Increased plasma 11-deoxycorticosterone during spironolactone medication

Area of Science:

• Endocrinology
• Pharmacology
• Clinical Chemistry

Background:

• Spironolactone is a medication used to treat conditions like heart failure and high blood pressure.
• Previous studies suggested that spironolactone might interfere with assays measuring deoxycorticosterone (DOC).
• Understanding potential assay interferences is crucial for accurate clinical interpretation of hormone levels.

Purpose of the Study:

• To determine if the observed increase in plasma deoxycorticosterone (DOC) levels after spironolactone administration is a genuine physiological effect.
• To investigate the potential for cross-interference by spironolactone and its metabolites in DOC assays.

Main Methods:

• In vitro and in vivo experiments were conducted to assess drug interference.
• Liquid-liquid extraction and paper chromatography were used to isolate and analyze metabolites.
• Highly specific antiserum was employed in the DOC assay.
• DOC levels were compared in normal subjects and patients with Addison's disease after spironolactone administration.

Main Results:

• Spironolactone administration leads to a real increase in plasma DOC levels.
• Canrenone, a metabolite of spironolactone, showed minor interference in the assay after specific extraction and chromatography steps.
• The high specificity of the antiserum ensured that the total procedural cross-interference was less than 2% of DOC plasma levels.
• Patients with Addison's disease exhibited only a minimal increase in DOC levels post-spironolactone, unlike normal subjects.

Conclusions:

• The increase in plasma DOC levels following spironolactone administration is a genuine effect.
• Assay interference from spironolactone and its metabolites is negligible due to the assay's high specificity.
• These findings validate the accuracy of DOC measurements in patients treated with spironolactone.