What is the appropriate workup for an adrenal adenoma?

From the Guidelines

The workup for adrenal adenoma should begin with a thorough clinical evaluation, laboratory testing, and imaging studies, prioritizing the identification of signs/symptoms of adrenal hormone excess, adrenal malignancy, and/or extra-adrenal malignancy, as recommended by the most recent guidelines 1.

Initial Evaluation

The initial evaluation should include a focused history and physical examination, as well as laboratory tests such as a complete metabolic panel, 24-hour urinary free cortisol, overnight dexamethasone suppression test (1 mg), plasma metanephrines, and aldosterone-to-renin ratio to assess for hormonal activity.

Imaging Studies

For imaging, a non-contrast CT scan with adrenal protocol is the first-line study, with MRI reserved for cases requiring further characterization, as suggested by the guidelines 1. Adenomas typically appear as well-circumscribed lesions with low attenuation (<10 Hounsfield units) on CT.

Functional Adenomas

For functional adenomas, specific testing is required:

• for suspected Cushing's syndrome, perform late-night salivary cortisol and ACTH levels;
• for primary aldosteronism, conduct confirmatory salt loading tests;
• and for pheochromocytoma, obtain 24-hour urinary catecholamines.

Management

Management depends on functionality and size - non-functioning adenomas smaller than 4 cm can typically be monitored with repeat imaging at 6,12, and 24 months, while functional adenomas or those larger than 4-6 cm generally require surgical removal, typically via laparoscopic adrenalectomy, as recommended by the guidelines 1. Some key points to consider in the management of adrenal adenomas include:

• The importance of screening for cortisol excess in all patients with adrenal incidentalomas, given the potential for autonomous cortisol secretion without overt Cushing’s syndrome 1.
• The role of adrenal vein sampling in distinguishing between unilateral adrenal adenoma and bilateral adrenal hyperplasia in patients with primary aldosteronism, as discussed in the guidelines 1.
• The recommendation for laparoscopic adrenalectomy for adenoma, whereas medical management with spironolactone or eplerenone for hypertension and hypokalemia is recommended for patients with bilateral adrenal hyperplasia and for nonsurgical candidates, as suggested by the guidelines 1.

From the Research

Adrenal Adenoma Workup

• The workup for adrenal adenoma typically involves diagnosing primary aldosteronism, which is characterized by the excess production of aldosterone 2.
• The diagnosis of primary aldosteronism is suggested by low renin activity and high plasma aldosterone concentration in patients with hypertension and hypokalemia 2.
• Confirmatory tests for primary aldosteronism include the lack of suppression of plasma aldosterone after saline infusion, oral salt loading, or oral administration of captopril 2.
• Once primary aldosteronism is diagnosed, it is essential to distinguish between unilateral adrenal adenoma (Conn's syndrome) and bilateral idiopathic adrenal hyperplasia, as the management of these conditions differs 2.
• Physiologic maneuvers, such as posture change, oral administration of cyproheptadine, and radiologic localization techniques (e.g., iodocholesterol scanning and adrenal venous sampling), can help distinguish between unilateral adenoma and bilateral hyperplasia 2.

Clinical Characteristics and Molecular Features

• Aldosterone- and cortisol-coproducing adrenal adenomas (A/CPAs) are a subtype of primary aldosteronism, characterized by the production of both aldosterone and cortisol 3.
• Patients with A/CPAs tend to have larger tumors and higher rates of cardiovascular complications, glucose intolerance, and osteopenia compared to those with pure aldosterone-producing adenomas (APAs) 3.
• Molecular analysis of A/CPAs has revealed similar CYP11B1 and CYP17A1 mRNA expressions as pure APAs, as well as the presence of KCNJ5 mutations in some cases 3, 4.

Diagnosis and Management

• Primary aldosteronism is increasingly recognized as a common cause of secondary hypertension, and its diagnosis and management are crucial for reducing the risk of cardiovascular disease 5.
• The clinical approach to diagnosing primary aldosteronism involves a combination of biochemical tests, imaging studies, and physiological maneuvers to confirm the diagnosis and distinguish between unilateral adenoma and bilateral hyperplasia 5.
• Metabolic reprogramming, including the activation of lipid metabolism and glycolysis, plays a role in the pathogenesis of aldosterone-producing adenomas, and may contribute to their growth and survival 6.