Medications That Cause Hyperaldosteronism
The medications that most commonly cause true hyperaldosteronism (elevated aldosterone levels) are systemic corticosteroids, particularly fludrocortisone, which directly increases aldosterone-like activity through mineralocorticoid receptor activation. 1, 2
However, it's critical to distinguish between true hyperaldosteronism (elevated aldosterone) and pseudohyperaldosteronism (suppressed aldosterone with mineralocorticoid-like effects), as the latter is far more common with medication use.
Medications Causing True Hyperaldosteronism
Systemic Corticosteroids
- Fludrocortisone is the primary medication that causes true mineralocorticoid excess, acting on distal renal tubules to enhance sodium reabsorption and increase potassium and hydrogen ion excretion 2
- Other systemic corticosteroids (dexamethasone, methylprednisolone, prednisone, prednisolone) can elevate blood pressure through mineralocorticoid effects, though less potently than fludrocortisone 1
Medications Causing Pseudohyperaldosteronism (Suppressed Aldosterone)
These agents mimic aldosterone's effects while actually suppressing both renin and aldosterone levels—this is the more common medication-related scenario:
Licorice and Glycyrrhizin-Containing Products
- Glycyrrhizic acid (licorice) inhibits 11-beta-hydroxysteroid dehydrogenase type-2, allowing cortisol to activate mineralocorticoid receptors, causing hypertension, hypokalemia, and metabolic alkalosis with suppressed renin and aldosterone 3, 4, 5
- Found in herbal supplements, confectionary products, and some traditional medicines 4, 5
- Can cause life-threatening refractory hypokalemia and hypertensive crisis 5
- Drug interactions: Cilostazol combined with glycyrrhizin can precipitate severe pseudohyperaldosteronism even in patients who previously tolerated glycyrrhizin alone 6
Other Medications That Raise Blood Pressure (But Don't Cause Hyperaldosteronism)
The following medications elevate blood pressure through non-aldosterone mechanisms and should not be confused with causes of hyperaldosteronism:
- Oral contraceptives 1
- NSAIDs (antagonize antihypertensive effects but don't cause hyperaldosteronism) 1
- CNS stimulants (amphetamines, methylphenidate) 1
- Decongestants (pseudoephedrine, phenylephrine) 1
- Immunosuppressants (cyclosporine) 1
- Antidepressants (MAOIs, SNRIs, TCAs) 1
- Recreational drugs (cocaine, methamphetamine, anabolic steroids) 1
- Herbal supplements (ephedra/ma huang, St. John's wort with MAOIs) 1
Clinical Pitfalls to Avoid
- Don't confuse medication-induced hypertension with hyperaldosteronism—most blood pressure-elevating medications do NOT cause aldosterone excess 1
- Always obtain a comprehensive medication history including over-the-counter products, herbal supplements, dietary habits (especially licorice-containing foods), and recreational drugs when evaluating hypertension with hypokalemia 1, 4
- Pseudohyperaldosteronism from licorice presents identically to primary hyperaldosteronism (hypertension, hypokalemia, metabolic alkalosis) but has suppressed renin and aldosterone levels, not elevated aldosterone 3, 4, 5
- Licorice toxicity can be refractory to potassium replacement and requires discontinuation of the offending agent for resolution 5