation. Early ligation of the adrenal vein is a critical step to minimize catecholamine surges during tumor manipulation. Agents such as glucagon, metoclopramide, and histamine should be avoided because they can trigger catecholamine release.

General surgical principles include understanding adrenal vein anatomy: the left adrenal vein drains into the left renal vein and is longer and easier to control, whereas the right adrenal vein drains directly into the IVC, is short (2-5 mm), and represents the highest risk structure. Preservation of surrounding structures, especially the spleen on the left and the liver on the right, as well as the renal hilum, is essential. Hemostasis is critical because the adrenal gland is highly vascular; energy devices like harmonic scalpels or LigaSure and clips should be used judiciously. Specimen integrity must be maintained by extracting the tumor in a bag and never morcellating adrenal tumors to prevent tumor spillage.

Outcomes and Follow-Up

Benign functional tumors generally have excellent outcomes. Pheochromocytoma has a cure rate of 90-95%, but there is a 10-15% risk of recurrence or metachronous tumors, necessitating lifelong annual metanephrine screening. Aldosteronomas cure hypokalemia in over 95% of cases, while hypertension is cured in 30-60%. Cortisol-producing adenomas achieve cortisol normalization in over 95% of patients, with hypothalamic-pituitary-adrenal axis recovery occurring over 6 to 18 months.

Adrenocortical carcinoma has a more guarded prognosis. Five-year survival rates vary by stage: 60-80% for Stage I-II, 30-50% for Stage III, and 10-15% for Stage IV. Despite R0 resection, recurrence rates range from 50 to 80%. Surveillance includes CT scans of the chest and abdomen every 3 to 6 months for the first 2 years, then every 6 to 12 months thereafter. Hormonal markers are monitored if the tumor was initially functional.

<image>Posterior retroperitoneoscopic adrenalectomy (PRA) setup showing patient in prone jackknife position with three trocar positions through the posterior lumbar flank, retroperitoneal endoscopic view of the adrenal gland being dissected from the upper pole of the kidney with the adrenal vein identified and clipped, and surrounding landmarks including the diaphragm, kidney, and perirenal fat</image>

Key Clinical Pearls

It is imperative never to operate on a pheochromocytoma without adequate alpha-blockade, as beta-blockade alone leads to unopposed alpha stimulation and hypertensive crisis. The right adrenal vein, which drains directly into the inferior vena cava, is the most dangerous structure encountered during right adrenalectomy because of its short length and proximity to the IVC, requiring meticulous dissection. Adrenocortical carcinoma should be resected via open surgery, as laparoscopic approaches are associated with higher rates of capsule violation and peritoneal seeding. After resection of a cortisol-producing adenoma, stress-dose steroids and physiologic glucocorticoid replacement are mandatory because the contralateral adrenal gland is suppressed and adrenal crisis will ensue without replacement. Mitotane is the only available adrenolytic drug and is recommended as adjuvant therapy for high-risk and advanced ACC. Finally, lifetime surveillance is necessary after pheochromocytoma resection due to the 10-15% risk of recurrence or metachronous disease, especially in hereditary syndromes such as MEN2, von Hippel-Lindau disease, and succinate dehydrogenase mutations.

References

1. Fassnacht M, Dekkers OM, Else T, et al. European Society of Endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults. Eur J Endocrinol. 2018;179(4):G1-G46.
2. Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915-1942.
3. Stefanidis D, Goldfarb M, Kercher KW, et al. SAGES guidelines for minimally invasive treatment of adrenal pathology. Surg Endosc. 2013;27(11):3960-3980.
4. Fassnacht M, Terzolo M, Allolio B, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012;366(23):2189-2197.

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