Adrenal Mass Evaluation and Management

Introduction to Adrenal Masses

• Adrenal masses are categorized into three groups: benign non-functional lesions, benign hyperfunctioning lesions, and malignant lesions, as stated by The Journal of Urology 1, 2, 3

Differential Diagnosis

• Adenomas are the most common type of adrenal mass, representing the majority of incidentalomas, according to The Journal of Urology 1, 3
• Myelolipomas are a type of benign non-functional lesion that contain macroscopic fat, as noted in Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4
• Cortisol-secreting adenomas are present in 5.3% of incidentalomas, as reported by The Journal of Urology 3
• Aldosterone-secreting adenomas are present in 1% of incidentalomas, according to The Journal of Urology 3
• Pheochromocytomas are present in 5.1% of incidentalomas, as stated by The Journal of Urology 3
• Adrenocortical carcinoma is present in 4.7% of incidentalomas, as noted by The Journal of Urology 3
• Metastases are present in 2.5% of incidentalomas, but up to 50% in patients with known extra-adrenal malignancy, according to The Journal of Urology, however, the second part of the fact contains [ignore ref] and will be rephrased, Metastases are present in 2.5% of incidentalomas 3

Laboratory Work-Up Algorithm

• All patients with adrenal incidentalomas ≥1 cm require biochemical screening for hormone excess, regardless of imaging characteristics or symptoms, as recommended by The Journal of Urology and Praxis Medical Insights: Practical Summaries of Clinical Guidelines, however, The Journal of Urology is preferred 1, 4, 5
• The 1 mg overnight dexamethasone suppression test is mandatory for all patients, as stated by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4, 6
• The test measures serum cortisol at 8 AM the next morning, and the interpretation is as follows: ≤50 nmol/L (1.8 μg/dL) excludes autonomous cortisol secretion, 51-138 nmol/L (1.9-5.0 μg/dL) suggests possible autonomous cortisol secretion, and >138 nmol/L (>5.0 μg/dL) is evidence of autonomous cortisol secretion, as noted by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4, 6
• Pheochromocytoma screening should be performed if the adrenal mass is ≥10 HU on non-contrast CT, or if symptoms of catecholamine excess are present, as recommended by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4, 5
• Primary aldosteronism screening should be performed if hypertension or hypokalemia is present, as stated by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4
• Androgen testing should be performed if suspected adrenocortical carcinoma or clinical signs of virilization or feminization are present, as noted by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4, 6

History and Physical Examination Targets

• The history and physical examination should focus on identifying signs and symptoms of hormone excess and malignancy, as recommended by The Journal of Urology and Praxis Medical Insights: Practical Summaries of Clinical Guidelines, however, The Journal of Urology is preferred 1, 7, 2
• Signs and symptoms of cortisol excess include weight gain, central obesity, moon facies, buffalo hump, purple striae, easy bruising, proximal muscle weakness, hypertension, diabetes, and osteoporosis, as noted by The Journal of Urology 1
• Signs and symptoms of aldosterone excess include resistant hypertension, hypokalemia, muscle weakness, and cramping, as stated by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4
• Signs and symptoms of catecholamine excess include episodic or sustained hypertension, headaches, palpitations, diaphoresis, anxiety, tremor, and pallor, as noted by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4
• Signs and symptoms of androgen or estrogen excess include virilization in women, feminization in men, hirsutism, deepening voice, clitoromegaly, gynecomastia, and testicular atrophy, as stated by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4, 6

Medication Interference Considerations

• Interfering medications should be held before testing when possible, as recommended by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4
• Beta-blockers, ACE inhibitors, and ARBs can affect the aldosterone/renin ratio, as noted by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4
• Tricyclic antidepressants and decongestants can affect metanephrine testing, as stated by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4
• Estrogen and rifampin can affect cortisol testing, as noted by Praxis Medical Insights: Practical Summaries of Clinical Guidelines, but a similar fact from The Journal of Urology is preferred, however, it is not available 4

When to Involve Multidisciplinary Team

• A multidisciplinary team should be involved when imaging is not consistent with a benign lesion, evidence of hormone hypersecretion is present, tumor growth is >5 mm/year during surveillance, or adrenal surgery is being considered, as recommended by The Journal of

Management of Calcified Adrenal Masses

Clinical Presentation

• Calcified adrenal myelolipomas often contain macroscopic fat, distinguishing them from other calcified adrenal lesions. 8
• Autonomous cortisol secretion may manifest as weight gain, central obesity, facial rounding, dorsocervical fat pad, skin changes (purple striae, easy bruising), proximal muscle weakness, hypertension, and glucose intolerance. 8
• Androgen or estrogen excess can present with virilization, hirsutism, deepening of voice, precocious puberty, or gynecomastia. 8
• Primary aldosterone excess is suggested by resistant hypertension, unexplained low potassium levels, and associated muscle weakness. [9][10]
• A known history of extra‑adrenal malignancy markedly raises the likelihood that a calcified adrenal mass represents metastatic disease. 11

Biochemical Evaluation

• All patients with a calcified adrenal mass ≥1 cm should undergo comprehensive hormonal testing irrespective of imaging characteristics. 9
• To exclude pheochromocytoma, plasma free metanephrines or 24‑hour urinary fractionated metanephrines are measured; values >2 × the upper reference limit confirm the diagnosis. 9
• In individuals with hypertension or low potassium, an aldosterone‑to‑renin ratio >20 ng/dL per ng·mL⁻¹·hr⁻¹ indicates primary aldosteronism. [9][10]

Imaging Assessment

• Non‑contrast computed tomography (CT) is the mandatory first‑line imaging modality for adrenal lesions. [9][8]
• On non‑contrast CT, an attenuation ≤10 HU reliably identifies a benign adenoma with essentially 0 % risk of malignancy. 9
• Lesions demonstrating attenuation >10 HU require secondary imaging—either contrast‑enhanced washout CT or chemical‑shift magnetic resonance imaging—to further characterize lesion nature. [9][8]

Size‑Based Risk Stratification

• Adrenal masses <3 cm are predominantly benign; however, hormonal assessment remains obligatory. 11
• For lesions measuring 3–5 cm, surgical removal should be contemplated when imaging is indeterminate or functional activity is demonstrated. 11
• Masses >5 cm warrant surgical resection because of a substantially increased risk of malignancy. 11

Follow‑up and Multidisciplinary Review

• Benign‑appearing, non‑functional adenomas <4 cm with CT attenuation ≤10 HU do not require further imaging or repeat hormonal testing. 8
• Radiologically benign lesions ≥4 cm should undergo repeat imaging at 6–12 months; adrenalectomy is advised if growth exceeds 5 mm per year after reassessment of hormonal status. 8
• Immediate multidisciplinary consultation (endocrinology, surgery, radiology) is indicated when imaging is atypical for a benign lesion, when hormone hypersecretion is confirmed, when tumor growth surpasses 5 mm per year, or when surgical intervention is being considered. 9
• Adrenal biopsy is reserved for rare scenarios where metastatic disease from a known extra‑adrenal primary would alter management, and only after pheochromocytoma has been definitively excluded. 8