An Abbreviated History of Aldosterone Metabolism, Current and Future Challenges.

The initial isolation of adrenal steroids from large quantities of animal adrenals resulted in an amorphous fraction resistant to crystallization and identification that had potent effects on electrolyte transport. Aldosterone was eventually isolated and identified in the fraction and was soon shown to cause hypertension when in excess. The autonomous and excessive production of aldosterone, primary aldosteronism, is the most common cause of secondary hypertension. Aldosterone is metabolized in the liver and kidney and its metabolites conjugated with glucuronic acid for excretion. The most common liver metabolite is 3,5-tetrahydroaldosterone-3-glucuronide; that of the kidney is aldosterone-18-oxo-glucuronide. Their values, especially the aldosterone-18-oxo-glucuronide, are commonly used for the diagnosis of primary aldosteronism because they provide and integrated value of the total daily production of aldosterone. Conversion of aldosterone to 18-oxo-glucuronide is impeded by drugs, like some common NSAIDS that compete for UGT2B7, the most important glucuronosyltransferase for aldosterone metabolism. Tetrahydroaldosterone is the most abundant metabolite and most reliable for the diagnosis of primary aldosteronism, but is not commonly measured.