What are the guidelines for monitoring a patient with an adrenal nodule, particularly those with a history of hypertension or symptoms suggestive of hormonal excess, such as Cushing's syndrome or primary aldosteronism?

Adrenal Nodule Monitoring Guidelines

Initial Hormonal Screening (Required for All Patients)

All patients with adrenal incidentalomas ≥1 cm must undergo a 1 mg overnight dexamethasone suppression test to screen for autonomous cortisol secretion, regardless of imaging characteristics or symptoms. 1, 2, 3

• Administer 1 mg dexamethasone at 11 PM and measure serum cortisol at 8 AM the following morning 2
• Interpret results as follows: ≤50 nmol/L (1.8 μg/dL) excludes autonomous cortisol secretion; 51-138 nmol/L (1.9-5.0 μg/dL) indicates possible autonomous secretion; >138 nmol/L (>5.0 μg/dL) confirms autonomous cortisol secretion 1, 2, 3

For patients with hypertension and/or hypokalemia, measure plasma aldosterone-to-renin ratio to screen for primary aldosteronism. 1, 2, 4

• A ratio >20 ng/dL per ng/mL/hr has excellent sensitivity and specificity for hyperaldosteronism 2, 4, 3
• If primary aldosteronism is confirmed, adrenal vein sampling is recommended before offering adrenalectomy to distinguish unilateral adenoma from bilateral hyperplasia 1

Screen for pheochromocytoma only if the mass measures ≥10 Hounsfield Units (HU) on non-contrast CT or if symptoms of catecholamine excess are present (episodic hypertension, headaches, palpitations, diaphoresis). 1, 2, 4

• Use plasma free metanephrines or 24-hour urinary metanephrines and normetanephrines 1, 2, 3
• Do not screen patients with confirmed lipid-rich adenomas (<10 HU) who lack symptoms 1, 3

Imaging Surveillance Protocol

For benign-appearing adenomas <4 cm with <10 HU on non-contrast CT and normal hormonal workup: repeat imaging at 12 months, then discontinue surveillance if stable. 1

• The CUA recommends reimaging at 12 months from diagnosis, then clinical follow-up annually for 4 years 1
• No further imaging follow-up is required for benign non-functional adenomas <4 cm, myelolipomas, and other small masses containing macroscopic fat 2

For benign-appearing adenomas 4-6 cm: repeat imaging at 3-6 months, then at 6-12 month intervals for 1-2 years. 1

• If the mass enlarges by >1 cm in 1 year, consider adrenalectomy for suspected carcinoma 1
• For radiologically benign (≤10 HU) but ≥4 cm non-functional lesions, repeat imaging in 6-12 months 2

For indeterminate masses on initial imaging: obtain washout CT or chemical-shift MRI, then repeat imaging in 3-6 months. 1

• If >60% absolute washout at 15 minutes on contrast-enhanced CT, the tumor is likely benign 1
• Continue annual imaging for 1-2 additional years if stable 1

Hormonal Surveillance Protocol

For non-functional adenomas: ESE does not recommend repeat hormonal testing if initial values were normal. 1

However, there is significant divergence among guidelines:

• AACE/AAES recommend annual hormonal panels for 5 years after diagnosis 1
• CUA recommends annual hormonal testing for 4 years 1
• KES recommends annual testing for 4-5 years if the tumor is >3 cm 1

For masses with growth of 3-5 mm/year: continued surveillance is appropriate without extensive hormonal testing. 2

For masses with growth >5 mm/year: repeat complete functional workup before considering surgical intervention. 2

Post-Surgical Surveillance

For patients who underwent complete resection of adrenocortical carcinoma: follow-up every 3 months for 2 years with abdominal CT (or MRI), thoracic CT, and monitoring of initially elevated steroids. 1

• After 2 years, intervals may be gradually increased 1
• Continue follow-up for at least 10 years due to risk of late recurrence 1

For patients who underwent successful surgery for pheochromocytoma: repeat biochemical testing 14 days post-surgery to check for residual disease, then every 3-4 months for 2-3 years, followed by every 6 months thereafter. 1

• Lifelong surveillance is recommended, especially for patients with extra-adrenal primary disease, tumor size >5 cm, or SDHB mutations 1

Critical Pitfalls to Avoid

Do not skip dexamethasone suppression testing even in small, benign-appearing masses, as autonomous cortisol secretion is present in 5.3% of incidentalomas. 3

Do not perform adrenal biopsy routinely—only consider when diagnosis of metastatic disease from an extra-adrenal malignancy would change management. 1, 2, 3

• Always rule out pheochromocytoma before biopsy to avoid precipitating a hypertensive crisis 1, 3

Do not rely solely on CT imaging to distinguish unilateral aldosterone-producing adenoma from bilateral hyperplasia—adrenal vein sampling is the gold standard. 1

• CT imaging is not always reliable for lateralization 1
• However, adrenal vein sampling may be excluded in patients <40 years with unilateral disease on imaging, as bilateral hyperplasia is rare in this population 1

For patients with cortisol-secreting adenomas undergoing adrenalectomy, postoperative corticosteroid supplementation is required until recovery of the hypothalamus-pituitary-adrenal axis. 1