What is the diagnostic approach for primary aldosteronism?

Diagnostic Approach for Primary Aldosteronism

The diagnostic approach for primary aldosteronism begins with screening using the plasma aldosterone-to-renin ratio (ARR) in patients with risk factors, followed by confirmatory testing, and subtype determination through imaging and adrenal venous sampling to guide appropriate treatment. 1

Who to Screen

• Screen patients with any of the following risk factors:
  • Resistant hypertension (BP not controlled on 3 medications including a diuretic) 1
  • Hypokalemia (spontaneous or diuretic-induced) 1, 2
  • Incidentally discovered adrenal mass 1
  • Family history of early-onset hypertension 1
  • Stroke at a young age (<40 years) 1, 3
  • First-degree relative with primary aldosteronism 3
  • Severe hypertension (BP >180/110 mmHg) 1
  • Atrial fibrillation or obstructive sleep apnea with hypertension 3

Initial Screening Test

• Use the plasma aldosterone-to-renin ratio (ARR) as the initial screening test 1, 2
• For a positive ARR test:
  • ARR >30 (when aldosterone is measured in ng/dL and renin activity in ng/mL/h) 1, 4
  • Plasma aldosterone concentration should be at least 10 ng/dL 1, 2
  • Low renin can artificially elevate the ARR even without truly elevated aldosterone 2

Patient Preparation for ARR Testing

• Ensure patient is potassium-replete before testing (hypokalemia can suppress aldosterone production) 4
• Two approaches for medication management:
  1. Test without changing medications and interpret results in context of medications 1, 4
  2. When feasible, discontinue interfering medications before testing: 1, 4
     • Beta-blockers, centrally acting drugs (clonidine, alpha-methyldopa), diuretics
     • Mineralocorticoid receptor antagonists should be withdrawn at least 4 weeks before testing
• Medications that minimally interfere with ARR and can be continued: 1
  • Long-acting calcium channel blockers (dihydropyridine or non-dihydropyridine)
  • Alpha-receptor antagonists
• Collect blood in the morning, with patient seated for 5-15 minutes before collection 4

Confirmatory Testing

• Required after positive ARR screening to confirm diagnosis 1, 2
• Common confirmatory tests include: 1, 2, 4
  • Intravenous saline suppression test
  • Oral salt-loading test with 24-hour urine aldosterone measurement
  • Captopril challenge test
  • Fludrocortisone suppression test
• Testing should be performed with unrestricted salt intake and normal serum potassium levels 1, 4

Subtype Determination

• After confirmation, determine if primary aldosteronism is unilateral or bilateral: 1, 5
  • Adrenal CT imaging is the first step
  • When CT shows a solitary unilateral macroadenoma (>1 cm) with normal contralateral adrenal in a young patient, laparoscopic adrenalectomy may be reasonable 6, 7
  • In cases with normal-appearing adrenals or ambiguous findings, adrenal venous sampling is recommended 6, 7
  • Without adrenal venous sampling, 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 2

Treatment Based on Subtype

• Unilateral disease (aldosterone-producing adenoma): 8, 3

  • Laparoscopic adrenalectomy is the treatment of choice
  • Can cure hypertension or significantly reduce antihypertensive medication requirements
  • Resolves hypokalemia in most cases

• Bilateral disease (idiopathic hyperaldosteronism): 8

  • Medical management with mineralocorticoid receptor antagonists
  • Spironolactone (25-400 mg daily) is first-line therapy
  • Eplerenone is an alternative when spironolactone side effects occur

Common Pitfalls to Avoid

• Not screening high-risk patients (only ~2-4% of eligible patients get screened) 1
• Relying solely on hypokalemia as a marker (absent in majority of cases) 1, 2
• Not considering primary aldosteronism in resistant hypertension (present in up to 20% of cases) 7, 3
• Relying on CT imaging alone for subtype determination without adrenal venous sampling 6, 5
• Not referring patients with suspected primary aldosteronism to specialized centers with expertise in hypertension management 1

Referral Considerations

• Patients with resistant hypertension should be considered for referral to clinical centers with expertise in hypertension management 1
• If primary aldosteronism is confirmed, referral to a hypertension specialist or endocrinologist is recommended for further evaluation and treatment 1