How to diagnose primary aldosteronism?

Diagnosis of Primary Aldosteronism

Primary aldosteronism should be diagnosed using a stepwise approach beginning with plasma aldosterone-to-renin ratio (ARR) screening, followed by confirmatory testing, and finally subtype differentiation with adrenal imaging and adrenal venous sampling. 1

Initial Screening

• Indications for screening:

  • Resistant hypertension
  • Hypertension with unprovoked hypokalemia
  • Incidentally discovered adrenal mass
  • Family history of early-onset hypertension
  • Stroke at a young age 1
  • Patients with well-controlled hypertension and a first-degree relative with primary aldosteronism 2
  • Hypertension with atrial fibrillation or obstructive sleep apnea 2

• First-line screening test:

  • Plasma aldosterone-to-renin ratio (ARR) 3, 1
  • ARR cutoff value >30 when plasma aldosterone concentration is reported in ng/dL and plasma renin activity in ng/mL/h 3
  • Plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive 3

• Pre-test considerations:

  • Patients should have unrestricted salt intake 3
  • Serum potassium should be in normal range 3, 1
  • Mineralocorticoid receptor antagonists (spironolactone, eplerenone) should be withdrawn for at least 4 weeks before testing 3
  • Morning collection is preferred 1
  • Consider menstrual cycle timing in females 1
  • Be aware that medications can affect results:
    • Beta-blockers, NSAIDs (can falsely elevate ARR)
    • ACE inhibitors, ARBs, diuretics (can falsely lower ARR) 1

Confirmatory Testing

After a positive ARR screening test, confirmatory testing is required to definitively diagnose primary aldosteronism:

• Recommended confirmatory tests:

  • Intravenous saline suppression test 3, 2
  • Oral salt-loading test 3, 2
  • Fludrocortisone suppression test 1, 2
  • Captopril challenge test 2

• Interpretation:

  • Positive result: Failure to suppress aldosterone production despite sodium/volume expansion or captopril administration 2
  • This confirms autonomous aldosterone production independent of the renin-angiotensin system 2

Subtype Differentiation

After biochemical confirmation, determine if the primary aldosteronism is unilateral or bilateral:

1. Adrenal imaging:

   • Computed tomography (CT) of adrenal glands is the first-line imaging study 1
   • MRI if CT is contraindicated 1
   • Note: Imaging alone may be insufficient to determine subtype 1, 4

2. Adrenal venous sampling (AVS):

   • Gold standard for distinguishing unilateral from bilateral disease 1, 4, 5
   • Essential before considering adrenalectomy, particularly in:
     • Patients >40 years old
     • Normal-appearing adrenal glands on imaging
     • Discordance between biochemical and imaging results 1
   • Measures aldosterone concentrations (expressed as aldosterone/cortisol ratio) in each adrenal vein 4
   • 100% accuracy in localizing aldosterone-producing adenomas 5

3. Postural testing:

   • An anomalous postural decrease in plasma aldosterone concentration may indicate adenoma 5

Pitfalls to Avoid

• Don't rely on hypokalemia for screening:

  • At least 20% of primary aldosteronism patients have normal potassium levels 4
  • Only screening patients with hypokalemia will miss many cases 2

• Don't proceed directly to adrenalectomy based on imaging alone:

  • CT or MRI findings can be misleading (nodular hyperplasia can mimic adenoma) 3
  • Without AVS, 25% of patients might undergo unnecessary adrenalectomy 3

• Don't forget to rule out familial forms:

  • Consider genetic testing for suspected familial hyperaldosteronism 6
  • Familial forms include glucocorticoid-remediable aldosteronism 3, 4

Treatment Based on Subtype

• Unilateral disease (adenoma):

  • Laparoscopic adrenalectomy is treatment of choice 3, 1
  • Improves BP in virtually 100% of patients
  • Complete cure of hypertension in ~50% 3, 1

• Bilateral disease (idiopathic hyperaldosteronism):

  • Medical therapy with mineralocorticoid receptor antagonists 3, 1
  • Spironolactone (initial dose 25-100 mg daily, can be titrated up to 400 mg) 7
  • Eplerenone as alternative with fewer side effects 3, 1

Primary aldosteronism is significantly underdiagnosed, with screening rates as low as 2-4% even in high-risk groups 1. Early diagnosis and appropriate treatment can resolve hypokalemia, lower blood pressure, reduce antihypertensive medication requirements, and improve cardiac and kidney function 3.