Summary

We describe a married couple who both presented with hypertension and hypokalaemia. Both patients were diagnosed with pseudohyperaldosteronism triggered by the widely used antifungal drug itraconazole. This effect appears to be dose-dependent, where a daily intake of 100 mg itraconazole is enough to induce pseudohyperaldosteronism. Clinicians should be aware of pseudohyperaldosteronism as a possible adverse effect of itraconazole, and we recommend monitoring potassium levels and blood pressure in all patients receiving this drug over a longer period of time. Voriconazole is probably an alternative antifungal treatment to itraconazole but also with this drug potassium levels should be monitored.

Background

Hypertension is a common disease, and for 90%–95% of the people suffering from this, an underlying causality cannot be identified.1 Many secondary reasons for hypertension do however exist, including primary hyperaldosteronism and adverse effects to different types of medication.2

Patients suffering from primary hyperaldosteronism have abnormally high levels of aldosterone, which induces hypertension and hypokalaemia through its binding to the mineralocorticoid receptor along with a suppression of plasma renin levels.3 Aldosterone and cortisol are both able to bind and activate the mineralocorticoid receptor in the kidneys, but cortisol’s activation is normally inhibited by the 11-β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme, which converts cortisol into cortisone (see figure 1). Reduced activity of the 11β-HSD2 enzyme may cause cortisol activating the mineralocorticoid receptor. This causes a state of apparent mineralocorticoid excess,4 and results in patients presenting with clinical features resembling primary hyperaldosteronism.