What are the diagnostic criteria and treatment options for hyperaldosteronism?

Diagnosis and Treatment of Hyperaldosteronism

Primary aldosteronism is diagnosed through a systematic approach involving screening with aldosterone-to-renin ratio (ARR), confirmatory testing, and subtype differentiation, with treatment determined by whether the condition is unilateral or bilateral.

Screening and Initial Evaluation

• Primary aldosteronism occurs in 5-10% of patients with hypertension and up to 20% of patients with resistant hypertension, making it one of the most common causes of secondary hypertension 1
• Screening is recommended for patients with:
  • Resistant hypertension 2, 3, 1
  • Hypertension with spontaneous or diuretic-induced hypokalemia 3, 1
  • Adrenal incidentaloma 2, 1
  • Early-onset hypertension or stroke at young age (<40 years) 2, 3, 1
  • Family history suggesting familial hyperaldosteronism 3, 1

Diagnostic Testing

• The aldosterone-to-renin ratio (ARR) is the recommended initial screening test 2, 3, 1

  • Most commonly used cutoff value is ARR >30 when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h 2
  • Plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive 2
  • Patients should have unrestricted salt intake, normal serum potassium, and mineralocorticoid receptor antagonists withdrawn for at least 4 weeks before testing 2

• Confirmatory testing is required after a positive ARR screening 2, 1

  • Options include intravenous saline suppression test, oral salt-loading test, captopril challenge, or fludrocortisone suppression test 2, 4
  • These tests confirm diagnosis when aldosterone levels remain elevated despite interventions that should suppress aldosterone production 4

Subtype Differentiation

• Approximately 50% of primary aldosteronism cases are unilateral (usually aldosterone-producing adenoma) and 50% are bilateral (idiopathic hyperaldosteronism) 2, 3
• After biochemical confirmation, adrenal imaging (CT or MRI) should be performed to identify potential adenomas and exclude adrenocortical carcinoma 2, 4
• Adrenal venous sampling is the gold standard for differentiating unilateral from bilateral disease, especially in patients >40 years 2, 1, 4
  • This procedure should be performed by an experienced radiologist 1
  • CT/MRI alone is insufficient for subtype differentiation as it may miss small adenomas or show non-functioning nodules 1

Treatment

For Unilateral Disease (Adenoma)

• Laparoscopic unilateral adrenalectomy is the treatment of choice for unilateral disease 2, 3
• Surgery improves blood pressure in virtually 100% of patients and results in complete cure of hypertension in approximately 50% 2, 3
• Early diagnosis and treatment improve cure rates, as delayed treatment may lead to irreversible vascular remodeling 3

For Bilateral Disease (Idiopathic Hyperaldosteronism)

• Medical therapy with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of treatment 2, 3
• Spironolactone is the first-line treatment 3, 5
  • Initial dosage: 25-100 mg daily 5
  • Can be titrated up to 300-400 mg daily if needed 6
  • FDA-approved for long-term maintenance therapy for bilateral micro or macronodular adrenal hyperplasia 5
• Eplerenone (50-100 mg daily) is an alternative with fewer sexual side effects compared to spironolactone 3

Special Considerations

• For familial hyperaldosteronism type 1 (glucocorticoid-remediable), low-dose dexamethasone treatment is recommended 3, 6
• Preoperative treatment with spironolactone (100-400 mg daily) is recommended for patients preparing for surgery 5
• For patients unsuitable for surgery, spironolactone can be used as long-term maintenance therapy at the lowest effective dosage 5

Monitoring and Follow-up

• Close monitoring of electrolytes and renal function is essential when initiating treatment with MRAs 6
• Avoid combining MRAs with other potassium-sparing medications or potassium supplements due to risk of hyperkalemia 3
• Use MRAs with caution in patients with significant renal dysfunction (eGFR <45 mL/min) 3

Common Pitfalls

• Hypokalemia is absent in the majority of primary aldosteronism cases and has low negative predictive value for diagnosis 3
• False positive ARR results can occur with low-renin states, certain medications, and advanced age 1
• False negative ARR results can occur with concurrent use of mineralocorticoid receptor antagonists and severe potassium depletion 1
• Medications that can affect ARR interpretation include MRAs, beta-blockers, direct renin inhibitors, ACE inhibitors, ARBs, and diuretics 1