What is the recommended treatment for bilateral adrenal adenomas?

Treatment of Bilateral Adrenal Adenomas

For bilateral adrenal adenomas, medical management with mineralocorticoid receptor antagonists (MRAs) is the primary treatment approach, as bilateral disease precludes unilateral adrenalectomy which would result in lifelong steroid dependency. 1

Initial Diagnostic Considerations

The treatment strategy depends critically on whether the bilateral adenomas are functioning or non-functioning:

Hormonal Evaluation Required

Every patient with bilateral adrenal adenomas requires comprehensive hormonal testing to determine functionality 1:

• Primary aldosteronism screening: Plasma aldosterone-to-renin ratio (ARR >20-30 suggests hyperaldosteronism) 2
• Autonomous cortisol secretion: 1-mg overnight dexamethasone suppression test (cortisol >1.8 μg/dL or >50 nmol/L indicates mild autonomous cortisol secretion) 3, 4
• Pheochromocytoma exclusion: Plasma fractionated metanephrines or 24-hour urinary metanephrines 5, 4

Treatment Based on Functionality

Bilateral Hyperaldosteronism (Primary Aldosteronism)

Medical management with MRAs is the definitive treatment for bilateral adrenal hyperplasia causing primary aldosteronism 2, 1:

• First-line agent: Spironolactone is preferred due to low cost and widespread availability 3
• Alternative: Eplerenone for patients intolerant to spironolactone 2
• Monitoring: Titrate MRA dose to raise renin from baseline, monitor potassium, renal function, and blood pressure 3
• Goal: Normalize blood pressure and mitigate cardiovascular and renal damage from aldosterone excess 1

The 2024 Endocrine consensus explicitly states that bilateral adrenal hyperplasia is an absolute indication for medical treatment rather than surgery 1.

Bilateral Mild Autonomous Cortisol Secretion (MACS)

For bilateral MACS, management focuses on treating cortisol-related comorbidities rather than the adenomas themselves 6, 4:

• Screen for and aggressively treat: Hypertension, type 2 diabetes, osteoporosis, cardiovascular disease 4
• Surgical consideration: Unilateral adrenalectomy may be considered in highly selected cases with marked adrenal asymmetry on imaging and severe comorbidities, though this may only provide temporary remission or improvement 6, 7
• Medical therapy: Adrenostatic agents (ketoconazole 400-1200 mg/day) can be considered when surgery is not an option, though not FDA-approved for MACS 2, 7

Bilateral Cushing Syndrome (ACTH-Independent)

When bilateral multinodular hyperplasia causes symmetric cortisol production, medical management is indicated 2:

• Adrenal vein sampling: Determines if cortisol production is symmetric or asymmetric 2
• If symmetric: Medical management with ketoconazole (400-1200 mg/day) or mitotane 2
• If asymmetric: Unilateral adrenalectomy of the most active side with postoperative corticosteroid supplementation 2
• Severe cases: Bilateral adrenalectomy reserved only for severe, uncontrolled hypercortisolism, accepting lifetime steroid dependency 2, 7

Non-Functioning Bilateral Adenomas

Observation is appropriate for non-functioning bilateral adenomas with benign imaging characteristics 4, 8:

• Benign features: Homogeneous, Hounsfield units ≤10 on unenhanced CT, no growth on follow-up 4
• Follow-up imaging: Not routinely required if clearly benign (HU ≤10) 4
• Surveillance: Consider repeat imaging at 6-12 months if initial characteristics are indeterminate 4, 8

Critical Pitfalls to Avoid

Never perform bilateral adrenalectomy for bilateral adenomas unless dealing with life-threatening, uncontrolled Cushing syndrome, as this creates permanent adrenal insufficiency requiring lifelong glucocorticoid and mineralocorticoid replacement 2, 7. The 2024 guidelines emphasize that bilateral disease is an absolute indication for medical rather than surgical management 1.

Do not rely on CT imaging alone to determine laterality in primary aldosteronism—adrenal vein sampling is the gold standard, as CT misidentifies laterality in approximately 25% of cases 2, 5. However, in bilateral disease confirmed by imaging or AVS, this distinction becomes moot as medical therapy is indicated 1.

Assess each adrenal mass separately on imaging, as bilateral masses do not necessarily share the same etiology—one could be benign while the other is malignant 9, 8.

Special Populations

Advanced age (>65-70 years): Medical treatment is strongly preferred given higher comorbidity rates and lower surgical efficacy for blood pressure control 1

Genetic/familial forms: MRAs are the standard treatment, except for glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type 1), which requires low-dose dexamethasone or prednisone at night to suppress ACTH, with MRA added if blood pressure goals are not achieved 1