How is primary hyperaldosteronism diagnosed and treated?

Diagnosis and Treatment of Primary Hyperaldosteronism

Primary hyperaldosteronism is diagnosed through a stepwise approach starting with screening via aldosterone-to-renin ratio, followed by confirmatory testing, and subtype determination to guide treatment with either surgical adrenalectomy for unilateral disease or mineralocorticoid receptor antagonists for bilateral disease.

Screening and Diagnosis

When to Screen

• Screen for primary hyperaldosteronism in patients with:
  • Resistant hypertension 1, 2
  • Hypokalemia (spontaneous or diuretic-induced) 1, 2
  • Adrenal incidentaloma 1, 2
  • Family history of early-onset hypertension 1
  • Stroke at a young age (<40 years) 2

Diagnostic Algorithm

1. Initial Screening Test:

   • Measure the aldosterone-to-renin ratio (ARR) - the most accurate and reliable screening method 1, 2
   • Common cutoff value: 30 when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h 1
   • Plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive 1

2. Pre-Test Conditions:

   • Patients should have unrestricted salt intake 1
   • Serum potassium should be in normal range 1
   • Mineralocorticoid receptor antagonists should be withdrawn for at least 4 weeks before testing 1

3. Confirmatory Testing:

   • Required after positive screening to confirm diagnosis 1, 2
   • Options include intravenous saline suppression test or oral salt-loading test 1
   • Fludrocortisone suppression test is another option (failure of 4-day administration to reduce plasma aldosterone below threshold) 1

4. Subtype Determination:

   • Adrenal venous sampling is crucial to determine if aldosterone production is unilateral or bilateral 1, 2, 3
   • Imaging (CT or MRI) should be performed but may not be sufficient alone 1, 3
   • Without adrenal venous sampling, up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 1

Treatment

Unilateral Disease (50% of cases)

• Surgical Treatment:
  • Unilateral laparoscopic adrenalectomy is the treatment of choice 1, 2, 3
  • Improves blood pressure in virtually 100% of patients 1, 2
  • Results in complete cure of hypertension in approximately 50% of patients 1, 2
  • Minimal morbidity with mean post-operative stay of 2.6 days 1

Bilateral Disease (50% of cases)

• Medical Treatment:
  • Mineralocorticoid receptor antagonists are the cornerstone of treatment 1, 2, 3
  • Spironolactone is the first-line treatment at doses of 100-400 mg daily 4
  • Eplerenone (50-100 mg daily) is an alternative with fewer sexual side effects 3

Special Situations

• For familial hyperaldosteronism type-1 (glucocorticoid-remediable aldosteronism), low-dose dexamethasone treatment is recommended 3
• For patients unsuitable for surgery with unilateral disease, medical therapy with mineralocorticoid receptor antagonists is recommended 4

Common Pitfalls and Caveats

• Diagnostic Pitfalls:

  • Hypokalemia is absent in the majority of primary aldosteronism cases and has low negative predictive value 3
  • Aldosterone-to-renin ratio can be influenced by very low renin levels 1
  • False positive results on imaging are common - adrenal nodules may be non-functioning 1

• Treatment Pitfalls:

  • Avoid combining mineralocorticoid receptor antagonists with other potassium-sparing medications or potassium supplements due to hyperkalemia risk 3, 4
  • Use mineralocorticoid receptor antagonists with caution in patients with significant renal dysfunction 3
  • Delayed diagnosis and treatment may lead to irreversible target organ damage 3, 5
  • Spironolactone can cause side effects such as gynaecomastia which may reduce its usefulness 1

• Monitoring:

  • Regular monitoring of serum potassium is essential when using mineralocorticoid receptor antagonists 4
  • Spironolactone acts as a competitive antagonist of aldosterone, causing increased sodium and water excretion while retaining potassium 4

Primary hyperaldosteronism is an important and increasingly prevalent cause of hypertension that requires prompt diagnosis and targeted treatment to mitigate aldosterone-specific target organ damage and improve outcomes 5.