What medications can cause hyperaldosteronism?

Medications That Cause Hyperaldosteronism

Fludrocortisone is the primary medication that causes true hyperaldosteronism through direct mineralocorticoid receptor activation, while most other blood pressure-elevating medications do not cause actual aldosterone excess. 1

Medications Causing True Hyperaldosteronism

Fludrocortisone (Primary Culprit)

• Fludrocortisone is the most potent medication causing true hyperaldosteronism by directly activating mineralocorticoid receptors in the distal renal tubules, enhancing sodium reabsorption and increasing potassium and hydrogen ion excretion 1, 2
• The FDA label confirms that even small oral doses produce marked sodium retention, increased urinary potassium excretion, and elevated blood pressure through these electrolyte effects 2
• The biological half-life is 18-36 hours, meaning effects persist well beyond the plasma half-life of 3.5 hours 2

Other Systemic Corticosteroids (Weaker Effect)

• Dexamethasone, methylprednisolone, prednisone, and prednisolone can elevate blood pressure through mineralocorticoid effects, though significantly less potently than fludrocortisone 1
• These agents work through similar mechanisms but have lower mineralocorticoid activity relative to their glucocorticoid effects 1

Substances Causing Pseudo-Hyperaldosteronism

Licorice and Related Compounds

• Glycyrrhizic acid (licorice) causes pseudo-hyperaldosteronism by saturating 11β-hydroxysteroid dehydrogenase type 2, allowing cortisol to activate mineralocorticoid receptors 3, 4
• This presents with resistant hypertension and hypokalemia but with suppressed renin AND aldosterone levels, distinguishing it from true hyperaldosteronism 4
• Carbenoxolone and excessive grapefruit consumption can cause similar effects through the same mechanism 3

Critical Clinical Distinction

Medications That Elevate Blood Pressure WITHOUT Causing Hyperaldosteronism

The following medications raise blood pressure through non-aldosterone mechanisms and should NOT be confused with causes of hyperaldosteronism 1:

• NSAIDs: Antagonize antihypertensive effects but do not cause aldosterone excess 1
• Oral contraceptives: Elevate blood pressure through non-aldosterone mechanisms 1
• CNS stimulants (amphetamines, methylphenidate): Raise blood pressure through sympathetic activation 1
• Decongestants (pseudoephedrine, phenylephrine): Cause vasoconstriction without aldosterone involvement 1
• Immunosuppressants (cyclosporine): Elevate blood pressure through vascular mechanisms 1
• Antidepressants (MAOIs, SNRIs, TCAs): Increase blood pressure through neurotransmitter effects 1
• Recreational drugs (cocaine, methamphetamine, anabolic steroids): Raise blood pressure through various non-aldosterone pathways 1

Common Pitfalls to Avoid

Diagnostic Confusion

• The most critical error is confusing medication-induced hypertension with true hyperaldosteronism, as most blood pressure-elevating medications do not cause aldosterone excess 1
• When evaluating hypertension with hypokalemia, obtain a comprehensive medication history including over-the-counter products, herbal supplements, dietary habits (especially licorice-containing foods), and recreational drugs 1

Interference with Diagnostic Testing

• Beta-blockers cause marked renin suppression without significantly altering aldosterone levels, leading to a falsely elevated aldosterone-to-renin ratio and false-positive screening for primary aldosteronism in patients with essential hypertension 5
• Spironolactone causes renin to escape suppression and reach very high levels, interfering with diagnostic accuracy 5
• Calcium channel blockers have minimal impact on the renin-aldosterone system and may be continued during screening 5

Key Distinguishing Features

• True hyperaldosteronism: Elevated aldosterone with suppressed renin 1, 6
• Pseudo-hyperaldosteronism (licorice toxicity): Suppressed aldosterone AND suppressed renin 3, 4
• Medication-induced hypertension: Normal aldosterone and renin unless the medication interferes with testing 1