Residency · Residency · General Surgery
Adrenal Incidentaloma and Adrenalectomy
Overview
An adrenal incidentaloma is an adrenal mass discovered on imaging performed for unrelated reasons. They are found in 4-5% of abdominal CT scans, with prevalence increasing with age. Two key questions must be answered for every incidentaloma: Is it functional? Is it malignant? Most adrenal incidentalomas are benign, non-functional cortical adenomas.
Workup
Hormonal Evaluation (All Patients)
All patients with adrenal incidentalomas require a hormonal evaluation. Cortisol excess (previously termed subclinical Cushing's, now called autonomous cortisol secretion) is screened with a 1 mg overnight dexamethasone suppression test; a cortisol level below 1.8 mcg/dL is normal. If abnormal, further evaluation includes 24-hour urine free cortisol, midnight salivary cortisol, and ACTH level. The term "autonomous cortisol secretion" has replaced "subclinical Cushing's" to reflect the spectrum of cortisol overproduction.
Pheochromocytoma is screened with plasma free metanephrines or 24-hour urine metanephrines and catecholamines. This must be ruled out in every patient before any intervention, including biopsy. Primary aldosteronism is evaluated if the patient is hypertensive or hypokalemic, using the plasma aldosterone concentration and plasma renin activity. An aldosterone-to-renin ratio greater than 30 with a PAC greater than 15 ng/dL is suggestive, and confirmatory testing with a salt loading test or fludrocortisone suppression test follows. Sex steroid excess is evaluated with DHEA-S and testosterone if virilization is present; elevated levels raise concern for adrenocortical carcinoma.
Imaging Characteristics
CT Features
A benign adenoma appears homogeneous with smooth borders and an unenhanced CT attenuation of 10 HU or less (lipid-rich), with rapid contrast washout exceeding 50% absolute washout at 15 minutes. A lipid-poor adenoma has attenuation greater than 10 HU on unenhanced imaging but shows rapid washout on contrast-enhanced CT. Malignant features include a size greater than 4-6 cm, irregular borders, heterogeneous density, attenuation greater than 10 HU without washout, calcifications, and invasion of adjacent structures. Pheochromocytoma has a variable appearance, may be heterogeneous with necrosis, and enhances briskly. Myelolipoma has pathognomonic macroscopic fat with attenuation below -30 HU and is benign, requiring no resection unless symptomatic.
MRI Features
Chemical shift MRI demonstrates loss of signal on out-of-phase images in lipid-rich adenomas, which is useful for characterizing lipid-poor lesions that are indeterminate on CT. Pheochromocytoma classically appears "light bulb bright" on T2-weighted images, though this finding is variable.
PET-CT
Adrenocortical carcinoma is typically FDG-avid, while benign adenomas demonstrate low FDG uptake. Pheochromocytoma has variable FDG uptake.
<image>CT scan comparing a benign adrenal adenoma (homogeneous, low density, <=10 HU) with an adrenocortical carcinoma (large, heterogeneous, irregular borders with areas of necrosis)</image>
Indications for Adrenalectomy
Functional Tumors
All pheochromocytomas should be resected after appropriate alpha-blockade. Primary aldosteronism from a unilateral adenoma is treated with adrenalectomy, which is curative for hypertension in 30-60% and improves blood pressure control in more than 90%; adrenal vein sampling is the gold standard for lateralization and subtype differentiation before surgery. Cortisol-producing adenomas causing overt Cushing's syndrome require surgery, and autonomous cortisol secretion may warrant adrenalectomy if associated comorbidities such as diabetes, hypertension, osteoporosis, or obesity are present and may improve with surgery. Sex steroid-producing tumors should be resected due to high concern for adrenocortical carcinoma.
Nonfunctional Tumors -- Size Criteria
Lesions smaller than 4 cm are managed with surveillance, including repeat imaging at 6-12 months and then annually for 2-4 years, along with repeat hormonal evaluation annually for 5 years. Lesions between 4 and 6 cm warrant adrenalectomy per most guidelines due to increasing malignancy risk, though some guidelines accept observation if imaging characteristics are unequivocally benign (10 HU or less, homogeneous). Lesions larger than 6 cm should undergo adrenalectomy given significant malignancy risk. Growth exceeding 1 cm per year or development of suspicious features on follow-up imaging warrants surgery.
Adrenal Metastases
The adrenal gland is a common site for metastases from lung, breast, melanoma, renal, and colon cancers. In patients with a known malignancy and an adrenal mass, PET-CT and/or biopsy should be performed to confirm the diagnosis. For an isolated adrenal metastasis, adrenalectomy may improve survival in selected patients, especially those with lung cancer.
Adrenal Biopsy
Adrenal biopsy is rarely indicated and is appropriate only when a known extra-adrenal malignancy exists and the result would change management. Pheochromocytoma must be ruled out before biopsy to avoid hypertensive crisis. Biopsy cannot reliably distinguish adrenal adenoma from adrenocortical carcinoma. The technique is CT-guided percutaneous biopsy, with risks including hemorrhage, pneumothorax, and needle-track seeding.
Surgical Approaches
Laparoscopic Transabdominal Adrenalectomy
Laparoscopic transabdominal adrenalectomy is the gold standard for most adrenal lesions smaller than 6-8 cm. For left adrenalectomy, the patient is positioned in lateral decubitus, the splenic flexure and spleen are mobilized, and the left adrenal vein (which drains into the left renal vein) is ligated. For right adrenalectomy, also in lateral decubitus, the liver is mobilized and the right adrenal vein (which drains directly into the IVC and is short and easily torn) is ligated. Advantages include low morbidity, shorter recovery, and less pain.
Posterior Retroperitoneoscopic Adrenalectomy (PRA)
This approach is performed in the prone position with a direct retroperitoneal approach. Its advantages include avoiding the peritoneal cavity, faster recovery, and suitability for bilateral adrenalectomy and patients with prior abdominal surgery. Disadvantages include a limited working space, steeper learning curve, and unsuitability for large tumors. It is increasingly popular among experienced adrenal surgeons.
Open Adrenalectomy
Open adrenalectomy is reserved for large tumors (greater than 8-10 cm), suspected adrenocortical carcinoma, and locally invasive tumors. En bloc resection with adjacent organs (kidney, IVC, liver) is performed if involved. Morcellation or capsular violation must be avoided in suspected adrenocortical carcinoma to prevent peritoneal seeding.
Robotic Adrenalectomy
Robotic adrenalectomy can be performed via a transabdominal or retroperitoneal approach. Outcomes are similar to laparoscopic surgery and the robotic platform may facilitate complex dissection, though it has higher cost and no proven superiority.
<image>Laparoscopic transabdominal adrenalectomy for left adrenal adenoma showing identification and ligation of the left adrenal vein draining into the left renal vein</image>
Adrenocortical Carcinoma (ACC)
Overview
Adrenocortical carcinoma is a rare aggressive malignancy with an incidence of 0.7-2 per million per year. It has a bimodal age distribution, occurring in children under 5 years and adults aged 40-50 years. Fifty to sixty percent of cases are functional, with cortisol being the most commonly secreted hormone, followed by androgens or mixed secretion. These tumors are often large at diagnosis (greater than 6 cm) and may present with mass effect or hormonal symptoms.
Staging (ENSAT)
| ENSAT Stage | Description | 5-Year Survival |
|---|---|---|
| I | Tumor ≤5 cm, confined to adrenal | 60–80% |
| II | Tumor >5 cm, confined to adrenal | 60–80% |
| III | Local invasion or regional lymph node metastases | 30–50% |
| IV | Distant metastases (lung, liver, bone) | <15% |
Stage I denotes a tumor 5 cm or less confined to the adrenal. Stage II denotes a tumor greater than 5 cm confined to the adrenal. Stage III involves local invasion or regional lymph node metastases. Stage IV involves distant metastases, most commonly to lung, liver, and bone.
Surgical Management
Complete surgical resection (R0) is the only curative treatment. An open approach is preferred for suspected ACC to allow en bloc resection and avoid capsular violation. Lymph node dissection is performed if suspicious nodes are present. Adjacent organ resection (nephrectomy, splenectomy, distal pancreatectomy) is performed if organs are involved. IVC tumor thrombus may require vascular surgery support.
Adjuvant Therapy
Mitotane is an adrenolytic agent that is the standard adjuvant therapy for ACC. Serum levels should be monitored (target 14-20 mcg/mL), and the drug carries significant side effects including gastrointestinal, neurologic, and adrenal insufficiency. Patients on mitotane require cortisol replacement because the drug increases cortisol-binding globulin and accelerates cortisol metabolism. For advanced disease, adjuvant cisplatin, etoposide, doxorubicin, and mitotane is the standard regimen, as studied in the FIRM-ACT trial. Radiation has a limited role but may be considered for positive margins or local recurrence.
Prognosis
Stage I-II with R0 resection has a 5-year survival of 60-80%. Stage III has a 5-year survival of 30-50%. Stage IV has a 5-year survival of less than 15%.
Clinical Pearls
Pheochromocytoma must be ruled out biochemically in every adrenal incidentaloma before surgery or biopsy, as failure to do so can result in intraoperative hypertensive crisis and death. Unenhanced CT attenuation of 10 HU or less is the most reliable single feature for diagnosing a benign lipid-rich adenoma. Adrenal biopsy cannot distinguish adenoma from carcinoma, and a primary adrenal tumor should never be biopsied to make this distinction. For suspected adrenocortical carcinoma, open en bloc resection is preferred because capsular violation and morcellation dramatically worsen outcomes. The right adrenal vein drains directly into the IVC and is short, making it the most dangerous step of right adrenalectomy. Adrenal vein sampling is essential before surgery for primary aldosteronism to lateralize the source, unless CT shows a clear unilateral adenoma in a young patient with a suppressed contralateral gland. After unilateral adrenalectomy for a cortisol-producing adenoma, the contralateral adrenal is suppressed, and patients need stress-dose steroids perioperatively and a prolonged cortisol replacement taper.
<image>Algorithm for workup and management of adrenal incidentaloma showing biochemical evaluation, imaging characterization, and decision tree for surgery versus surveillance</image>
References
- Fassnacht M, et al. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenal incidentalomas. Eur J Endocrinol. 2016;175(2):G1-G34.
- Zeiger MA, et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocr Pract. 2009;15(Suppl 1):1-20.
- Fassnacht M, et al. Combination chemotherapy in advanced adrenocortical carcinoma (FIRM-ACT). N Engl J Med. 2012;366(23):2189-2197.
- Young WF Jr. Clinical practice: The incidentally discovered adrenal mass. N Engl J Med. 2007;356(6):601-610.
- Terzolo M, et al. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med. 2007;356(23):2372-2380.
