The Pathogenic Role of Diuretic-Induced Aldosterone Secretion

After the introduction of chlorothiazide in 1958,1 as the first of many sulfonamide thiazide diuretics, these orally active diuretics rapidly became the cornerstone for treatment of patients with congestive heart failure (CHF) and other edematous states. These diuretics were also widely adopted for primary or adjuvant antihypertensive drug therapy. Since the beginning, it was recognized that such natriuretic-diuretic therapy in both of these disorders is regularly accompanied by demonstrable body potassium and magnesium deficiencies, often reflected by significant, albeit generally mild, observed decrements in plasma K and Mg levels. But because no particular problems were recognized with broad use of these diuretics, over the years physicians became increasingly sanguine about their occurrence. Accordingly, thiazide diuretics and then, beginning in 1966, the similar but more powerful loop diuretics (eg, furosemide) also became broadly used as primary or adjuvant treatments for high blood pressure and for the edematous state of CHF, cirrhosis with ascites, and nephrotic syndrome.