What is the workup for an adrenal adenoma?

From the Guidelines

The workup of an adrenal adenoma should begin with a thorough clinical evaluation, including a focused history and physical examination, to determine if the mass is functioning or non-functioning, as recommended by the most recent guidelines 1. The initial step in the workup of an adrenal adenoma is to identify signs/symptoms of adrenal hormone excess, adrenal malignancy, and/or extra-adrenal malignancy through a clinical evaluation. Initial laboratory tests should include:

• a 1mg overnight dexamethasone suppression test to screen for cortisol excess,
• plasma metanephrines or 24-hour urinary metanephrines to rule out pheochromocytoma,
• and plasma aldosterone-to-renin ratio to assess for primary aldosteronism, as suggested by 1. For imaging, a non-contrast CT scan should be performed first to determine the density of the mass; adenomas typically have low attenuation (<10 Hounsfield units) due to their high lipid content. If the adenoma is non-functioning and smaller than 4 cm with benign radiographic features, surveillance with repeat imaging at 6-12 months is appropriate, as recommended by 1. For functioning adenomas, referral to an endocrinologist is necessary for management of hormonal excess. Surgical resection is generally recommended for adenomas that are hormonally active, larger than 4 cm, or show concerning features on imaging such as irregular borders or heterogeneity, with the laparoscopic adrenalectomy approach preferred when surgery is indicated, as suggested by 1. This systematic approach helps distinguish benign adenomas from potentially malignant lesions and identifies those requiring intervention versus observation. Key considerations in the workup and management of adrenal adenomas include:
• The importance of a multidisciplinary review by endocrinologists, surgeons, and radiologists when the imaging is not consistent with a benign lesion, there is evidence of hormone hypersecretion, the tumor has grown significantly during follow-up imaging, or adrenal surgery is being considered, as recommended by 1.
• The need for shared decision-making between patients and their clinicians in the management of indeterminate non-functional adrenal lesions, as suggested by 1.

From the Research

Work-up of Adrenal Adenoma

To work up an adrenal adenoma, the following steps should be taken:

• Dedicated adrenal imaging should be performed for each adrenal mass 2
• A thorough clinical and endocrine work-up should be done to exclude hormone excess, including: + Measurement of plasma or urinary metanephrines + A 1-mg overnight dexamethasone suppression test (with a cutoff value of serum cortisol ≤50 nmol/L [≤1.8 µg/dL]) 2, 3, 4
• Patients with adrenal incidentalomas should be screened for potential cortisol-related comorbidities, such as hypertension and type 2 diabetes mellitus 2
• The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health, and patient preference 2

Evaluation of Malignancy Risk

• Homogeneous lesions with Hounsfield unit (HU) ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size 2
• Lesions >4 cm that are inhomogeneous or have HU >20 have a sufficiently high risk of malignancy that surgery will be the usual management of choice 2
• Malignancy is diagnosed in 5% to 8% of patients with adrenal tumors, with a higher risk in young patients, those with a history of extra-adrenal malignancy, and those with large adrenal tumors with indeterminate imaging characteristics 3

Hormone Excess Evaluation

• Mild autonomous cortisol secretion can be diagnosed in up to 30% to 50% of patients with adrenal incidentalomas 3
• Autonomous cortisol secretion is associated with increased cardiovascular morbidity and metabolic abnormalities 3, 5
• Testing for hyperaldosteronism should be performed in hypertensive and/or hypokalemic patients 4
• The prevalence of autonomous aldosterone secretion is increased in hypertensive patients with adrenal adenomas, even when the latter represented an incidental finding 6