Endocrine Abstracts

Introduction: Rifampicin is a widely prescribed antibiotic primarily used in the treatment of tuberculosis and other serious infections. Arterial hypertension destabilisation during rifampicin therapy is frequent but remains under-recognised, despite the drug’s widespread and prolonged use. Rifampicin is well known for its potent induction of cytochrome P450 (CYP) enzymes, which leads to significant pharmacokinetic interactions with various drugs, including antihypertensives. However, beyond these pharmacokinetic interactions, rifampicin might induce hypertensive effects by other mechanisms.

Case presentation: A 64-year-old woman with a 10-year history of reasonably controlled arterial hypertension, was hospitalized for spondylodiscitis and treated with rifampicin. Soon, severe grade III hypertension emerged despite maximal doses of five antihypertensive drugs, alongside worsening hypokalemia despite supplementation. Extensive workup excluded secondary causes of arterial hypertension, revealed suppressed renin and aldosterone with increased kaliuria, and showed elevated serum free cortisol and ACTH. Adjustments of antihypertensive treatment for rifampicin’s drug interactions failed to improve blood pressure control. Rifampicin was discontinued after six weeks, resulting in gradual normalization of blood pressure, potassium levels, and endocrine markers.

Discussion: Rifampicin induces CYP3A4, which lowers the potency of many antihypertensives. However, in this case, the use of drugs that demonstrate minimal or no interaction with rifampicin fails to control blood pressure, suggesting the existence of other mechanisms leading to arterial hypertension destabilisation. Our patient developed pseudohyperaldosteronism associated with rifampicin therapy. This could be mediated by accelerated cortisol metabolism by CYP3A4, which increases ACTH-driven corticosterone with mineralocorticoid effects. Rifampicin is also an agonist of the pregnane X receptor, an emerging receptor with hypertensive effects.

Conclusion: This case highlights rifampicin as a cause of severe hypertension. This effect is mainly, but not exclusively, linked to pharmacokinetic drug interactions. Rifampicin-driven pseudohyperaldosteronism and pregnane X receptor agonisation may also be involved.

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Keywords: Malignant hypertension, Rifampicin, Cytochrome P450, Pseudohyperaldosteronism, Pregnane X receptor