What are the management and treatment options for an adult patient with a history of hypertension and newly diagnosed adrenal adenoma?

Management of Adrenal Adenoma with Hypertension

All patients with an adrenal adenoma and hypertension must be screened for primary aldosteronism using an aldosterone-to-renin ratio (ARR), and if confirmed, should receive targeted treatment with either unilateral adrenalectomy for unilateral disease or mineralocorticoid receptor antagonists for bilateral disease. 1

Initial Diagnostic Workup

Focused History and Physical Examination

• Assess for signs/symptoms of hormone excess: resistant hypertension (BP not controlled on 3 medications including a diuretic), spontaneous or diuretic-induced hypokalemia, muscle weakness, polyuria, and polydipsia 1
• Critical caveat: Hypokalemia is absent in approximately 50% of primary aldosteronism cases, so normal potassium does NOT exclude the diagnosis 1
• Evaluate for signs of Cushing's syndrome (central obesity, moon facies, striae, proximal muscle weakness) or pheochromocytoma (episodic headaches, palpitations, sweating) 1

Imaging Characterization

• Obtain non-contrast CT to measure Hounsfield units (HU) as first-line imaging 1
• Benign adenoma: HU <10 on non-contrast CT indicates lipid-rich adenoma 1
• If HU >10 or indeterminate, proceed to washout CT or chemical-shift MRI 1
• Do NOT perform adrenal biopsy routinely 1

Comprehensive Hormonal Screening

Mandatory Screening Tests

1. Screen for Primary Aldosteronism (Most Important in Hypertensive Patients)

• Measure simultaneous plasma aldosterone concentration and plasma renin activity to calculate ARR 1, 2
• Patient preparation:
  • Ensure potassium repletion (target 4.0-5.0 mEq/L) before testing, as hypokalemia suppresses aldosterone production 2, 3
  • Discontinue interfering medications when feasible: beta-blockers, centrally acting drugs, and diuretics (cause false-positives by suppressing renin) 2
  • Withdraw mineralocorticoid receptor antagonists at least 4 weeks before testing 2, 3
  • Use long-acting calcium channel blockers or alpha-receptor antagonists as alternatives during testing 2
• Blood collection: Morning (0800-1000 hours), patient out of bed for 2 hours, seated for 5-15 minutes before draw 2
• Positive screening: ARR ≥20-30 AND plasma aldosterone ≥10-15 ng/dL 2, 3

2. Screen for Autonomous Cortisol Secretion

• Perform 1 mg overnight dexamethasone suppression test in ALL patients with adrenal adenomas 1, 3
• This identifies subclinical Cushing's syndrome, which affects treatment decisions 1

3. Screen for Pheochromocytoma (Conditional)

• Skip screening if unequivocal adenoma (HU <10) with no adrenergic symptoms 1
• Perform screening with plasma or 24-hour urinary metanephrines if HU >10 or patient has headaches, palpitations, or sweating 1

4. Screen for Androgen Excess (Conditional)

• Only if suspected adrenocortical carcinoma or clinical virilization present 1

Management Algorithm for Primary Aldosteronism

Step 1: Confirmatory Testing (If ARR Positive)

• Perform confirmatory testing to demonstrate autonomous aldosterone secretion 2, 3
• Options include:
  • Intravenous saline suppression test (2L normal saline over 4 hours; failure to suppress aldosterone <5 ng/dL confirms diagnosis) 2
  • Oral sodium loading with 24-hour urine aldosterone measurement 2
  • Fludrocortisone suppression test 1

Step 2: Subtype Determination (Unilateral vs. Bilateral)

• Adrenal CT imaging: Identify presence and size of adenomas 1
• Adrenal venous sampling (AVS): MANDATORY before offering adrenalectomy to distinguish unilateral from bilateral disease 1, 2
  • Critical pitfall: Up to 25% of patients would undergo unnecessary adrenalectomy based on CT alone, as CT-detected adenomas may be non-functioning and bilateral hyperplasia can coexist 1
  • Exception: AVS may be omitted in patients <40 years with unilateral adenoma on imaging, as bilateral disease is rare in this population 2
• Refer to multidisciplinary team (endocrinologist, surgeon, radiologist) for AVS interpretation and treatment planning 1

Step 3: Treatment Based on Lateralization

For Unilateral Aldosterone-Producing Adenoma:

• Laparoscopic unilateral adrenalectomy is the treatment of choice 1, 4, 5
• Improves blood pressure in virtually 100% of patients and cures hypertension in approximately 50% 2, 4
• Normalizes hypokalemia, reduces antihypertensive medication requirements, and improves cardiac and kidney function 2
• Use minimally-invasive surgery when feasible 1

For Bilateral Disease (Idiopathic Hyperaldosteronism):

• Medical therapy with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of treatment 4, 5
• Spironolactone is first-line: Start 50-100 mg once daily, titrate up to 300-400 mg daily if needed 2, 4, 5
• Eplerenone is an alternative: 50-100 mg daily in 1-2 doses; fewer anti-androgenic side effects (gynecomastia, sexual dysfunction) but less potent than spironolactone 1, 4, 5
• Monitoring protocol:
  • Check potassium and creatinine at 3 days, 1 week, then monthly for first 3 months, then every 3 months if stable 4
  • Monitor renin; if hypertension remains uncontrolled and renin is suppressed, titrate MRA dose upward 3
• Safety precautions:
  • Verify serum potassium ≤5.0 mEq/L and eGFR >30 mL/min before initiating 4
  • Discontinue potassium supplements 4
  • Avoid combining with ACE inhibitors, ARBs, potassium-sparing diuretics, or NSAIDs without close monitoring due to hyperkalemia risk 4
  • Use with caution if eGFR <45 mL/min 4

For Patients Not Candidates for Surgery:

• Treat with MRAs as above 4, 5

Follow-Up for Non-Functional Adenomas

If adenoma is benign and non-functional:

• <4 cm and HU <10: No further imaging or functional testing required 1
• ≥4 cm and HU <10: Repeat imaging in 6-12 months 1
• Growth >5 mm/year: Consider adrenalectomy after repeating functional workup 1
• Growth <3 mm/year: No further imaging or functional testing required 1

Special Considerations

Mild Autonomous Cortisol Secretion

• Younger patients with progressive metabolic comorbidities (diabetes, obesity, osteoporosis) attributable to cortisol excess can be considered for adrenalectomy after shared decision-making 1
• If managed non-surgically, perform annual clinical screening for new or worsening comorbidities 1

Suspected Adrenocortical Carcinoma

• Minimally-invasive adrenalectomy can be offered if tumor can be safely resected without capsule rupture 1
• Open adrenalectomy for larger tumors or locally advanced disease with lymph node metastases or tumor thrombus 1

Post-Adrenalectomy Outcomes

• Even after successful surgery, some patients have residual hypertension due to irreversible vascular remodeling from delayed diagnosis 2
• Earlier diagnosis and treatment improves cure rates 2

Key Pitfalls to Avoid

• Do not rely on hypokalemia as a screening trigger—it's absent in 50% of primary aldosteronism cases 1, 2
• Do not proceed to surgery based on CT findings alone—AVS is essential to prevent unnecessary adrenalectomy 1, 2
• Do not skip screening for primary aldosteronism in hypertensive patients with adrenal adenomas—it's present in up to 20% of resistant hypertension cases 2
• Do not forget to correct hypokalemia before ARR testing—it causes false-negative results 2, 3
• Do not combine MRAs with potassium supplements or ACE inhibitors/ARBs without careful monitoring 4