Isn't plasma renin activity (PRA) supposed to be suppressed in primary hyperaldosteronism?

Yes, Plasma Renin Activity (PRA) is Typically Suppressed in Primary Hyperaldosteronism

In primary hyperaldosteronism, plasma renin activity (PRA) is characteristically suppressed due to the autonomous overproduction of aldosterone, which leads to sodium retention and volume expansion that inhibits renin release. 1

Pathophysiology and Diagnostic Implications

Primary hyperaldosteronism (also called primary aldosteronism) is defined as a group of disorders characterized by:

• Inappropriately high aldosterone production for sodium status
• Relative autonomy from normal regulators (angiotensin II and potassium)
• Inability to suppress aldosterone with sodium loading

The classic pathophysiological sequence is:

1. Autonomous aldosterone overproduction
2. Increased sodium retention
3. Mild extracellular volume expansion
4. Suppression of renin release
5. Low plasma renin activity

This is why the aldosterone-to-renin ratio is the recommended screening test for primary hyperaldosteronism, with a ratio >30 (when aldosterone is measured in ng/dL and PRA in ng/mL/h) generally considered positive. 1

Exceptions to Suppressed Renin

While suppressed PRA is the hallmark of primary hyperaldosteronism, there are important exceptions:

• Hypertensive kidney damage: In patients with longstanding, severe hypertension due to primary hyperaldosteronism, renal arteriolosclerosis can develop, causing PRA to escape from suppression 2

• Advanced disease: Patients with elevated serum creatinine may have normal or even elevated PRA despite having primary hyperaldosteronism 2

• Medication effects: Certain antihypertensive medications can artificially raise PRA

In these cases, the aldosterone-to-renin ratio may still be elevated due to disproportionately high aldosterone levels relative to the renin levels, allowing the diagnosis to be made despite the absence of completely suppressed renin. 2

Diagnostic Considerations

When screening for primary hyperaldosteronism:

• The plasma aldosterone concentration should be at least 10 ng/dL to interpret a high aldosterone-to-renin ratio as positive 1

• Patients should have:

  • Unrestricted salt intake
  • Normal serum potassium
  • Mineralocorticoid receptor antagonists (spironolactone, eplerenone) withdrawn for at least 4 weeks before testing 1

• Confirmatory testing (IV saline suppression test or oral salt-loading test) is generally required after a positive screening test 1

Clinical Implications

Early diagnosis and treatment of primary hyperaldosteronism is crucial because:

• It's more common than previously thought (8-20% of hypertensive patients) 1
• Hypokalemia is absent in the majority of cases 1
• The deleterious effects of aldosterone overproduction are often reversible with proper treatment 1
• Delayed diagnosis can lead to vascular remodeling and permanent hypertension 1

Remember that even in cases where PRA is not completely suppressed, an elevated aldosterone-to-PRA ratio remains a useful screening tool for primary hyperaldosteronism. 2