Adrenal Gland Disorders

Diagnostic Criteria

• The American Urological Association and the Endocrine Society suggest that tumors greater than 4 cm without characteristic benign imaging features are suspicious for malignancy, and smaller tumors with suspicious radiological features should be further evaluated 1, 2
• A 1mg overnight dexamethasone suppression test is recommended for cortisol assessment, with values ≤50 nmol/L indicating normal results, 51-138 nmol/L indicating possible autonomous cortisol secretion, and >138 nmol/L indicating autonomous cortisol secretion, as recommended by the American College of Physicians and the Endocrine Society 1, 3
• Plasma free metanephrines or 24-hour urinary fractionated metanephrines are recommended for catecholamine assessment, with values >2× upper limit of normal strongly suggesting pheochromocytoma, as recommended by the American College of Physicians 3, 4, 5
• An aldosterone-to-renin ratio (ARR) is recommended in patients with hypertension/hypokalemia, with ARR >20 ng/dL per ng/mL/hr having >90% sensitivity/specificity for hyperaldosteronism, as recommended by the Endocrine Society 3
• The following table summarizes the recommended hormonal evaluation for adrenal masses:

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• The following imaging modalities are recommended for evaluating adrenal masses:

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Surgical Management

• The American Urological Association recommends laparoscopic/robotic adrenalectomy for smaller (<5 cm), contained masses, and open adrenalectomy for larger (>5 cm) tumors or those with features concerning for malignancy 1
• Laparoscopic adrenalectomy is recommended for aldosterone-producing adenoma if unilateral, and for cortisol-producing adenoma, as per the National Comprehensive Cancer Network 2
• Adrenal vein sampling may be necessary to distinguish unilateral adenoma from bilateral hyperplasia in cases of hyperaldosteronism, according to the National Comprehensive Cancer Network 2
• Unilateral adrenalectomy is recommended for clinically apparent Cushing's syndrome, and considered in younger patients with progressive metabolic comorbidities and mild autonomous cortisol secretion (MACS), as recommended by the American College of Surgeons 3
• Surgical resection is the definitive treatment for catecholamine-secreting lesions (pheochromocytoma), with preoperative alpha-blockade essential to prevent hypertensive crisis during surgery, as recommended by the European Society of Medical Oncology 7
• Minimally invasive surgery (MIS) is preferred for benign adenomas when feasible, while open adrenalectomy is considered for larger tumors or those with features concerning for malignancy, as recommended by the American College of Surgeons 3

Patient Evaluation and Management

• The American Urological Association recommends urgent assessment for pregnant women, children, and people younger than 40 years due to greater risk of adrenal malignancy, and MRI is preferred over CT in these populations 1
• The American Urological Association suggests considering quality of life and medical comorbidities in management decisions for elderly patients 1
• Medical therapy, including ketoconazole or metyrapone, mifepristone, and mineralocorticoid receptor antagonists, is used when surgery is contraindicated or as a bridge to surgery, as recommended by the National Comprehensive Cancer Network 4
• Autonomous mild cortisol secretion (previously called subclinical Cushing's syndrome) is associated with type 2 diabetes, hypertension, cardiovascular events, vertebral fractures, and mortality 3

Common Pitfalls to Avoid

• Using minimally invasive approaches for suspected adrenocortical carcinoma, which can lead to higher recurrence rates 1
• Performing unnecessary biopsies, which have limited clinical value and should not be part of initial workup 1
• Missing congenital adrenal hyperplasia in patients with bilateral adrenal masses, and collecting 17-hydroxyprogesterone levels to rule out this condition 1
• Malignancy should be suspected if the tumor has irregular morphology, is lipid-poor, does not wash out on contrast-enhanced CT, or is secreting more than one hormone, as suggested by the National Comprehensive Cancer Network 2

Follow-up and Surveillance

• Lifelong surveillance is recommended for malignant pheochromocytoma, with regular monitoring for recurrence in both Cushing's syndrome and pheochromocytoma, as recommended by the National Comprehensive Cancer Network 8
• Benign-appearing adenomas <4 cm require no further follow-up imaging or functional testing if clearly benign (HU ≤10), as recommended by the American College of Radiology 3
• Benign-appearing adenomas ≥4 cm require repeat imaging in 6-12 months, with consideration of surgery if growth >5 mm/year after repeating functional workup, as recommended by the American Urological Association 3
• Functional testing follow-up is recommended for non-operated patients with non-functioning masses, with consideration of repeat screening for pheochromocytoma and hypercortisolism at 1-2 years, as noted by the Endocrine Society 3
• Adrenal myelolipomas less than 4 cm in size, asymptomatic, and containing macroscopic fat detected on initial imaging require no further follow-up imaging or functional testing, as recommended by the American Urological Association 3
• For adrenal myelolipomas greater than or equal to 4 cm but radiologically benign, repeat imaging in 6-12 months is recommended, and if growth is greater than 5 mm/year, consider adrenalectomy after repeating functional workup, as recommended by the American Urological Association 3